tbuckley/cabot-search huggingface dataset:
Hemochromatosis Gene Mutations, Body Iron Stores, Dietary Iron, and Risk of Colorectal Adenoma in Women
Authors: Andrew T. Chan, Jing Ma, Gregory J. Tranah, Edward L. Giovannucci, Nader Rifai, David J. Hunter, Charles S. Fuchs
Journal: JNCI Journal of the National Cancer Institute (2005)

Some experimental evidence suggests that iron may play a role in colorectal carcinogenesis, but human data for this role have been conflicting, possibly because of problems related to study design or measurement of iron exposure. We assessed dietary iron intake and genetic and biochemical markers of iron status in a prospective, nested case-control study of women enrolled in the Nurses' Health Study.Among 32 826 women who provided a blood specimen, we identified 527 women with colorectal adenoma and 527 matched control subjects who underwent endoscopy but were not diagnosed with adenoma after blood collection. We assessed iron intake, mutations in the HFE gene that are associated with hereditary hemochromatosis (i.e., H63D and C282Y), and plasma biochemical measures of total body iron, including transferrin saturation and the ratio of the concentrations of transferrin receptors to ferritin. Logistic regression models were used to estimate relative risks (RR) and 95% confidence intervals (CI). All statistical tests were two-sided.Women with any HFE gene mutation had higher total body iron stores, as reflected by higher transferrin saturations (P < .001) and lower levels of the ratio of transferrin receptors to ferritin (P = .02), than women with no HFE gene mutation. However, HFE gene mutations were not associated with risk of adenoma (multivariable RR = 1.08, 95% CI = 0.83 to 1.39; P = .58). Moreover, comparison of extreme categories showed no associations between adenoma and the extent of transferrin saturation (multivariable RR = 0.96, 95% CI = 0.63 to 1.47; Ptrend = .66), the ratio of transferrin receptors to ferritin (multivariable RR = 0.98, 95% CI, 0.60 to 1.60; Ptrend = .99), or dietary iron intake (multivariable RR = 1.04, 95% CI = 0.68 to 1.57; Ptrend = .94).Although our study used several distinct measures of iron status (i.e., genetic mutations, biochemical markers, and dietary intake) and a nested case-control design, we did not observe a role for iron in the pathogenesis of colorectal neoplasia in women.
New Strategies in Prostate Cancer: Targeting Lipogenic Pathways and the Energy Sensor AMPK
Authors: Giorgia Zadra, Carmen Priolo, Akash Patnaik, Massimo Loda
Journal: Clinical Cancer Research (2010)

Although the role of metabolic syndrome (MS) and a high fat diet in prostate cancer (PCa) risk is still a matter of intense debate, it is becoming increasingly clear that obesity can cause perturbations in metabolic pathways that contribute to the pathogenesis and progression of PCa. Moreover, prostate epithelial cells per se undergo a series of metabolic changes, including an increase in de novo lipogenesis, during the process of tumor formation. These metabolic alterations, at both the cellular and organismal levels, are intertwined with genetic aberrations necessary for neoplastic transformation. Thus, altered metabolism is currently subject to intense research efforts and might provide preventative and therapeutic opportunities, as well as a platform for biomarker development. In this article, we review evidence that the metabolic sensor 5'-AMP-activated protein kinase (AMPK), which physiologically integrates nutritional and hormonal signals and regulates cell survival and growth-related metabolic pathways to preserve intracellular ATP levels, represents a link between energy homeostasis and cancer. Thus, when AMPK is not activated, as in the setting of MS and obesity, systemic metabolic alterations permissive to the development of PCa are allowed to proceed unchecked. Hence, the use of AMPK activators and inhibitors of key lipogenic enzymes may represent a promising therapeutic strategy for PCa.
Self-experimentation as science
Authors: Harold L. Miller, Jr.
Journal: Behavioral and Brain Sciences (2004)

