tbuckley/cabot-search huggingface dataset:
Sorafenib Cardiotoxicity Increases Mortality After Myocardial Infarction
Authors: Jason M. Duran, Catherine A. Makarewich, Danielle Trappanese, Polina Gross, Sharmeen Husain, Jonathan Dunn, Hind Lal, Thomas E. Sharp, Timothy Starosta, Ronald J. Vagnozzi, Remus M. Berretta, Mary Barbe, Daohai Yu, Erhe Gao, Hajime Kubo, Thomas Force, Steven R. Houser
Journal: Circulation Research (2014)

Rationale: Sorafenib is an effective treatment for renal cell carcinoma, but recent clinical reports have documented its cardiotoxicity through an unknown mechanism. Objective: Determining the mechanism of sorafenib-mediated cardiotoxicity. Methods and Results: Mice treated with sorafenib or vehicle for 3 weeks underwent induced myocardial infarction (MI) after 1 week of treatment. Sorafenib markedly decreased 2-week survival relative to vehicle-treated controls, but echocardiography at 1 and 2 weeks post MI detected no differences in cardiac function. Sorafenib-treated hearts had significantly smaller diastolic and systolic volumes and reduced heart weights. High doses of sorafenib induced necrotic death of isolated myocytes in vitro, but lower doses did not induce myocyte death or affect inotropy. Histological analysis documented increased myocyte cross-sectional area despite smaller heart sizes after sorafenib treatment, further suggesting myocyte loss. Sorafenib caused apoptotic cell death of cardiac- and bone-derived c-kit+ stem cells in vitro and decreased the number of BrdU+ (5-bromo-2’-deoxyuridine+) myocytes detected at the infarct border zone in fixed tissues. Sorafenib had no effect on infarct size, fibrosis, or post-MI neovascularization. When sorafenib-treated animals received metoprolol treatment post MI, the sorafenib-induced increase in post-MI mortality was eliminated, cardiac function was improved, and myocyte loss was ameliorated. Conclusions: Sorafenib cardiotoxicity results from myocyte necrosis rather than from any direct effect on myocyte function. Surviving myocytes undergo pathological hypertrophy. Inhibition of c-kit+ stem cell proliferation by inducing apoptosis exacerbates damage by decreasing endogenous cardiac repair. In the setting of MI, which also causes large-scale cell loss, sorafenib cardiotoxicity dramatically increases mortality.
Transcutaneous measurement of blood velocity profiles and flow
Authors: M. B. HISTAND, C. W. MILLER, F. D. MCLEOD
Journal: Cardiovascular Research (1973)

A comprehensive report is presented of the application of a pulsed ultrasound Doppler velocity meter for transcutaneous measurement of time varying velocity, velocity profiles, and instantaneous flow in arteries of anaesthetized dogs. The procedure used to provide direct velocity and flow calibration using the Doppler equation is outlined. Typical transcutaneous recordings obtained from the femoral artery, abdominal aorta, and carotid artery are illustrated. The results compare favourably with data obtained by invasive means such as electromagnetic cuff flowmeters. The possibility of high resolution, non-invasive haemodynamic measurements on dogs is demonstrated and the application to conscious human subjects suggested.
Abstract 4841: Lysis of cancer cells by highly purified T regulatory cells engaged via an EpCAM/CD3-bispecific BiTE antibody
Authors: Markus Münz, Alexander Murr, Petra Hoffmann, Matthias Edinger, Patrick A. Baeuerle, Peter Kufer, Tobias Raum
Journal: Cancer Research (2012)

