tbuckley/cabot-search huggingface dataset:
Wakefield was dishonest and irresponsible over MMR research, says GMC
Authors: C. Dyer
Journal: BMJ (2010)

Andrew Wakefield, the gastroenterologist whose suggestion of a link between autism, bowel disease and the measles virus sparked a UK wide scare over the safety of the measles, mumps, and rubella (MMR) vaccine, has been found guilty of dishonesty and irresponsibility by the General Medical Council.

The UK regulator held that Dr Wakefield abused his position, subjected children to intrusive procedures such as lumbar puncture and colonoscopy that were not clinically indicated, carried out research which flouted the conditions of ethics committee approval and brought the medical profession into disrepute.

One of the biggest public health scares in UK history was triggered by Dr Wakefield’s study …
Ter die sumendus
Authors: Chris Ellis
Journal: BMJ (2006)

In 1964 I was in one of the last years of UK medical students trained at the old Charing Cross Medical School in the art of making mixtures and the use of the pestle and mortar. Our pharmacology classes took place in what had once been a fashionable restaurant across the road from the hospital, by then converted into laboratories. The ornate pressed ceilings and chandeliers had been left, which gave the laboratories a rather bizarre atmosphere—a mixture of Georgian elegance and Neo-Gothic pillars fused with Bunsen burners and a modernistic skyline of distillation flasks.

I have the printed pharmacology lecture notes in front of me. I see …
Have Regulatory Efforts to Reduce Organophosphorus Insecticide Exposures Been Effective?
Authors: Alison L. Clune, P. Barry Ryan, Dana Boyd Barr
Journal: Environmental Health Perspectives (2012)

The Food Quality Protection Act (FQPA) was signed into law in 1996 to strengthen the regulation of pesticide tolerances in food. Organophosphorus (OP) insecticides were the first group of pesticides reviewed by the U.S. Environmental Protection Agency (EPA) under the new law.Our goal was to determine whether urinary concentrations of dialkylphosphate (DAP) metabolites of OP pesticides declined between the National Health and Nutrition Examination Survey (NHANES) III and NHANES 1999-2004.Using mass spectrometry-based methods, we analyzed urine samples from a nationally representative sample of 2,874 adults 20-59 years of age in NHANES 1999-2004 and samples from a non-nationally representative sample of 197 adult participants for NHANES III (1988-1994) for six common DAP metabolites of OP pesticides.Median urinary DAP concentrations decreased by more than half between NHANES III and NHANES 2003-2004. Reductions of about 50%-90% were also observed for 95th percentile concentrations of five of the six metabolites. Frequencies of detection (FODs) decreased in all six metabolites (< 50% reduction). On average, median and 95th percentile concentrations and FODs showed a larger decrease in diethylphosphate metabolites than dimethylphosphate metabolites.Human exposure to OP insecticides as assessed by urinary DAP concentrations has decreased since the implementation of the FQPA, although we cannot be certain that U.S. EPA actions in response to the FQPA directly caused the decrease in DAP concentrations.
Prevalence of Attempting Weight Loss and Strategies for Controlling Weight
Authors: Mary K. Serdula
Journal: JAMA (1999)

Overweight and obesity are increasing in the United States. Changes in diet and physical activity are important for weight control.To examine the prevalence of attempting to lose or to maintain weight and to describe weight control strategies among US adults.The Behavioral Risk Factor Surveillance System, a random-digit telephone survey conducted in 1996 by state health departments. Setting The 49 states (and the District of Columbia) that participated in the survey.Adults aged 18 years and older (N = 107 804).Reported current weights and goal weights, prevalence of weight loss or maintenance attempts, and strategies used to control weight (eating fewer calories, eating less fat, or using physical activity) by population subgroup.The prevalence of attempting to lose and maintain weight was 28.8% and 35.1 % among men and 43.6% and 34.4% among women, respectively. Among those attempting to lose weight, a common strategy was to consume less fat but not fewer calories (34.9% of men and 40.0% of women); only 21.5% of men and 19.4% of women reported using the recommended combination of eating fewer calories and engaging in at least 150 minutes of leisure-time physical activity per week. Among men trying to lose weight, the median weight was 90.4 kg with a goal weight of 81.4 kg. Among women, the median weight was 70.3 kg with a goal weight of 59.0 kg.Weight loss and weight maintenance are common concerns for US men and women. Most persons trying to lose weight are not using the recommended combination of reducing calorie intake and engaging in leisure-time physical activity 150 minutes or more per week.
Recent Trends in Cutaneous Melanoma Incidence Among Whites in the United States
Authors: A. Jemal, S. S. Devesa, P. Hartge, M. A. Tucker
Journal: JNCI Journal of the National Cancer Institute (2001)