Examination of the target article for its relevance to the analysis of private behavior leads to three concerns: the absence of a new methodology for studying private behavior, the undisclosed possibility of interactions, and insufficient attention to the social context of idea generation. Regardless of these concerns, a larger issue remains: Can a science of n = 1 be credible?
Lack of Community Insurance and Mammography Screening Rates Among Insured and Uninsured Women
Authors: José A. Pagán, David A. Asch, Cynthia J. Brown, Carmen E. Guerra, Katrina Armstrong
Journal: Journal of Clinical Oncology (2008)

Purpose To evaluate whether the proportion of the local population without health insurance coverage is related to whether women undergo mammography screening. Methods Survey data on 12,595 women 40 to 69 years of age from the 2000 to 2001 Community Tracking Study Household Survey were used to analyze the relation between community lack of insurance and whether the respondent had a mammogram within the past year. Results Women age 40 to 69 were less likely to report that they had a mammogram within the last year if they resided in communities with a relatively high uninsurance rate, even after adjusting for other factors. After adjusting for individual insurance and other factors, a 10-percentage-point decrease in the proportion of the local insured population is associated with a 17% (95% CI, 13% to 21%) decrease in the odds that a woman age 40 to 69 years will undergo mammography screening within a year. Conclusion Women living in communities with high uninsurance are substantially less likely to undergo mammography screening. These results are consistent with the view that the negative impact of uninsurance extends to everyone in the community regardless of individual health insurance status.
Two Distinct Routes to Oral Cancer Differing in Genome Instability and Risk for Cervical Node Metastasis
Authors: Aditi Bhattacharya, Ritu Roy, Antoine M. Snijders, Gregory Hamilton, Jesse Paquette, Taku Tokuyasu, Henrik Bengtsson, Richard C. K. Jordan, Adam B. Olshen, Daniel Pinkel, Brian L. Schmidt, Donna G. Albertson
Journal: Clinical Cancer Research (2011)

Problems in management of oral cancers or precancers include identification of patients at risk for metastasis, tumor recurrence, and second primary tumors or risk for progression of precancers (dysplasia) to cancer. Thus, the objective of this study was to clarify the role of genomic aberrations in oral cancer progression and metastasis.The spectrum of copy number alterations in oral dysplasia and squamous cell carcinomas (SCC) was determined by array comparative genomic hybridization. Associations with clinical characteristics were studied and results confirmed in an independent cohort.The presence of one or more of the chromosomal aberrations +3q24-qter, -8pter-p23.1, +8q12-q24.2, and +20 distinguishes a major subgroup (70%-80% of lesions, termed 3q8pq20 subtype) from the remainder (20%-30% of lesions, non-3q8pq20). The 3q8pq20 subtype is associated with chromosomal instability and differential methylation in the most chromosomally unstable tumors. The two subtypes differ significantly in clinical outcome with risk for cervical (neck) lymph node metastasis almost exclusively associated with the 3q8pq20 subtype in two independent oral SCC cohorts.Two subtypes of oral lesions indicative of at least two pathways for oral cancer development were distinguished that differ in chromosomal instability and risk for metastasis, suggesting that +3q,-8p, +8q, and +20 constitute a biomarker with clinical utility for identifying patients at risk for metastasis. Moreover, although increased numbers of genomic alterations can be harbingers of progression to cancer, dysplastic lesions lacking copy number changes cannot be considered benign as they are potential precursors to non-3q8pq20 locally invasive, yet not metastatic oral SCC.
Two-Year Clinical Outcomes With Drug-Eluting Stents for Diabetic Patients With De Novo Coronary Lesions
Authors: Paolo Ortolani, Marco Balducelli, Paolo Marzaroli, Giancarlo Piovaccari, Alberto Menozzi, Vincenzo Guiducci, Pietro Sangiorgio, Fabio Tarantino, Giuseppe Geraci, Fausto Castriota, Stefano Tondi, Francesco Saia, Robin M.T. Cooke, Paolo Guastaroba, Roberto Grilli, Antonio Marzocchi, Aleardo Maresta
Journal: Circulation (2008)

