tbuckley/cabot-search huggingface dataset:
Are we going OTT about ITT?
Authors: H.C. Williams
Journal: British Journal of Dermatology (2001)

The article by Schiffner and colleagues in this month’s British Journal of Dermatologyprovides some important data on the difference between analysing clinical trial data in study participants who comply fully to a study protocol and those who do not.1 In the context of a large multicentre uncontrolled open study of Dead Sea salt and UVB ultraviolet light for treating people with psoriasis and atopic dermatitis, Schiffner et al. present the relative improvement for each disease in two ways. One was for patients who completed and fully complied with the protocol: the according‐to‐protocol population or ATP. The other was for the entire recruited study population, i.e. including those that subsequently dropped out or failed to fully comply: the intention‐to‐treat population or ITT. They found that improvement, as measured objectively by the PASI score for psoriasis and SCORAD for atopic dermatitis, was considerably higher for the ATP than the ITT populations for both diseases (68% vs. 57% for psoriasis and 55% vs. 39% for atopic dermatitis).
Antimalarial properties of n-3 and n-6 polyunsaturated fatty acids: in vitro effects on Plasmodium falciparum and in vivo effects on P. berghei.
Authors: L M Kumaratilake, B S Robinson, A Ferrante, A Poulos
Journal: Journal of Clinical Investigation (1992)

The polyunsaturated fatty acids docosahexaenoic acid (C22:6,n-3), eicosapentaenoic acid, arachidonic acid, and linoleic acid caused marked in vitro growth inhibition of Plasmodium falciparum, assessed by a radiometric assay. In contrast, negligible parasite killing was seen with oleic acid or docosanoic acid. Parasite killing was significantly increased when oxidized forms of polyunsaturated fatty acids were used. Antioxidants greatly reduced the fatty acid-induced killing. Mice infected with P. berghei and treated for 4 d with C22:6,n-3 showed marked reduction in parasitemia. The anemia associated with the infection was also alleviated by treatment with C22:6,n-3. The data provide new information that could be explored in order to develop new strategies in malaria treatment.
Obama and Romney disagree over future of healthcare funding
Authors: J. H. Tanne
Journal: BMJ (2012)

President Barack Obama and the Republican presidential candidate, Mitt Romney, have disagreed over how to tackle rising healthcare costs in the United States and the number of people who lack health insurance.

Speaking at the first of the presidential debates on 3 October, Romney, a former governor of Massachusetts, moved closer to the center than his far right positions in campaign speeches.

He said that he would repeal the health reform law passed in 2010 but would retain several of its provisions, such as requiring insurers to cover people with pre-existing conditions and allowing young people to stay on their parents’ insurance.

When Romney was governor of Massachusetts he introduced universal healthcare coverage in a …
Evaluation of the antiinflammatory and phospholipase-inhibitory activity of calpactin II/lipocortin I.
Authors: J K Northup, K A Valentine-Braun, L K Johnson, D L Severson, M D Hollenberg
Journal: Journal of Clinical Investigation (1988)

We have examined the ability of a highly purified 38-kD phospholipase-inhibitory protein (p38) isolated from human placental membranes that is also a preferred substrate for the epidermal growth factor-urogastrone (EGF-URO) receptor/kinase, to block the release of arachidonate from zymosan-stimulated murine peritoneal macrophages in vitro and to exhibit antiinflammatory activity in a carrageenin rat paw edema test in vivo. The ability of glucocorticoids to increase the amounts of this protein in macrophage cultures was also examined. p38 represents the naturally occurring, intact, NH2-terminally blocked human placental form of the protein termed calpactin II (or lipocortin I), for which partial amino acid sequence data and a complete amino acid sequence deduced from cDNA analysis have been reported. Our data demonstrated that, whereas p38 was an effective inhibitor of pancreatic phospholipase A2 in vitro, it was unable to inhibit either the release of arachidonate from cultured zymosan-stimulated mouse peritoneal macrophages or inflammation in a rat paw edema test. At comparatively high protein concentrations, p38 enhanced either arachidonate release from intact macrophages in vitro (0.5-10 micrograms/ml) or carrageenin-induced paw swelling in vivo (2.5 or 25 micrograms per injection). Furthermore, we were unable to detect induced amounts of p38 in cultures of glucocorticoid-treated peritoneal macrophages obtained from either mice or rats. Our data indicate that the antiphospholipase activity of p38 in vitro and the ability of p38 to serve as a receptor/kinase substrate may in no way relate to the putative ability of the protein to modify eicosanoid release from macrophages in vivo, so as to modulate the inflammatory process. Our data also raise the possibility that p38 (calpactin II) may not be a true representative of the lipocortin family of glucocorticoid-inducible antiinflammatory proteins, despite its ability to inhibit phospholipase A2 in vitro.
Mitochondrial plasticity in classical ischemic preconditioning—moving beyond the mitochondrial KATP channel
Authors: J Minners
Journal: Cardiovascular Research (2003)

