tbuckley/cabot-search huggingface dataset:
<i>In vitro</i> and <i>In vivo</i> Radiosensitization with AZD6244 (ARRY-142886), an Inhibitor of Mitogen-activated Protein Kinase/Extracellular Signal-regulated Kinase 1/2 Kinase
Authors: Eun Joo Chung, Aaron P. Brown, Hiroaki Asano, Mariana Mandler, William E. Burgan, Donna Carter, Kevin Camphausen, Deborah Citrin
Journal: Clinical Cancer Research (2009)

The mitogen-activated protein (MAP) kinase pathway is important for cell proliferation, survival, and differentiation, and is frequently up-regulated in cancers. The MAP kinase pathway is also activated after exposure to ionizing radiation. We investigated the effects of AZD6244 (ARRY-142886), an inhibitor of MAP kinase/extracellular signal-regulated kinase 1/2, on radiation response.The effects of AZD6244 on the in vitro radiosensitivity of human cancer cell lines (A549, MiaPaCa2, and DU145) were evaluated using clonogenic assays. DNA damage repair was evaluated using gammaH2AX, and mitotic catastrophe was measured using nuclear fragmentation. Cell cycle effects were measured with flow cytometry. Growth delay was used to evaluate the effects of AZD6244 on in vivo tumor radiosensitivity.Exposure of each cell line to AZD6244 before irradiation resulted in an increase in radiosensitivity with dose enhancement factors at a surviving fraction of 0.1, ranging from 1.16 to 2.0. No effects of AZD6244 on radiation-induced apoptosis or persistence of gammaH2AX foci after irradiation were detected. Cells treated with AZD6244 had an increased mitotic index and decreased Chk1 phosphorylation at 1 and 2 hours after irradiation. Mitotic catastrophe was increased in cells receiving AZD6244 and irradiation compared with the single treatments. In vivo studies revealed that AZD6244 administration to mice bearing A549 tumor xenografts resulted in a greater than additive increase in radiation-induced tumor growth delay (dose enhancement factor of 3.38).These results indicate that AZD6244 can enhance tumor cell radiosensitivity in vitro and in vivo and suggest that this effect involves an increase in mitotic catastrophe.
Evidence for a new mineralocorticoid in patients with low-renin essential hypertension.
Authors: J A Sennett, R D Brown, D P Island, L R Yarbro, J T Watson, P E Slaton, J W Hollifield, G W Liddle
Journal: Circulation Research (1975)

Patients with low-renin essential hypertension have certain features consistent with excessive mineralocorticoid activity. Because known mineralocorticoids are normal in the majority of low-renin essential hypertension patients, an unknown mineralocorticoid was sought in the urine of such patients. Urine extracts from patients with low-renin essential hypertension were assayed for mineralocorticoid activity in adrenalectomized rats and found to contain more such activity than could be accounted for by the known mineralocorticoids in the extracts. The factor responsible for the unexplained mineralocorticoid activity was purfied and then identified by mass spectral analysis as 16beta-hydroxydehydroepiandrosterone (16beta-OH-DHEA). Synthetic 16beta-OH-DHEA was found to have a mineralocorticoid potency one-fortieth that of aldosterone in the rat bioassay. The mineralocorticoid effects of both the urine extracts and the synthetic steroid were blocked in the rat by spironolactone, a mineralocorticoid antagonist. A specific assay for 16beta-OH-DHEA was developed, and its level in the urine was found to be elevated in patients with low-renin essential hypertension.
Broncholith as a Cause of Fatal Hemoptysis
Authors: Ching-Shen Lin
Journal: JAMA (1978)

EPISODES of minor hemoptysis in a patient with old, calcific tuberculous scars may herald massive pulmonary hemorrhage. We report such a case that was due to erosion of a pulmonary artery by a broncholith. <h3>Report of a Case</h3> A 70-year-old woman was admitted to the hospital because of hemoptysis of two days' duration. Her pulmonary tuberculosis had been treated with thoracoplasty, streptomycin sulfate, and isoniazid 26 years ago. During the past two years, she was hospitalized three times for minor and self-limiting episodes of hemoptysis, which were attributed to old pulmonary tuberculosis with bilateral fibrocalcific scarring and bronchiectasis. No bronchoscopic study had been done during that period. She received isoniazid prophylactically, although repeated smears and cultures of sputum for acid-fast bacilli were negative. Two days before admission, she started coughing up copious amounts of bright red blood. She felt mild shortness of breath until the bleeding ceased, after which she
Gonadotrophin and the human secondary sex ratio.
Authors: W H James
Journal: BMJ (1982)

