tbuckley/cabot-search huggingface dataset:
Abstract 2706: Crizotinib, a selective c-Met inhibitor, prevents metastasis to the liver and lungs in a primary uveal melanoma mouse model.
Authors: Oliver Surriga, Rajasekhar Vinagolu, Grazia Ambrosini, Gary Schwartz
Journal: Cancer Research (2013)

Abstract Uveal melanoma is the most common primary intraocular malignant tumor in adults. About half of patients with uveal melanoma will develop metastatic disease to the liver and the lung. These tumors are characterized by mutations in G-proteins (GNAQ and GNA11) and also the over-expression of c-Met. Crizotinib is a selective inhibitor for c-Met as well as anaplastic lymphoma kinase (ALK). We found that crizotinib inhibited cell proliferation of uveal melanoma cell lines in a dose dependent manner with an IC50 in the range of 0.75 μM to 2 μM. Phospho-c-Met was inhibited by crizotinib starting at 10 nM with inhibition of downstream signaling including p-ERK1/2, p-AKT and p-STAT. In our xenograft model there was only a modest inhibition of tumor growth after treatment with doses of ≥ 50 mg/kg crizotinib. As crizotinib also prevented cell migration regardless of G-protein status, we established a primary metastatic uveal mouse model in which we created a GFP-luciferase expressing uveal melanoma cell line that developed liver and lung metastases 6 weeks after primary implantation into the eye. At a dose of 50 mg/kg daily, starting 4 weeks after primary implantation, there was a dramatic reduction in the liver and lungs metastases when compared to untreated controls. These results indicate that the inhibition of c-Met alone may be sufficient to prevent metastasis of uveal melanoma and suggest there may be a potential for using crizotinib as an adjuvant therapy in uveal melanoma. Citation Format: Oliver Surriga, Rajasekhar Vinagolu, Grazia Ambrosini, Gary Schwartz. Crizotinib, a selective c-Met inhibitor, prevents metastasis to the liver and lungs in a primary uveal melanoma mouse model. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2706. doi:10.1158/1538-7445.AM2013-2706
Treatment of Hyperhomocysteinemia in Renal Transplant Recipients
Authors: Andrew G. Bostom
Journal: Annals of Internal Medicine (1997)

Background: Stable renal transplant recipients have an excess prevalence of hyperhomocysteinemia, which is a risk factor for arteriosclerosis. Objective: To determine the effect of treatment with 1) vitamin B6 or 2) folic acid plus vitamin B12 on fasting and post-methionine-loading plasma total homocysteine levels in renal transplant recipients. Design: Block-randomized, placebo-controlled, 2 × 2 factorial study. Setting: University-affiliated transplantation program. Patients: 29 clinically stable renal transplant recipients. Intervention: Patients were randomly assigned to one of four regimens: placebo (n = 8); vitamin B6, 50 mg/d (n = 7); folic acid, 5 mg/d, and vitamin B12, 0.4 mg/d (n = 7); or vitamin B6, 50 mg/d, folic acid, 5 mg/d, and vitamin B12, 0.4 mg/d (n = 7). Measurements: Fasting and 2-hour post-methionine-loading plasma total homocysteine levels. Results: Vitamin B6 treatment resulted in a 22.1% reduction in geometric-mean post-methionine-loading increases in plasma total homocysteine levels (P = 0.042), and folic acid plus vitamin B12 treatment caused a 26.2% reduction in geometric-mean fasting plasma total homocysteine levels (P = 0.027). These results occurred after adjustment for age; sex; and pretreatment levels of total homocysteine, B vitamins, and creatinine. Conclusions: Vitamin B6 should be added to the combination of folic acid and vitamin B12 for effective reduction of both post-methionine-loading and fasting plasma total homocysteine levels in renal transplant recipients.
Avian exposure and risk of lung cancer in women in Missouri: population based case-control study
Authors: M. C. Alavanja, R. C Brownson, E. Berger, J. Lubin, C. Modigh
Journal: BMJ (1996)

