tbuckley/cabot-search huggingface dataset:
The Necessary End
Authors: Edward W. Bixby
Journal: JAMA (1965)

the Editor:—  Dr. H. H. Neumann writes a letter, To Tell the Truth. He objects to informing patients of impending death with no possible alternative or hope. I most sincerely agree. One can prevent a patient from seeking quack cures for incurable disease, see that he is legally and philosophically prepared for demise, but  the door open. There is almost always someone else to whom the diagnosis and prognosis can be explained.  I disagree with advice to tell patients when they have cancer. I avoid this word. It implies complete hopelessness—as is physical life anyway. I always leave room for hope and encouragement while attempting to prepare the patient for death tomorrow if not today.
A more reliable photometric technique for the measurement of scalp sebum excretion
Authors: N.B. SIMPSON, A.R. MARTIN
Journal: British Journal of Dermatology (1983)

The objective assessment of antiseborrhoeic therapy for the scalp requires a reliable technique for the measurement of sebaceous gland activity. Previously published methods were tried but found to be unreliable. This paper describes a photometric technique which gave repeatable results and demonstrated a reduction of sebaceous gland activity on the scalp with both oral isotretinoin and topical 1 1α‐hydroxyprogesterone. The accuracy of the method was achieved by careful preparation of the scalp but was affected by recent shampooing.
Doctor must pay child support after inadequate warning of disability
Authors: Bojan Pancevski
Journal: BMJ (2006)

An Austrian court has ordered a gynaecologist to pay child support for a child with Down's syndrome because the doctor had not warned the mother strongly enough of the likelihood that her baby would be disabled.

This precedent setting ruling has polarised the public and has sparked a heated debate within the medical community.

The case was dropped by two lower courts and went all the way to the …
Abstract 2576: Mechanism of action of a novel Stat3 inhibitor for cancer therapy
Authors: Ralf R. Buettner, Renzo Corzano, Jianping Lin, Nagarajan Vaidehi, Richard Yip, Yuan Chen, Richard Jove, David Horne, John Williams
Journal: Cancer Research (2011)

Abstract Stat3 is a latent transcription factor that promotes cell survival and proliferation and is often constitutively active in multiple cancers. Inhibition of Stat3 signaling pathways suppresses cell survival signals and leads to apoptosis in cancer cells, suggesting direct inhibition of Stat3 function is a viable therapeutic approach. Herein, we identify a small molecule, C48, as a selective Stat3-family member inhibitor. To determine its mechanism of action, we used site-directed mutagenesis and multiple biochemical techniques to show that C48 alkylates Cys468 in Stat3, a residue at the DNA-binding interface. We further demonstrate that C48 blocks accumulation of activated Stat3 in the nucleus in tumor cell lines that over-express active Stat3 leading to impressive inhibition of tumor growth in mouse models. Collectively, these findings suggest Cys468 in Stat3 represents a novel site for therapeutic intervention and demonstrates the promise of alkylation as a potentially effective chemical approach for Stat3-dependent cancers. 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 2576. doi:10.1158/1538-7445.AM2011-2576
Role of sulphasalazine in the aetiology of folate deficiency in ulcerative colitis.
Authors: C M Swinson, J Perry, M Lumb, A J Levi
Journal: Gut (1981)

Only two (2.5%) of 80 outpatients with histologically proven ulcerative colitis had folate deficiency associated with anaemia or macrocytosis. Mean folate absorption, measured using micrograms/kg body weight of a tritium-labelled physiological folate derivative, 5-methyltetrahydroteroylglutamic acid, in six newly diagnosed patients was 76.7% (normal greater than 95%) but fell to 69.4% after three months' treatment with sulphasalazine. Mean difference in individual patients was 7.5% +/- 5.2% (SD) (p less than 0.02). Mean folate absorption in four patients with megaloblastic anaemia or macrocytosis which developed during treatment with sulphasalazine was 66.3%. This rose to 82.4% after the drug was stopped. Mean difference in individual patients was 16.6 +/- 6.6% (SD) (p less than 0.001). All patients who developed anaemia or macrocytosis with sulphasalazine had additional reasons for folate deficiency. These included coeliac disease, severe nutritional deficiencies, and haemolysis. It was concluded that sulphasalazine impairs folate absorption but this only becomes significant if other reasons for folate deficiency are also present.
Familial Mitral Valve Prolapse and Myotonic Dystrophy
Authors: STEPHEN J. WINTERS
Journal: Annals of Internal Medicine (1976)

