tbuckley/cabot-search huggingface dataset:
Verdict of the professional conduct committee
Authors: J. Walton
Journal: BMJ (1983)

sagittal plane.The portal vein is not a cylindrical structure in vivo and varies in shape with phase of respiration, position of the patient, and altered intra-abdominal pressure, as in ascites.Using high resolution real time ultrasound we record superior-inferior diameter of the portal vein as it crosses the inferior vena cava in the supine position on inspiration.Our extremes of non-correlation are a diameter of 2-5 cm in the presence of normal portal pressure and a diameter of 0-9 cm with portal hypertension.Previous experience with phlebography had also shown great variation between calibre of the vein and portal pressure.As a rule of thumb the larger the collaterals the smaller the portal vein for a given degree of portal hypertension.We believe it is not possible to predict either the presence or degree of portal hypertension by ultrasonic assessment of portal vein dia- meter.Moreover, we do not accept that one may predict the likelihood of variceal bleeding from such assessment.The evidence quoted to support that one can predict the probability of variceal bleeding from variceal calibre does not stand up to statistical analysis.'It is true that patients with large varices had significantly more gastrointestinal haemorrhage than patients with small varices but there was not a significantly greater risk of variceal bleeding.
Abstract 105: Establishment of imaging-based orthotopic tumor models for pharmacological evaluation of anticancer agents
Authors: Ning Zhang, Wei Wang, Dan Meng, Jinjin Pan, Jing Jin, Yanxia Fan, Wenhao Jin, Shuo Zhang, Ze Chen, Xueqin Yang, Hongjun Wang
Journal: Cancer Research (2014)

Abstract Since its emergence in the mid 90's, the in vivo bioluminescent imaging (BLI) technology has been widely accepted by academia and pharmaceutical industry for research and pre-clinical drug development. The non-invasiveness and high sensitivity nature of BLI enables tumor lesions to be detectable far before they are palpable, allowing longitudinal tracking of tumors from their early development stages. BLI is particularly advantageous for monitoring systemic and orthotopic tumors that are not accessible by caliper measurement. Current preclinical evaluation of anti-cancer agents relies heavily on subcutaneous xenograft models. However, ectopically developed tumors in the subcutaneous tissue differ drastically in tumor stromata in aspects of cell contents and drug permeability, thus will often poorly predict pharmacological efficacy of the test agents. The notion that orthotopic models can better recapitulate the clinical tumor development and metastasis, thus better predict the clinical outcome of the anticancer drugs has gradually gained acceptance. Towards the development of better mouse models for pre-clinical drug development, we have established over twenty imaging based orthotopic tumor cell lines, including U87MG and AM38 brain tumors, HCT116, LoVo and SW620 colorectal cancers, A549 lung cancer, MSTO-211H mesothelioma, Raji and Namalwa lymphoma, MiaPaca-3 and Panc-1 pancreatic cancer, HepG2 liver cancer, and DU145 prostatic cancer. These tumor cells are extremely bright in luminescence emission, ranging from 1085 to 6397 photons/second/cell, thus allowing very sensitive detection in orthotopic tissues even with a few hundred cells. The tumorigenicity of the luciferase labeled cells has been validated in the pertinent orthotopic models. Evaluation of the responsiveness of some of the models to standard therapeutic agents has been conducted. In the U87MG orthotopic glioma model, we observed tumor regression in mice treated with temozolomide in a 5 mg/kg, po, q2d x 5 regimen. Current study of the orthotopic MSTO-211H mesothelioma model in response to standard clinical treatment drugs, such as pemetrexed, carboplatin and paclitaxel is in progress. It is expected that these imaging based orthotopic models will improve the pre-clinical pharmacological evaluation of anti-cancer agents and therefore better bridge the preclinical to clinical translation. Citation Format: Ning Zhang, Wei Wang, Dan Meng, Jinjin Pan, Jing Jin, Yanxia Fan, Wenhao Jin, Shuo Zhang, Ze Chen, Xueqin Yang, Hongjun Wang. Establishment of imaging-based orthotopic tumor models for pharmacological evaluation of anticancer agents. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 105. doi:10.1158/1538-7445.AM2014-105
LASTING BIOLOGICAL EFFECTS OF EARLY ENVIRONMENTAL INFLUENCES
Authors: Chi-Jen Lee, René Dubos
Journal: The Journal of Experimental Medicine (1971)

