tbuckley/cabot-search huggingface dataset:
Secretion of bicarbonate by rat distal tubules in vivo. Modulation by overnight fasting.
Authors: D Z Levine, M Iacovitti, L Nash, D Vandorpe
Journal: Journal of Clinical Investigation (1988)

We have performed microperfusion studies on distal tubule bicarbonate reabsorption (JtCO2) of fed and fasted rats to extend our previous observations of in vivo bicarbonate secretion and to resolve certain discrepancies between free-flow and microperfusion data. When rats are fasted overnight, as in previous free-flow studies, distal tubule microperfusion with a 28-mM tCO2 solution results in significant JtCO2 (53 +/- 6 pmol.min-1.mm-1) at normal flow and increases briskly (91 +/- 16 pmol.min-1.mm-1) with bicarbonate load. This response is not influenced by the addition of other normal tubular fluid constituents. However, when normally fed rats are used, as in our previous microperfusion studies, distal tubule JtCO2 is not different from zero when a 28-mM tCO2 solution is perfused at normal flow rates but becomes negative (-54 +/- 13 pmol.min-1.mm-1) at high flow rates, which indicates the existence of bicarbonate secretion against a concentration gradient. Alkali loading of fasted rats also elicits bicarbonate secretion at high flow. These results demonstrate for the first time that normal feeding or alkali loading can induce bicarbonate secretion in a mammalian nephron segment in vivo, and resolves previous discrepancies between free-flow and microperfusion data.
Abstract 2339: Specific binding of modified ZD 6474 (Vandetanib) monomer and its dimer with VEGF receptor 2
Authors: Yoo-Shin Kim, Feng Li, Brian Edward O'neill, King CP Li, Zheng Li
Journal: Cancer Research (2012)

Abstract Introduction: Tumor angiogenesis is an important component of cancer biology driven in part by the thesis that tumor vessel growth is a necessary requirement for tumor growth. Angiogenesis does not only depend on endothelial cell invasion and proliferation: it also requires pericyte coverage of vascular sprouts for vessel stabilization. These processes are coordinated by vascular endothelial growth factor (VEGF). A significant portion of research on tumor angiogenesis has focused on VEGF and its blockage with the expectation that dramatic results would be demonstrated in cancer patients as previously documented in animal models. Vandetanib, also known as ZD6474, is an antagonist of the vascular endothelial growth factor (VEGF) receptor-2 (VEGFR-2) and the epidermal growth factor receptor (EGFR or HER1 or ErbB1). It is an orally bioavailable small molecule tyrosine kinase inhibitor of multiple growth factors, and is now available in the US for the treatment of metastatic medullary thyroid cancer (MTC). Methods: ZD 6474 monomer was purchased modified to add a fluorescent dye (6-FAM). Its coupled ZD 6474 dimer was also prepared using a PEG linker, similarly with FAM fluorescent dye. The two compounds were compared in a series of in vitro studies using human endothelial cell (HUVECs) and several cancer cell lines. We first looked at VEGFR binding affinity and specificity with cell uptake and blocking study. Then, the effects on cellular viability and angiogenesis were compared using with tubular formation of HUVECs in vitro, also matrigel plug assay, and bio-distribution test on VEGF over expressed U87 human glioma tumor model in vivo. Results: Imaging of ZD 6474 dimer showed much better binding and uptake in HUVECs and other VEGFR expressing cells than ZD 6474 monomer, including during systemic delivery to tumors. However, the therapeutic and anti-angiogenic effects were mixed, with most tests showing the dimer to have same or weaker effects than the monomer. Conclusion: This study provides a rational for the evaluation of dimeric ZD 6474 as a potential imaging agent. Paradoxically, it also demonstrates that the enhanced receptor binding achieved by multivalency does not always translate into enhanced therapeutic effectiveness. Keyword: Vandetanib (ZD 6474), anti-angiogenesis, VEGFR 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 2339. doi:1538-7445.AM2012-2339
Vitamin B12 in Macrocytic Anaemia of -Pregnancy and the Puerperium
Authors: J. C. Patel, B. R. Kocher
Journal: BMJ (1950)