A review of published reports showed that the sex ratio (proportion of boys) was low among infants conceived after ovulation had been induced. The difference between the observed sex ratio and an expected one of 0 . 514 was highly significant. These findings suggest that maternal gonadotrophin concentrations at the time of conception directly affect the sex of the zygote.
PERSISTENT VITALITY.Read in the Section on Dental and Oral Surgery, at the Forty-fifth Annual Meeting of the American Medical Association, held at San Francisco, June 5-8, 1894.
Authors: F. O. JACOBS
Journal: JAMA (1894)

The interest that has lately been created in the operations of replantation, transplantation, etc., has raised the question among dentists as to whether a tissue will survive after having been removed from its natural position and again replaced, or after having been removed, can it again be transplanted to another individual without suffering death? And if so what time may elapse between the two operations? And if it should be determined that such operations were possible, what tissues are the most favorable to such operations? Or, in other words, and more briefly, is there such a thing as persistent vitality?  In surgical operations, just as in every other department of science, we are constantly meeting with surprises. What had been classed with the impossible yesterday is the practicable operation of today, and we are constantly being driven back to first principles to account for some unexpected results.  This subject involved
Aspirin protects men over 60 from prostate cancer, study says
Authors: S. Gottlieb
Journal: BMJ (2002)

Regular use of aspirin, ibuprofen, and other non-steroidal anti-inflammatory drugs may protect against the development of prostate cancer in older men, says a study in the United States.

Men aged over 60 who took a daily dose of one of the drugs known collectively as non-steroidal anti-inflammatory drugs (NSAIDs) were half as likely to develop the disease.

The six year study of 1362 white men in Minnesota aged 50 to 79 found that 4% of men who took the drugs developed prostate cancer, compared with 9% of the control group ( Mayo Clinic Proceedings 2002;77:219-25). The older the patient, the …
MAJOR DERMATOSES OF CHILDREN
Authors: W. J. O'Donovan
Journal: BMJ (1930)

hrzDlc Jovu_&_ Mr. Levy conisidered that the conidition had definitely been caused by the accident.Ocular injuries tlhrough electricity are not coimmon, as shock of sufficient severity to produce fundus clhaniges is genier-ally fatal.The imiodes of injur-y are as follows:alghtnlin, exposture of tlle ey-es to electric flasl, anid electric Shiock.The followinig fulndus changes have beell reported:(a) Hy-peraerneia, oedema, chianiges in calibre of arteries anid veinis.(b) Localized lesionis, including scar formation observed rounid disc (Terrieu), niear niiacuila (Haab).Hole at iacula w-itlh piigmienitation at perip)hery (Kramer).(c) Fully establislhed clhoiroido-retinial changes, with and without gr'oss inter'fer'ence in vistIal acuity (Lundsgaard, Juniius, Schirmer, Robinson, anid Terrieni).(d) Clhoroido-retinlitis leading to detachlmienit (Lunidsgaardl).(e) Detachlmjienit in onie eye anid optic neuritis in the otlhei (Pfailh).(/) Optic atrophy (Ulbrichl, Haas, Junius, Dor).I am greatly indebted to Mr.
Coexistence of Leishmaniasis and Hodgkin's Lymphoma in a Lymph Node
Authors: Mariana Domingues, Yara Menezes, Fabiana Ostronoff, Rodolfo Calixto, Rodrigo Florencio, Alexandre Sucupira, Ana Patricia Souto-Maior, Mauricio Ostronoff
Journal: Journal of Clinical Oncology (2009)
Phantom Itching Relieved by Scratching Phantom Feet
Authors: Daniel Jacome
Journal: JAMA (1978)

To the Editor.—  Phantoms are indeed a puzzling and poorly understood phenomenon. In amputees the phantom limb occupies a definite position in space, is capable of movement, and has, in a great majority, a pleasant tingling feeling.1In paraplegics, proprioceptive and nociceptive sensations and awareness of the extremities are recognized.2Phantom experiences are also described after eye enucleation (phantom vision),3after visceral surgery,4and after brachial plexus, epidural, or subarachnoid anesthesia.5  I had the opportunity recently of taking care of a patient with a curious phantom experience. A 69-year-old man was admitted to the hospital because of tarry stools. He gave a history of syncopal attacks for which he was receiving warfarin sodium (Coumadin) at a dose of 12.5 mg/day. His gastrointestinal series showed a large duodenal diverticulum, and his prothrombin time was 120 seconds. His anamnesis disclosed that he had a diagnosis of Buerger's
Liver resection for patients with hepatocellular carcinoma and macrovascular invasion, multiple tumours, or portal hypertension: Table 1
Authors: Jian-Hong Zhong, Yang Ke, Yan-Yan Wang, Le-Qun Li
Journal: Gut (2014)

Sir,

We read with great interest the leading article by Bruix et al 1 published in Gut . This article recommended palliative treatments for patients with hepatocellular carcinoma (HCC) involving macrovascular invasion, multiple tumours, or portal hypertension.

