tbuckley/cabot-search huggingface dataset:
The Genetics of Multiple Endocrine Neoplasia Syndromes
Authors: M S Nanes, B D Catherwood
Journal: Annual Review of Medicine (1992)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
Surveillance of acute respiratory virus infections in general practice
Authors: K. W. Martin, W. Blair, W. K. Brown, A. Clarke, A. M. T. McAlister
Journal: BMJ (1969)

The ordinary postal system provides a simple method for the transportation of specimens for virus isolation to the laboratory. This was used to carry out an epidemiological survey, in general practice, of respiratory viruses in patients with acute respiratory disease. Three distinct outbreaks of myxovirus infections were recognized and most other types of respiratory viruses were isolated sporadically. After the initial "pilot" phase of the study an isolation rate of 24% was obtained over the months from October 1968 to June 1969 (20% isolations from adults' specimens and 29% from those of children).
Randomized placebo-controlled trial of isotretinoin in chemoprevention of bronchial squamous metaplasia.
Authors: J S Lee, S M Lippman, S E Benner, J J Lee, J Y Ro, J M Lukeman, R C Morice, E J Peters, A C Pang, H A Fritsche
Journal: Journal of Clinical Oncology (1994)

PURPOSE Retinoids have proven chemopreventive efficacy in both preclinical and clinical studies. This trial was designed to confirm the finding of an earlier uncontrolled trial that the synthetic retinoid etretinate had major activity in reversing squamous metaplasia found in the bronchial epithelium of chronic smokers. PATIENTS AND METHODS We prospectively evaluated 152 smokers with bronchoscopy and obtained biopsies from six sites. Subjects with dysplasia and/or a metaplasia index of greater than 15% were randomly assigned to receive either 1 mg/kg isotretinoin or placebo daily for 6 months. Of 86 subjects randomized (41 isotretinoin, 45 placebo), 69 were reevaluated at the completion of treatment. RESULTS In the group as a whole, the metaplasia index decreased over time from a mean +/- SE of 35.8% +/- 2.7% at baseline to 28.1% +/- 3.3% at the completion of treatment (P = .01) by repeated measures analysis of variance [ANOVA]); a reduction in the metaplasia index (&gt; 8%) was noted in both isotretinoin and placebo groups (19 of 35 [54.3%] and 20 of 34 [58.8%], respectively). Complete reversal of squamous metaplasia was noted in nine subjects from each group. However, the magnitudes of the mean metaplasia index changes did not differ significantly in the two treatment groups. In both groups, smoking cessation resulted in significant declines in the extent of squamous metaplasia, whereas no significant change in metaplasia index was found among those who continued to smoke. CONCLUSION Squamous metaplasia was frequently observed in bronchial biopsy samples from chronic smokers. From this study, we conclude that isotretinoin has no effect on squamous metaplasia, a potential intermediate end point of bronchial carcinogenesis. Although determining the exact role of isotretinoin in lung cancer prevention requires further study, the finding that there was a significant decrease in squamous metaplasia in the placebo group emphasizes the critical importance of a placebo-controlled study design in chemoprevention trials using intermediate end points.
Chemohormonal therapy in advanced carcinoma of the breast: Cancer and Leukemia Group B protocol 8081.
Authors: M C Perry, C G Kardinal, A H Korzun, S J Ginsberg, P C Raich, J F Holland, R R Ellison, S Kopel, A Schilling, J Aisner
Journal: Journal of Clinical Oncology (1987)

In a prospective, randomized trial Cancer and Leukemia Group B (CALGB) evaluated CAF chemotherapy (cyclophosphamide + doxorubicin + 5-fluorouracil [5-FU]) v CAF plus tamoxifen (TCAF) in advanced breast cancer. Patients were stratified by estrogen receptor (ER) status, dominant site of metastatic disease, menopausal status, and prior adjuvant therapy. Regardless of ER status or menopausal status, the addition of tamoxifen conferred no significant advantage in response rate, response duration, time to treatment failure (TTF) or survival over CAF alone. A secondary objective was to compare the response to CAF of ER positive (ER+) and ER negative (ER-) patients to determine if there was a differential response to cytotoxic chemotherapy. Response rates of ER+ and ER- patients to CAF were identical (56%), but the response duration, time to treatment failure, and survival of ER+ patients were significantly longer than ER- patients. This lack of differential response implies that chemotherapy and hormonal therapy may compete for the same pool of ER+ cells. It also suggests that chemotherapy kills breast cancer cells indiscriminately, regardless of ER status.
Internal Fixation of the Unstable Rheumatoid Cervical Spine
Authors: J. C. F. Cregan
Journal: Annals of the Rheumatic Diseases (1966)