Ischemic preconditioning is a powerful biologic phenomenon that activates innate cell survival programs to protect the heart from ischemic injury. The preponderance of research into classical ischemic preconditioning has focused on signaling pathways orchestrating cardioprotection. Conceptually classified into triggers, mediators and end effectors of preconditioning multiple distinct signaling pathways appear to 'converge' on the mitochondria possibly via activation of the mitochondrial ATP-sensitive potassium (mKATP) channel. The mechanisms by which mKATP channel activation induces preconditioning are incompletely elucidated but include perturbations of mitochondrial architecture and function. Since evidence invoking the mKATP channel has almost exclusively been based on studies using diazoxide and 5-hydroxydecanote the finding that these two compounds have mitochondrial effects independent of the mKATP channel has initiated a controversy regarding the exclusivity of this particular channel in preconditioning. A concerted effort to characterize the mitochondrial phenotype is important to advance our understanding of the mechanistic events that underlie the robust cardioprotective phenotype unmasked by preconditioning. The purpose of this review is to collate the information available on mitochondrial biology associated with classical preconditioning, to delineate the distinct temporal presentation of these mitochondrial perturbations, to reassess the role of the mitochondrial KATP channel and to propose a working model integrating the mitochondrial adaptations into the biology driving this cyto-protective phenotype.
Distinctive Characteristics of Non-small Cell Lung Cancer (NSCLC) in the Young: A Surveillance, Epidemiology, and End Results (SEER) Analysis
Authors: Janakiraman Subramanian, Daniel Morgensztern, Boone Goodgame, Maria Q. Baggstrom, Feng Gao, Jay Piccirillo, Ramaswamy Govindan
Journal: Journal of Thoracic Oncology (2010)
Wanted: an appropriate evaluation template
Authors: P. McCulloch
Journal: BMJ (2011)

Both US and EU regulatory regimes need to be updated to deal with the myriad new devices, whose invasiveness, capabilities, and potential for harm are hugely greater than they were 20 years ago.1 2 In developing rules for evaluating these devices, however, the development process needs to be taken into account. The IDEAL framework may prove more useful than …
IDIOCY AND HEREDITARY SYPHILISSTUDY OF 204 CASES WITH THE SERUM DIAGNOSIS TEST
Authors: CHARLES E. ATWOOD
Journal: JAMA (1910)

[BLOOD TESTS BY DR. NOGUCHI, ROCKEFELLER INSTITUTE]  The present study was undertaken to obtain positive knowledge of the proportionate relationship between syphilis in the progenitor and idiocy in the offspring. Wassermann and Plaut 1 first demonstrated by the serum reaction test the connection between syphilis and some of the psychoses, while Stertz 2 showed further by the same method that inherited as well as acquired syphilis can produce disorders of the nervous system. It has long been recognized that syphilis plays an important role in the causation of idiocy and the arrest of brain development. The exact percentage, however, could not be ascertained, until the application of the phenomenon of complement fixation made it possible, since which definite positive serum reactions have been found in idiocy, imbecility, epilepsy, dementia praecox, and nearly all cases of general paresis; while the utilization of the test is of daily occurrence in all diseases,
Breast-feeding in Erythroblastosis Foetalis
Authors: K. S. Ranganathan
Journal: BMJ (1948)

of Raffaele's findings by saying that they have not been confirmed or received any support.But it is just that negative assumption that needs support, a support that would exact a long painstaking work as was Raffaele's work.I am sure that your readers may be surprised in learning from Davey that to succeed in finding these forms, with the same diffi- culties that one meets in finding them in a six-days-old chick, it would be necessary to inoculate in the human the contents of 50,000 infected salivary glands.All malariologists who took the trouble of looking at Raffaele's smears have not hesitated in con- sidering them as belongfng to the exo-erythrocytic stage.I think that the authors' findings in the monkey is a confirmation of Raffaele's work on man.By the way, owing to the authority of Raffaele in that field his observations should have been accepted.
TL-201 REINJECTION DOES NOT IMPROVE DETECTION OF DEFECT REVERSIBILITY COMPARED WITH QUANTITATIVE TL-201 REDISTRIBUTION
Authors: D K Glover, M Ruiz, J P Simanis, W H Smith, D D Watson, G A Beller
Journal: Clinical Nuclear Medicine (1992)

