tbuckley/cabot-search huggingface dataset:
<i>BRAF</i>V600E Mutation and Papillary Thyroid Cancer
Authors: Mingzhao Xing
Journal: JAMA (2013)

To the Editor Our recent multicenter study 1 reported an association between BRAF V600E and PTC-related patient mortality.However, this association was not independent of tumor behaviors and the prognostic value of BRAF V600E was debated in an accompanying Editorial. 2This issue warrants further discussion in several aspects.First, the synergistic interaction between BRAF V600E and tumor behaviors demonstrated in our study 1 suggests that BRAF V600E promotes aggressive tumor behaviors to exert its effect on mortality.Thus, multivariable analyses adjusting for tumor behaviors would artificially nullify the association between BRAF V600E and mortality, underestimating its prognostic value.
The Use of Inhibitors to Study Endocytic Pathways of Gene Carriers: Optimization and Pitfalls
Authors: Dries Vercauteren, Roosmarijn E Vandenbroucke, Arwyn T Jones, Joanna Rejman, Joseph Demeester, Stefaan C De Smedt, Niek N Sanders, Kevin Braeckmans
Journal: Molecular Therapy (2009)

Nonviral gene complexes can enter mammalian cells through different endocytic pathways. For efficient optimization of the gene carrier it is important to profile its cellular uptake, because this largely determines its intracellular processing and subsequent transfection efficiency. Most of the current information on uptake of these gene-delivery vehicles is based on data following the use of chemical inhibitors of endocytic pathways. Here, we have performed a detailed characterization of four commonly used endocytosis inhibitors [chlorpromazine, genistein, methyl-beta-cyclodextrin (MbetaCD), and potassium depletion] on cell viability and endocytosis in five well-described cell lines. We found that chlorpromazine and to a lesser extent MbetaCD significantly decreased cell viability of some cell lines even after short incubation periods and at concentrations that are routinely used to inhibit endocytosis. Through analyzing the uptake and subcellular distribution of two fluorescent endocytic probes transferrin and lactosylceramide (LacCer) that are reported to enter cells via clathrin-dependent (CDE) and clathrin-independent (CIE) mechanisms, respectively, we showed poor specificity of these agents for inhibiting distinct endocytic pathways. Finally, we demonstrate that any inhibitory effects are highly cell line dependent. Overall, the data question the significance of performing endocytosis studies with these agents in the absence of very stringent controls.
Acquired Resistance of Lung Adenocarcinomas to Gefitinib or Erlotinib Is Associated with a Second Mutation in the EGFR Kinase Domain
Authors: William Pao, Vincent A Miller, Katerina A Politi, Gregory J Riely, Romel Somwar, Maureen F Zakowski, Mark G Kris, Harold Varmus
Journal: PLoS Medicine (2005)

Lung adenocarcinomas from patients who respond to the tyrosine kinase inhibitors gefitinib (Iressa) or erlotinib (Tarceva) usually harbor somatic gain-of-function mutations in exons encoding the kinase domain of the epidermal growth factor receptor (EGFR). Despite initial responses, patients eventually progress by unknown mechanisms of "acquired" resistance.We show that in two of five patients with acquired resistance to gefitinib or erlotinib, progressing tumors contain, in addition to a primary drug-sensitive mutation in EGFR, a secondary mutation in exon 20, which leads to substitution of methionine for threonine at position 790 (T790M) in the kinase domain. Tumor cells from a sixth patient with a drug-sensitive EGFR mutation whose tumor progressed on adjuvant gefitinib after complete resection also contained the T790M mutation. This mutation was not detected in untreated tumor samples. Moreover, no tumors with acquired resistance had KRAS mutations, which have been associated with primary resistance to these drugs. Biochemical analyses of transfected cells and growth inhibition studies with lung cancer cell lines demonstrate that the T790M mutation confers resistance to EGFR mutants usually sensitive to either gefitinib or erlotinib. Interestingly, a mutation analogous to T790M has been observed in other kinases with acquired resistance to another kinase inhibitor, imatinib (Gleevec).In patients with tumors bearing gefitinib- or erlotinib-sensitive EGFR mutations, resistant subclones containing an additional EGFR mutation emerge in the presence of drug. This observation should help guide the search for more effective therapy against a specific subset of lung cancers.
Psychiatric Disorders Among Survivors of the Oklahoma City Bombing
Authors: Carol S. North
Journal: JAMA (1999)

