tbuckley/cabot-search huggingface dataset:
Thirty-Gene Pharmacogenomic Test Correlates with Residual Cancer Burden after Preoperative Chemotherapy for Breast Cancer
Authors: Florentia Peintinger, Keith Anderson, Chafika Mazouni, Henry M. Kuerer, Christos Hatzis, Feng Lin, Gabriel N. Hortobagyi, W. Fraser Symmans, Lajos Pusztai
Journal: Clinical Cancer Research (2007)

We examined whether the response predicted by a 30-gene pharmacogenomic test correlated with the residual cancer burden (RCB) after preoperative chemotherapy with paclitaxel, 5-fluorouracil, doxorubicin, and cyclophosphamide (T/FAC).Gene expression profiling was done at diagnosis in 74 patients with stages I to III breast cancer and was used to calculate a pharmacogenomic score and predict response to chemotherapy [pathologic complete response (pCR) or residual disease (RD)]. All patients received 6 months of preoperative T/FAC. Following pathologic review, a RCB score was calculated based on residual tumor and lymph node features. Four RCB classes were assigned; RCB-0 (pCR), RCB-I (near-PCR), RCB-II (moderate RD), and RCB-III (extensive RD). The correlations between the pharmacogenomic score, predicted pathologic response, RCB score, and RCB class were examined.Thirty-three patients were predicted to have pCR, and 40 were predicted to have RD. Observed responses were RCB-0: n=20 (27%); RCB-I: n=5 (7%); RCB-II: n=36 (49%); and RCB-III: n=13 (16%) patients. Pharmacogenomic and RCB scores were correlated (Pearson's R=-0.501, P<0.0001). There was no difference between the mean genomic predictor scores for RCB-0/I groups (P=0.94), but these were different from the mean scores of the RCB-II/III groups (P<0.001). Among the 25 patients with RCB-0/I response, 19 (76%) were predicted to achieve pCR. The pharmacogenomic test correctly predicted RD in 92% of the patients with RCB-III, which corresponds to chemotherapy-resistant disease.The 30-gene pharmacogenomic test showed good correlation with the extent of residual invasive cancer burden measured as both continuous and categorical variables.
Profiling Chemicals Based on Chronic Toxicity Results from the U.S. EPA ToxRef Database
Authors: Matthew T. Martin, Richard S. Judson, David M. Reif, Robert J. Kavlock, David J. Dix
Journal: Environmental Health Perspectives (2008)

Thirty years of pesticide registration toxicity data have been historically stored as hardcopy and scanned documents by the U.S. Environmental Protection Agency (EPA). A significant portion of these data have now been processed into standardized and structured toxicity data within the EPA's Toxicity Reference Database (ToxRefDB), including chronic, cancer, developmental, and reproductive studies from laboratory animals. These data are now accessible and mineable within ToxRefDB and are serving as a primary source of validation for U.S. EPA's ToxCast research program in predictive toxicology.We profiled in vivo toxicities across 310 chemicals as a model application of ToxRefDB, meeting the need for detailed anchoring end points for development of ToxCast predictive signatures.Using query and structured data-mining approaches, we generated toxicity profiles from ToxRefDB based on long-term rodent bioassays. These chronic/cancer data were analyzed for suitability as anchoring end points based on incidence, target organ, severity, potency, and significance.Under conditions of the bioassays, we observed pathologies for 273 of 310 chemicals, with greater preponderance (>90%) occurring in the liver, kidney, thyroid, lung, testis, and spleen. We observed proliferative lesions for 225 chemicals, and 167 chemicals caused progression to cancer-related pathologies.Based on incidence, severity, and potency, we selected 26 primarily tissue-specific pathology end points to uniformly classify the 310 chemicals. The resulting toxicity profile classifications demonstrate the utility of structuring legacy toxicity information and facilitating the computation of these data within ToxRefDB for ToxCast and other applications.
Effect of Rifampicin and Isoniazid on Liver Function
Authors: S. Lal, S. N. Singhal, D. M. Burley, G. Crossley
Journal: BMJ (1972)

The effects of rifampicin and isoniazid on liver function have been studied in 63 patients with pulmonary tuberculosis; 29% showed abnormalities of serum aspartate aminotransferase (SGOT) and a similar percentage abnormalities of serum bilirubin. These usually occurred during the first 12 weeks of therapy. The average duration of the abnormalities was 14½ days, irrespective of whether treatment was interrupted or not. The relationship between raised SGOT and acetylator phenotype in a small number of patients suggests that those with raised SGOT are usually slow acetylator phenotypes. It seems that hepatic reactions in patients with previously normal liver function are usually mild and non-specific. However, patients who continue with rifampicin should be kept under close biochemical observation.
UK MPs demand more stringent regulation of medical devices across Europe
Authors: I. Torjesen
Journal: BMJ (2012)

European Union regulations on the safety of medical implants must be tightened urgently to prevent manufacturers from seeking approval for devices in member states where the regulations are most lax, a report by a committee of MPs has found. 