In 1961 internal fixation by spinous process wiring and cancellous grafting was carried out (Fig. 5, opposite).She made a good recovery and returned to her previous somewhat limited activity, but died a year later from amyloidosis of the kidney, liver, and spleen.242
Physiologic Role of the Normal Pericardium
Authors: Matthew W. Watkins, Martin M. LeWinter
Journal: Annual Review of Medicine (1993)

Because of the characteristics of the parietal pericardial tissue, the intact pericardial sac has a limited reserve volume, becoming relatively non-compliant when the heart volume is at the high end of the normal physiologic range. Pericardial restraint of the heart is best considered as a contact force. Measured with flattened balloons, the magnitude of pericardial contact pressure is probably several mmHg less than right atrial pressure. The diastolic pressure-volume relationship of the right ventricle, and to a lesser degree of the left ventricle, shifts downward following pericardiectomy. In dogs, the pericardium has been shown to limit maximal cardiac output. Some disease states associated with a rapid increase in total heart volume, including subacute mitral regurgitation and right ventricular infarction, demonstrate an increased pericardial influence on cardiac filling.
Molecular Components of T-Cell Recognition
Authors: J L Jorgensen, P A Reay, E W Ehrich, M M Davis
Journal: Annual Review of Immunology (1992)

We review recent data that increase our understanding of the ternary complex of the T cell receptor (TCR), antigenic peptides, and molecules of the major histocompatibility complex (MHC). Studies using synthetic peptide analogs for T-cell antigens have identified peptide residues that appear to interact with the MHC molecule and/or the TCR. The logical extension of these studies, using a complete replacement set of peptide analogues for a model peptide antigen, has more precisely defined the biochemical character of putative MHC and TCR contact residues, and indicated that the TCR is highly sensitive to subtle changes in peptide conformation. Insight into the binding site for peptide on the TCR has recently come from variant peptide immunization of TCR single-chain transgenic mice. These experiments indicate that residues encoded by the V(D)J junctions of both TCR chains contact peptide directly. TCR-MHC contacts have also been studied, using in vitro-mutagenized MHC molecules, particularly those altered at residues predicted to point "up," toward the TCR. These studies reveal that TCR-MHC contacts appear to be quite flexible, and vary between even closely related TCRs. A measure of the affinity of TCR for peptide/MHC complexes has come from competition experiments using soluble MHC complexed with specific peptides. This affinity, with a KD of 5 x 10(-5) M, is several orders of magnitude lower than that of most antibodies for their protein antigens and suggests that the sequence of events leading to T-cell activation begins with antigen-independent adhesion.
Detection of low abundant somatic mutations in circulating exosomal RNA and cfDNA with next-generation sequencing.
Authors: Vincent J. O'Neill, Daniel Enderle, Jennifer J. Wheler, Tina Koestler, Carola Berking, Johan Skog, Mikkel Noerholm, Keith Flaherty, Filip Janku
Journal: Journal of Clinical Oncology (2015)