ISASTERS OFFER UNIQUE OPportunities to study mental health effects of traumatic events in unselected populations.][4][5][6] The bombing of the Alfred P. Murrah Federal Building in Oklahoma City on April 19, 1995, was the most severe incident of terrorism ever experienced on American soil. 7,8The death count totaled 167, including 19 children; the number of persons injured totaled 684.The fatality rate inside the Murrah Building was 46%, and 93% of survivors who were in the building were injured. 9 The explosion demolished or damaged more than 800 building structures, with an estimated property damage of $625 million.We studied direct survivors of the blast.Our research objectives in-cluded documenting rates of postdisaster psychopathology, examining functional impact, and identifying predictors of these difficulties to help guide mental health intervention workers in future disasters.We anticipated that the scope and severity of this event would elicit higher rates of psychopathology than previous disasters studied using similar research methods.
Abstract 1161: The relationship between the 14-3-3zeta expression pattern and the clinicopathological variables of the 192 gastric cancer patients.
Authors: Tetsuya Aizawa, Yoshiyuki Tsukamoto, Masatsugu Moriyama, Tsuyoshi Noguchi
Journal: Cancer Research (2013)

Abstract Gastric cancer remains one of the most common malignant diseases, despite its steady declining trend worldwide. Overall, gastric cancer mortality is estimated to be 700000 cases annually (10.4% of all cancer related death), ranking second only after lung cancer. 14-3-3zeta, a member of 14-3-3 proteins, have important roles in a wide range of biological processes through the interactions with &amp;gt;100 key proteins, such as FOXO3a, Bad and CCND1. Recent studies have revealed that up-regulation of 14-3-3zeta contribute to the transformation phenotype of breast and lung cancer. However, the relevance of 14-3-3zeta expression in gastric carcinogenesis remained poorly understood. In this study, we aimed to clarify the clinicopathological significance of 14-3-3zeta expression in patients with gastric cancer. A total of 192 gastric cancer specimens were obtained from patients undergoing curative surgery at Oita University Hospital. The expression levels of 14-3-3zeta were investigated by immunohistochemistry. The relationship between the 14-3-3zeta expression pattern and the clinicopathological variables of the gastric cancer patients were analyzed. 14-3-3zeta was strongly expressed in 102of the 192 cases. Strong expression of 14-3-3zeta was correlated with Lymph node metastasis, Histological subtype and Tumor stage (Fisher's exact test, p&amp;lt;0.05). These results suggest that up-regulation of 14-3-3zeta is associated with the clinically malignant features of gastric cancer. Citation Format: Tetsuya Aizawa, Yoshiyuki Tsukamoto, Masatsugu Moriyama, Tsuyoshi Noguchi. The relationship between the 14-3-3zeta expression pattern and the clinicopathological variables of the 192 gastric cancer patients. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1161. doi:10.1158/1538-7445.AM2013-1161
Social Conditions and Self-Management Are More Powerful Determinants of Health Than Access to Care
Authors: Theodore Pincus, Robert John Esther, Darren A Dewalt, Leigh F Callahan
Journal: Annals of Internal Medicine (1998)

Professional organizations advocate universal access to medical care as a primary approach to improving health in the population. Access to medical services is critical to outcomes of acute processes managed in an inpatient hospital, the setting of most medical education, research, and training, but seems to be limited in its capacity to affect outcomes of outpatient care, the setting of most medical activities. Persistent and widening disparities in health according to socioeconomic status provide evidence of limitations of access to care. First, job classification, a measure of socioeconomic status, was a better predictor of cardiovascular death than cholesterol level, blood pressure, and smoking combined in employed London civil servants with universal access to the National Health Service. Second, disparities in health according to socioeconomic status widened between 1970 and 1980 in the United Kingdom despite universal access (similar trends were seen in the United States). Third, in the United States, noncompletion of high school is a greater risk factor than biological factors for development of many diseases, an association that is explained only in part by age, ethnicity, sex, or smoking status. Fourth, level of formal education predicted cardiovascular mortality better than random assignment to active drug or placebo over 3 years in a clinical trial that provides optimal access to care. Increased recognition of limitations of universal access by physicians and their professional societies may enhance efforts to improve the health of the population.
Evidence for Cardiomyopathy in Familial Diabetes Mellitus
Authors: Timothy J. Regan, Michael M. Lyons, S. Sultan Ahmed, Gilbert E. Levinson, Henry A. Oldewurtel, Mehmood R. Ahmad, Bunyad Haider
Journal: Journal of Clinical Investigation (1977)