Abstract BiTE antibodies are single-chain bispecific antibody constructs with dual specificity for CD3 on T cells and a surface antigen on target cells. By bridging cytotoxic T cells and cancer cells, BiTE antibodies are capable to temporarily mount a polyclonal T cell response that is not restricted by T cell receptor specificity, presence of MHC class I, generation and presentation of peptide antigen, or the need for T cell co-stimulation. Examples are the CD19/CD3-bispecific BiTE antibody blinatumomab, which has shown high response rates and durable remissions in leukemia and lymphoma patients, and EpCAM/CD3-bispecific BiTE antibody solitomab (MT110), which is in a dose-escalating phase 1 study in patients with solid tumors. CD8+ and CD4+ effector memory T cells were found to be the most potent effector cells for BiTE antibodies. Here, we have assessed whether highly purified T regulatory cells (T regs) can also serve as effector cells for BiTE antibody MT110, despite multiple reports suggesting that T regs rather suppress the anti-tumor activity of cytotoxic T cells. T regs were purified from human peripheral blood mononuclear cells (PBMC) using anti-CD25 magnetic beads and fluorescence-activated cell sorting (FACS) for expression of CD4 and CD45RA markers, followed by expansion in the presence of IL-2 (Hoffmann P. et al., Methods Mol. Biol. 677:15-30, 2011). Purified naïve CD4+/CD25high/CD45RA+/FOXP3+ T regs had a purity of 96-99.6%, and contained no detectable CD8+ T cells. In co-culture experiments, a small fraction of purified T regs up-regulated the expression of granzyme B and perforin when stimulated with MT110 in the presence of EpCAM+ target cells. As shown by chromium release assay and phase contrast microscopy, T regs caused a MT110 dose-dependent, redirected lysis of target cells. No target cell lysis was observed with a BiTE antibody solely binding to CD3 on T cells, and by T regs alone. We then tested the activity of T regs against spheroids formed in vitro from colorectal cancer stem cells. Only in the presence of MT110, T regs could significantly reduce the size and integrity of spheroids. In that respect, T regs had a similar activity as PBMC. Our study suggests that T regs, which often are associated with immune escape of tumors, can be effectively engaged for redirected cancer cell lysis by a BiTE antibody. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4841. doi:1538-7445.AM2012-4841
Emerging role of hepatocellular carcinoma among liver-related causes of deaths in HIV-infected patients: The French national Mortalité 2005 study
Authors: Dominique Salmon-Ceron, Eric Rosenthal, Charlotte Lewden, Vincent Bouteloup, Thierry May, Christine Burty, Fabrice Bonnet, Dominique Costagliola, Eric Jougla, Caroline Semaille, Philippe Morlat, Patrice Cacoub, Geneviève Chêne
Journal: Journal of Hepatology (2009)
Treatment of irritable bowel syndrome in primary care
Authors: R. Jones
Journal: BMJ (2008)

Ispaghula, antispasmodics, and peppermint oil should be considered

Irritable bowel syndrome is a common condition with a community prevalence of 10-15% of the general population.1 2 The annual incidence in primary care is around 0.8%, and the prevalence of patients diagnosed in primary care is about 3-4%.3 The disorder is difficult to treat, hence the wide range of treatments used—dietary exclusion, fibre supplements, and probiotics; antispasmodic drugs, antidiarrhoeal agents, and laxatives; antidepressants, hypnotherapy, and cognitive behavioural therapy. This unusual spectrum of drug and non-drug treatments also highlights our ignorance about the cause of the condition. In the linked systematic review (doi:10.1136/bmj.a2313), Ford and colleagues summarise the effects of three different agents—fibre, antispasmodic drugs, and peppermint oil—in people with the syndrome.4

In the 1990s a range of new agents acting on 5-hydroxytryptamine type 3 and type 4 receptors in the enteric nervous system held considerable therapeutic promise. Most of them, however, failed to find a …
AN OBSERVATION CONCERNING CHANGING ATTITUDES TOWARD MENTAL ILLNESS
Authors: ANDREW TERSHAKOVEC
Journal: American Journal of Psychiatry (1964)

Judiciary intervention such as the process of commitment is defined in social terms as a mediator facilitating communications between the public and psychiatry. A recent change in a long-standing pattern in which there is a decline in the use of commitment in New York State's two large metropolitan areas is interpreted as providing one sign of a change in public attitudes toward mental illness favorable to a direct contact and interaction between the public and medicine. The theoretical significance of such an interaction is discussed.
ARMSTRONG'S OXYCATALYST TO DENTISTS
Authors: Harvey Stallard
Journal: JAMA (1928)

To the Editor:  —Referring to your report on Armstrong's Oxycatalyst, I should like to report you the activity of Armstrong among the dental profession. During July or August, 1923, introduced by W. G. Crandall, 802 Merritt Building, Los Angeles, Mr. Armstrong appeared before the San Diego Dental Society and spoke for two or more hours on the possibility of radium salts as curative agents. He advocated their use in baths, drinking water and foods. He reported how glorious plants grew when radium salts were used as fertilizers. Dr. Crandall at that time reported how splendid root-canal fillings could be made quickly and carelessly (without skill) by using radium salts in certain pastes. Later, the dental profession was circularized by some company in Los Angeles on radium paste for root-canal fillings.  At that time Mr. Armstrong was selling for $75 a small stick, a radioactivating substance, which users could place in
Nutlin-3 up-regulates the expression of Notch1 in both myeloid and lymphoid leukemic cells, as part of a negative feedback antiapoptotic mechanism
Authors: Paola Secchiero, Elisabetta Melloni, Maria Grazia di Iasio, Mario Tiribelli, Erika Rimondi, Federica Corallini, Valter Gattei, Giorgio Zauli
Journal: Blood (2009)
Sentiweb: French communicable disease surveillance on the world wide web
Authors: E Boussard, A Flahault, J-F Vibert, A-J Valleron
Journal: BMJ (1996)