Glover, D K; Ruiz, M; Simanis, J P; Smith, W H; Watson, D D; Beller, G A Author Information
Validation of a Web-Based Predictive Nomogram for Ipsilateral Breast Tumor Recurrence After Breast Conserving Therapy
Authors: Mona Sanghani, Pauline T. Truong, Rita Abi Raad, Andrzej Niemierko, Mary Lesperance, Ivo A. Olivotto, David E. Wazer, Alphonse G. Taghian
Journal: Journal of Clinical Oncology (2010)

Purpose IBTR! version 1.0 is a web-based tool that uses literature-derived relative risk ratios for seven clinicopathologic variables to predict ipsilateral breast tumor recurrence (IBTR) after breast-conserving therapy (BCT). Preliminary testing demonstrated over-estimation in high-risk subgroups. This study uses two independent population-based datasets to create and validate a modified nomogram, IBTR! version 2.0. Methods Cox regression modeling was performed on 7,811 patients treated with BCT at the British Columbia Cancer Agency (median follow-up, 9.4 years). Population-based hazard ratios were generated for the seven variables in the original nomogram. A modified nomogram was then tested against 664 patients from Massachusetts General Hospital (median follow-up, 9.3 years). The mean predicted and observed 10-year estimates were compared for the entire cohort and for four groups predefined by nomogram-predicted risks: group 1: less than 3%; group 2: 3% to 5%; group 3: 5% to 10%; and group 4: more than 10%. Results IBTR! version 2.0 predicted an overall 10-year IBTR estimate of 4.0% (95% CI, 3.8 to 4.2), while the observed estimate was 2.8% (95% CI, 1.6 to 4.7; P = .10). The predicted and observed IBTR estimates were: group 1 (n = 283): 2.2% versus 1.3%, P = .40; group 2 (n = 237): 3.8% versus 3.5%, P = .80; group 3 (n = 111): 6.7% versus 3.2%, P = .05; and group 4 (n = 33): 12.5% versus 8.7%, P = .50. Conclusion IBTR! version 2.0 is accurate in the majority of patients with a low to moderate risk of in-breast recurrence. The nomogram still overestimates risk in a minority of patients with higher risk features. Validation in a larger prospective data set is warranted.
Genetic polymorphisms in the endotoxin receptor may influence platelet count as part of the acute phase response in critically ill children
Authors: Rachel S. Agbeko, John W. Holloway, Meredith L. Allen, Shu Ye, Katy J. Fidler, John Pappachan, Allan Goldman, David Pontefract, John Deanfield, Nigel J. Klein, Mark J. Peters
Journal: Intensive Care Medicine (2010)
HATs off to Hop: recruitment of a class I histone deacetylase incriminates a novel transcriptional pathway that opposes cardiac hypertrophy
Authors: Yasuo Hamamori, Michael D. Schneider
Journal: Journal of Clinical Investigation (2003)

Histone acetylation, regulated by two antagonistic enzymes - histone acetyltransferases (HATs) and histone deacetylases (HDACs) - results in transcriptional changes and also plays a critical role in cardiac development and disease. A new study shows that overexpression of the atypical transcriptional corepressor homeodomain-only protein (Hop) causes cardiac hypertrophy via recruitment of a class I HDAC. In contrast to the body of work on transcriptional mechanisms that drive cardiac hypertrophy, including class II HDACs, this report elucidates a novel growth-suppressing transcriptional pathway in cardiac muscle that opposes hypertrophic growth.
An Improtant Role of IL-17 in the Development of Non-eosinophilic Airway Inflammation induced by LPS-contaminated allergens
Authors: S. Jeon, Y. Kim, Y. Tae, J. Choi, S. Kang, S. Hong, T. Shin, Y. Jee, Y. Kim
Journal: Journal of Allergy and Clinical Immunology (2009)
Bacteriuria in the Catheterized Patient
Authors: Paul Gonick
Journal: JAMA (1975)