Objective-To investigate the association, previously reported in three European studies, between ownership ofpet birds and the risk oflung cancer.Design-A population based case-control study with a structured questionnaire administered by telephone.Setting-Missouri, a midwestern state in the United States with a population ofabout 5 million.Subjects-All newly diagnosed cases ofprimary lung cancer in women aged 30-84 years in Missouri from 1 January 1993 to 31 January 1994 reported to the state cancer registry were invited to participate (n = 652); and 629 population based controls.Main outcome measures-Odds ratios were computed in relation to whether or not the study subject ever kept pet birds, the type of bird kept, and several measures of intensity or duration of exposure.Odds ratios were adjusted for smoking.Results-The odds ratio (95% confidence interval) for the development oflung cancer asso- ciated with keeping pet birds was 0.84 (0.65 to 1.09).The results were similar for the type of pet bird kept, the number ofbirds kept, the location of the bird in the house, and the duration of ownership.Conclusion-The keeping ofpet birds carries no excess risk for the development oflung cancer.
Vegetarians and Atherosclerosis
Authors: M. Elliot
Journal: BMJ (1951)

In equity markets, the opening and closing of trading are particularly stressful periods. Ozenbas, Pagano, and Schwartz investigate the quality of price determination at these times (compared to midday periods) for large-, mid-, and smallcapitalization stocks on the NYSE, NASDAQ, and London Stock Exchange. Using three different metrics, they consistently find lower quality at both the open and the close.The deterioration of market quality at openings is greatest for large-cap stocks, but no systematic association with cap size is observed at the close. Large-cap stocks evidently lead smaller-cap stocks in finding new equilibrium values, and accentuated volatility at the open is in large part attributable to the complexities of price discovery. <b>TOPICS:</b>In markets, VAR and use of alternative risk measures of trading risk, volatility measures
Conclusions are uncertain
Authors: T. A. Ball
Journal: BMJ (2010)

Respiratory data can be extracted from pulse oximeter plethysmogram (pleth) traces using low pass filtering (LPF) in infants and children (Wertheim D et al. Arch Dis Child Fetal Neonatal Ed.2009;94:F301-3). Flattening of the LPF pleth trace has been observed associated with central apnoeas in infants(Wertheim D et al. Acta Paediatr.2014;103:e222-4). The study aim was to examine changes in LPF pleth traces associated with obstructive apnoeas in children. Polysomnographic data were analysed from recordings on 4 children undergoing respiratory polysomnography for suspected obstructive sleep apnoea. Signals were acquired using a Visi-3 Polysomnography system (Stowood Scientific Instruments Ltd., UK). Oximetry pleth, thoracic and abdominal Respiratory Inductance Plethysmography (RIP) bands, oxygen saturation (SpO<sub>2</sub>) and heart rate data were downloaded. Software was written in MATLAB (The MathWorks Inc., USA) to LPF the pleth signal &amp; view with other signals. Different patterns in LPF pleth traces associated with periods of apnoea were seen. Pattern A:In 2 cases there was an increase in LPF pleth signal amplitude associated with increase in the abdominal RIP band trace, increased thoracoabdominal asynchrony and increased respiratory rate during a period of obstructive apnoea. Pattern B:In 3 recordings periods of flattening on RIP bands were associated with flattening on the LPF pleth signal as seen in central apnoeas; 1 of these recordings also included periods with pattern A. There appear to be different patterns seen on the filtered pleth traces in apnoeas which may suggest some periods were not pure obstructive apnoeas. Thus our results suggest there can be changes in the LPF pleth signal associated with obstructive apnoeas.
The low-dose monoethylglycinexylidide test: Assessment of liver function with fewer side effects
Authors: C Reichel, A Nacke, T Sudhop, G Wienkoop, C Luers, C Hahn, C Pohl, U Spengler, T Sauerbruch
Journal: Hepatology (1997)

The hepatic metabolism of lidocaine (1 mg/kg intravenously) to its metabolite monoethylglycinexylidide (MEG-X) is the basis of the standard MEG-X test. To reduce the lidocaine-induced side effects, we evaluated the MEG-X formation after 0.5 and 1 mg/kg lidocaine intravenously in subjects with normal (n = 5) and severely impaired liver function (n = 7) (study I). From this study, a low-dose test (MEG- X concentration 30 minutes after 50 mg lidocaine intravenously [MEG- X 30min ] normalized to standard MEG-X test results) was developed. Sensory side effects from this low dose and from the standard MEG-X test were compared in a double-blind, randomized, cross-over study (study II) comprising 15 individuals with normal liver function and 45 patients with cirrhosis (15 Child A, 15 Child B, and 15 Child C). In study I, MEG-X formation rate was dose-independent in patients with severely impaired liver function. In study II, normalized MEG-X test results (ranging from &lt; or = 4 to 120 μg/L) were virtually identical to the standard test results (mean difference: -1.9 μg/L; 95% confidence interval [CI]: -5.3; 1.5 μg/L). Fewer individuals experienced side effects (30% vs. 53%) with the low-dose test ( P = .0013). In a multivariate analysis, the Child-Pugh score was inversely related to the occurrence of side effects. The low-dose MEG-X test gives almost identical results to the standard MEG-X test and is associated with fewer side effects, which occur less often in individuals with more severely compromised liver function.
Unilateral Osteoarthritis of the Hand
Authors: H. Ralph Schumacher
Journal: JAMA (1965)

