tbuckley/cabot-search huggingface dataset:
Reserving mental health detention for conditions that can be treated
Authors: J. M. Rampling
Journal: BMJ (2015)

Evidence for the rehabilitation of sex offenders is contentious and inconsistent and Ho is justified in sharing his concerns with the medical fraternity,1 but he argues for doctors to “take ownership” without presenting evidence for psychiatric interventions.

Continued mental health detention is appropriate only if relevant medical treatment, which may include pharmacological, psychological, occupational, or nursing …
Lessons from America: primary care
Authors: Des Spence
Journal: BMJ (2012)

If you think NHS reforms are complex, try looking at the organisation of healthcare in the United States. Contrary to our perceptions, the US government does care about its poor, young, and old. Through programs like Medicare and Medicaid the government is, in fact, the biggest provider of healthcare in the US. For those not covered by the state, there are a vast array of medical insurers and plans. But despite free market “competition,” insurance remains unaffordable to many middle income families. These companies have dividends to pay, and this leaves 50 million US residents without adequate …
Hepatitis Drug Reduces Effects of HIV Medications
Authors: Bridget M. Kuehn
Journal: JAMA (2012)

The new findings reinforce that autism is a very heterogeneous disorder, explained Christine Fountain, PhD, lead author of the study, and they raise concerns about socioeconomic disparities in children’s access to care. Overall, the researchers found that white children with well-educated mothers were more likely to be high-functioning than minority children with mothers who had a lower level of education. Children with intellectual disabilities were also more likely to be on the low-functioning end of the spectrum. These disparities were particularly acute among the bloomers. Fountain explained that these children were very unlikely to have comorbid learning disabilities or a mother with a high school education or less. The data didn’t contain information about the types of treatment children received, and Fountain said it wasn’t clear if the differences in the bloomers group reflected a different etiology of autism or the treatments those children received. “It’s probably both,” she said. “With the economic differences, it is less likely to be a biological difference alone.” She argued that more randomized trials of therapies are needed to help clinicians identify the most effective treatments and to determine if a particular treatment can shift a child from one trajectory to another. In the meantime, however, it is important for clinicians to identify children early and to ensure that children are referred to appropriate treatment, especially if the child comes from a socioeconomically disadvantaged background.
Unwrapping the Implications of BRCA1 and BRCA2 Mutations in Ovarian Cancer
Authors: David M. Hyman, David R. Spriggs
Journal: JAMA (2012)

2][3] These trials have combined BRCA1 and BRCA2 mutation carriers because of the relative rarity of BRCA1 and BRCA2 mutations, which only account for approximately 10% and 5% of unselected cases of serous ovarian cancer, respectively. 4However, although both mutations are associated with hereditary breast and ovarian cancers, it has been suggested that these cancer predisposition syndromes represent related but clinically distinct entities. 5The lifetime risk of ovarian cancer is higher in BRCA1 than BRCA2 mutation carriers, estimated at 36-60% and 16-27%, respectively.6,7 BRCA1 mutation carriers tend to develop ovarian cancer on average about eight years earlier than BRCA2 mutation carriers. 1,4Microarrays of BRCA1 and BRCA2associated ovarian cancers also show significant differences in gene expression. 8Moreover, the protection conferred by risk-reducing salpingo-oophorectomy against breast and gynecologic cancers may differ between carriers of BRCA1 and BRCA2 mutations. 9In light of these observations, two recent reports have examined survival separately in BRCA1 and BRCA2-associated ovarian cancers in small cohorts. 10,11Both studies found significantly improved survival in BRCA2-associated ovarian cancers and smaller statistically non-significant improvement in survival in BRCA1-associated ovarian cancers.In this issue of JAMA, Bolton et al 12 report their analysis of patients with BRCA1 and BRCA2 ovarian cancer who were included in a large international dataset.Incident cases of ovarian cancer were pooled from 26 international prospective clinical genetics protocols, the majority of which were affiliated with either the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) or the Ovarian Cancer Association Consortium (OCAC).Baseline clinical characteristics such as year of diagnosis, age, stage, grade, and histology were controlled for, when available, with respect to overall survival.In their analysis of 3879 patients with ovarian cancer (2666 non-carriers, 909 BRCA1 mutation carriers, and 304 BRCA2 mutation carriers), the authors report fully adjusted hazard ratios for overall mortality at five years of 0.73 and 0.49 for BRCA1 and BRCA2 mutation carriers, respectively, compared to non-carriers.The differences in overall survival observed in BRCA1 and BRCA2 mutation carriers was statistically (and clinically) significant compared to both the sporadic cohort and each other.In a secondary analysis, the authors also found that the survival advantage conferred by BRCA1 mutations may be partially mitigated as the mutation site moved from the 5' to 3' end, suggesting that the site of BRCA1 mutation may have individual prognostic significance.
Association Between Periodontitis and Impaired Fasting Glucose and Diabetes
Authors: Youn-Hee Choi, Robert E. McKeown, Elizabeth J. Mayer-Davis, Angela D. Liese, Keun-Bae Song, Anwar T. Merchant
Journal: Diabetes Care (2011)