The long-term effectiveness of drug-eluting stents (DES) in unselected diabetics in routine practice is currently unclear.To evaluate the long-term effectiveness of bare metal stents and DES in a real-world setting of diabetic patients, we analyzed 2-year follow-up data from all diabetic patients with de novo lesions enrolled in a prospective Web-based multicenter registry (Registro Regionale Angioplastiche dell'Emilia-Romagna; study period, 2002 to 2004) comprising all 13 hospitals performing percutaneous coronary interventions in the Emilia-Romagna region of Italy. Among the 1648 eligible patients treated with either bare metal stents alone (n=1089) or DES alone (n=559), 27% were insulin dependent and 83% had multivessel coronary disease. At 2 years, use of DES was associated with lower crude incidence of major adverse cardiac advents (all-cause mortality, nonfatal myocardial infarction, and target vessel revascularization) compared with bare metal stents (22.5% versus 28.1%; P=0.01). After propensity score adjustment, only target vessel revascularization appeared significantly lower in the DES group (11.6% versus 15.0%; hazard ratio, 0.66; 95% confidence interval, 0.46 to 0.96; P=0.041). Two-year angiographic stent thrombosis occurred in 1.5% DES patients and 0.7% of the bare-metal-stents patients (P=0.18). At Cox regression analysis, predictors of 2-year major adverse cardiac advents were left ventricular ejection fraction <35%, Charlson comorbidity index, insulin-dependent diabetes, and total lesion length.In this large, real-world, diabetic population, the use of DES was associated with a moderate reduction in the 2-year risk of target vessel revascularization, a benefit that was limited to non-insulin-dependent diabetic patients. Larger long-term studies are needed to clarify the long-term effectiveness and safety of such devices in diabetic patients.
Androgen regulation of epidermal growth factor receptor binding activity during fetal rabbit lung development.
Authors: J M Klein, H C Nielsen
Journal: Journal of Clinical Investigation (1993)

Fetal lung development progresses in a sex-specific manner with male fetuses exhibiting delayed maturation. Androgens, both exogenous and endogenous, inhibit while epidermal growth factor (EGF) enhances fetal lung development. We hypothesized that one mechanism responsible for the delay in male fetal lung development is an androgen-induced delay in EGF receptor binding activity. We measured EGF binding in sex-specific fetal rabbit lung plasma membranes isolated from control fetuses (days 21, 23, 25, 27, 29, and 30 of gestation) and from androgen-treated fetuses (days 21, 23, and 27 of gestation) that had been continuously exposed in vivo to exogenous 5 alpha-dihydrotestosterone from day 12 through 27 of gestation. Specific binding of EGF was significantly lower in male than in female fetal lung tissue isolated from controls at day 21 of gestation. Scatchard analysis revealed that this decrease in EGF binding was associated with decreased EGF receptor density without any significant change in affinity. Prenatal exogenous androgen treatment led to decreased EGF binding in fetal rabbit lung tissue from both sexes secondary to a decrease in EGF receptor density. These findings suggest that one mechanism responsible for the delay in male fetal lung maturation is an androgen-induced delay in EGF receptor binding activity during fetal lung development.
Child Mortality Estimation: Accelerated Progress in Reducing Global Child Mortality, 1990–2010
Authors: Kenneth Hill, Danzhen You, Mie Inoue, Mikkel Z. Oestergaard
Journal: PLoS Medicine (2012)

Kenneth Hill and colleagues provide an introductory overview of how the latest United Nations Inter-agency Group for Child Mortality Estimation estimates were produced, summarizes the key findings of these estimates and describe current methodology and recent methodological innovations.
Dynamic Aspects of CNS Synapse Formation
Authors: A. Kimberley McAllister
Journal: Annual Review of Neuroscience (2007)