Recent epidemiologic studies have suggested that cardiac disease in common in diabetics and may often have a noncoronary basis. To examine the status of the left ventricle, 17 adult-onset diabetics of familial type without hypertension or obesity underwent hemodynamic study and were compared to 9 controls of similar age.
Effects of Off-Pump Versus On-Pump Coronary Artery Bypass Grafting on Early and Late Right Ventricular Function
Authors: Tammy J. Pegg, Joseph B. Selvanayagam, Theodoros D. Karamitsos, Ranjit J. Arnold, Jane M. Francis, Stefan Neubauer, David P. Taggart
Journal: Circulation (2008)

Background— Off-pump CABG (OPCABG) results in better preservation of left ventricular function in the perioperative period than conventional on-pump CABG (ONCABG); however, evidence is conflicting as to the effect of OPCABG and ONCABG on right ventricular (RV) function, possibly because of the complexity involved in measuring this. Methods and Results— In a single-center randomized pilot study, 60 patients with normal left ventricular function undergoing CABG were randomly assigned to OPCABG or ONCABG. Patients underwent cardiac magnetic resonance imagine for assessment of RV function preoperatively, early postoperatively, and at 6 months after surgery. Fifty-one patients completed the first 2 scans, and 47 completed all 3 scans. Preoperative characteristics and RV function did not differ significantly between the 2 groups (mean±SD): RV stroke volume index was 49±10 mL/m 2 for OPCABG and 49±16 mL/m 2 for ONCABG. After surgery, RV stroke volume index fell to 36±7 mL/m 2 in the OPCABG group and 39±11 mL/m 2 in the ONCABG group, but this did not differ significantly between the 2 groups ( P =0.41). All markers of RV function recovered to preoperative levels by 6 months, with no long-term difference between the surgical techniques. Conclusions— RV function is impaired early after surgery but recovers by 6 months. The changes were similar in both the OPCABG and ONCABG groups.
Comparison between fat intake assessed by a 3-day food record and phospholipid fatty acid composition of red blood cells: Results from the monitoring of cardiovascular disease-Lille study
Authors: Monique Romon, Marie-Christine Nuttens, Nathalie Théret, Christine Delbart, Jean-Michel Lecerf, Jean-Charles Fruchart, Jean-Louis Salomez
Journal: Metabolism (1995)
Sporadic Cases of Hemorrhagic Colitis Associated with<i>Escherichia coli</i>0157:H7
Authors: CHlK H. PAI
Journal: Annals of Internal Medicine (1984)

During a 6-month period in 1983, Escherichia coli O157:H7 was isolated from 19 (15%) of 125 patients with grossly bloody diarrhea and 1 sibling with non-bloody diarrhea in the Calgary area. There was no clustering of the cases geographically or in time. All but 1 had clinical manifestations typical of hemorrhagic colitis associated with E. coli O157:H7. The illness appeared to be associated with consumption of hamburgers by 15 patients. The diarrheal illness was usually self-limited, but 3 children developed the hemolytic-uremic syndrome shortly after onset of illness. The organism was excreted in the stools very briefly in adults, although bacterial shedding continued for a longer period in children. All isolates produced verotoxin, and cytotoxic activities were present in stool filtrates. The results suggest that the incidence of sporadic cases of hemorrhagic colitis due to E. coli O157:H7 may be higher than has been suspected, and that patients with grossly bloody diarrhea should be studied promptly for E. coli O157:H7 infection. Specific techniques for identifying this serotype must be applied to the stool cultures. Detection of free cytotoxin in stool filtrates may be an effective diagnostic procedure.
Oral Drug Therapy for Multiple Neglected Tropical Diseases
Authors: Madhuri Reddy, Sudeep S. Gill, Sunila R. Kalkar, Wei Wu, Peter J. Anderson, Paula A. Rochon
Journal: JAMA (2007)