Specific pathogen-free mice were exposed to three different kinds of environmental stress during early life: (a) by infecting them with a mouse enterovirus on the second day after birth; (b) by placing the mother during pregnancy and lactation on a mildly deficient diet containing wheat gluten supplemented with See PDF for Structure small amounts of lysine and threonine; (c) by combining a (neonatal infection) and b (early malnutrition). All animals survived the three types of stresses, but all exhibited marked depressions of metabolic activity, and of body weights and organ weights. These depressions lasted throughout the experimental period even though all animals were placed under optimum conditions of nutrition and husbandry after weaning, and maintained under these same conditions thereafter. Metabolic activity was determined by measuring the turnover of (14)C-acetate and (14)C-glucose in respiratory CO(2), and their incorporation in total lipids of liver and brain. The utilization of (14)C-acetate was profoundly depressed in all experimental groups with regard to both elimination in respiratory CO(2) and their incorporation in total lipids of liver and brain. In contrast, the utilization of (14)C-glucose was much less affected; its incorporation into lipids was not decreased and its elimination in respiratory CO(2) was depressed only in animals having experienced both neonatal infection and early malnutrition. The extent of weight depression per 100 g of body weight differed according to the organ and the type of stress. Irrespective of the organ, however, depression of weight was largest in animals having experienced both neonatal infection and early malnutrition. And irrespective of the type of stress, the brain exhibited the smallest depression of weight relative to total body weight.
Restoration of Impaired Endothelial Myocyte Enhancer Factor 2 Function Rescues Pulmonary Arterial Hypertension
Authors: Jongmin Kim, Cheol Hwangbo, Xiaoyue Hu, Yujung Kang, Irinna Papangeli, Devi Mehrotra, Hyekyung Park, Hyekyung Ju, Danielle L. McLean, Suzy A. Comhair, Serpil C. Erzurum, Hyung J. Chun
Journal: Circulation (2014)

Background— Pulmonary arterial hypertension (PAH) is a progressive disease of the pulmonary arterioles, characterized by increased pulmonary arterial pressure and right ventricular failure. The cause of PAH is complex, but aberrant proliferation of the pulmonary artery endothelial cells (PAECs) and pulmonary artery smooth muscle cells is thought to play an important role in its pathogenesis. Understanding the mechanisms of transcriptional gene regulation involved in pulmonary vascular homeostasis can provide key insights into potential therapeutic strategies. Methods and Results— We demonstrate that the activity of the transcription factor myocyte enhancer factor 2 (MEF2) is significantly impaired in the PAECs derived from subjects with PAH. We identified MEF2 as the key cis-acting factor that regulates expression of a number of transcriptional targets involved in pulmonary vascular homeostasis, including microRNAs 424 and 503, connexins 37, and 40, and Krűppel Like Factors 2 and 4, which were found to be significantly decreased in PAH PAECs. The impaired MEF2 activity in PAH PAECs was mediated by excess nuclear accumulation of 2 class IIa histone deacetylases (HDACs) that inhibit its function, namely HDAC4 and HDAC5. Selective, pharmacological inhibition of class IIa HDACs led to restoration of MEF2 activity in PAECs, as demonstrated by increased expression of its transcriptional targets, decreased cell migration and proliferation, and rescue of experimental pulmonary hypertension models. Conclusions— Our results demonstrate that strategies to augment MEF2 activity hold potential therapeutic value in PAH. Moreover, we identify selective HDAC IIa inhibition as a viable alternative approach to avoid the potential adverse effects of broad spectrum HDAC inhibition in PAH.
Rat cholangiocytes absorb bile acids at their apical domain via the ileal sodium-dependent bile acid transporter.
Authors: K N Lazaridis, L Pham, P Tietz, R A Marinelli, P C deGroen, S Levine, P A Dawson, N F LaRusso
Journal: Journal of Clinical Investigation (1997)