OSTEOARTHRITIS involving all interphalangeal joints but confined to one hand is unusual. Previous reports have described the failure of Heberden's nodes to develop in the paralyzed hand in hemiplegia, peripheral nerve injury,<sup>1</sup>and polio.<sup>2</sup>The unilateral osteoarthritis in the case presented here appeared only in the hand that had been severely frostbitten seven years earlier. <h3>Report of a Case</h3> This patient, a 39-year-old white man, was admitted to the USAF Hospital Travis on March 9, 1964, for retirement evaluation of arthritis. In 1944 the patient had sustained a frostbite injury to both hands while flying in a B-24. At the time he was 18 years of age. The left hand was minimally frostbitten and only slight peeling followed but the right hand was severely involved with much pain, and rapidly developed blisters and blackening of the skin. All changes were predominantly in the fingers and extended to the
Right to Treatment-Reply
Authors: William B. Smith
Journal: JAMA (1980)

<h3>In Reply.—</h3> The correspondents state that<i>Addington vs Texas</i>did not mandate any particular "right to treatment." Indeed, neither the main article nor the editorial comment so stated, and no such contention was intended. The<i>Addington</i>opinion related solely to the standard of proof required for the involuntary commitment of the mentally ill. The question of the right to treatment is much too complex to debate in this limited response. However, it is certainly clear that a person who has been involuntarily committed to a state mental institution is entitled to receive the care and treatment that are appropriate and available for his condition. The state incurs that obligation when it involuntarily deprives the patient of his liberty. The state cannot involuntarily commit a person to a mental institution as a sort of "human garage" where mentally ill are simply "parked" or "stored." In addition to food, clothing, and shelter,
Two patients with heparin‐induced thrombocytopenia followed by idiopathic (immune) thrombocytopenic purpura: Case Report
Authors: Faisal Waheed, Nauman Naseer, Tauseef Ahmed, John C. Nelson
Journal: American Journal of Hematology (2003)

Abstract Heparin‐induced thrombocytopenia (HIT) and idiopathic thrombocytopenic purpura (ITP) are separate and well‐recognized clinical syndromes, 10both having potential for disastrous outcomes. Sequential occurrence of these two diseases has not been reported in the literature. We report herein two patients who were initially diagnosed as having HIT but whose later clinical course was similar to ITP. Although dysfunction of immune system seems to play a role, the precise mechanisms for the development of these diseases are unclear. As both conditions have different natural histories and require different treatment modalities, it is important to recognize that these two diseases may be seen sequentially. Am. J. Hematol. 73:290–293, 2003. © 2003 Wiley‐Liss, Inc.
Hepatosplenic T cell lymphoma responsive to 2′‐deoxycoformycin therapy
Authors: Michael Bennett, Estella Matutes, Philippe Gaulard
Journal: American Journal of Hematology (2010)

Hepatosplenic T cell lymphoma (HSTL) is a rare condition usually with an aggressive course and a poor prognosis even after extensive treatment. We describe here a patient who presented with hemophagocytosis. The lymphoma had unusual phenotypic features, an indolent course and responded to 20-deoxycoformycin therapy as a single agent. We suggest that this therapy be used in further cases as part of the treatment strategy.
Cessation of Smoking
Authors: Wellington S. Tichenor
Journal: JAMA (1981)

<h3>To the Editor.—</h3> In the QUESTIONS AND ANSWERS column, Alan Blum, MD (1980;244:191), made several comments concerning our nicotine neutralization treatment to stop smoking, to which we would like to respond. While we would agree that any smoking cessation treatment program should be proven by doubleblind studies, there must be some physicians who work out the details of the technique before it is ready for use by all physicians. (Incidentally, initial, unpublished reports from the ongoing double-blind study at the University of Miami indicate a statistical difference between treatment and needle stick placebo [personal communication, Roger Palmer, MD].) In the meantime, as private physicians, we must make the choice of using a technique which, in our office, has been found to be over 50% effective in follow-up to one year, or refer patients to other programs. We have considered doing a double-blind study in this office, however, our patients (particularly
Deletion Bias in Avian Introns over Evolutionary Timescales
Authors: Kevin P. Johnson
Journal: Molecular Biology and Evolution (2004)