Once approval has been granted in one member state, the device can be used throughout Europe, regardless of the laxity of the approval process in the chosen member state.

Recent recalls of certain devices, such as metal-on-metal hip replacements and the faulty Poly Implant Prosthese (PIP) breast implants,1 2 have also highlighted the need for manufacturers and regulators to be compelled to publish much more rigorous clinical data on the safety of new implants and to be subject to greater scrutiny, says the report from the Science and Technology Committee, published …
Assessing observer variability: Authors' reply
Authors: P. Brennan, A. Silman
Journal: BMJ (1992)

Gall stones induced by octreotide EDITOR, -The beneficial effects of treatment with octreotide are accompanied by an increased risk of gall stones.Grant W Bigg-Wither and colleagues found that in 22 patients (13 of whom had acromegaly) octreotide increased the fasting gall bladder volume; they propose that this may predispose to the formation of gall stones.'We believe, however, that this is unlikely to be the main factor in the pathogenesis of gall stones induced by octreotide.We have measured fasting gall bladder volumes in nine acromegalic patients before and after octreotide and found no significant increase during treatment.2Furthermore, although the fasting gall bladder volume in 31 untreated acromegalic patients was 30% larger than that in normal subjects, we found only a minor increase in the prevalence of gall stones.3Octreotide impairs contraction ofthe gall bladder in response to a fatty meal and increases the residual volume of the gall bladder.This might be expected to promote the formation of stones because of relative stasis of the gall bladder.The residual volume of the gall bladder in untreated acromegalic patients, however, is three times that ofnormal subjects and yet the increase in gall stone prevalence in these individuals is small.Our data suggest that although a reduction in gall bladder emptying may well play a role in the formation of stones, an increased fasting gall bladder volume is not a major factor in their pathogenesis.Native somatostatin increases the cholesterol saturation in bile,4 and we have found similar changes in acromegalic patients with gall stones associated with octreotide.5These observations suggest that changes in bile chemistry may be at least as important as motor dysfunction of the gall bladder in the pathogenesis ofgall stones induced by octreotide.
Stopping Bleeding in Hereditary Telangiectasia
Authors: Martin D. Phillips
Journal: New England Journal of Medicine (1994)

Hereditary hemorrhagic telangiectasia, also known as Rendu-Osler-Weber syndrome, is a familial disease in which telangiectases occur in the skin, mucosal surfaces, and solid organs1,2. Small telangiectases are a mild cosmetic problem, but larger lesions can be a source of chronic blood loss, systemic emboli, hypoxemia, hepatic dysfunction, and high-output cardiac failure. The treatment of troublesome telangiectasia in patients with this disease has always been difficult, because bleeding sites may be many and scattered. Treatment often requires multiple blood transfusions, large doses of iron, and various invasive procedures in order to make the diagnosis, staunch bleeding, or prevent recurrent . . .
Audit Commission blames poor management for variations in waiting times
Authors: S. Hargreaves
Journal: BMJ (2002)

The length of time that patients wait for outpatient appointments and for surgery in ear, nose, and throat departments in the United Kingdom varies widely by NHS trust. But waiting times are not directly linked to levels of demand and capacity, according to a report released this week by the country’s public spending watchdog, the Audit Commission.