Many studies have reported that periodontal disease is associated with diabetes, but its relation with impaired fasting glucose (IFG) has been understudied. This study investigated the relationship between chronic periodontitis, IFG, and diabetes in the U.S. population.Participants in the National Health and Nutrition Examination Survey III, aged ≥ 20 years, who received periodontal examinations and provided blood samples (n = 12,254) were grouped into quintiles of mean clinical attachment loss (CAL) and pocket depth, with the lowest category being the reference. Plasma fasting glucose was categorized into three groups (normal, <100 mg/dL; IFG, ≥ 100 but <126 mg/dL; and diabetic, ≥ 126 mg/dL). Sociodemographic factors and other potential risk factors were obtained by interview or examination. SAS 9.1 was used for statistical analysis accounting for the complex weighted sampling.Participants in the top quintile category of CAL had higher prevalence odds of IFG (odds ratio [OR] 1.55 [95% CI 1.16-2.07]) and diabetes (4.77 [2.69-8.46]) after adjustment for related confounders, compared with those in the bottom quintile. The highest quintile of pocket depth was positively associated with IFG (1.39 [1.00-1.92]) and diabetes (1.63 [1.10-2.42]) compared with the lowest quintile. ORs for CAL increased from the lowest to the highest quintile (P value test for trend <0.01) for all outcomes. The ORs for pocket depth also tended to rise across quintiles.Chronic periodontitis measured by CAL and pocket depth was positively associated in a linear relation with IFG and diabetes in U.S. adults.
Sulfadoxine-pyrimethamine for uncomplicated falciparum malaria: Sulfadoxine-pyrimethamine is not working in Malawi
Authors: Nicholas White
Journal: BMJ (2004)

EDITOR—The paper by Plowe et al entitled “Sustained clinical efficacy of sulfadoxine-pyrimethamine for uncomplicated falciparum malaria” might be better titled “Sustained lack of efficacy of sulfadoxine-pyrimethamine….”1 By the start of the study period five years ago, molecular genotyping showed that Plasmodium falciparum in Malawi had already acquired significant resistance to the combination.1 2 This explains the sustained lack of efficacy; …
REFRIGERATING SYSTEMS AND PUBLIC HEALTH
Authors: SHIRLEY W. WYNNE
Journal: JAMA (1930)

Refrigerating systems may be discussed from two angles, the fire hazard and the health hazard. The code of ordinances of the city of New York relating to these systems is, with several exceptions which will be discussed in detail, adequate to safeguard life and property. The laws of New York City relating to refrigerating systems were adopted in 1927, and are based on a thorough study and report made by C. K. Michaels, engineering inspector of the Bureau of Fire Prevention of the city of New York. In this article we give first a brief discussion of the present laws in force in New York with a view to show the safety afforded by strict compliance with all the provisions of the code, and follow this with several recommendations which, in the light of newer knowledge on this subject, should be incorporated in the present law. In New York City
Effect of binding of ionised calcium on the in vitro nucleation of cholesterol and calcium bilirubinate in human gall bladder bile.
Authors: S Gallinger, P R Harvey, C N Petrunka, S M Strasberg
Journal: Gut (1986)