The role that introns play in the function and evolution of nuclear genomes is not fully understood. Recent models of intron evolution suggest that selection and drift may interact to maintain introns in multicellular organisms. In addition, deletion mutations are more likely to become fixed than insertion mutations. Examination of indel substitutions over macroevolutionary timescales in pigeons and doves (Aves: Columbiformes) reveals that deletion substitutions outnumber insertion substitutions by over six times. The length of indel events is variable.
The appropriateness of tympanostomy tubes for children
Authors: J. L. Pulec
Journal: JAMA (1995)

To the Editor.  —As the editor of a medical journal, I recognize the desirability to publish provocative and controversial articles. The article by Dr Kleinman and colleagues 1 involves a more significant issue.  Before publication, articles in most medical journals are carefully reviewed by experts in the field being discussed to determine the scientific validity, statistical accuracy, and general worth of the communication. This article seems to be deficient on all counts. There is no evidence that any of the authors are trained to perform the procedure themselves nor did they personally collect the data. In addition, by their own admission, the information was obtained from the proprietary database maintained by a utilization review firm (VHS), a for-profit company listed on the New York Stock Exchange whose main interest is to restrict payment for medical care.  As a member of the American Medical Association, I feel that it is outrageous
Abstract 2428: Molecular determinants of dasatinib response in uterine carcinoma.
Authors: Jie Huang, Wei Hu, Justin Bottsford-Miller, Tao Liu, Behrouz Zand, Robert L. Coleman, Anil K. Sood
Journal: Cancer Research (2013)

Abstract Despite the many attractive features of EphA2 as a therapeutic target in cancer, approaches to block it have lagged behind. Dasatinib is a multi-kinase inhibitor and may be useful for targeting EphA2. However, reliable predictive markers of response are needed. Additionally, the underlying mechanism deciding whether responsive or resistant to dasatinib and biological impact of EphA2 function in the context of EphA2 targeted therapy in cancer are not known. We undertook a large number of studies to fully characterize the effects of dasatinib using in vitro (cell viability, RPPAs, gene expression, and confocal imaging) and in vivo uterine cancer models. Molecular markers for response prediction were identified by using RPPA and immunohistochemistry. In vitro, the effects of dasatinib treatment varied among the different endometrial cancer cell lines tested, (IC50 values ranged from 30 nM to 17,792 nM), which was associated with varying levels of EphA2 and tyrosine phosphorylation and serine897 phosphorylation of EphA2, and with varying status of caveolin-1 (CAV-1), PTEN and RAS/MAPK . A set of markers that are essential for dasatinib response was identified, including EphA2, CAV-1, pAKTs473, BRAF/CRAF (MAPK pathway) and ppS6s240/244 (mTOR pathway). A novel mechanism for response was identified by which dasatinib can drive the BRAF and EphA2 to CAV-1 at the plasma membrane, resulting in breaking off the BRAF/CRAF heterodimer induced by dasatinib, and blocking compensatory activation of the MAPK pathway. In vivo data using orthotopic mouse models of uterine carcinoma were entirely concordant with our in vitro findings. The efficacy of dasatinib therapy in uterine carcinoma depends on EphA2 phosphorylation at its S897 site and high CAV-1 levels are predictive of response to dasatinib. These findings may have clinical implications for ongoing dasatinib-based clinical trials. Citation Format: Jie Huang, Wei Hu, Justin Bottsford-Miller, Tao Liu, Behrouz Zand, Robert L. Coleman, Anil K. Sood. Molecular determinants of dasatinib response in uterine carcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2428. doi:10.1158/1538-7445.AM2013-2428
A NEW CASE OF SYPHILITIC TUMOR OF THE STOMACH.
Authors: MAX EINHORN
Journal: JAMA (1902)