When a patient with mitral valve prolapse was found to have myotonic dystrophy, his family was studied to ascertain the occurrence of these abnormalities. Of 25 relatives screened, 8 had evidence of both myotonic dystrophy and mitral valve prolapse and 2 had evidence of myotonic dystrophy alone. Thirteen patients had evidence of neither condition and 1 had mitral valve prolapse alone. The association of these two conditions within a family has not previously been observed and valvular heart disease has not been recognized in myotonic dystrophy. This association should be looked for in other patients.
Academics should use their intellectual property to produce cheap drugs for poor countries
Authors: Geoff Watts
Journal: BMJ (2007)

It is time to stop leaving the development of new drugs entirely to the marketplace, say two London academics. Universities should not only retain control over their intellectual property but use it for long term social goals rather than short term revenue, they say.

The physician Sunil Shaunak, of Imperial College London, and the chemist Steve Brocchini, of the School of Pharmacy, London, were speaking last week at a meeting of the House of Commons all-party pharmacy group.

Most drugs begin their life at high prices and under patent. In due …
Report XCVI. THE INFLUENCE OF INCREASED BAROMETRIC PRESSURE ON MAN
Authors: M. Greenwood
Journal: BMJ (1906)

bacteriology of the disease is not well marked.Dr. Batten informs me in this respect that the distinction between these two types is not very definite, and it may very well be that the acute infective type is merely an aggravated form of the catarrhal.The presence of a certain bacillus in the stools, or in the intestines, in cases of disease, even although that bacillus be not found in tlle stools of healthy individuals, hardly proves it to be the cause of the disease.If, however, it has been found to invade the blood or the spleen.this evidence is very strongly in its favour.-Unfortunately, nleither the blood nor the spleen of fatal cases were ex- amined bacteriologically, so that the presence or absence of bacteria in these localities are matters for future in- vestigation by me next summer.MIy thanks are due to Dr. F. E. Batten, who took the greatest interest in this research, and supplied me with the material fromn the Hospital for Sick Children, Great Ormond Street; also to Dr.
Fatal Case of Atypical Pneumonia with Encephalitis
Authors: H. Perrone, M. Wright
Journal: BMJ (1943)

indicates that the term " atypical primary pneu- monia" embraces a clinical group of closely related infec- tious diseases, in certain cases of which viruses have been definitely established as the aetiological agents.In other ,instances where no virus has yet been isolated the patho- logical and clinical evidence suggests a virus infection.Such viruses hitherto isolated appear to be antigenically related to, although not identical with, the viruses of psitta- cosis, lymphocytic choriomeningitis, and lymphogranuloma venereum, all of which can produce meningitis as well as pneumonia in man or animal.Moreover, Smadel and his co-workers (1942) report two cases of lymphocytic chorio- meningitis, in both of which extensive pneumonitis was found at necropsy.The lungs closely resenibled those described in the few available pathological descriptions of atypical pneumonia.
Non-immunogenic Murine Hepatocellular Carcinoma Hepa1-6 Cells Expressing the Membrane Form of Macrophage Colony Stimulating Factor Are Rejected in Vivo and Lead to CD8+ T-Cell Immunity Against the Parental Tumor
Authors: Qinghong Dan, Ramon Sanchez, Christina Delgado, H.Terry Wepsic, Kengathevy Morgan, Yijun Chen, Edward W.B. Jeffes, Clifford A. Lowell, Timothy R. Morgan, Martin R. Jadus
Journal: Molecular Therapy (2001)