“We noted very wide variations in waiting times within trusts and between trusts,” Jane Laughton, author of the report, told the BMJ . “This is to do with …
Prevention of lipid accumulation in experimental vein bypass grafts by antiplatelet therapy.
Authors: L I Bonchek, L E Boerboom, G N Olinger, J R Pepper, J Munns, L Hutchinson, A H Kissebah
Journal: Circulation (1982)

The ameliorative effect of antiplatelet therapy on atherogenesis of vein grafts was assessed in autologous cephalic veins grafted into femoral arteries of 16 normolipemic and 11 hyperlipemic stump-tailed macaque monkeys. Before grafting, one half of each vein was distended at high pressure (700 mm Hg) and the other half at low pressure (350 mm Hg). Eight normolipemic monkeys were treated with aspirin, 80 mg/day, and dipyridamole, 50 mg/day, and eight were controls. When grafts were harvested at 12 weeks, tissue cholesterol and beta-apoprotein content in grafts from untreated monkeys were significantly higher than in ungrafted, uninjured veins. Antiplatelet therapy eliminated the increase in lipid content of vein segments distended at low pressure, and significantly lowered lipid content of segments distended at high pressure, though not to be control levels of ungrafted veins. Seven of the 11 hyperlipemic monkeys received antiplatelet drugs and four did not. The lipid content of all graft segments was significantly higher than in grafted or ungrafted veins from normolipemic monkeys. Antiplatelet therapy again significantly reduced the lipid content in vein segments distended at both levels of pressure, and also reduced the elevated cholesterol content in ungrafted veins. Although this animal preparation differs in many ways from human coronary bypass operations, these observations may be pertinent to the prevention of atherosclerosis in human vein bypass grafts.
THE INFLUENCE OF MILK FEEDING ON MORTALITY AND GROWTH, AND ON THE CHARACTER OF THE INTESTINAL FLORA
Authors: Leo F. Rettger
Journal: The Journal of Experimental Medicine (1915)

Throughout the investigations upon which a large part of this paper is based the favorable influence of milk feeding on mortality and growth was most apparent. Mortality from all causes was frequently reduced to at least one-half of what obtained among the chicks that received no milk, while the milk-fed chicks in some experiments gained twice as much in weight as those that were without this article of diet. Although the influence of milk feeding was less pronounced on the mortality of chicks that were artificially infected with Bacterium pullorum, quite an appreciable difference in mortality was always noted if the milk was fed at least one or two days before the first administration of the bouillon cultures of the organism in question. Practically the same results were obtained, whether sweet or sour milk was fed, and no differences could be observed in the relative value of ordinary sour milk and of the so called bulgaricus product. Hence, the unique properties of this food exist in the milk as such, rather than in any milk acids or milk bacteria that may be present. Milk and lactose diet exert a very important influence on the character of the intestinal bacteria, especially in white rats and in the common domestic fowl. Within a few days after the ingestion of milk or lactose a transformation of the flora takes place in which the usual mixed bacterial flora give way to ones that are more simplified, and in which Bacillus acidophilus and Bacillus bifidus are, as a rule, prominent. It is to be assumed that milk has this influence in virtue of the large amount of lactose which it contains. Other carbohydrates, besides milk sugar, failed to bring about such a transformation. The ingestion of foreign bacteria, even in large numbers, does not of itself bring about an elimination or displacement of the common intestinal microörganisms. Vastly more important is the influence of diet, especially milk and lactose. The feeding of Bulgara tablets or other preparations which contain as the supposedly active agent the bacillus of Metchnikoff and Mazé, without due regard to the use of milk, can, therefore, be of little, if indeed of any, value. The beneficial effects which it is claimed have been derived from the use of yoghurt, and other oriental sour milk products have in all probability been due to the milk as such, rather than to the bacteria which they contained. This view is strongly supported by the extensive milk feeding experiments on chicks which are recorded in this paper, and also by the results which show the influence of milk and of lactose feeding on the intestinal flora of white rats and of the common domestic fowl.
The anatomical distribution of sunlight
Authors: B.L. DIFFEY, M. KERWIN, A. DAVIS
Journal: British Journal of Dermatology (1977)

The relative distribution of natural ultraviolet radiation has been measured at ten sites on the surface of an unclothed manikin for 2 h around solar noon on 19 different days during late summer in Canterbury, U.K. The dosimeter used was polysulphone film. The results obtained indicate that vertical surfaces of the body receive about one half of the dose relative to the vertex and that the relative doses at different sites are independent of weather conditions.
Studies on the stability of vitamin A in the stomach and small intestine
Authors: O. Fitzgerald, J. J. Fennelly, D. J. Hingerty
Journal: Gut (1962)