Seventy-two patients with indwelling urethral catheters had urine specimens cultured to detect bacteriuria. Bacterial sediments were examined to find the source of the bacteria, with use of an antibody immunofluorescence (IF) technique. Antibody coating demonstrated by fluorescence was considered evidence for pyelonephritis. In cystitis, the bacteria did not fluoresce. Repeat culture and immunofluorescence studies were done 3 to 18 weeks later. One third of the patients had a urinary infection. Two (13%) of the patients catheterized for one day and 17 patients (55%) catheterized four or more days had appreciable bacteriuria. One patient catheterized less than three days had positive IF, while 5 patients (16%) catheterized four or more days had positive IF. Only two of the ten patients observed, with an initial infection, had sterile urine on follow-up culture. On follow-up study, of the four patients with bacteriuria of renal origin, one showed a sterile urine, two had cystitis, and one still had pyelonephritis. (<i>JAMA</i>233:253-255, 1975)
Chernobyl and public health
Authors: K. Baverstock
Journal: BMJ (1998)

In 1992, when the first effects of the Chernobyl accident on the prevalence of thyroid cancer in children were reported,1 they were met with scepticism by the radiological community. 2 3 Some of this scepticism was undoubtedly scientific (“iodine-131 has a low carcinogenic potential”), though some was not. These reservations have now mostly been resolved by re-examination of the data on the relation of exposure to x rays and thyroid cancer and a realisation of just how many children were exposed. It is a cautionary tale of how scientific instinct can mislead: help could have been provided more quickly had it not been for this debate. Nevertheless, similar debates are now obscuring our ability to learn longer term lessons from Chernobyl and provide further help to its victims.

Some sceptics, relieved that the fallout had not originated and fallen in western Europe or America, where populations are litigious, were reluctant to concede that environmental sources of radiation could be strongly associated with serious disease. Childhood thyroid cancer has a very low spontaneous incidence in most countries (<1/1 000 000/year). Thus, the appearance of several tens of cases in the region round Chernobyl from a population of under half a million children, giving relative annual incidences of ≥100/1 000 000, should have left little room for doubt that something was seriously amiss.

Today there is little dispute that a real increase in thyroid cancer occurred among young people in Belarus, …
Detection of Liver Masses with Spiral Computed Tomography
Authors: Klaus Mergener, Erik K. Paulson, John Baillie
Journal: New England Journal of Medicine (1999)

Sasazuki et al. (Oct. 22 issue) 1 report increased survival at one year among patients who underwent transplantation of hematopoietic stem cells from unrelated donors that was associated with matching of HLA-A alleles.They do not report the effect of isolated HLA-A mismatches.Thus, the effect of HLA-A mismatches could be due to multiple mismatches of linked HLA-C, B, and DRB1 alleles.
Symbolic behavior and perspective-taking are forms of derived relational responding and can be learned
Authors: Simon Dymond, Louise McHugh
Journal: Behavioral and Brain Sciences (2005)

Numerous questions remain unanswered concerning the functional determinants of symbolic behavior and perspective-taking, particularly regarding the capabilities of children with autism. An alternative approach that considers these behaviors to be forms of derived relational responding allows for the design of functional intervention programs to establish such repertoires in individuals for whom they are absent.
Diagnosing Hemolytic Disease of the Fetus — Time to Put the Needles Away?
Authors: Kenneth J. Moise
Journal: New England Journal of Medicine (2006)

The RhD (Rh0[D]) antigen is considered the most immunogenic of the antigens found on the surface of the human red cell. In 1941, Levine, Katzin, and Burham1 showed that antibodies to the RhD antigen in pregnant women caused hemolysis and anemia in their offspring. Originally called erythroblastosis fetalis secondary to the finding of a large number of immature red cells in the neonatal circulation, today this condition is known as hemolytic disease of the fetus and newborn.When RhD-positive fetal cells enter the maternal circulation as a result of pregnancy-related events such as miscarriage or delivery, anti-D antibody . . .
Mammon and Medicine
Authors: Howard M. Spiro
Journal: JAMA (1986)