Hepatocellular carcinoma is a lethal disease and methods that develop effective cellular-based immunotherapy are needed. We retrovirally transduced non-immunogenic mouse Hepa1-6 hepatoma cells with the gene encoding the membrane form of macrophage colony stimulating factor (mM-CSF). Excess recombinant M-CSF and phagocytosis-inhibiting chemicals blocked macrophage-mediated killing of cloned mM-CSF transfected Hepa1-6 hepatoma cells. Macrophages derived from Hck−/−Fgr−/− and Lyn−/− triple knockout mice, which are incapable of performing phagocytosis, failed to kill the mM-CSF transduced cells. The mM-CSF transfected tumor clones failed to grow when injected into C57BL/6 or C57L/J mice. Splenocytes from these vaccinated mice displayed cytotoxicity against parental Hepa1-6 cells, but not against B16 and CT-26 tumor cells in vitro. Mice that rejected the mM-CSF transfected Hepa1-6 tumor subsequently rejected parental Hepa1-6 cells but not the B16 melanoma cells when rechallenged. Elimination of the CD8+ effector cells by an anti-CD8 antibody and complement treatment prevented the adoptive transfer of anti-Hepa1-6-specific immunity into naive animals. Thus, mM-CSF provides a method of generating effective anti-tumor immune responses by macrophages and cytotoxic T cells against the parental Hepa1-6 cells. Our work suggests that mM-CSF transduced hepatoma cells could be used as a tumor vaccine to stimulate immune responses against hepatocellular carcinoma.
A stepwise algorithm for finding minimum evolution trees
Authors: S. Kumar
Journal: Molecular Biology and Evolution (1996)

A stepwise algorithm for reconstructing minimum evolution (ME) trees from evolutionary distance data is proposed. In each step, a taxon that potentially has a neighbor (another taxon connected to it with a single interior node) is first chosen and then its true neighbor searched iteratively. For m taxa, at most (m-1)!/2 trees are examined and the tree with the minimum sum of branch lengths (S) is chosen as the final tree. This algorithm provides simple strategies for restricting the tree space searched and allows us to implement efficient ways of dynamically computing the ordinary least squares estimates of S for the topologies examined. Using computer simulation, we found that the efficiency of the ME method in recovering the correct tree is similar to that of the neighbor-joining method (Saitou and Nei 1987). A more exhaustive search is unlikely to improve the efficiency of the ME method in finding the correct tree because the correct tree is almost always included in the tree space searched with this stepwise algorithm. The new algorithm finds trees for which S values may not be significantly different from that of the ME tree if the correct tree contains very small interior branches or if the pairwise distance estimates have large sampling errors. These topologies form a set of plausible alternatives to the ME tree and can be compared with each other using statistical tests based on the minimum evolution principle. The new algorithm makes it possible to use the ME method for large data sets.
Abstract PD05-07: Use of Natural ER Beta Modulators in Treating Hormonal Therapy Resistant Breast Tumors
Authors: M Ganapathy, NB Hareesh, NB Kirma, M Tagliaferri, I Cohen, N Krishnegowda, RK Vadalamudi, RR. Tekmal
Journal: Cancer Research (2010)

Abstract Although systemic hormone therapies that either block local estrogen production by aromatase inhibitors (AI) such as letrozole or block actions of estrogen/ER actions by anti-estrogens (AEs) like tamoxifen are well tolerated, unfortunately, essentially all breast cancers in women with advanced breast cancer develop resistance to these two classes of agents, and the benefit of adjuvant therapy (where micrometastatic disease is present but cannot be directly observed) is also limited by the development of resistance. In addition, side effects associated with the systemic inhibition of aromatase with current compounds limits their long-term utility of them as chemopreventative agents. We have investigated whether treatment of letrozole resistant breast cancer cells with selective plant-derived ER beta agonists (Liquiritigenin; LIQ or Nyasol; NYA) alone or in combination with letrozole affects the growth of AI resistant breast cancer cells, thereby restores sensitivity to AI. To test whether combination therapy restores sensitivity to letrozole, we have treated letrozole resistant breast cancer cells [LTLTca, derived from MCF-7-aromatase tumors resistant to letrozole] with either letrozole alone or with a combination of letrozole and LIQ/NYA. In addition, effects of these compounds on cell growth was also tested using different breast cancer cells including MCF-7, MCF-7-aromatase, ZR-75-1, ZR-75-aromatase, MDA-MB-231 along with tamoxifen resistant MCF-7 or MCF-7- PELP/ZR-75-PELP1. Compared to single agents, combination treatment not only restored sensitivity to letrozole but also resulted in decreased cell proliferation and increased apoptosis as well as increased ERα and decreased ERα levels in resistant cells. Combination of LIQ or NYA not only diminished cell growth in MCF-7-HER2, MCF-7-PELP1, and SKBR-3 breast cancer cells (that express endogenous aromatase) but also affected the expression of aromatase. Detailed investigations indicated that LIQ/NYA affects the induction of aromatase by specifically inhibiting breast cancer specific aromatase promoter 1.3 as well as its activity through inflammatory cytokine-mediated actions. These studies suggest the therapeutic benefit of LIQ or NYA ERα agonist to resensitize breast cancer cells that are resistant to AEs or AI and their ability to selectively inhibit tumor induction of aromatase. Our study suggests a novel role of natural ER beta agonists as valuable therapeutic modulators to treat endocrine sensitive as well as resistant tumors. (Supported by V-Foundation &amp; P30 CA 54174, RRT) Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD05-07.
Selenium and Breast Cancer-Reply
Authors: David J. Hunter, Meir J. Stampfer, Graham A. Colditz, Frank E. Speizer, Walter C. Willett, J. Steven Morris
Journal: JAMA (1991)