With better patient selection and improvement of perioperative care, liver resection (LR) offers the most consistent and clinically meaningful long-term survival in HCC over the past 20 years, which has been documented by both Eastern and Western centres.2 ,3 However, Western official guidelines do not recommend LR for treating intermediate and advanced stage HCC.4 ,5 Here, we systematically searched PubMed database for studies investigating the safety and efficacy of LR for treating patients with HCC involving macrovascular invasion, multiple tumours (≥2) or portal hypertension. We only included studies which were published in English on …
Abstract P5-13-10: Quality of care for premenopausal patients with early-onset breast cancer in Germany
Authors: D Fischer, M Hedderich, A Heinrich, B Wedel, C Banz-Jansen, A Rody, A Waldmann
Journal: Cancer Research (2013)

Abstract Background and objective: The objective of the study is to evaluate how young breast cancer patients between 2002 and 2011 are treated adjuvantly and whether treatment adheres to the guidelines. The distinction between this cohort and a normally distributed cohort was verified. Materials and methods: The study evaluates the data from a total of 2500 patients who were treated adjuvantly in the period from 2002 until 2011 and participated in a resident mother-child program. Until now, the data of 1053 patients have been analyzed. In cohort I (date of diagnose: 2002 - 2006) 535 women were analyzed, in cohort II (date of diagnose: 2010-2011) 518. The data includes TNM-stage, the biology of tumor, therapies and their guideline-adherence. In addition the amount of participation in studies was evaluated. All data were compared to an age-heterogeneous cohort from the state of Schleswig-Holstein and the DMP- report of the state of North Rhine-Westphalia (“older group”). Results: The median age of the cohort I and II was 39 years. The median age of the age-heterogeneous groups was 59 years. 53% were diagnosed with stage pT1, 37% pT2, 7% pT3 or pT4. 49% of the patients in cohort I were pN0 (cohort II 58%), 31% pN1 (cohort II: 28%) and 20% (cohort II: 14%) had a more intense infestation of lymph nodes. The size of the tumors and the involvement of the lymph nodes were significant higher in the younger patients as in the older patients. 44% of the tumors showed G3, 34% were ER negative, 36% PR negative and 76% Her2 negative. 23% of the patients showed a triple negative carcinoma. The tumor biology was also worse in the younger patients than in the age-heterogeneous group. All in all in cohort I 47% of the patients underwent mastectomie (cohort II:37%, older patients: 29%). 59% of the patients in cohort I with stage pT1 underwent breast-conserving surgery (cohort II: 69%, older group: 82%). Overall 15% of the women in cohort I received mastectomy with subsequent reconstruction (cohort II: 17%, older patients: 7%). 25% of the patients in cohort I received sentinel node biopsy only (cohort II 48%), 90% of the young patients received chemotherapy (older patients 59%), overall 21% of them were treated within studies. 51% of the young patients with antiendocrine therapy received GnRH-analoga, in the age of 40 years or younger 41%. The examination with regard to the conformity with guidelines showed a high guideline adherence in the younger group. Conclusion: Young breast cancer patients provide a special challenge for the therapists because their prognosis is often worse because of a larger tumor and more metastatic lymph nodes as well as the worse tumor biology. They get a more aggressive therapy analogue to their worse situation. The therapies have a high guidelines adherence. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-13-10.
Self-Control, Biofeedback, and Change in ‘Psychosomatic’ Approach
Authors: Hoyle Leigh
Journal: Psychotherapy and Psychosomatics (1978)