The author raises the question of whether physicians should disclose the stakes they have as researchers in persuading their patients to participate in clinical trials. In the course of giving informed consent, patients are rarely told that their doctors may have strong financial and professional interests in recruiting them as subjects, that pharmaceutical companies and the National Institutes of Health pay research centers and physicians well for completed patient studies, and that professional advancement and distinction depend on the amount of research done. Spiro believes controlled clinical trials are valuable, but argues that full disclosure of the benefits that physicians expect to achieve from their patients' willingness to serve as subjects will enhance the latters' freedom to decide on participation.
Adapalene 0·1% gel for the treatment of acne vulgaris: its superiority compared to tretinoin 0·025% cream in skin tolerance and patient preference
Authors: None Dunlap, None Mills, None Tuley, None Baker, None Plott
Journal: British Journal of Dermatology (1998)

One hundred patients with acne vulgaris applied adapalene (Differin®) 0·1% gel to one side of their face and tretinoin 0·025% cream to the other once a day for 4 weeks; the side of application was determined by randomization code. Patient tolerance (assessed as the side of the face least irritated by drug application) was recorded weekly and patient preference (assessed as the preparation more easily spread, absorbed more quickly, smelled better, felt best on the skin and least greasy to the feel) at completion of the study. The investigator measured skin irritation weekly, scoring erythema, skin dryness, desquamation and burning/stinging on a 10‐point scale. After each week of treatment, 64–68% of patients found adapalene 0·1% gel more tolerable than tretinoin 0·025% cream (P < 0·05). At study completion, 65% of patients preferred adapalene 0·1% gel over tretinoin 0·025% cream (P = 0·003). An overall assessment showed adapalene 0·1% gel was significantly less irritating to the skin in terms of producing erythema, dryness, desquamation and burning/stinging, at Visits 2, 3 and 4 (P < 0·02). Thirty‐two patients experienced mild to moderately severe adverse events; three had adverse events considered to be drug related (two with skin discomfort; one with skin dryness). One patient stopped using the study drugs because of dry skin. This study showed that a majority of patients preferred adapalene 0·1% gel over tretinoin 0·025% cream and that it caused significantly less skin irritation.
Delayed-onset caspase-dependent massive hepatocyte apoptosis upon fas activation in bak/bax-deficient mice
Authors: Hayato Hikita, Tetsuo Takehara, Takahiro Kodama, Satoshi Shimizu, Minoru Shigekawa, Atsushi Hosui, Takuya Miyagi, Tomohide Tatsumi, Hisashi Ishida, Wei Li, Tatsuya Kanto, Naoki Hiramatsu, Shigeomi Shimizu, Yoshihide Tsujimoto, Norio Hayashi
Journal: Hepatology (2011)

Abstract: The proapoptotic Bcl-2 family proteins Bak and Bax serve as an essential gateway to the mitochondrial pathway of apoptosis. When activated by BH3-only proteins, Bak/Bax triggers mitochondrial outer membrane permeabilization leading to release of cytochrome c followed by activation of initiator and then effector caspases to dismantle the cells. Hepatocytes are generally considered to be type II cells because, upon Fas stimulation, they are reported to require the BH3-only protein Bid to undergo apoptosis. However, the significance of Bak and Bax in the liver is unclear. To address this issue, we generated hepatocyte-specific Bak/Bax double knockout mice and administered Jo2 agonistic anti-Fas antibody or recombinant Fas ligand to them. Fas-induced rapid fulminant hepatocyte apoptosis was partially ameliorated in Bak knockout mice but not in Bax knockout mice, and was completely abolished in double knockout mice 3 hours after Jo2 injection. Importantly, at 6 hours, double knockout mice displayed severe liver injury associated with repression of XIAP, activation of caspase-3/7 and oligonucleosomal DNA breaks in the liver, without evidence of mitochondrial disruption or cytochrome c–dependent caspase-9 activation. This liver injury was not ameliorated in a cyclophilin D knockout background nor by administration of necrostatin-1, but was completely inhibited by administration of a caspase inhibitor after Bid cleavage. Conclusion: Whereas either Bak or Bax is critically required for rapid execution of Fas-mediated massive apoptosis in the liver, delayed onset of mitochondria-independent, caspase-dependent apoptosis develops even in the absence of both. The present study unveils an extrinsic pathway of apoptosis, like that in type I cells, which serves as a backup system even in type II cells. (HEPATOLOGY 2011 )
Herbal products are often contaminated, study finds
Authors: J. Wise
Journal: BMJ (2013)

Herbal medicines are frequently contaminated or contain plant species that are a substitute for the plants listed on the label or contain other species that may be a filler, a DNA analysis has found.

Some of the herbal medicines analysed were contaminated with plants that have known toxicity or can interact with other supplements or medications, the study reported in the open access journal BMC Medicine …