It is not yet clear whether increasing melanoma incidence is real or whether recent incidence trends mainly reflect improved diagnosis. To address this question, we examined the most recent melanoma incidence patterns among the white population stratified by sex, age, tumor stage, and tumor thickness by use of data from the Surveillance, Epidemiology, and End Results Program.We examined log-transformed age-specific rates for melanoma by 5-year age groups and time periods by year of diagnosis and birth cohort. Melanoma trends were further examined among broader age groups (<40 years, 40-59 years, and > or =60 years) by tumor stage and tumor thickness. Rates were age-adjusted to the 1970 U.S. standard population, and trends were tested by use of a two-sided Student's t test.Melanoma incidence increased in females born since the 1960s. From 1974-1975 through 1988-1989, upward trends for the incidence of localized tumors and downward trends for the incidence of distant-stage tumors occurred in the age group under 40 years. In the more recent time period, 1990-1991 through 1996-1997, age specific rates among females compared with males generally remained stable or declined more for distant-stage tumors and increased less for local-stage tumors. Thin tumors (<1 mm) increased statistically significantly in all age groups (P<.05 for all), except in men under age 40 years. In contrast, rates for thick tumors (> or =4 mm) increased statistically significantly (P =.0003) only in males aged 60 years and older.Melanoma incidence may well continue to rise in the United States, at least until the majority of the current population in the middle-age groups becomes the oldest population. The recent trends may reflect increased sunlight exposure.
Trypanosoma cruzi: mechanism of entry and intracellular fate in mammalian cells.
Authors: N Nogueira, Z Cohn
Journal: The Journal of Experimental Medicine (1976)

The mode of entry and intracellular fate of epimastigotes and trypomastigotes of Trypanosoma cruzi in cultured cells was studied. Electron microscopic observations indicated the uptake by phagocytosis of both forms into mouse peritoneal macrophages and of trypomastigotes and transition forms into other cultured cell types. In each instance the organisms were initially surrounded by a plasma membrane-derived phagosome. Trypsin and chymotrypsin treatment of the macrophages completely abolished attachment and ingestion of both forms, indicating that protease-sensitive structures on the macrophage plasma membrane mediate ingestion. The macrophage Fc or C3b receptors were not essential for uptake of T. cruzi in the conditions used. Cytochalasin B inhibited ingestion but not the attachment of both forms by macrophages. Epimastigotes were not taken up by HeLa, L cells, and calf embryo fibroblasts. In macrophages, epimastigotes were killed and digested within phagolysosomes. In contrast, trypomastigotes and transition forms escaped from the phagocytic vacuole and then multiplied in the cytoplasmic matrix. Amastigotes released from infected cells exhibited properties similar to those of trypomastigotes and were able to enter all cell types studied and multiply intracellularly.
5 IDENTIFICATION OF RECURRENT SOMATIC MUTATION ACTIVATING GP130 IN INFLAMMATORY HEPATOCELLULAR TUMORS: A NEW PATHWAY OF TUMORIGENESIS IN HUMAN/S
Authors: J. Zucman-Rossi, S. Rebouissou, M. Amessou, G. Couchy, K. Poussin, C. Balabaud, P. Bioulac-Sage, G. Genthep
Journal: Journal of Hepatology (2009)
Second Messengers of Insulin Action
Authors: Alan R Saltiel
Journal: Diabetes Care (1990)