The mammalian central nervous system (CNS) requires the proper formation of exquisitely precise circuits to function correctly. These neuronal circuits are assembled during development by the formation of synaptic connections between thousands of differentiating neurons. Proper synapse formation during childhood provides the substrate for cognition, whereas improper formation or function of these synapses leads to neurodevelopmental disorders, including mental retardation and autism. Recent work has begun to identify some of the early cellular events in synapse formation as well as the molecular signals that initiate this process. However, despite the wealth of information published on this topic in the past few years, some of the most fundamental questions about how, whether, and where glutamatergic synapses form in the mammalian CNS remain unanswered. This review focuses on the dynamic aspects of the early cellular and molecular events in the initial assembly of glutamatergic synapses in the mammalian CNS.
Combination therapy with gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, gemcitabine and cisplatin in patients with advanced solid tumors
Authors: G. Giaccone, J.L. González-Larriba, A.T. van Oosterom, R. Alfonso, E.F. Smit, M. Martens, G.J. Peters, W.J.F. van der Vijgh, R. Smith, S. Averbuch, A. Fandi
Journal: Annals of Oncology (2004)
Endostatin Binding to Ovarian Cancer Cells Inhibits Peritoneal Attachment and Dissemination
Authors: Yumi Yokoyama, Gerald Sedgewick, S. Ramakrishnan
Journal: Cancer Research (2007)

Ovarian cancer cells use integrins to attach to the peritoneal wall. Integrin alpha(5)beta(1) is also the target for the angiogenesis inhibitor, endostatin. Therefore, the ability of endostatin to competitively inhibit tumor cell seeding of the peritoneum was investigated. An imaging method was developed to determine early phases of peritoneal dissemination of ovarian cancer cells. Using this method, endostatin was found to bind ovarian cancer cells through integrin alpha(5)beta(1) and inhibit vessel cooption efficiently. Although both angiostatin and endostatin are potent inhibitors of tumor angiogenesis, peritoneal attachment and vessel cooption was blocked only by the endostatin. Knocking down the expression of integrins alpha(5) and beta(1) in ovarian cancer cells interfered with endostatin-mediated inhibition of peritoneal seeding. Furthermore, adenovirus-mediated in situ expression of endostatin either inside the peritoneum or by the ovarian tumor cells inhibited peritoneal seeding and dissemination in vivo. Endostatin treatment also prevented primary ovarian cancer cells from attaching to mouse peritoneal wall. These studies show a paraendothelial mechanism by which endostatin can inhibit peritoneal dissemination of ovarian cancer cells and raises the possibility of intraperitoneal expression of endostatin to reduce recurrence.
Teenager who died after having HPV vaccine had a malignant chest tumour
Authors: A. O'Dowd
Journal: BMJ (2009)

An English teenager who died shortly after receiving the human papillomavirus (HPV) vaccine Cervarix had a large malignant tumour in her chest, which caused her death, public health doctors have said.

A pathologist confirmed on 1 October that results of a post mortem examination into the death of 14 year old Natalie Morton from Coventry …
Trusts will regularly check how patients use personal health budgets
Authors: A. O'Dowd
Journal: BMJ (2010)

People taking part in pilots in which they receive personal health budgets directly into their bank account will be monitored to ensure that the money is used appropriately.

The government this week announced that 12 primary care trusts would take part in eight pilots of direct payments for personal health budgets, with the intention of giving individuals the power to decide how, where, and from whom they receive health care.

Under the pilot scheme, which runs until 2012, trusts are authorised to make direct payments to patients once a care plan is agreed between a patient and the trust. The plan will set out the individual’s health needs and desired outcomes, the amount of money in their budget, and how the money will be spent to meet their …
Allergy to diazepam.
Authors: A Padfield, J Watkins
Journal: BMJ (1977)

reflection on our current values.Surely the time has come to call a halt to such nonsense.The journal advertising of drugs also leaves much to be desired.In the BMJ of 30 October 1976 there was an advertisement for Fortral (pentazocine) which claimed that with this drug there was "relief from the disadvantages usually associated with the opiates" (stated to be "nausea, vomiting, smooth muscle effects and respiratory depression").This is quite untrue and dangerously misleading.Pentazocine is a potent respiratory depressant.In equianalgesic doses it can produce the same degree of respiratory depression as morphine and pethidine,2 4 and in larger doses it can cause apnoea.5I know of cases of acute respiratory failure precipitated by the unwise administration of pentazocine by junior doctors who were under the false impression that it does not depress respiration.The perpetuation of this myth by such advertisements is totally irresponsible.The promotional activities of the pharma- ceutical industry have often been criticised by members of the medical profession and this criticism has been extended to the news media.'"Although the Government is currently restricting expenditure on drug promotion, further measures are obviously required.
Immunological studies in frozen shoulder.
Authors: D Bulgen, B Hazleman, M Ward, M McCallum
Journal: Annals of the Rheumatic Diseases (1978)