For 12 years the French Sentinel system has collected about 330 000 cases of eight communicable diseases in France from a sample of about 1% of the country's general practitioners (see box).1 These sentinel general practitioners use a PC with a modem or a videotex home terminal to transmit data to a front server.2 Case records are automatically stored in a relational database (Oracle), and the incidence of each disease, expressed in cases per 100 000 inhabitants, is calculated weekly. Incidences are calculated for each administrative district (96 departments and 22 regions in metropolitan France). Weekly electronic bulletins give feedback to the sentinel general practitioners and public health authorities.

Since September 1995 the results of this communicable disease surveillance have been available on a worldwide web site called Sentiweb (http://www.b3e. jussieu.fr/sentiweb). Sentiweb also provides an …
Raised serum human chorionic gonadotrophin concentrations in hyperemesis gravidarum.
Authors: A Kauppila, I Huhtaniemi, O Ylikorkala
Journal: BMJ (1979)

Serum human chorionic gonadotrophin (HCG) concentrations were determined by radioimmunoassay with an antiserum specific to HCG beta-subunit in 42 patients with hyperemesis gravidarum and 115 women with normal pregnancies. Mean concentrations (+/- SE of mean) were higher in the women with hyperemesis gravidarum at 7-8 weeks (40.8 +/- 5.2 IU/ml v 22.1 +/- 1.4 IU/ml; P less than 0.001), 9-11 weeks (38.1 +/- 2.3 IU/ml v 27.1 +/- 2.1 IU/ml; P less than 0.0025), and 12-14 weeks of gestation (35.9 +/- 4.2 IU/ml v 25.1 +/- 1.7 IU/ml; P less than 0.005), but there was no difference between the two groups at 15-20 weeks of gestation. In the hyperemesis gravidarum group primigravid women had a higher (P less than 0.005) mean HCG concentration (41.8 +/- 4.0 IU/ml) than multigravid women (32.2 +/- 2.3 IU/ml). The results suggest a causal relation between a high serum HCG concentration and hyperemesis gravidarum.
Phosphatase-1 and -2A inhibition modulates apoptosis in human osteoarthritis chondrocytes independently of nitric oxide production
Authors: M J Lopez-Armada
Journal: Annals of the Rheumatic Diseases (2005)

Objective: To characterise the role of phosphatase-1 and -2A (PP1/2A) in the modulation of apoptosis in human osteoarthritis (OA) chondrocytes. Methods: Human OA chondrocytes were isolated from cartilage obtained from the femoral heads of patients undergoing joint replacement surgery. Cell viability was evaluated by MTT assay. Apoptosis was quantified by ELISA, which measures DNA fragmentation. Nitric oxide (NO) production was evaluated by the Greiss method, and inducible nitric oxide synthase (iNOS) protein synthesis was studied by western blotting. Results: Inhibition of PP1/2A by the specific inhibitor okadaic acid (OKA) dose and time dependently caused a reduction of cell viability (OKA at 50 nmol/l: a reduction to 60% and 43% at 48 and 72 hours, respectively). Genomic DNA from chondrocytes treated with OKA at 50 and 100 nmol/l for 48 hours displayed increased internucleosomal DNA fragmentation by 11 and 13 fields, respectively. Light microscopy and DAPI studies showed that OKA induced DNA condensation and fragmentation, typical of death by apoptosis. The caspase inhibitors Z-VAD-FMK and Z-DEVD-FMK increased cell viability, reduced by OKA at 50 nmol/l to 87% and 73%, respectively. OKA did not increase iNOS protein synthesis or NO production. Conclusion: PP1/2A modulate apoptosis in human OA chondrocytes; this is independent of NO production but dependent on caspases.
Bromsulfalein Retention Due to Administration of a Gall-Bladder Dye (Bunamiodyl)
Authors: Donald Shotton, Martha Carpenter, William B. Rinehart
Journal: New England Journal of Medicine (1961)