Despite significant advances in past years on the chemistry and biology of insulin and its receptor, the molecular events that couple the insulin-receptor interaction to the regulation of cellular metabolism remain uncertain. Progress in this area has been complicated by the pleiotropic nature of the actions of insulin. These most likely involve a complex network of pathways resulting in the coordination of mechanistically distinct cellular effects. Because the well-recognized mechanisms of signal transduction (i.e., cyclic nucleotides, ion channels) appear not to be central to insulin action, investigators have searched for a novel second-messenger system. A low-molecular-weight substance has been identified that mimics certain actions of insulin on metabolic enzymes. This substance has an inositol glycan structure, and is produced by the insulin-sensitive hydrolysis of a glycosylphosphatidylinositol in the plasma membrane. This hydrolysis reaction, which is catalyzed by a specific phospholipase C, also results in the production of a structurally distinct diacylglycerol that may selectively regulate one or more of the protein kinases C. The glycosyl-phosphatidylinositol precursor for the inositol glycan enzyme modulator is structurally analogous to the recently described glycosyl-phosphatidylinositol membrane protein anchor. Preliminary studies suggest that a subset of proteins anchored in this fashion may be released from cells by a similar insulin-sensitive phospholipase-catalyzed reaction. Future efforts will focus on the precise role of the metabolism of glycosyl phosphatidylinositols in insulin action.
Exploiting Warburg's Effect for Clinical Gain: Pdk-3 is a Potential Target for Mitochondrial Modulation in Colorectal Cancer (CRC)
Authors: S. Yeluri, B. Madhok, P. Prasad, M.J. Alemkunnapuzzha, H.L. Thorpe, S.L. Perry, T.A. Hughes, K.R. Prasad, P. Quirke, D.G. Jayne
Journal: International Journal of Surgery (2010)
Carotenaemia Occurring in a Case of Anorexia Nervosa
Authors: P. J. Dally
Journal: BMJ (1959)

Another interesting point is the ratio of four males to one female having a duodenal ulcer.Numerous investigations have shown that the sex incidence shows a far greater percentage of duodenal ulcers occurring in the male than in the female, the average being in the region of 80% male.I Summary A family is described in which duodenal ulcers occurred in several members.Five of the family-four brothers and one sister-had partial gastrectomies.Apart from a direct family relationship, no other common factor has been found which might be significant in the aetiology.
Exaggerated responsiveness to thyrotrophin releasing hormone: a risk factor in women with coronary artery disease.
Authors: J W Dean, P B Fowler
Journal: BMJ (1985)

Thyroid function tests were performed and thyroid antibodies and serum cholesterol concentrations measured in 12 women aged 60 years or under with severe coronary artery disease proved by coronary angiography. This group was compared with 11 women with normal coronary angiography. Ten out of the 12 women with coronary artery disease had an exaggerated response of thyroid stimulating hormone to thyrotrophin releasing hormone compared with two out of 11 controls (p less than 0.008). The mean serum cholesterol concentration was significantly higher in those with coronary artery disease than in the controls. Thyroid antibodies were present in four of those with coronary artery disease and one of the controls. There was no difference in the risk factors for coronary artery disease between the two groups except for cigarette smoking. Eleven out of 12 in the coronary artery disease group smoked cigarettes compared with four out of 11 in the control group (p less than 0.01). Minimal impairment of thyroid function is an important risk factor for coronary artery disease in women.
Electronic Patient Portals: Evidence on Health Outcomes, Satisfaction, Efficiency, and Attitudes
Authors: Caroline Lubick Goldzweig, Greg Orshansky, Neil M. Paige, Ali Alexander Towfigh, David A. Haggstrom, Isomi Miake-Lye, Jessica M. Beroes, Paul G. Shekelle
Journal: Annals of Internal Medicine (2013)

Background: Patient portals tied to provider electronic health record (EHR) systems are increasingly popular. Purpose: To systematically review the literature reporting the effect of patient portals on clinical care. Data Sources: PubMed and Web of Science searches from 1 January 1990 to 24 January 2013. Study Selection: Hypothesis-testing or quantitative studies of patient portals tethered to a provider EHR that addressed patient outcomes, satisfaction, adherence, efficiency, utilization, attitudes, and patient characteristics, as well as qualitative studies of barriers or facilitators, were included. Data Extraction: Two reviewers independently extracted data and addressed discrepancies through consensus discussion. Data Synthesis: From 6508 titles, 14 randomized, controlled trials; 21 observational, hypothesis-testing studies; 5 quantitative, descriptive studies; and 6 qualitative studies were included. Evidence is mixed about the effect of portals on patient outcomes and satisfaction, although they may be more effective when used with case management. The effect of portals on utilization and efficiency is unclear, although patient race and ethnicity, education level or literacy, and degree of comorbid conditions may influence use. Limitation: Limited data for most outcomes and an absence of reporting on organizational and provider context and implementation processes. Conclusion: Evidence that patient portals improve health outcomes, cost, or utilization is insufficient. Patient attitudes are generally positive, but more widespread use may require efforts to overcome racial, ethnic, and literacy barriers. Portals represent a new technology with benefits that are still unclear. Better understanding requires studies that include details about context, implementation factors, and cost. Primary Funding Source: U.S. Department of Veterans Affairs.
Wilms Tumor in an Adult Associated With Androgen Abuse
Authors: Jaime Prat
Journal: JAMA (1977)