VITAMIN B12 AND FOLIC ACID IN ANAEMIA been partly or entirely due to spontaneous remission.In no case was there a response to injections of crude liver extract after refined liver extract had failed.Yeast extracts were effective in some and failed in others.There were no failures with whole liver by mouth or with folic acid.
Targeted therapies in systemic lupus erythematosus: successes, failures and future
Authors: Bevra H Hahn
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Purpose</h3> The author9s goal is to review recent phase III clinical trials in patients with systemic lupus erythematosus (SLE), with emphasis on outcomes and on mechanisms by which the experimental drugs/biological agents suppress autoimmunity. <h3>Methods</h3> Prospective, randomised, controlled clinical trials in SLE published in the past 3 years identified in a PubMed search were reviewed, as well as abstracts describing similar but currently unpublished clinical trials presented at international meetings 2008–10. <h3>Conclusions</h3> Two interventions have been proved in large multicentre prospective trials to be useful in the management of SLE: mycophenolate mofetil (equivalent to cyclophosphamide with a similar safety profile) and anti-BLyS (Benlysta), which was superior to placebo when added to background immunosuppression and did not appear to increase toxicity. The anti-BLyS trial outcome measure was an anchored composite index that required reduction of disease activity measure by the systemic lupus erythematosus disease activity index. Other trials that failed or the results of which are pending are also discussed.
Chemical genetics identifies Rab geranylgeranyl transferase as an apoptotic target of farnesyl transferase inhibitors
Authors: Mark R. Lackner, Rachel M. Kindt, Pamela M. Carroll, Katherine Brown, Michael R. Cancilla, Changyou Chen, Heshani de Silva, Yvonne Franke, Bo Guan, Tim Heuer, Tak Hung, Kevin Keegan, Jae Moon Lee, Veeraswamy Manne, Carol O’Brien, Dianne Parry, Juan J. Perez-Villar, Rajashekar K. Reddy, Hong Xiao, Hangjun Zhan, Mark Cockett, Greg Plowman, Kevin Fitzgerald, Michael Costa, Petra Ross-Macdonald
Journal: Cancer Cell (2005)
Diphenylhydantoin And Arrhythmia
Authors: Harvey L. Gaspar
Journal: JAMA (1966)

<h3>To the Editor:—</h3> The case report may be of significant interest to merit further investigation, or may present misleading information to physicians who are not familiar with the current use of this drug in cardiac arrhythmias. The authors report on the possible toxicity of a drug in which the definite therapeutic dosage, intravenously, has not yet been established. They fail to report the dosage of diphenylhydantoin given, the rate of infusion, how long after beginning the infusion the arrhythmia occurred, or the protein bound iodine level just before or after the arrhythmia was observed. What the four authors of this short article do report is a possible sudden release of bound levothyroxine in a patient who is receiving (purposely) subtherapeutic amounts of this drug.
Abstract 2410: Crucial role of the non-BRCT automodification domain of PARP1 in either DNA binding and PARP inhibitor-mediated cell toxicity
Authors: Jun Nakamura, Xu Tian
Journal: Cancer Research (2014)

Abstract Poly(ADP-ribose)polymerase (PARP) inhibitor (PARPi)-mediated synthetic lethality is an attractive new paradigm for cancer therapy. While it has been recently proposed some of PARPi may cause DNA single strand break (SSB)-PARP1 or -PARP2 complexes, leading to cell toxicity, the mode of action of PARPi-mediated synthetic lethality is not well understood. We analyzed DNA damage response to PARPi using an isogenic set of DT40 cells. Both PARP-1 ko mutants and PARP-1 ko mutants expressing DNA bindin domain-defficient PARP1 showed markedly more resistance to olaparib than parental DT40 cells, indicating that PARP1 binding to DNA strand break through DNA binding domain is critical in olaparib-mediated cell toxicity. While non-BRCT automodomain domain deletion mutant showed a resistant phenotype, olaparib causes similar toxicity in BRCT domain deletion mutant and parental DT40 cells. Furthermore, PARP1 localized in chromatin binding fraction in BRCT1 deletion mutant, but not in non-BRCT automodomain domain deletion mutant. These results indicate that non-BRCT automodification domain plays crucial role for the formation of stable DNA SSB-PARP1 complex and olaparib-mediated synthetic lethality. Citation Format: Jun Nakamura, Xu Tian. Crucial role of the non-BRCT automodification domain of PARP1 in either DNA binding and PARP inhibitor-mediated cell toxicity. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2410. doi:10.1158/1538-7445.AM2014-2410
Aneurysm Formation during Closure of Ventricular Septal Defects
Authors: Julien I. E. Hoffman
Journal: New England Journal of Medicine (1970)

Aneurysms of the membranous ventricular septum were once regarded as rare congenital lesions found only at autopsy. In 1957 Steinberg1 demonstrated this lesion by angiocardiography, and in 1961 Peräsalo et al.2 described a ventricular septal defect (VSD) at the apex of the aneurysm. This association has often been noted since then, the highest frequency being 16 out of 48 consecutive patients with VSD studied with catheterization of the right and left sides of the heart by Varghese et al.3 These authors found that the aneurysms occurred almost exclusively when the defects were small, and postulated that the aneurysm might not . . .
More on bird flu
Authors: Hilary G Pickles
Journal: BMJ (2006)