Biliary calcium may be a nucleating agent in cholesterol cholelithiasis. A study was designed to determine the effect of binding of ionised calcium on in vitro nucleation time. Ultracentrifuged and microscopically clear gall bladder bile from cholesterol gall stone patients was divided into two aliquots. One aliquot served as control and ionised calcium was bound in the second aliquot by addition of EDTA. Nucleation time was observed for the two groups. Addition of EDTA had no effect on lipid composition of the biles. EDTA bound all ionised calcium. Calcium bilirubinate precipitated from all controls on day 1 but was absent in all samples with EDTA. Addition of EDTA had no effect on cholesterol crystal nucleation time; nucleation time was rapid in both the controls and samples with EDTA. Ionised calcium is essential for calcium bilirubinate precipitation but is not responsible for the rapid nucleation time of bile from cholesterol gall stone patients.
Government plans to let GPs buy from "any willing provider" are not sophisticated enough, report says
Authors: J. Wise
Journal: BMJ (2011)

The government should be less directive in terms of the timetable for implementation of the NHS reforms and allow for local flexibility, the NHS Confederation has suggested.

In a discussion paper, it proposes some practical solutions to the many concerns that have been raised about the changes.

Nigel Edwards, the organisation’s acting chief executive, said: “There is a recurring theme running through our analysis. We have often found a reality gap between ideas that are good in principle and the details of practical delivery, which have often looked …
A systematic review on endoscopic detection rate, endotherapy, and surgery for pancreas divisum
Authors: Z. Liao, R. Gao, W. Wang, Z. Ye, X.-W. Lai, X.-T. Wang, L.-H. Hu, Z.-S. Li
Journal: Endoscopy (2009)

Background and study aims: The rates for endoscopic detection of pancreas divisum at routine endoscopic retrograde cholangiopancreatography (ERCP) vary worldwide, and the sample sizes in the reported studies on endoscopy and surgery for pancreas divisum are very small and variable. The aim of this study was to systematically analyze the pooled data and determine endoscopic detection rates for pancreas divisum and pain relief rates in patients with pancreas divisum after endotherapy or surgery.
Rolling and adhesion of human tumor cells on vascular endothelium under physiological flow conditions.
Authors: R Giavazzi, M Foppolo, R Dossi, A Remuzzi
Journal: Journal of Clinical Investigation (1993)

We investigated the interaction of different human tumor types with resting and IL-1-activated human umbilical vein endothelial cells under laminar flow conditions using a parallel plate flow chamber. Three tumor cell lines (the HT-29M colon carcinoma, the OVCAR-3 ovarian carcinoma, and the T-47D breast carcinoma) showed limited adhesion to unstimulated endothelial cells at any of the shear stress levels tested, while rolling and massive adhesion of tumor cells were observed on IL-1-activated endothelial cells. Three other tumor cell lines (the A375M and A2058 melanomas and the MG-63 osteosarcoma) did not adhere on resting endothelial cells at high shear stress (> 1.5 dyn/cm2) and started to adhere with decreasing shear stress; the number of adherent cells increased steeply on IL-1-activated endothelial cells, but no cell rolling was observed even at the highest shear stress. These mechanisms of tumor cell interaction with endothelial cells were analyzed in detail using the HT-29M colon carcinoma and the A375M melanoma. Incubation of activated endothelial cells with a monoclonal antibody against E-selectin inhibited rolling and adhesion of HT-29M, but had no effect on the adhesion of A375M cells; monoclonal antibody against vascular cell adhesion molecule-1 reduced the adhesion of A375M cells and had no effect on HT-29M. The selective interaction of these two molecules with tumor cells was confirmed by measuring the adhesion of tumor cells on immobilized soluble proteins. On E-selectin-coated surfaces, HT-29M cells rolled during perfusion experiments without subsequent adhesion, while A375M cells did not adhere. On vascular cell adhesion molecule-1-coated surfaces, HT-29M cells neither adhered nor rolled, while A375M cells adhered massively without rolling. Under flow conditions, therefore, cells from different tumor types interact with the endothelial surface by different mechanisms, depending on adhesion molecules expressed on the tumor and endothelial cell surface.
Abstract 3753: Genome wide association study of HCV-induced hepatocellular carcinoma
Authors: Koichi Matsuda, Vinod Kumar, Yusuke Nakamura
Journal: Cancer Research (2011)