Serum immunoglobulin levels were determined in 25 patients with frozen shoulder and in 25 age- and sex-matched controls. Serum IgA levels were significantly reduced (P less than 0.001) in the patients with frozen shoulder and remained so after clinical recovery. Lymphocyte transformation to phytohaemagglutinin in 21 patients also showed significant depression (P less than 0.01). These results support the suggested immunological pathogenesis of this condition.
A STUDY OF FRONTAL LOBOTOMY
Authors: EDWARD A. STRECKER, HAROLD D. PALMER, FRANCIS C. GRANT
Journal: American Journal of Psychiatry (1942)

1. Twenty-two psychotic patients have been subjected to frontal lobotomy. Of sixteen agitated depressions twelve recovered sufficiently to live in their own homes, and continue to live at home in a relatively satisfactory degree of emotional adjustment. Of the five advanced schizophrenics two have made apparent recoveries. Two have improved to some degree and one, after making only slight improvement, succumbed to a virulent lobar pneumonia. The case of sexual psychopathy, operated upon as a last resort, made no improvement. 2. Two patients died, one was an anesthetic death and one was the result of postoperative hemorrhage. The mortality rate in general has not been a discouraging feature of frontal lobotomy. 3. The operation should be employed only in chronic psychotic cases and only after other less drastic therapeutic methods have failed. 4. The constellation of symptoms of fear, anxiety, acute mental suffering, aggressive violence, etc., is a better criterion of anticipated improvement from the operation than the diagnostic label.
Validation of Diabetes Risk Scores for Predicting Diabetes Diagnosed by Oral Glucose Tolerance Test
Authors: Hung-Yuan Li, Yi-Cheng Chang, Jung-Nan Wei, Lee-Ming Chuang
Journal: Diabetes Care (2010)

Recently, we have reported a study evaluating the performance of 11 diabetes risk scores (DRSs) to find subjects with diabetes, metabolic syndrome, and chronic kidney diseases (1), including a DRS developed by that database (DRS-Lin), i.e., in male subjects, x = −8.3805 + age*0.0325 + waist circumference*0.0423 + 0.5866 if using hypertension drugs + 0.2429 if there was a positive diabetes family history; in female subjects, x = −9.523 + age*0.0446 + waist circumference*0.0468 + 0.4264 if using hypertension drugs + 0.5060 if there was a positive diabetes family history; risk of diabetes = 1/(1 + e−x). In that report, diabetes was diagnosed based on fasting plasma glucose instead of a 75-g oral …
Telemedicine: A New Health Care Delivery System
Authors: Rashid L. Bashshur, Timothy G. Reardon, Gary W. Shannon
Journal: Annual Review of Public Health (2000)

▪ Abstract The resurgence of telemedicine can be attributed to its potential for addressing intransigent problems in health care, including limited accessibility, cost inflation, and uneven quality. After discussing definitions and the genesis of telemedicine, this review focuses on conceptual issues and an assessment of past research. The scope and methodological rigor necessary for sustained development and policy making have been limited in this area of research, owing to the nature of extant telemedicine projects and the lack of a comprehensive research strategy that specifies the objectives of telemedicine research regarding accessibility, cost, and quality. Research strategies and a framework for analysis are discussed. Without a commitment to the types of research objectives, framework, and strategy presented here, the considerable promise of telemedicine, as an innovative system of care, may not be fully realized.
Effects of immunosuppression on herpes simplex virus growth in lymphocytes of patients with connective tissue diseases.
Authors: P Hollingworth, W Hylton, B K Pelton, A M Denman
Journal: Annals of the Rheumatic Diseases (1983)

The growth of herpes simplex virus (HSV) was measured in blood lymphocytes isolated from patients with connective tissue diseases receiving immunosuppressive drugs. Whereas lymphocytes from such patients were frequently nonpermissive for HSV before treatment, they became permissive in most patients after treatment. The exception was the persistence of nonpermissiveness in lymphocytes of treated patients whose disease was associated with malignant disease.