The literature on syphilis of the stomach can be found in a paper<sup>1</sup>on the subject I wrote a few years ago. I divided syphilis of the stomach into three distinct groups: 1, gastric ulcer of syphilitic origin; 2, syphilitic tumor of the stomach; 3, syphilitic stenosis of the pylorus. The second group, "Syphilitic tumor of the stomach," appears to be the most interesting one. For, on one hand the resemblance to cancer of the stomach is great, on the other hand the diagnosis, while at first merely probable, can soon be made positive by the result of treatment and the gradual disappearance of the growth. As cases of syphilitic tumors of the stomach are quite rare I take pleasure in reporting the following new observation: Max F., 42 years old, has been complaining for the last seven years of digestive disturbances. He frequently suffers from gastric pains. His
Participation of the Prostaglandins in the Control of Renal Blood Flow during Acute Reduction of Cardiac Output in the Dog
Authors: Juan A. Oliver, Robert R. Sciacca, John Pinto, Paul J. Cannon
Journal: Journal of Clinical Investigation (1981)

To determine whether renal prostaglandins participate in the regulation of renal blood flow during acute reduction of cardiac output, cardiac venous return was decreased in 17 anesthetized dogs by inflating a balloon placed in the thoracic inferior vena cava. This maneuver decreased cardiac output from 3.69±0.09 liters/min (mean±SEM) to 2.15±0.19 liters/min (P < 0.01) and the mean arterial blood pressure from 132±4 to 111±5 mm Hg (P < 0.01) and increased total peripheral vascular resistance from 37.6±2.5 to 57.9±4.8 arbitrary resistance units (RU) (P < 0.01). In marked contrast, only slight and insignificant decreases in the renal blood flow from 224±16 to 203±19 ml/min and renal vascular resistance from 0.66±0.06 to 0.61±0.05 arbitrary resistance units (ru) were observed during inflation of the balloon. Concomitant with these hemodynamic changes, plasma renin activity and plasma norepinephrine concentration increased significantly in both the arterial and renal venous bloods. Plasma concentration of prostaglandin E2 in renal venous blood increased from 34±6 to 129±24 pg/ml (P < 0.01). The subsequent administration of indomethacin or meclofenamate had no significant effect on mean arterial pressure, cardiac output, and total peripheral vascular resistance, but reduced renal blood flow from 203±19 to 156±21 ml/min (P < 0.01) and increased renal vascular resistance from 0.61±0.05 to 1.05±0.21 ru (P < 0.01). Simultaneously, the plasma concentration of prostaglandin E2 in renal venous blood fell from 129±24 to 19±3 pg/ml (P < 0.01). Administration of indomethacin to five dogs without prior obstruction of the inferior vena cava had no effect upon renal blood flow or renal vascular resistance. The results indicate that acute reduction of cardiac output enhances renal renin secretion and the activity of the renal adrenergic nerves as well as renal prostaglandin synthesis without significantly changing renal blood flow or renal vascular resistance. Inhibition of prostaglandin synthesis during acute reduction of cardiac output results in an increased renal vascular resistance and reduced renal blood flow. Accordingly, that data provide evidence that renal prostaglandins counteract in the kidney the vasoconstrictor mechanisms activated during acute reduction of cardiac output.
Synergistic genetic defect in B-lymphocyte function. I. Defective responses to B-cell stimulants and their genetic basis.
Authors: C Bona, J J Mond, W E Paul
Journal: The Journal of Experimental Medicine (1980)

CBA/N female mice, which express an X-linked defect in B-lymphocyte function, were mated with C3H/HeJ male mice, which are unresponsive to lipopolysaccharide (LPS). The resulting F1 hybrid females were mated to C3H/HeJ males. Approximately one-half of the backcross (BC.1) males obtained from this mating expressed a more profound immunologic defect than either of the parental strains. Spleen cells from these mice were unresponsive to a series of B-cell mitogens including LPS prepared from Escherichia coli K235 and from E. coli 0111:B4, lipoprotein mitogen from E. coli, and Nocardia water-soluble mitogen (NWSM). They failed to give in vitro antibody responses to the thymus-independent type 2 (TI-2) antigen trinophenylated Ficoll and most were unresponsive to the TI-1 antigens trinitrophenylated Brucella abortus, trinitrophenylated LPS, and trinitrophenylated NWSM. This synergistic defect in B-lymphocyte function depended on the presence of the CBA/N xid gene but the critical gene(s) from the C3H strain was not the defective Lps gene (Lpsd). These mice should provide a valuable tool for the elucidation of B-lymphocyte ontogeny, heterogeneity, and function.