<h3>In Reply.—</h3> The women in our study live in 11 large, geographically diverse US states, including Texas, a state with a high soil selenium level,<sup>1</sup>and thus their selenium intake is broadly representative of the average intake for US women. The median toenail selenium concentration of the upper quintile in our study was 0.99 μg/g, approximately equal to the value of toenail selenium (0.999 μg/g) among women consuming more than 90 μg/d of selenium supplements in the Nurses' Health Study.<sup>2</sup> Dr Schrauzer states that our study "actually suggests" a reduced risk of breast cancer in subjects with the highest selenium levels. In fact, the relative risk in the highest quintile of toenail selenium is 1.10, in the opposite direction to that hypothesis. We agree that the confidence interval (0.70 to 1.69) does not exclude a modest protective association, as stated in our original article. Indeed, we are conducting
Outcome Assessment and Clinical Improvement in Panic Disorder: Evidence From a Randomized Controlled Trial of Fluoxetine and Placebo
Authors: David Michelson, R. Bruce Lydiard, Mark H. Pollack, Roy N. Tamura, Sharon L. Hoog, Rosalinda Tepner, Mark A. Demitrack, Gary D. Tollefson, None the Fluoxetine Panic Disorder Study Group
Journal: American Journal of Psychiatry (1998)

Although panic attacks account for only a portion of the morbidity of panic disorder and panic attack frequency assessments are unreliable, studies of drug efficacy in panic disorder have generally used reduction in panic attack frequency as the primary measure of improvement. The authors studied the efficacy of fluoxetine treatment in panic disorder and measured the relative contributions of changes in symptoms to overall improvement.Patients with a diagnosis of panic disorder (N = 243) were randomly assigned to treatment with 10 or 20 mg/day of fluoxetine or placebo. Primary outcome measures were change in panic attack frequency and clinician-rated Clinical Global Impression improvement scores. Other assessments included a panic attack inventory, clinician-rated and patient-rated versions of the Panic and Phobic Disorder Change Scale, a phobia rating scale, the Hamilton Anxiety Rating Scale, the 21-item Hamilton Depression Rating Scale, and the Sheehan Disability Scale. Correlations were determined between outcomes in individual symptom domains and overall clinical outcome.Fluoxetine, particularly the 20-mg/day dose, was associated with more improvement than was placebo in patients with panic disorder across multiple symptom measures, including global improvement, total panic attack frequency, phobic symptoms, and functional impairment. Global improvement was most highly correlated with reductions in overall anxiety and phobic symptoms and least correlated with reduction in panic attacks. Fluoxetine treatment for panic disorder was well tolerated, with a safety profile consistent with that observed for fluoxetine in other disorders.These data provide support for the efficacy and safety of fluoxetine treatment in reducing panic attacks, phobic symptoms, anxiety, and depressive symptoms in patients with panic disorder. Reductions in panic attack frequency in subjects given either fluoxetine or placebo were less closely related to overall clinical improvement than reductions in phobic avoidance, anxiety, depressive symptoms, and functional impairment, suggesting that outcome measures in this disorder should be more broadly based.
Saline solutions: the quest for fresh water.
Authors: C G Reuther
Journal: Environmental Health Perspectives (2000)