11061 Background: Circulating nucleic acids (NA) in the bloodstream of cancer patients are of interest because of their potential to provide tumor mutation status without requiring a tissue sample. Blood plasma contains at least two sources of circulating cell-free NA: circulating free DNA (cfDNA), from apoptotic/necrotic cells, and RNA enclosed in exosomes (exoRNA), which are secreted by living cells through active metabolic processes. However, tumor derived mutated sequences are often of very low abundance against a background of wildtype. Therefore, efficient extraction of all available circulating NA as well as a highly sensitive mutation detection method, are paramount to development of clinically relevant liquid biopsies. Methods: We used a single-step isolation platform for both exoRNA and cfDNA from plasma (EXO52) in combination with a quantitative NGS method detecting a panel of actionable mutations (EXO1000). The assay uses a PCR-based selection of 9 mutation hotspots from 6 genes, a custom library preparation protocol and bioinformatics pipeline. We analyzed mutations present in nucleic acids from plasma of patients with various types of cancer including NSCLC, mCRC and melanoma. Results: EXO52 columns simultaneously isolate both cfDNA and exoRNA from plasma samples up to 4 mL with close to 100% efficiency, allowing somatic mutations to be readily detected in both exoRNA and cfDNA. The combination of both was found to provide a superior mutation signal and yield compared to cfDNA alone. The EXO1000 actionable mutation panel and associated bioinformatics pipeline were demonstrated to be quantitative, reproducible and highly sensitive. The assay faithfully detected low copy numbers of mutations using clinical plasma samples from 102 patients with different types of cancer. Conclusions: We demonstrate the superiority of isolating both cfDNA and exoRNA from plasma for the purpose of detecting circulating somatic mutations in cancer patients. The EXO52 isolation method combined with the EXO1000 actionable mutation panel overcomes current technical limitations by maximizing mutation signal from all sources of circulating NA, thereby enhancing assay sensitivity.
Loss in MCL-1 function sensitizes non-Hodgkin’s lymphoma cell lines to the BCL-2-selective inhibitor venetoclax (ABT-199)
Authors: D C Phillips, Y Xiao, L T Lam, E Litvinovich, L Roberts-Rapp, A J Souers, J D Leverson
Journal: Blood Cancer Journal (2015)

Abstract As a population, non-Hodgkin’s lymphoma (NHL) cell lines positive for the t(14;18) translocation and/or possessing elevated BCL2 copy number (CN; BCL2 High ) are exquisitely sensitive to navitoclax or the B-cell lymphoma protein-2 (BCL-2)-selective inhibitor venetoclax. Despite this, some BCL2 High cell lines remain resistant to either agent. Here we show that the MCL-1-specific inhibitor A-1210477 sensitizes these cell lines to navitoclax. Chemical segregation of this synergy with the BCL-2-selective inhibitor venetoclax or BCL-X L -selective inhibitor A-1155463 indicated that MCL-1 and BCL-2 are the two key anti-apoptotic targets for sensitization. Similarly, the CDK inhibitor flavopiridol downregulated MCL-1 expression and synergized with venetoclax in BCL2 High NHL cell lines to a similar extent as A-1210477. A-1210477 also synergized with navitoclax in the majority of BCL2 Low NHL cell lines. However, chemical segregation with venetoclax or A-1155463 revealed that synergy was driven by BCL-X L inhibition in this population. Collectively these data emphasize that BCL2 status is predictive of venetoclax potency in NHL not only as a single agent, but also in the adjuvant setting with anti-tumorigenic agents that inhibit MCL-1 function. These studies also potentially identify a patient population ( BCL2 Low ) that could benefit from BCL-X L (navitoclax)-driven combination therapy.
Ovarian cancer screening.
Authors: S E Mackey, W T Creasman
Journal: Journal of Clinical Oncology (1995)

PURPOSE To review potential screening tools of early ovarian cancer and the associated risk factors for the development of ovarian carcinoma. DESIGN AND RESULTS A review of pertinent literature was conducted, restricted to English-language published reports, book chapters, and articles. The value of serum tumor markers, particularly CA 125, ultrasound, transabdominal and transvaginal ultrasonography, and transvaginal color Doppler imaging as screening tools for ovarian cancer was assessed. CONCLUSION Based on the literature, a large-scale long-term study that compares the mortality rates of a screened versus unscreened patient population is required before the efficacy of any screening method can be determined definitively.
Integration of a clinical pathways software into an EHR in a large, multisite, hospital-affiliated community oncology setting.
Authors: Corey J. Shamah, Thomas James Saphner, Jacob C. Frick, Carol Huibregtse, Gail S. Stiemke
Journal: Journal of Clinical Oncology (2016)