Although bile acid transport by bile duct epithelial cells, or cholangiocytes, has been postulated, the details of this process remain unclear. Thus, we performed transport studies with [3H]taurocholate in confluent polarized monolayers of normal rat cholangiocytes (NRC). We observed unidirectional (i.e., apical to basolateral) Na+-dependent transcellular transport of [3H]taurocholate. Kinetic studies in purified vesicles derived from the apical domain of NRC disclosed saturable Na+-dependent uptake of [3H]taurocholate, with apparent Km and Vmax values of 209+/-45 microM and 1.23+/-0.14 nmol/mg/10 s, respectively. Reverse transcriptase PCR (RT-PCR) using degenerate primers for both the rat liver Na+-dependent taurocholate-cotransporting polypeptide and rat ileal apical Na+-dependent bile acid transporter, designated Ntcp and ASBT, respectively, revealed a 206-bp product in NRC whose sequence was identical to the ASBT. Northern blot analysis demonstrated that the size of the ASBT transcript was identical in NRC, freshly isolated cholangiocytes, and terminal ileum. In situ RT-PCR on normal rat liver showed that the message for ASBT was present only in cholangiocytes. Immunoblots using a well-characterized antibody for the ASBT demonstrated a 48-kD protein present only in apical membranes. Indirect immunohistochemistry revealed apical localization of ASBT in cholangiocytes in normal rat liver. The data provide direct evidence that conjugated bile acids are taken up at the apical domain of cholangiocytes via the ASBT, and are consistent with the notion that cholangiocyte physiology may be directly influenced by bile acids.
Better to modify the EWTD than go to India for surgical experience
Authors: A. Luther, C. Hart, C. Mann
Journal: BMJ (2012)

The introduction of the European Working Time Directive (EWTD) means that new generations of surgeons will not have had access to the hours in theatre that their seniors did.1 This may lead to consultants having less experience or training taking longer.2 But is moving a portion of …
Alexithymia: Relationship to Severity of Medical Illness and Depression
Authors: Thomas N. Wise, Niranjan N. Jani, Ethan Kass, Kenneth Sonnenschein, Lee S. Mann
Journal: Psychotherapy and Psychosomatics (1988)

The relationship of depression and the severity of medical illness to alexithymia was investigated in 75 medically ill patients seen in psychiatric consultation. Both depression and living alone predicted alexithymia but severity of medical illness was not related to an individual's alexithymic characteristics measured by the revised Schalling-Sifneos Scale. The implications of the findings are discussed in relationship to previous data regarding alexithymia in a psychiatric consultation population.
Governors resist Bush plan to rein in Medicaid costs
Authors: F. Charatan
Journal: BMJ (2003)

The National Governors Association, a lobbying group representing the views of state governors, is in tough negotiations with President Bush over his proposal to set a firm limit on federal Medicaid spending in each state over the next decade.

Bush administration officials have been negotiating over the past two months with a team of 10 governors representing the association. The team, which has members from both parties, includes the president's …
Achieving health for children in public care
Authors: C. M Hill
Journal: BMJ (2003)

Every year in England and Wales over 80 000 children experience public care because their parents are unable to look after them, enough to fill the new stadium at Wembley on cup final day. Unlike football crowds their voices remain largely silent. A primary care trust serving a population of 200 000 will be responsible for the health of about 300 looked after children, equivalent to a medium sized primary school.1 The recent guidance from the Department of Health, Promoting the health of looked after children , for the first time explicitly charges chief executives of primary care trusts with improving the health of these most disadvantaged children.2

Efforts to address the poor health of looked after children are not new. Since 1948 children entering care have been subject to regular medical surveillance. Despite 50 years of medical checks the House of Commons Select Committee published a damning report in 1998, highlighting the appalling health outcomes for these children and the failings of a system that should have been protective.3 …
Reduced retinoid content in hepatocellular carcinoma with special reference to alcohol consumption
Authors: Sadashi Adachi, Hisataka Moriwaki, Yasutoshi Muto, Yasuhiro Yamada, Yasushi Fukutomi, Makoto Shimazaki, Masataka Okuno, Mitsuo Ninomiya
Journal: Hepatology (1991)

Although alcohol is known to enhance hepatocarcinogenesis, the mechanism of this action remains to be explained. To test the hypothesis that ethanol depletes the liver of antitumor promoters such as retinoid, we measured the retinoid concentration in hepatocellular carcinoma tissues and noncancerous surrounding liver tissues in humans known to have a history of alcohol consumption. By high-performance liquid chromatography, the retinoid contents of 29 surgically resected hepatocellular carcinoma specimens and their noncancerous surrounding tissues were measured. Retinoid contents were decreased in both the cancerous and the surrounding noncancerous liver tissues of patients with a high intake of alcohol. The levels correlated inversely with the estimated cumulative lifetime ethanol consumption. The decrease in the retinoid content of hepatic parenchymal cells paralleled that in stellate cells. When compared with the surrounding liver tissues, the cancerous liver tissues were in the state of retinoid deficiency. In summary, alcohol abuse may help promote the hepatocarcinogenesis in man by depleting the liver of the antitumor promoter, retinoid. (Hepatology 1991;14:776-780).
Abstract 5053: ß-catenin inhibitor SST-024 selectively kills tumor initiating cells (TICs)
Authors: Wei Xu
Journal: Cancer Research (2011)