IT has been observed that in the study of patients hospitalized for investigation of liver or gall-bladder disease, or both, studies of bromsulfalein excretion and cholecystography are often done concomitantly. In the usual manner this implies the administration of an iodine dye for the cholecystogram on the night before x-ray studies and the addition of a bromine-containing compound (bromsulfalein) on the next morning. On a number of occasions we have noted that the bromsulfalein retention measured in this fashion is frequently out of proportion to existing liver disease, and with repeated determinations at a later date, the values have shown . . .
THE FAVORABLE LONG TERM CLINICAL OUTCOMES OF A HIGH-DOSE DEXAMETHASONE-ELUTING STENT: RANDOMIZED CONTROLLED PROSPECTIVE STUDY
Authors: Yae Min Park, Seung Hwan Han, Kwen-Chul Shin, Myeong Gun Kim, Kyung-Hoon Lee, Woong Chol Kang, Kwang Kon Koh, Tae Hoon Ahn, In Suk Choi, Eak Kyun Shin
Journal: Journal of the American College of Cardiology (2011)
Effect of Alcohol (Ethanol) Administration on Sex-Hormone Metabolism in Normal Men
Authors: Gary G. Gordon, Kurt Altman, A. Louis Southren, Emanuel Rubin, Charles S. Lieber
Journal: New England Journal of Medicine (1976)

To determine whether ethanol per se affects testosterone metabolism, alcohol was administered to normal male volunteers for periods up to four weeks, resulting in an initial dampening of the episodic bursts of testosterone secretion followed by decreases in both the mean plasma concentration and the production rate of testosterone. The volunteers received adequate nutrition and none lost weight during the study, which tended to exclude a nutritional disturbance as the cause of the decreased testosterone levels. The changes in plasma luteinizing hormone suggested both a central (hypothalamus-pituitary) and gonadal effect of alcohol. In addition, alcohol consumption increased the metabolic clearance rate of testosterone in most subjects studied, probably owing to the combined effects of a decreased plasma binding capacity for the androgen and increased hepatic testosterone A-ring reductase activity. These results indicate that alcohol markedly affects testosterone metabolism independently of cirrhosis or nutritional factors.
Combination of Somatostatin Analog, Dexamethasone, and Standard Androgen Ablation Therapy in Stage D3 Prostate Cancer Patients with Bone Metastases
Authors: Michael Koutsilieris, Constantine S. Mitsiades, John Bogdanos, Theodoros Dimopoulos, Dimitrios Karamanolakis, Constantine Milathianakis, Athanassios Tsintavis
Journal: Clinical Cancer Research (2004)

Androgen ablation-refractory prostate cancer patients (stage D3) develop painful bone metastases and limited responsiveness to conventional therapies, hence the lack of universally accepted "gold standard" treatment for this poor prognosis clinical setting. We tested the safety and efficacy in stage D3 patients of the combination hormonal therapy, which combines administration of somatostatin analog and dexamethasone with standard androgen ablation monotherapy (luteinizing-hormone releasing-hormone analog or orchiectomy).Thirty eight patients with stage D3 prostate cancer (mean age 71.8 +/- 5.9 years) continued receiving androgen ablation therapy in combination with oral dexamethasone (4 mg daily for the 1st month of treatment, tapered down to 1 mg daily by the 4th month, with 1 mg daily maintenance dose thereafter) and somatostatin analog (20 mg octreotide i.m. injections every 28 days).Twenty-three of 38 patients (60.5%) receiving this combination regimen had partial responses [PR, >/=50% prostate-specific antigen (PSA) decline], 9 (21.1%) had stable disease, and 7 (18.4%) had progressive disease. In 47.7% (18 of 38) of patients, their serum PSA levels decreased with treatment but did not return to their respective baselines until the end of follow-up (or death from non-prostate cancer-related causes). The median time-to-return to baseline PSA was 12 months (95% CI, 7-17 months), median progression-free survival was 7 months (95% CI, 4.5-9.5 months), median overall survival was 14 months (95% CI, 10.7-17.4 months), and median prostate cancer-specific overall survival (defined as time from onset of combination therapy until prostate cancer-related death) was 16.0 months (95% CI, 11.9-20.1 months). All patients reported significant and durable improvement of bone pain and performance status (for a median duration of 14 months; 95% CI, 9-19 months), without major treatment-related side effects. We observed a statistically significant (P < 0.01) reduction in serum insulin-like growth factor-1 levels at response to the combination therapy. T levels remained suppressed within castration levels at baseline and throughout therapy, including relapse.The combination therapy of dexamethasone plus somatostatin analog and standard androgen ablation manipulation produces objective clinical responses and symptomatic improvement in androgen ablation-refractory refractory prostate cancer patients.
Acute leukemia and myelodysplasia in patients with a Philadelphia chromosome negative chronic myeloproliferative disorder treated with hydroxyurea alone or with hydroxyurea after busulphan
Authors: Iben Nielsen, Hans Carl Hasselbalch
Journal: American Journal of Hematology (2003)