Despite steady advances in the technology, desalination remains one of the most expensive ways to produce potable water. But as water scarcity forces communities to find new sources of drinking water, scientists are developing innovations that may soon make desalination a reasonable option for many more communities. The newest approach to desalination is membrane systems, which include reverse osmosis and electrodialysis systems. Current research seeks to make these systems more effective and less likely to produce environmentally hazardous by-products. Many facilities use traditional distillation to desalinate water, and efforts are being made to combine membranes and distillation for more efficient systems.
Intestinal Obstruction From Medication Bezoars
Authors: Michael D. Korenman
Journal: JAMA (1978)

MEDICATION bezoars are an unusual cause of intestinal obstruction. In two previous reports from this institution,<sup>1,2</sup>six cases of patients with intestinal obstruction due to aluminum hydroxide gel or aluminum hydroxide gel and polystyrene sodium sulfonate (Kayexalate) bezoars were reported. Half the patients were adults with acute renal failure, and half were children who had undergone renal transplantation. Aluminum hydroxide gel was given for phosphate binding and as an antacid, and the polystyrene sodium sulfonate was used as an intestinal ionexchange resin for potassium control. Bezoar formation from the medications was potentiated by the lack of intestinal activity and the intermittent relative dehydration from dialysis for the renal failure. <h3>Report of Cases</h3><h3>CASE 1.—</h3> On April 22, 1977, a 32-year-old man received burns over 83% of his body surface area during an industrial flash fire. After five days of treatment at a local hospital, he was transferred to the
Organization and evolution of D region class I genes in the mouse major histocompatibility complex.
Authors: D Stephan, H Sun, K F Lindahl, E Meyer, G Hämmerling, L Hood, M Steinmetz
Journal: The Journal of Experimental Medicine (1986)

Chromosome walking has been used to study the organization of the class I genes in the D and Qa regions of the MHC of the BALB/c mouse and in the D region of the AKR mouse. Five and eight class I genes are found in the D and Qa regions of the BALB/c mouse, respectively, while the AKR mouse contains only a single class I D region gene that has been identified by transfection as the Dk gene. Restriction map homologies and crosshybridization experiments suggest that the multiple class I genes in the D region of the BALB/c mouse have been generated by unequal crossing-over involving class I genes from the Qa region. The expanded D region of BALB/c and other H-2d haplotype mouse strains appears to be metastable, since evidence for gene contraction in the Dd region has been found in two mutant strains. Thus the D region and also the Qa region class I genes are in a dynamic state, evolving by gene expansion and contraction.
Abstract P6-15-19: PI3K-MTOR Inhibitor BEZ235 Shows Antitumor Activity Against a Panel of Basal-Like Cells and Potentiates the Antitumor Activity of Taxanes and Vinorelbine
Authors: JC Montero, A Esparis-Ogando, A Pandiella, A. Ocana
Journal: Cancer Research (2010)

Abstract Background: Intracellular signalling pathways associated with the oncogenesis of basal-like breast cancer are relatively unknown. Basal-like breast cancer constitutes 15% of all breast tumors. Although chemotherapy is the only treatment, no data support the use of one agent over others. Furthermore, combinations of chemotherapies with targeted agents against activated signalling pathways have not been explored. Here we have analyzed the action of the dual PI3K-AKT-mTOR pathway inhibitor BEZ235 on a panel of basal-like breast cancer cell lines. Methods: We used several triple negative breast cancer cell lines, and analyzed the action of BEZ235 on their proliferation and cell survival using MTT metabolization and other apoptosis assays. Biochemical experiments were performed to investigate the molecular bases of the action of BEZ235. Experiments in combination with chemotherapies were also performed to identify synergic combinations. Results: PI3K-AKT pathway was activated in most of the cell lines studied. Administration of the dual PI3K-mTOR inhibitor BEZ235 decreased AKT phosphorylation in a dose dependent manner. It also reduced signalling through the mTORC1 and mTORC2 complexes. BEZ235 also decreased proliferation of most cell lines with IC50 values &amp;lt;1 μM. Administration of BEZ 235 with taxanes and vinorelbine showed synergy. Conclusions: The PI3K-AKT-mTOR signalling axis is frequently activated in basal-like cells. The efficient antitumoral effect of the inhibition of this route with BEZ235 indicates that targeting this pathway may be a relevant therapeutic strategy in triple negative breast cancer. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-15-19.