The new psychosomatic treatment modalities of biofeedback and relaxation techniques have in common an emphasis on self-control or self-regulation. The surging popularity of the self-control techniques at present may reflect a change in the self-image of medicine, which emphasizes its role as a collaborator of the patient in his self-control of disease processes. The modern concept of psychosomatic medicine emphasizes a systems or field approach to evaluation and treatment rather than 'psychogenic' causes of physical illness. The self-control treatment modalities form an important part of the armamentaria of a modern 'psychosomaticist'. We present preliminary data suggesting that 'potentiation' of biofeedback treatment may be useful. In borderline hypertensives, using pharmacologic means to reduce blood pressure during a biofeedback session may help subjects identify and re-create the 'low blood pressure states' without further aid of drugs. Hypertensives seeking biofeedback treatment are extremely internal in locus of control and tend to generalize their self-control to other areas of life to foster health and to prevent illness.
NMDA receptors: Substrates or modulators of memory formation
Authors: David L. Walker, Paul E. Gold
Journal: Behavioral and Brain Sciences (1997)

We agree with Shors &amp; Matzel's general hypothesis that the proposed link between NMDA-dependent LTP and memory is weak. They suggest that NMDA-dependent LTP is important to arousal or attentional processes which influence learning in an anterograde manner. However, current evidence is also consistent with the view that NMDA receptors modulate memory consolidation retroactively, as occurs in several other receptor classes.
Merritt's Textbook of Neurology
Authors: Terrence Riley
Journal: JAMA (1995)

This is a good neurology text, a good fundamental reference of neurological facts and pearls. My first neurology text was the fifth edition of<i>Merritt</i>, and what I liked then continues in this volume. It is thorough, facts about most neurological problems are easy to find, and they are presented in a predictable format. The writing is clear, and although<i>Merritt</i>has not been a single-author work since the sixth edition, the editor, Lewis Rowland, has generally succeeded in keeping the style uniform. Although the text does not have as much material as multivolume works like<i>Clinical Neurology</i>, edited by Joynt (formerly Baker and Baker), it is an authoritative compendium of the fundamentals of clinical neurology. This book is about as up-to-date as a textbook can be in such a dynamic field. A fine section on DNA diagnosis by Rowland begins, "We are still in the midst of the whirlwind
Hepatitis B Surface Antigenemia in Renal Transplant Recipients
Authors: William D. Hillis
Journal: JAMA (1979)

To determine effects of circulating hepatitis B surface antigen (HBsAg) on patient survival following renal transplantation, we studied 168 recipients of cadaveric grafts in whom HBsAg status was defined at transplantation by comparison of survivorships determined by actuarial life-table methods. Survival in HBsAg-positive recipients, as compared with those who were HBsAg-negative at the time of transplantation, was markedly diminished. Although graft survival appeared to be favored in the HBsAg-positive group in the early posttransplant period, the apparent protective effect was lost at nine months after grafting and thereafter, due to increased mortality in the HBsAg-positive recipients. Deaths in the antigenemic subjects were principally due to infections other than hepatitis and to cardiovascular events. We conclude that preexisting HBs antigenemia forebodes an ominous outcome for immunosuppressed renal transplant recipients, although hepatic disorders do not account for most deaths. (<i>JAMA</i>242:329-332, 1979)
Population Pharmacokinetics of C1 Esterase Inhibitor Used to Treat Patients with Acute Hereditary Angioedema Attacks in a Multicenter, Randomized, Placebo-controlled Study (I.M.P.A.C.T.1)
Authors: B. Ritchie, R. Levy, R. Wasserman, A. Bewtra, D. Hurewitz, K. Obtulowicz, A. Reshef, D. Moldovan, T. Shirov, V. Grivcheva-Panovska, J. Bernstein, P. Kiessling, F. Schindel, T. Craig
Journal: Journal of Allergy and Clinical Immunology (2010)
Role of mechanical factors in modulating cardiac fibroblast function and extracellular matrix synthesis
Authors: D MacKenna
Journal: Cardiovascular Research (2000)

The cardiac fibroblast is the most abundant cell type present in the myocardium and is mainly responsible for the deposition of extracellular matrix (ECM). Important components of cardiac ECM include structural and adhesive proteins such as collagen and fibronectin. Excess deposition of cardiac ECM (fibrosis) has been associated with the pathophysiological mechanical overload of the heart. Therefore, the role of cardiac fibroblasts in "sensing", "integrating" and "responding" to mechanical stimuli is of great interest. The development of in vitro strain apparatuses has allowed scientists to investigate the effects of mechanical stimuli on cardiac fibroblast function. Cardiac fibroblasts express ECM receptors (integrins) which couple mechanical stimuli to functional responses. Mechanical stimulation of cardiac fibroblasts has been shown to result in activation of various signal transduction pathways. The application of defined mechanical stimuli to cultured cardiac fibroblasts has been associated with ECM gene expression, growth factor production, release and/or bioactivity as well as collagenase activity. Ultimately, for fibrosis to develop the overproduction of ECM must overcome any associated increases in collagenase activity. Mechanically induced upregulation of ECM production may follow direct or indirect pathways through the autocrine or paracrine action of growth factors. Given the complex nature of the interstitial milieu of the working heart, additional research is needed to further our understanding of the roles that mechanical stimuli play in excess deposition of myocardial ECM.
C-Reactive Protein, the Metabolic Syndrome, and Prediction of Cardiovascular Events in the Framingham Offspring Study
Authors: Martin K. Rutter, James B. Meigs, Lisa M. Sullivan, Ralph B. D’Agostino, Peter W.F. Wilson
Journal: Circulation (2004)