129 Background: Via Oncology (Via) is a decision support tool that integrates patient information, their disease, and goals of care to develop a treatment algorithm. Via prioritizes treatments by efficacy first, toxicity second, and cost third. The recommended regimen is offered to the doctor and patient who may accept it or choose an off pathway treatment. The pathways are updated quarterly and are expected to speed the integration of new treatments into practice, standardize therapy, improve quality, and decrease cost. Physicians are often unaware that a trial is available for a patient and EHR’s are not commonly used to facilitate accrual to clinical trials. A pathway system could also alert doctors to the availability of a clinical trial and is designed to increase accrual to clinical trials. Methods: The integration of Via into the Epic EHR was facilitated by 3 major interfaces: patient information sent from the EHR to Via, the providers’ schedules sent from the EHR to Via, and the protocol selected in Via sent back to the EHR. Within the decision algorithm, clinical trials were recommended as the first option in all lines of therapy when available. Results: After 11 months and 103,515 visits, the visit capture rate was 82.7%%. With 3,844 decisions made, 83.9% of all treatment decisions were on pathway. Clinical trial enrollment was 122 patients in the 459 days prior to Via implementation, and 102 patients in the 271 days afterwards. This increase in accrual rate was significant (p = 0.00174.) Conclusions: The pathway program was rapidly accepted by physicians and the recommendations were commonly accepted. The subsequent increase in clinical accrual, while not definitive of causation, is promising. An upgrade of the Epic EHR is planned in the near future. A single log in to open Via and the EHR concomitantly is planned. An additional interface to bring staging information from the EHR to Via is being planned.
Mutations and Molecules Influencing Biological Rhythms
Authors: J C Hall, M Rosbash
Journal: Annual Review of Neuroscience (1988)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More
HISTAMINE IN THE TREATMENT OF PSYCHOSIS
Authors: R. W. ROBB, B. KOVITZ, D. RAPAPORT
Journal: American Journal of Psychiatry (1940)

A. The administration of histamine was followed by slight improvement both in the clinical picture and Rorschach test for the group, particularly in the characteristic catatonics. From the absence of striking change, one might reflect that while histamine may be able to influence the psychosis in certain cases, cases of long duration and resistant to metrazol were refractory material for eliciting improvement, and cautious administration precluded the effects of a truly profound vascular shock. For future trials, a sharper increase in dosage and even cautious intravenous administration should be considered. Comparison of post-histamine tests with metrazol prognosis studies9 suggests that these patients are somewhat more likely candidates for metrazol improvement than they were before histamine. B. Following histamine, the catatonics showed psychological test changes identical in direction with the changes observed after metrazol. In the depressive cases, the changes differed from those of the catatonics as was also the case with metrazol. Although control series with water injections and without injection were not carried out, the essentially uniform test changes serve to validate the findings. Similarity in psychological response to widely different pharmacodynamic agents without discernible physiological similarity, seems to permit formulation of a therapeutic moment in terms of "nonspecificity." The psychological effects of histamine as of metrazol appear to depend on the personality and illness structure of the patient. The fact that psychological changes following histamine, as shown in the Rorschach test, are in the same direction as those elicited by metrazol and sodium amytal,14 suggests a non-specific action of the drugs on psychoses. This non-specific action might perhaps be explained by the hypothesis that these drugs interfere with the homeostatic equilibrium, which was shown to be rigid in schizophrenia.15 There is no clear reason as yet to consider even the profound disturbances of cerebral oxidation by metrazol or insulin as other than more potent exemplars of this principle. C. The method applied in this experiment is suggested as a means of investigating the psychological effects of drugs capable, on proper application, of a degree of objectivity and quantitative measurement which seems to the authors otherwise unattainable at the present time.
STUDIES OF THE KIDNEY IN ACUTE INFECTION
Authors: William Goldring
Journal: Journal of Clinical Investigation (1931)