The instability of vitamin A alcohol relative to vitamin A acetate has been studied in vivo and in vitro. Vitamin A alcohol is more unstable than vitamin A acetate in human gastric and duodenal juice and in rats' stomachs and intestines and is more marked at lower pH levels and in rats' stomachs. Alpha tocopherol improved the absorption curve of vitamin A alcohol in man by protecting it in gastric and duodenal juice. This protective effect could not be demonstrated in the rat.
Cosmetic surgery gets under Dutch skin
Authors: Tony Sheldon
Journal: BMJ (2007)

A documentary has seen thousands rally against cosmetic surgery for young people

Television programmes in the United States and Italy have been criticised in the past for trivialising cosmetic surgery and misrepresenting the realities of taking such a step ( BMJ 2003;327:295 doi: 10.1136/bmj.327.7409.295 and BMJ 2004;328:520 doi: 10.1136/bmj.328.7438.520) 

Now a frank Dutch documentary, in which the film-maker is shown consulting a surgeon on whether to have vaginal surgery, has ignited a campaign in the Netherlands to ban non-essential cosmetic surgery for under-18s.

In Beperkt Houdbaar (Over the Hill), broadcast in the Netherlands this …
Serodiagnosis of chronic hepatitis C in Japan by second-generation recombinant immunoblot assay
Authors: Nobukazu Yuki, Norio Hayashi, Hideki Hagiwara, Tetsuo Takehara, Masahide Oshita, Akinori Kasahara, Hideyuki Fusamoto, Takenobu Kamada
Journal: Journal of Hepatology (1993)
Corrected likelihood for proportional hazards measurement error model and its application.
Authors: T Nakamura, K Akazawa
Journal: Environmental Health Perspectives (1994)

Consider the case where the exact values of covariates in the proportional hazards model may not be observed but instead, only surrogates for them involving measurement errors are available. The maximum likelihood estimate based on the partial likelihood with the true covariate replaced by the observed surrogate is even asymptotically biased and may cause seriously misleading results in covariance analysis based on the partial likelihood. These facts are illustrated by Monte Carlo simulation. A correction to partial likelihood proposed by the first author is studied to gain insight into its merits and limitations in practical applications. The results indicate that when the "effective magnitude of the measurement error" as defined in this article is small, which is indeed the case for most applications, the method will be useful. Some other correction methods for the measurement error in censored survival models are also reviewed and discussed.
MPs call for free personal care for elderly people
Authors: Madeleine Brettingham
Journal: BMJ (2005)

The distinction between health and social care should be abolished, allowing elderly people to be looked after by a single generic agency, a parliamentary committee recommended this week. The lack of integration between the sectors is a “serious stumbling block” to providing a good quality service to elderly patients, the committee's report argues.

Three weeks after Stephen Ladyman, the minister for community care, insisted to the House of Commons Health Committee that the government would “absolutely not” consider offering free personal care to elderly people on the NHS, members of the committee have nevertheless gone on to criticise the unfairness and inefficiency of a system that is based on an “artificial …
NGS technology applied to melanoma cell lines
Authors: Valeria De Giorgi, Zhi Xie, Jinguo Chen, Rongye Shi, Huizhi Zhou, Hui Liu, John Wunderlich, Michele Sommariva, Sara Tomei, Maria Libera Ascierto, Davide Bedognetti, Ena Wang, Francesco M Marincola
Journal: Journal for ImmunoTherapy of Cancer (2013)

Meeting abstracts High-throughput sequencing technology challenges the traditional histopathological classification of cancer, and proposes new taxonomies derived from global transcriptional patterns. They provided in-depth of new information that can reframe our understanding of human cancer
Evidence based medicine: an approach to clinical problem-solving
Authors: W. Rosenberg, A. Donald
Journal: BMJ (1995)

repression inflicted by the previous regime, or perhaps orchestrated by radical union leaders.Whatever the explanation, they show that the maturity displayed by the South Africans at the time of the elections has not been shown by its striking workers.The honeymoon phase between South African politicians and their electorate is becoming tumultuous and the honeymoon is being threatened.
141 USE OF ANTI-HBc POSITIVE DONORS IN LIVER TRANSPLANTATION: THE EXPERIENCE OF PADUA LIVER TRANSPLANT CENTRE
Authors: I. Bortoluzzi, M. Gambato, L. Albertoni, C. Mescoli, M. Pacenti, R. Cusinato, G. Germani, M. Senzolo, M. Rugge, G. Zanus, P. Boccagni, U. Cillo, P. Burra, F.P. Russo
Journal: Journal of Hepatology (2013)
Factor XIIIa Cross-links Lipoprotein(a) With Fibrinogen and Is Present in Human Atherosclerotic Lesions
Authors: Anne M. Romanic, Anthony J. Arleth, Robert N. Willette, Eliot H. Ohlstein
Journal: Circulation Research (1998)