Eighty-three patients with various chronic myeloproliferative disorders [polycythemia vera (PV), essential thrombocytosis (ET), idiopathic myelofibrosis (IMF)] were analyzed for the occurrence of acute myeloid leukemia (AML) and myelodysplasia (MDS) during treatment with hydroxyurea (HU) alone or HU following treatment with busulphan (BU). A total of 58 patients (29 PV, 14 ET, 12 IMF, 3 unclassified) had been treated with HU. Thirty-five of these patients had been treated with HU alone whereas 18 patients had received both HU and BU. The follow-up period was 7.8 years. Twenty-five patients had not been treated with HU. In this patient group, 4 patients had been treated with BU. The follow-up period was 10.5 years. In the HU-treated group (n = 58) 7 patients developed AML and 5 patients MDS. Five of the 12 patients had been treated with HU alone, and 4 patients had received both HU and BU. In the non-HU-treated group (n = 25) 1 patient with PV developed acute myeloid leukemia (AML). This patient had only been treated with phlebotomies. It is concluded that treatment with HU is leukemogenic, with an incidence of AML and MDS of approximately 14% when used alone. The incidence is markedly increased to about 30% when HU is preceded by treatment with BU. HU is not recommended for use in younger patients, in whom non-leukemogenic agents such as alpha-interferon and anagrelide should be used instead.
Nicotinic Acetylcholine Receptor-Based Blockade: Applications of Molecular Targets for Cancer Therapy
Authors: Chih-Hsiung Wu, Chia-Hwa Lee, Yuan-Soon Ho
Journal: Clinical Cancer Research (2011)

The nicotinic acetylcholine receptor (nAChR) was first characterized in 1970 as a membrane receptor of a neurotransmitter and an ion channel. nAChRs have been shown to be involved in smoking-induced cancer formation in multiple types of human cancer cells. In vitro and in vivo animal studies have shown that homopentameric nAChR inhibitors, such as methyllycaconitine and α-Bgtx, can attenuate nicotine-induced proliferative, angiogenic, and metastatic effects in lung, colon, and bladder cancer cells. Recent publications have shown that α9-nAChR is important for breast cancer formation, and in many in vivo studies, α9-nAChR-specific antagonists (e.g., α-ImI, α-ImI, Vc1.1, RgIA, and It14a) produced an analgesic effect. Vc1.1 functions in a variety of animal pain models and currently has entered phase II clinical trials. For cancer therapy, natural compounds such as garcinol and EGCG have been found to block nicotine- and estrogen-induced breast cancer cell proliferation through inhibition of the α9-nAChR signaling pathway. A detailed investigation of the carcinogenic effects of nAChRs and their specific antagonists would enhance our understanding of their value as targets for clinical translation.
An Address ON CHRONIC INTESTINAL STASIS: Delivered before the Dublin University Biological Association on November 22nd, 1913
Authors: S. S. Pringle
Journal: BMJ (1914)

CHRONIC INTESTINAL STASIS.[ TEDCnJ0aA I 83or subinfection are to be detected.I would, however, in all meekness, object that the intoxication theory has been tried, and, save as regards a singularly limited series of symptoms, has so far been found wanting when subjected to the test of experiment; while, on the contrary, it is possible to adduce experimental evidence in favour of each of nmy pleas in favour of the infective nature of the conditions discussed.CONCLUSIONS.To epitomize:1.It is more rational to regard the evil effects of in- testinal stasis as, in the main, a result of conditions favouring subinfection and low forms of infection than as a result of chronic intoxication.2. The term " gastro-intestinal autointoxication " is per- nicious and not to be employed by any self-respecting member of our profession, save for so limited a set of conditions that for ordinary purposes it may safely be wholly expunged from the medical vocabulary.3. While the symptoms and diseases enumerated by Sir Arbuthnot Lane may follow intestinal stasis, at least a large proportion of themu may originate independenftly of such stasis.4. Before recommnending the operation of short-cir- cuiting it is necessary, therefore, to make the fullest studies, so as to discover, if possible, the nature of tlle organism responsible for the disturbance and its probable seat of entry.5. A discovery of the cautse of the symptoms is calculated to suggest the appropriate means of treatment by means other than short-circuitinig.Only when these have been tried and found wanting is removal or slhort-circuiting of tlle colon justifiable.BIBLIOGrIAPHY.