In a previous study (lX)we showed by means of the urine sediment count (2), that in acute rheumatic infection there is an abnormal in- crease in the excretion of formed elements in the urine for varying periods up to ten weeks following the acute stage of the disease.In that study, no instances of diffuse glomerulonephritis occurred.Changes in renal function in the course of acute infections have been repeatedly investigated (3, 4, 5, 6, 7, 8, 9).These studies show a distinct lack of uniformity in the results obtained, and in their inter- pretation.This lack of agreement appeared to us to be in part due to the attempt to compare the results of different renal function tests.Those most frequently used were the blood urea nitrogen, phenolsulphonphthalein, and urea excreting power of the kidney.It is quite conceivable that these procedures not only test different functions of the kidney, but that they differ in their sensitivity to changes in renal function.Obviously then, they are not comparable.We felt that in order to obtain significant results in such a study, it would be necessary to select patients with the same infection of about the same degree of severity, and a single test sufficiently sensitive to indicate slight varia- tions from normal.We decided upon the urea clearance test described by M6ller, McIntosh and Van Slyke (10) shown to be highly sensitive as an index of the urea excreting activity of the kidney (13).Acute rheumatic infection was selected as the first disease to be studied.Care was taken in the selection of patients, to obtain as far as
Regulation of Iron Metabolism: Translational Effects Mediated by Iron, Heme, and Cytokines
Authors: David P. Mascotti, Diane Rup, Robert E. Thach
Journal: Annual Review of Nutrition (1995)

The objective of this review is to provide an overview of intermittent fasting regimens, summarize the evidence on the health benefits of intermittent fasting, and discuss physiological mechanisms by which intermittent fasting might lead to improved ...Read More
Acetazolamide Attenuates Lithium–Induced Nephrogenic Diabetes Insipidus
Authors: Theun de Groot, Anne P. Sinke, Marleen L.A. Kortenoeven, Mohammad Alsady, Ruben Baumgarten, Olivier Devuyst, Johannes Loffing, Jack F. Wetzels, Peter M.T. Deen
Journal: Journal of the American Society of Nephrology (2015)

To reduce lithium–induced nephrogenic diabetes insipidus (lithium-NDI), patients with bipolar disorder are treated with thiazide and amiloride, which are thought to induce antidiuresis by a compensatory increase in prourine uptake in proximal tubules. However, thiazides induced antidiuresis and alkalinized the urine in lithium-NDI mice lacking the sodium-chloride cotransporter, suggesting that inhibition of carbonic anhydrases (CAs) confers the beneficial thiazide effect. Therefore, we tested the effect of the CA–specific blocker acetazolamide in lithium-NDI. In collecting duct (mpkCCD) cells, acetazolamide reduced the cellular lithium content and attenuated lithium-induced downregulation of aquaporin-2 through a mechanism different from that of amiloride. Treatment of lithium-NDI mice with acetazolamide or thiazide/amiloride induced similar antidiuresis and increased urine osmolality and aquaporin-2 abundance. Thiazide/amiloride-treated mice showed hyponatremia, hyperkalemia, hypercalcemia, metabolic acidosis, and increased serum lithium concentrations, adverse effects previously observed in patients but not in acetazolamide-treated mice in this study. Furthermore, acetazolamide treatment reduced inulin clearance and cortical expression of sodium/hydrogen exchanger 3 and attenuated the increased expression of urinary PGE2 observed in lithium-NDI mice. These results show that the antidiuresis with acetazolamide was partially caused by a tubular-glomerular feedback response and reduced GFR. The tubular-glomerular feedback response and/or direct effect on collecting duct principal or intercalated cells may underlie the reduced urinary PGE2 levels with acetazolamide, thereby contributing to the attenuation of lithium-NDI. In conclusion, CA activity contributes to lithium-NDI development, and acetazolamide attenuates lithium-NDI development in mice similar to thiazide/amiloride but with fewer adverse effects.
IL-17 receptor A and adenosine deaminase 2 deficiency in siblings with recurrent infections and chronic inflammation
Authors: Florence Fellmann, Federica Angelini, Jacqueline Wassenberg, Matthieu Perreau, Natalia Arenas Ramirez, Gregoire Simon, Onur Boyman, Olivier Demaria, Stephanie Christen-Zaech, Daniel Hohl, Marco Belfiore, Annette von Scheven-Gete, Michel Gilliet, Pierre-Yves Bochud, Yannick Perrin, Maya Beck Popovic, Pierre-Alexandre Bart, Jacques S. Beckmann, Danielle Martinet, Michaël Hofer
Journal: Journal of Allergy and Clinical Immunology (2015)