The neglected tropical diseases include 13 conditions that occur in areas of extreme poverty and are poverty promoting. The neglected tropical diseases produce a disease burden almost as great as that associated with human immunodeficiency virus/AIDS, tuberculosis, or malaria, yet are virtually unknown by health care workers in North America, because they occur almost exclusively in the poorest regions of the world. Seven of the most prevalent diseases have existing oral drug treatments. Identifying treatments that are effective against more than 1 disease could facilitate efficient and inexpensive treatment.To systematically review the evidence for drug treatments and to increase awareness that neglected tropical diseases exist and that treatments are available.Using a MEDLINE search (1966 through June 2007), randomized controlled trials (RCTs) were reviewed that examined simultaneous treatment of 2 or more of the 7 most prevalent neglected tropical diseases using oral drug therapy.Twenty-nine RCTs were identified, of which 3 targeted 4 diseases simultaneously, 20 targeted 3 diseases, and 6 targeted 2 diseases. Trials were published between 1972 and 2005 and baseline prevalence of individual diseases varied among RCTs. Albendazole plus diethylcarbamazine significantly reduced prevalence of elephantiasis (16.7% to 5.3%), hookworm (10.3% to 1.9%), roundworm (34.5% to 2.3%), and whipworm (55.5% to 40.3%). Albendazole plus ivermectin significantly reduced prevalence of elephantiasis (12.6% to 4.6%), hookworm (7.8% to 0%), roundworm (33.5% to 6.1%), and whipworm (42.7% to 8.9%). Levamisole plus mebendazole significantly reduced prevalence of hookworm (94.0% to 71.8%), roundworm (62.0% to 1.4%), and whipworm (93.1% to 74.5%). Pyrantel-oxantel significantly reduced hookworm (93.4% to 85.2%), roundworm (22.8% to 1.4%), and whipworm (86.8% to 59.5%), while albendazole alone significantly reduced prevalence of hookworm (8.1% to 1.3%), roundworm (28.4% to 0.9%), and whipworm (51.9% to 31.9%). No RCT examined treatment of river blindness or trachoma as part of an intervention to target 2 or more neglected tropical diseases. Adverse events were generally inadequately reported.At least 2 of the most prevalent neglected tropical diseases can be treated simultaneously with existing oral drug treatments, facilitating effective and efficient treatment. Increasing awareness about neglected tropical diseases, their global impact, and the availability of oral drug treatments is an essential step in controlling these diseases.
Endothelial dysfunction of the coronary microvasculature is associated with coronary blood flow regulation in patients with early atherosclerosis.
Authors: A M Zeiher, H Drexler, H Wollschläger, H Just
Journal: Circulation (1991)

The vascular endothelium is capable of regulating tissue perfusion by the release of endothelium-derived relaxing factor to modulate vasomotor tone of the resistance vasculature.To test whether atherosclerosis is associated with a functional abnormality of endothelium-mediated microvascular relaxation affecting coronary blood flow regulation, we compared coronary blood flow responses with cold pressor testing with the response of the coronary vasculature to acetylcholine (an endothelium-dependent vasodilator) and to papaverin (a direct dilator of vascular smooth muscle) in 12 normal control patients and in 19 patients with non-flow-limiting epicardial atherosclerosis (CAD). The drugs were subselectively infused into the left anterior descending coronary artery via a Doppler catheter, and the response in coronary blood flow was assessed by measuring intracoronary blood flow velocity and cross-sectional arterial area (quantitative angiography). Coronary vascular resistance decreased in all normal control patients by -24.1 +/- 5.5% (mean +/- SD) during the cold pressor test, whereas the CAD patients demonstrated a variable coronary vascular resistance response to cold pressor testing despite comparable changes in the rate-pressure product. The slopes of the acetylcholine dose-blood flow response (percent change in coronary blood flow/dosage of acetylcholine) were significantly reduced in the CAD patients with 38.5 +/- 24.8 compared with the normal patients (80.8 +/- 28.1; p less than 0.001). Although coronary blood flow responses to papaverin were slightly but significantly (p less than 0.05) reduced in the CAD patients, the response to the endothelium-dependent dilator acetylcholine was considerably out of proportion to the papaverin response in these patients compared with the normal patients. The capacity of the coronary system to increase blood flow in response to acetylcholine expressed as relative proportion of the maximal papaverin response was 52.5 +/- 18.2% in the normal control patients but only 33.6 +/- 23.6% in the CAD patients (p less than 0.025 versus normals). There was a significant negative correlation (r = -0.69; p less than 0.0001) between cold pressor test-induced changes in coronary vascular resistance and the capacity of the coronary system to increase blood flow in response to acetylcholine.Early stages of epicardial atherosclerosis are associated with an impairment in endothelium-dependent dilation of the coronary microvasculature, indicating that the pathophysiological consequences of atherosclerosis may extend into the human coronary microcirculation. The correlation between cold pressor test-induced coronary vascular resistance changes and the extent of endothelial dysfunction suggests a relation between endothelial function of the microvasculature and coronary blood flow regulation during sympathetic stimulation associated with increased myocardial work.
Effect of Short Message Service on Infant Feeding Practice
Authors: Hong Jiang, Mu Li, Li Ming Wen, Qiaozhen Hu, Dongling Yang, Gengsheng He, Louise A. Baur, Michael J. Dibley, Xu Qian
Journal: JAMA Pediatrics (2014)