Background— Inflammation (assessed by C-reactive protein [CRP]) and the metabolic syndrome (MetS) are associated with cardiovascular disease (CVD), but population-based data are limited. Methods and Results— We assessed the cross-sectional relations of CRP to the MetS (National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, Adult Treatment Panel III definition) in 3037 subjects (1681 women; mean age, 54 years) and the utility of CRP and the MetS to predict new CVD events (n=189) over 7 years. MetS (≥3 of 5 traits) was present in 24% of subjects; mean age-adjusted CRP levels for those with 0, 1, 2, 3, 4, or 5 MetS traits were 2.2, 3.5, 4.2, 6.0, or 6.6 mg/L, respectively ( P trend &lt;0.0001). In persons with MetS, age-adjusted CRP levels were higher in women than men (7.8 versus 4.6 mg/L; P &lt;0.0001). MetS and baseline CRP were individually related to CVD events (for MetS: age-sex-adjusted hazard ratio [HR], 2.1; 95% CI, 1.5 to 2.8; for highest versus lowest CRP quartile: HR, 2.2; 95% CI, 1.4 to 3.5). Greater risk of CVD persisted for MetS and CRP even after adjustment in a model including age, sex, MetS (HR, 1.8; 95% CI, 1.4 to 2.5), and CRP (HR, 1.9; 95% CI, 1.2 to 2.9). The c-statistic associated with the age- and sex-adjusted model including CRP was 0.72; including MetS, 0.74; and including CRP and MetS, 0.74. Conclusions— Elevated CRP levels are related to insulin resistance and the presence of the MetS, especially in women. Although discrimination of subjects at risk of CVD events using both MetS and CRP is not better than using either phenotype alone, both CRP and MetS are independent predictors of new CVD events.
High-glucose-induced nuclear factor κB activation in vascular smooth muscle cells
Authors: Y Hattori
Journal: Cardiovascular Research (2000)

Objective: Vascular smooth muscle cell (VSMC) dysfunction plays a role in diabetic macrovasculopathy. This dysfunction may be caused or exacerbated by expression of many of genes potently activated by the transcriptional factor nuclear factor κB (NF-κB). We have examined whether culture of VSMCs under high glucose conditions to stimulate the diabetic state can lead to the activation of NF-κB. Methods: NF-κB activation was assessed in VSMCs stably transfected with a cis-reporter plasmid containing the NF-κB binding sites. Results: Within 3-h incubation, high glucose (27.5 or 55 mmol/l) alone induced an increase in NF-κB activity in VSMCs; this increase was mimicked by mannitol given to deliver the same osmolar stress to the cells. High glucose or mannitol also enhanced TNFα-stimulated NF-κB activity. Incubation with high glucose for 48 h followed by stimulation with TNFα led to a marked potentiation of NF-κB activation compared with normoglycemic (5.5 mmol/l) VSMCs exposed to TNFα, while mannitol attenuated this effect. A 48-h incubation with high glucose substantially reduced glutathione (GSH) levels compared with normoglycemic VSMCs, whereas mannitol significantly increased GSH levels. An antioxidant N-acetyl-l-cysteine and a selective protein kinase C (PKC) inhibitor GF109203X significantly suppressed the TNFα-induced NF-κB activation, and abrogated potentiation of TNFα-induced NF-κB activity caused by high glucose (27.5 mmol/l). Conclusion: These results suggest that acutely high glucose causes alterations in osmolarity leading to activation of NF-κB, but that exposure to high glucose for more prolonged times causes changes in antioxidant defences and activation of PKC, which potentiates cytokine activation of NF-κB. Further definition of these pathways will help to delineate important signals mediating the aberrant behavior of VSMCs under hyperglycemic/diabetic conditions.