AN INSTANCE of Wilms tumor in an adult man who had used large amounts of anabolic androgenic steroids as part of a body-building program is reported. The association of tumors of the liver with use of anabolic steroids has been increasingly documented in recent years, but, to the best of our knowledge, these drugs have not been associated with development of embryonal neoplasms of other organs.<sup>1</sup> <h3>Report of a Case</h3> A 38-year-old man with a two-year history of increasing left flank pain was admitted to The New York Hospital-Cornell Medical Center for examination of a renal mass identified at another hospital. He gave a history of having been involved in competitive body building, but an unusual drug history was not elicited from him. Sonography showed a mass 7 cm in diameter in the upper half of the left kidney and also suggested an infiltrative process in the lower half
Bahraini authorities jail 23 medical staff for three months for role in protests
Authors: S. Arie
Journal: BMJ (2012)

A court in Bahrain has sentenced 23 medical professionals to three months in jail or a fine of 200 dinars (£330; €410; $530) for taking part in protests against the authorities last year.

The defendants, 11 doctors, several nurses, and other medical professionals, “committed crimes and violations, breaching the law and the [medical] norms,” said the prosecutor Abdulrahman al-Sayyed, according to the state news service BNA. They have been charged with “taking part in unauthorised demonstrations.”

The 23, all of them Shia, were among a larger group who were accused of acting against …
Peroxisome proliferator-activated receptor α activates human multidrug resistance transporter 3/ATP-binding cassette protein subfamily B4 transcription and increases rat biliary phosphatidylcholine secretion
Authors: Nisanne S. Ghonem, Meenakshisundaram Ananthanarayanan, Carol J. Soroka, James L. Boyer
Journal: Hepatology (2013)

Multidrug resistance transporter 3/ATP-binding cassette protein subfamily B4 (MDR3/ABCB4) is a critical determinant of biliary phosphatidylcholine (PC) secretion. Clinically, mutations and partial deficiencies in MDR3 result in cholestatic liver injury. Thus, MDR3 is a potential therapeutic target for cholestatic liver disease. Fenofibrate is a peroxisome proliferator-activated receptor (PPAR) α ligand that has antiinflammatory actions and regulates bile acid detoxification. Here we examined the mechanism by which fenofibrate regulates MDR3 gene expression. Fenofibrate significantly up-regulated MDR3 messenger RNA (mRNA) and protein expression in primary cultured human hepatocytes, and stimulated MDR3 promoter activity in HepG2 cells. In silico analysis of 5′-upstream region of human MDR3 gene revealed a number of PPARα response elements (PPRE). Electrophoretic mobility shift (EMSA) and chromatin immunoprecipitation (ChIP) assays demonstrated specific binding of PPARα to the human MDR3 promoter. Targeted mutagenesis of three novel PPREs reduced inducibility of the MDR3 promoter by fenofibrate. In collagen sandwich cultured rat hepatocytes, treatment with fenofibrate increased secretion of fluorescent PC into bile canaliculi. Conclusion: Fenofibrate transactivates MDR3 gene transcription by way of the binding of PPARα to three novel and functionally critical PPREs in the MDR3 promoter. Fenofibrate treatment further stimulates biliary phosphatidylcholine secretion in rat hepatocytes, thereby providing a functional correlate. We have established a molecular mechanism that may contribute to the beneficial use of fenofibrate therapy in human cholestatic liver disease. (Hepatology 2014;59:1030–1042)
Aggressive vs. Conservative Phototherapy for Infants with Extremely Low Birth Weight
Authors: Brenda H. Morris, William Oh, Jon E. Tyson, David K. Stevenson, Dale L. Phelps, T. Michael O'Shea, Georgia E. McDavid, Rebecca L. Perritt, Krisa P. Van Meurs, Betty R. Vohr, Cathy Grisby, Qing Yao, Claudia Pedroza, Abhik Das, W. Kenneth Poole, Waldemar A. Carlo, Shahnaz Duara, Abbot R. Laptook, Walid A. Salhab, Seetha Shankaran, Brenda B. Poindexter, Avroy A. Fanaroff, Michele C. Walsh, Maynard R. Rasmussen, Barbara J. Stoll, C. Michael Cotten, Edward F. Donovan, Richard A. Ehrenkranz, Ronnie Guillet, Rosemary D. Higgins
Journal: New England Journal of Medicine (2008)