Abstract To identify the genetic susceptibility factor(s) for hepatitis C virus-induced hepatocellular carcinoma (HCV-induced HCC), a genome-wide association study (GWAS) was conducted using 432,703 autosomal SNPs in 721 HCV-induced HCC cases and 2,890 HCV-negative controls of Japanese origin. Eight SNPs which showed possible association (P &amp;lt; 1 × 10-5) in the GWAS were further genotyped in 673 cases and 2,596 controls. We found a novel locus in the 5 prime flanking region of HCRSP (hepatocellular carcinoma related soluble protein) gene (Pcombined = 4.21×10-13, odds ratio (OR) = 1.39) to be strongly associated with HCV-induced HCC. Subsequent analyses using patients with chronic hepatitis C (CHC) indicated that this SNP is not associated with CHC susceptibility (P = 0.61), but significantly associated with progression from CHC to HCC (P=3.13 × 10-8). We also found that risk allele of SNP was associated with lower level of HCRSP protein in HCV-induced HCC patients (P = 1.38 × 10-13). Thus, our results highlight the importance of genetic variations of HCRSP as a predictive biomarker for HCV-induced HCC. 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 3753. doi:10.1158/1538-7445.AM2011-3753
Scientific Misconduct Tackled by New NIH Office
Authors: L. Fintor
Journal: JNCI Journal of the National Cancer Institute (1990)

Journal Article Scientific Misconduct Tackled by New NIH Office Get access Lou Fintor Lou Fintor Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 82, Issue 16, 15 August 1990, Pages 1312–1314, https://doi.org/10.1093/jnci/82.16.1312 Published: 15 August 1990
Outcome selection and role of patient reported outcomes in contemporary cardiovascular trials: systematic review
Authors: K. Rahimi, A. Malhotra, A. P. Banning, C. Jenkinson
Journal: BMJ (2010)

<b>Objectives</b> To systematically assess the type of outcomes selected and the prevalence of patient reported outcomes in contemporary cardiovascular trials and to quantify any misuse or underuse of patient reported outcomes using a specially developed tool that would allow estimation of the relevance of such outcomes to clinical decision making. <b>Design</b> Systematic review. <b>Data sources</b> Medline and Embase. <b>Study selection</b> Randomised controlled trials of the treatment for or prevention of cardiovascular disease published in 10 leading general medical and cardiology journals from January 2005 to December 2008. <b>Results</b> Primary outcomes were patient important (death, morbidity, or patient reported outcomes) in only 93 of 413 trials (23%, SE 2%), whereas another 92 (22%, SE 2%) combined these outcomes with other less important ones into a composite. Sixty five trials (16%; SE 2%) used at least one instrument to measure patient reported outcomes, mostly in trials where such information would have been important or crucial for clinical decision making (52 trials). Patient reported outcomes were judged to be of little incremental value to a large number of, mostly explanatory, cardiovascular trials (152 trials). However, many trials in which patient reported outcomes would have been important or crucial for clinical decision making did not report such outcomes (122 of 174 trials, 70%). These included several trials that primarily aimed to improve symptoms or functional status, trials that tested interventions with a considerable potential for causing harm (mainly bleeding) that were not meaningfully measured, and trials with composite outcomes that were dominated by outcomes of questionable importance to patients. <b>Conclusions</b> Despite a continued rise in the reporting of patient reported outcomes with no evidence for their misuse in more recent cardiovascular trials, they seem to be still underused once their relevance to clinical decision making has been taken into account. This was largely explained by inappropriate use of composite outcomes and inadequate measurement of harms.
Human skin levels of retinoic acid and cytochrome P-450-derived 4-hydroxyretinoic acid after topical application of retinoic acid in vivo compared to concentrations required to stimulate retinoic acid receptor-mediated transcription in vitro.
Authors: E A Duell, A Aström, C E Griffiths, P Chambon, J J Voorhees
Journal: Journal of Clinical Investigation (1992)