Abstract Recent studies have shown that tumor initiating cells (TICs) are more resistant to therapies than differentiated cancer cells. We have previously shown that aberrant Wnt signaling contributes to the radio-resistance of TICs in breast cancer. Herein, we used SST-024 (StemSynergy), an inhibitor of ß-catenin and WNT signaling, to test whether pharmacologic inhibition of ß-catenin can selectively kills TICs. Sum-149 and MDA-IBC-3, two inflammatory breast cancer cell lines, Sum-159, a non-inflammatory basal-type breast cancer cell line and MCF-12F, a non-tumorigenic breast cell line were used in these studies. We found that SST-024 inhibits proliferation in Sum-159, Sum-149 and MDA-IBC-3 cells with an IC-50 of 140 nM, 200 nM and 15 nM respectively. We also found that SST-024 inhibits mammosphere formation in Sum-159, Sum-149 cells, and MDA-IBC-3 at IC-50 ∼ 5 nm, 0.5nm and 5 nM respectively. On the other hand, the IC-50 for mammosphere formation inhibition in MCF-12F was 100 nM. To test the effect of SST-024 on TICs self-renewal, the secondary mammosphere formation was examined. IC-50 of SST-024 for secondary mammosphere formation inhibition is 3 nM for Sum-159, 5 nM for Sum-149 and 15 nM for MBA-IBC-3. They are all lower than the IC-50 of proliferation inhibition except MAB-IBC-3. Similar efficacy against TICs was seen in assessments of alternative TIC surrogates including aldefluor staining by flow cytometry. In in vivo assay, intra-tumor injection at 0.1µg/per tumor caused tumor growth delay and massive necrosis in tumor. In the meantime, we also tried to find if SST-024 can sensitize the cancer stem cell to radiation therapies. In an in vitro assay, we found that SST-024 can not sensitize the cancer stem cell to radiation therapies, but can sensitize the differentiated cells to radiation therapies. Moreover, we found that SST-024 can significantly reduce the expression of a panel of EMT markers. In summary, SST-024 demonstrates significant efficacy against breast cancer TICs in vivo and in vitro. It can not sensitize TICs to radiation, but sensitize non-TICs to IR. The mechanism is probably through the down-regulation of EMT signaling. All these findings imply targeting Wnt β-catenin signaling may be a feasible strategy to target breast cancer TICs. 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 5053. doi:10.1158/1538-7445.AM2011-5053
Improved Glucose Excursions Using an Implantable Real-Time Continuous Glucose Sensor in Adults With Type 1 Diabetes
Authors: Satish K. Garg, Sherwyn Schwartz, Steven V. Edelman
Journal: Diabetes Care (2004)

OBJECTIVE—The capability of emerging glucose sensor technology to continuously monitor glucose levels may provide ways to achieve glycemic targets while reducing hypoglycemia. RESEARCH DESIGN AND METHODS—A first-generation, long-term continuous glucose sensor (DexCom, San Diego, CA) was implanted subcutaneously in 15 patients with type 1 diabetes. Safety, efficacy, and potential benefits were evaluated during a blinded control period and in a study period during which patients had real-time access to the glucose data. RESULTS—The bias differences between self-monitored blood glucose (SMBG) and sensor data were &amp;lt;15% at 2.8, 4.4, 5.6, 8.3, and 11.1 mmol/l. No procedure or device-related adverse events were observed. Of 15 patients, 13 (87%) had functional sensors during the 12-h simulated home use study with 96% of points in the A and B regions of the Clarke error grid, an R value of 0.88, and a mean absolute relative difference of 16% when retrospectively compared with SMBG. In actual home use, during the blinded control period (50 ± 16 days) data were not displayed to the patient, whereas during the unblinded study period (44 ± 17 days) the data were presented to the patient, and alerts were set at 3.1, 5.6, and 11.1 mmol/l. Patients spent a median of 47% less time below 3.1 mmol/l (P &amp;lt; 0.05) and 25% less time above 13.3 mmol/l (P &amp;lt; 0.05) during the nonblinded study period compared with the blinded control period. CONCLUSIONS—The availability of real-time continuous glucose values may help patients reduce their hyperglycemic excursions and lower the risk of hypoglycemia.
High frequency of autoantibodies bearing cross-reactive idiotopes among hybridomas using VH7183 genes prepared from normal and autoimmune murine strains.
Authors: B Bellon, A Manheimer-Lory, M Monestier, T Moran, A Dimitriu-Bona, F Alt, C Bona
Journal: Journal of Clinical Investigation (1987)