Appropriate infant feeding practices have the potential for long-term health effects. However, research findings on improving early infant feeding practices are limited. The wide use of mobile phone short message service (SMS) provides new opportunities for health promotion and services.To assess the effect of an SMS intervention on infant feeding practices.Quasiexperimental design with follow-up measures scheduled at 4, 6, and 12 months at 4 community health centers in Shanghai, China. Two community health centers represented the intervention group, and 2 other community health centers represented the control group.In total, 582 expectant mothers were recruited during the first trimester. Expectant mothers were eligible to participate if they owned a mobile phone, were first-time mothers, conceived a singleton fetus, were older than 20 years and less than 13 weeks' gestation, had completed at least a compulsory junior high school education, and had no illness that limited breastfeeding after childbirth.Mothers in the intervention group received weekly SMS messages about infant feeding from the third trimester to 12 months' post partum.The primary outcome was the duration of exclusive breastfeeding (EBF). Survival analysis was used to compare the duration of EBF between the intervention group and the control group.Compared with the control group, the intervention group had a significantly longer median duration of EBF at 6 months (11.41 [95% CI, 10.25-12.57] vs 8.87 [95% CI, 7.84-9.89] weeks). The hazard ratio for stopping EBF in the intervention group was 0.80 (95% CI, 0.66-0.97). The intervention resulted in a significantly higher rate of EBF at 6 months (adjusted odds ratio, 2.67 [95% CI, 1.45-4.91]) and a significantly lower rate of the introduction of solid foods before 4 months (adjusted odds ratio, 0.27 [95% CI, 0.08-0.94]).An SMS intervention may be effective in promoting EBF, delaying the introduction of solid foods, increasing awareness of the World Health Organization breastfeeding guidelines, and improving knowledge of appropriate infant feeding practices for new mothers.
GONORRHEA IN CHILDHOOD.
Authors: J. W. INGRAM
Journal: JAMA (1907)

<h3>Case 1.</h3> —Colored child, aged 7; previous history negative. <h3>History.</h3> —The child had been sick for three weeks when I was called. The father stated that the child had been treated for typhoid fever during the entire time, but without any appreciable change for the better. The history was misleading in many respects. The child complained of nausea, slight headache, loss of appetite, abdominal tenderness, pain through the small of the back, as the father put it, constipation, frequent and painful micturition. The temperature was less than 100 F., pulse was somewhat accelerated. The general appearance was that of one who had suffered long and patiently. <h3>Examination.</h3> —I suggested to the mother that a more thorough examination of the child be made, to which she readily consented. In the outward appearance of the vulva there was nothing to attract special attention, except that the tissues were slightly inflamed; on pressure
Law to end excessive consultancy fees and hospitality is delayed
Authors: C. Dyer
Journal: BMJ (2011)

Tough new anti-corruption legislation for the UK, which will put doctors who accept excessive consultancy fees and lavish hospitality from drug companies at risk of prosecution, has been delayed.

The Bribery Act, which became law in the last days of the previous Labour government, was on course to come into effect in April. But the coalition Conservative/Liberal Democrat government is reviewing the act after representations by business leaders that it could harm the UK’s competitiveness. …
Points: Antibiotics in surgical treatment of acute abscesses
Authors: R. Grace
Journal: BMJ (1980)

Hyperlipidaemia advances and retreatsDr A LEWIS (London WlN 1FJ) writes: How long will it be before the hazards of eating dairy foods (23 August, p 564) are remembered with amusement like those of eating meat.This dangerous stuff (especially red meat) "caused" kidney disease, hypertension, rheumatism, and gout because it was a source of uric acid and urea, with which these conditions were thought to be associated. Drugs and rheumatoid arthritisDr JACK BOURNE (Hornchurch, Essex) writes: In his letter on the effect of corticosteroids on the manifestations of rheumatoid arthritis,