Metabolism of retinoic acid to a less active metabolite, 4-hydroxyretinoic acid, occurs via cytochrome P-450 isozyme(s). Effect of a pharmacological dose of retinoic acid on the level of retinoic acid in skin and on cytochrome P-450 activity was investigated. A cream containing 0.1% retinoic acid or cream alone was applied topically to adult human skin for four days under occlusion. Treated areas were removed by a keratome and a microsomal fraction was isolated from each biopsy. In vitro incubation of 3H-retinoic acid with microsomes from in vivo retinoic acid treated sites resulted in a 4.5-fold increase (P = 0.0001, n = 13) in its transformation to 4-hydroxyretinoic acid in comparison to in vitro incubations with microsomes from in vivo cream alone treated sites. This cytochrome P-450 mediated activity was oxygen- and NADPH-dependent and was inhibited 68% by 5 microM ketoconazole (P = 0.0035, n = 8) and 51% by carbon monoxide (P = 0.02, n = 6). Cotransfection of individual retinoic acid receptors (RARs) or retinoid X receptor-alpha (RXR-alpha) and a chloramphenicol acetyl transferase (CAT) reporter plasmid containing a retinoic acid responsive element into CV-1 cells was used to determine the ED50 values for stimulation of CAT activity by retinoic acid and its metabolites. Levels of all trans and 13-cis RA in RA-treated tissues were greater than the ED50 values determined for all three RARs with these compounds. Furthermore, the level of all trans RA was greater than the ED50 for RXR-alpha whereas the 4-OH RA level was greater than the ED50 for RAR-beta and RAR-gamma but less than for RAR-alpha and RXR-alpha. These data suggest that there are sufficient amounts of retinoic acid in treated skin to activate gene transcription over both RARs and RXR-alpha.
Traumatic Rupture of The Nonpregnant Uterus
Authors: Charles E. Kalstone
Journal: JAMA (1969)

<h3>To the Editor:—</h3> Numerous cases have been reported in which the pregnant uterus has ruptured as a result of trauma from a vehicle crash. This occurs usually after the first trimester, when the enlarged, softened uterus is no longer protected by the bony pelvis. We know of no report of traumatic rupture of the normal-sized, nonpregnant uterus, such as the case described below. <h3>Report of a Case:—</h3> A 39-year-old gravida 2, para 2, white woman was the right-hand passenger in a 1968 car which went through a red light at 80 mph and was hit at 90° from the right by a car going about 10 mph. The car containing the patient came to a stop on the shoulder of the opposite side of the four-lane road. The patient was forced to the steering-wheel side against the driver who was partially out of the car, uninjured. Neither was wearing a
Abstract 4505: Akt1 is a potent molecular target for treatment of oral squamous cell carcinoma
Authors: Hiroyuki Goda, Koh-ichi Nakashiro, Hiroyuki Hamakawa
Journal: Cancer Research (2010)

Abstract Oral cancer has a severe impact on the quality of life (QOL) of patients. Treatment for the advanced cases is given priority for reducing deaths due to oral cancer and keeping QOL after the treatment. Several reports have demonstrated that inactivation of a single critical oncogene in cancer cells can induce the terminal differentiation or apoptosis. In this study, we have attempted to identify a critical oncogene for oral cancer progression. Using Applied Biosystems Human Genome Survey Arrays, we determined the gene expression profiles in 10 oral squamous cell carcinoma (OSCC) primary tissues and 10 human OSCC cell lines. This array contains 32,878 60-mer oligonucleotides probes representing a set of 29,098 individual human genes. We identified Akt1 mRNA that was commonly expressed in all OSCC tissues and cultured cells but not in non-neoplastic tissues and cells. Subsequently, immunohistochemical examination and Western blot analysis showed the overexpression of Akt1 protein in 59 of 63 OSCC primary tissues (94%) but not in oral normal epithelium. Overexpression of Akt1 and phosphorylated Akt1 proteins was also detected in all human OSCC cultured cells by sandwich ELISA. Akt is frequently activated in many types of human cancer, and has been implicated in tumorigenesis and malignancy. To clarify the oncogenic function of Akt1 in human OSCC cells, we used RNA interfering (RNAi) method. We designed and synthesized 8 small interfering RNAs for specific Akt1 (siAkt1), and then tested their RNAi effects. Akt in mammals comprises three highly homologous members known as Akt1, Akt2 and Akt3. Transfection with siAkt1 at the concentration of 1 nM markedly suppressed the expression of Akt1 protein but not Akt2 and Akt3, and significantly reduced the growth rate of human OSCC cells on the plastic surface and in collagen gels. Furthermore, atelocollagen-mediated systemic siAkt1 administration markedly inhibited the growth of human OSCC tumors which had been subcutaneously xenografted in athymic nude mice without interferon responses. These results suggest that Akt1 functions as a critical oncogene in human OSCC cells and targeting Akt1 appears a novel approach for treatment with oral cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4505.