Hybridomas obtained by in vitro stimulation with lipopolysaccharides (LPS) of BALB/c, MRL/lpr, and NZB splenocytes were selected for expression of VH7183 by hybridization using slot blotting. Northern blot analysis showed that the majority of hybrids produce a full length message complementary to the VH7183 probe. The frequency of VH7183 hybridomas was significantly higher in NZB mice as compared with BALB/c mice. Using multiple binding assays, 60% of the total antibodies encoded by VH7183 were specific for self-epitopes. Finally, the vast majority express cross-reactive idiotypes borne by autoantibodies of various specificities.
Pharmacological heterogeneity limits antidepressant study
Authors: A. S Hale
Journal: BMJ (2003)

EDITOR—MacGillivray et al potentially make a huge contribution to the understanding of the relative utility of selective serotonin reuptake inhibitors and older antidepressants in the treatment of depression in primary care.1 However, the usefulness of their meta-analysis is limited by the original data, as is so often the case.

These results …
Europe urged to tackle rise in allergies
Authors: R. Watson
Journal: BMJ (1997)

The medical profession, pharmaceutical industry, and public authorities are all being urged to give a higher priority to tackling allergies, which now affect one in three citizens in Europe and whose direct and indirect costs are estimated at Ecu29bn (£22bn; $36bn) annually.

The call for a rethink in present attitudes and policies is contained in a 120 page white paper, Allergic Diseases as a Public Health Problem , produced by the UCB Institute of Allergy, an independent, non-profit making association …
Invasive Illness with Salmonella Virchow Infection
Authors: V. Mani, J. Brennand, B. K. Mandal
Journal: BMJ (1974)

Salmonella virchow infection in man is usually sporadic and is little known in Britain. We report an outbreak of 21 cases in the Manchester area. The source of infection was believed to be chickens bought at different shops. Symptoms were typhoidal or septicaemic.
Ovarian Ablation Alone Promotes Aortic Intimal Hyperplasia and Accumulation of Fibroblast Growth Factor
Authors: Craig H. Selzman, Jaime S. Gaynor, A. Simon Turner, Sylene M. Johnson, Lawrence D. Horwitz, Thomas A. Whitehill, Alden H. Harken
Journal: Circulation (1998)

Background —Estrogen-mediated cardiovascular protection is incompletely explained by its beneficial lipid-modifying effects. Previous studies interrogating direct vascular effects of estrogens have used models of either diet- or injury-induced atherosclerosis. The purpose of this study was to determine the influence of ovarian ablation alone on vascular remodeling. We hypothesized that estrogens are atheroprotective, independent of their influence on lipid metabolism, by directly influencing the production and effects of a prototypical atherogenic mediator, basic fibroblast growth factor (bFGF). Methods and Results —Twenty-five female sheep were randomized to sham operation, ovariectomy, or ovariectomy plus 17β-estradiol replacement. Serum cholesterol and triglyceride levels were serially measured for 1 year and were similar among groups and in the normal range (30 to 60 mg/dL). At 6, 9, and 12 months, ovariectomy resulted in aortoiliac intimal hyperplasia compared with sham ( P &lt;0.01) and hormone replacement ( P &lt;0.01) groups. The neointima of ovariectomized animals was characterized immunohistochemically by increased vascular smooth muscle cells (VSMCs). Levels of bFGF protein were determined in adjacent aortic segments. Ovariectomized sheep had 2-fold more FGF than sham or ovariectomized sheep that received hormone replacement. In vitro, estradiol inhibited the mitogenic effect of bFGF on human aortic VSMCs. Conclusions —Without dietary manipulation, ovarian ablation alone induces aortic intimal hyperplasia in the ewe. Estradiol abrogates this response independently of its effects on serum lipids. Hormone replacement decreases the accumulation of the atherogenic peptide bFGF in vivo and inhibits the mitogenic response of VSMCs to bFGF in vitro. These results suggest that estrogens may provide atheroprotection both by modulating local production and by attenuating the influence of bFGF on VSMC growth.