It is unclear whether aggressive phototherapy to prevent neurotoxic effects of bilirubin benefits or harms infants with extremely low birth weight (1000 g or less).
EFFECT OF COMPOUND SOLUTION OF IODIN AND REST IN SURGERY OF EXOPHTHALMIC GOITER
Authors: HOWARD M. CLUTE
Journal: JAMA (1926)

For many years, iodin has been known to be of value in the treatment of disorders of the thyroid gland. Marine, in 1911, showed that iodin would produce involution in a hyperplastic thyroid gland and recommended the use of iodin to prevent hyperplasia of the thyroid. Neisser used potassium iodid in 1920 for treating exophthalmic goiter and reported definite improvement in eight cases. Loewy and Zondek, in 1921, published a similar series of results. Dr. H. S. Plummer was the first to show conclusively the great value of iodin in the treatment of exophthalmic goiter, and to him the credit for the present extensive clinical application of this medicine must be given.  Compound solution of iodin (Lugol's solution) has been used in 200 cases of primary hyperthyroidism in the clinic. Many patients come to the clinic who have had iodin in this or some other form, in length of time
Induction of autophagy by Imatinib sequesters Bcr‐Abl in autophagosomes and down‐regulates Bcr‐Abl protein
Authors: Baukje M. Elzinga, Michelle J. Nyhan, Lisa C. Crowley, Tracey R. O'Donovan, Mary R. Cahill, Sharon L. McKenna
Journal: American Journal of Hematology (2013)

Chronic Myeloid Leukemia (CML) is a disease of hematopoietic stem cells which harbor the chimeric gene Bcr-Abl. Expression levels of this constitutively active tyrosine kinase are critical for response to tyrosine kinase inhibitor treatment and also disease progression, yet the regulation of protein stability is poorly understood. We have previously demonstrated that imatinib can induce autophagy in Bcr-Abl expressing cells. Autophagy has been associated with the clearance of large macromolecular signaling complexes and abnormal proteins, however, the contribution of autophagy to the turnover of Bcr-Abl protein in imatinib treated cells is unknown. In this study, we show that following imatinib treatment, Bcr-Abl is sequestered into vesicular structures that co-localize with the autophagy marker LC3 or GABARAP. This association is inhibited by siRNA mediated knockdown of autophagy regulators (Beclin 1/ATG7). Pharmacological inhibition of autophagy also reduced Bcr-Abl/LC3 co-localization in both K562 and CML patient cells. Bcr-Abl protein expression was reduced with imatinib treatment. Inhibition of both autophagy and proteasome activity in imatinib treated cells was required to restore Bcr-Abl protein levels to those of untreated cells. This ability to down-regulate Bcr-Abl protein levels through the induction of autophagy may be an additional and important feature of the activity of imatinib.
Ambulatory small intestinal motility in 'diarrhoea' predominant irritable bowel syndrome.
Authors: D A Gorard, G W Libby, M J Farthing
Journal: Gut (1994)

Dysmotility of the duodenum and proximal jejunum has been reported in patients with irritable bowel syndrome. This study extended these findings by recording fasting ambulatory motility from electronic strain gauge sensors sited in the jejunum and ileum of eight diarrhoea predominant irritable bowel syndrome patients and 12 healthy controls. During the day, periodicity of migrating motor complexes mean (SEM) did not differ between patients (92 (10) min) and controls (85 (7) min). At night, periodicity was shorter in both patients and controls, and the daytime dominance of phase II was replaced by phase I. In both groups, aboral progression of phase III fronts was associated with a slowing of propagation velocity and maximum contractile rate, but an increase in mean amplitude of contraction. Discrete clustered contractions were seen in seven patients and 10 controls occupying 14 and 16% of daytime phase II activity, respectively. Pain episodes were not associated with any specific motility patterns. Despite the lack of motility differences between the two groups, orocaecal transit time in the irritable bowel syndrome patients was shorter at 57 (9) min than in the controls, 82 (6) min (p &lt; 0.05). This ambulant study has failed to show any abnormalities of fasting small intestinal motility that might distinguish diarrhoea predominant irritable bowel syndrome patients from healthy controls.