During the development of atherosclerotic lesions, lipoprotein(a) [Lp(a)], a highly atherogenic lipoprotein, accumulates within fibrin clots attached to blood vessel walls. As Lp(a) accumulates within the fibrin clot with time, fatty streaks are formed that develop into occlusive atherosclerotic plaques. It is not understood, however, which mechanisms are involved in the binding of Lp(a) to fibrin and, hence, the stable incorporation of Lp(a) into the fibrin clot. The results of the present study demonstrate that factor XIIIa, a transglutaminase that catalyzes the formation of amide bonds between endo-gamma-glutaminyl and endo-epsilon-lysyl residues of proteins, is capable of cross-linking Lp(a) to fibrinogen, the soluble precursor of fibrin. Biochemical assays were conducted to demonstrate that factor XIIIa cross-links Lp(a) with fibrinogen in a time- and concentration-dependent manner. Additionally, immunohistochemical studies revealed that factor XIII protein expression colocalizes with Lp(a) expression in human atherosclerotic plaques. It is proposed that factor XIIIa-mediated cross-linking of Lp(a) to fibrin effectively increases the local concentration of Lp(a) within a fibrin clot. The accumulation of Lp(a) within the blood vessel promotes an antifibrinolytic environment, foam cell formation, the generation of a fatty streak, and an increase in smooth muscle cell content, all of which may contribute to the pathogenesis of atherosclerosis.
Sexually transmitted disease in potential semen donors.
Authors: E F Monteiro, R C Spencer, G R Kinghorn, C L Barratt, S Cooke, I D Cooke
Journal: BMJ (1987)

atrial peptide values with the reduction in sodium intake (figure) may provide one explanation.The pronounced increase in plasma atrial peptide concentrations on changing from the normal to the high sodium diet but with no concomitant change in blood pressure, and given the potent vascular actions of the atrial peptides,' may perhaps account for the lack of rise in blood pressure with the increase in sodium intake, possibly through a direct vasodilatory action on the arterial or venous system.In conclusion, our study suggests that in hypertensive patients changes in circulating atrial peptide values with changes in sodium intake may not only contribute to the maintenance of sodium balance but may also contribute to the observed changes in blood pressure.These studies were supported by the National Kidney Research Fund (United Kingdom).1 MacGregor GA, Sagnella GA, Markandu ND, et al.Raised plasma levels of atrial natriuretic peptide in subjects with untreated essential hypertension.
Histone Deacetylase Inhibitors Modulate the Sensitivity of Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand–Resistant Bladder Tumor Cells
Authors: James K. Earel, Rebecca L. VanOosten, Thomas S. Griffith
Journal: Cancer Research (2006)

Abstract Urothelial carcinoma of the bladder accounts for ∼5% of all cancer deaths in humans. The large majority of tumors are superficial at diagnosis and, after local surgical therapy, have a high rate of local recurrence and progression. Current treatments extend time to recurrence but do not alter disease survival. The objective of the present study was to investigate the tumoricidal potential of combining the apoptosis-inducing protein tumor necrosis factor–related apoptosis inducing ligand (TRAIL) with histone deacetylase inhibitors (HDACi) against TRAIL-resistant bladder tumor cells. Pretreatment with HDACi at nontoxic doses, followed by incubation with TRAIL, resulted in a marked increase in TRAIL-induced apoptosis of T24 cells but showed no significant increase in toxicity to SV40 immortalized normal human uroepithelial cell-1. HDAC inhibition, especially with sodium butyrate and trichostatin A, led to increased TRAIL-R2 gene transcription that correlated with increased TRAIL-R2 surface expression. The increased TRAIL-R2 levels also resulted in accelerated death-inducing signaling complex (DISC) formation, caspase activation, and loss of mitochondrial membrane potential, which all contributed to the increase in tumor cell death. Collectively, these results show the therapeutic potential of combining HDAC inhibition with TRAIL as an alternative treatment for bladder cancer. (Cancer Res 2006; 66(1): 499-507)