EDITOR—Bonneux and Van Damme comment on wasteful investments in large stocks of drugs of no clear use in pandemic flu.1

Primary care trusts have been asked to provide safe storage and rapid access to antiviral medicines.2 Getting the logistics right is challenging. Supplies are enough for only 25%, and some wanting oseltamivir may not get …
The discussion of methodological limitations in number representation studies is incomplete
Authors: Guy A. Orban
Journal: Behavioral and Brain Sciences (2009)

Abstract Cohen Kadosh &amp; Walsh (CK&amp;W) discuss the limitations of the behavioral, imaging, and single-cell studies related to number representation in human parietal cortex. The limitations of the imaging studies are grossly underestimated, particularly those using adaptation paradigms, and the problem of establishing a link between single-cell studies and imaging is not even addressed. Monkey functional magnetic resonance imaging (fMRI), however, provides a solution to these problems.
Cardioverters, proteins, receptors studied in cardiovascular disorders
Authors: Kimberly Glasbrenner
Journal: JAMA (1985)

This year, as many as 1.5 million Americans may experience a heart attack and, according to the American Heart Association, approximately one third of them will die as a result. Despite a recent decline in the number of fatalities attributed to cardiovascular diseases, they are still considered to be the most widespread cause of death in this country. In addition to the cost in human lives, the economic cost of cardiovascular disease will exceed $72 billion in 1985, the association predicts. The following reports from the American Heart Association's Science Writers' Forum, held earlier this year in Monterey, Calif, summarize some of the recent developments in cardiovascular research. <b>Clinical investigations continue</b>on the efficacy and safety of a compact, programmable, transvenous cardioversion device at Indiana University School of Medicine, Indianapolis (<i>JAMA</i>[MEDICAL NEWS] 1983; 250:1809-1811). Douglas P. Zipes, MD, professor of medicine and one of the developers of the experimental
Cystourethroscopy in Children
Authors: S.A. Kramer
Journal: Endoscopy (1984)

Pediatric urologic evaluation by endoscopy is one of the most precise techniques in medicine. Recently developed endoscopic instrument permit an accurate and detailed examination of the child's urethra and bladder. Anomalies of the urethra and bladder in children may be divided into congenital, iatrogenic, infectious or inflammatory, and neoplastic groups. This review discusses the applicability of endoscopy for the diagnosis and treatment of urologic abnormalities in children.
Rehospitalization Rates of Patients Recently Discharged on a Regimen of Risperidone or Clozapine
Authors: Robert R. Conley, Raymond C. Love, Deanna L. Kelly, John J. Bartko
Journal: American Journal of Psychiatry (1999)

OBJECTIVE: The purpose of this study was to examine rehospitalization rates of people receiving risperidone or clozapine who had been discharged from state psychiatric hospitals in Maryland. METHOD: Rehospitalization status was monitored for all patients discharged from state psychiatric facilities on a regimen of either risperidone or clozapine between March 14, 1994, and Dec. 31, 1995. Patients were followed up with respect to readmission until Dec. 31, 1996. Time to readmission was measured by the product-limit (Kaplan-Meier) formula. Risk factors associated with rehospitalization were examined. RESULTS: One hundred sixty patients were discharged on risperidone, 75 having the diagnosis of schizophrenia. The patients with schizophrenia were more likely to be readmitted than the 85 patients with other mental disorders. Recidivism rates for schizophrenic patients discharged on risperidone versus those discharged on clozapine were not significantly different over the 24-month study period. However, no patient who received clozapine and remained discharged for more than 10 months (N=49) was readmitted, while the readmission rate for risperidone-treated patients appeared to be steady up to 24 months. At 24 months 87% of the clozapine-treated patients and 66% of the risperidone-treated patients remained in the community. No clinical or demographic variables were found to predict rehospitalization. CONCLUSIONS: This study demonstrates that the rehospitalization rates of patients taking the second-generation antipsychotics risperidone and clozapine are lower than those in previously published reports of conventional antipsychotic treatment.
Observations on the DIAGNOSIS AND TREATMENT OF FUNCTIONAL NERVOUS DISORDER
Authors: T. A. Ross
Journal: BMJ (1929)

oulng inel, we left hospital anid wveit into prac- tice nost of us hatd the experience encounterinr a gr-at niumber of patients whose aihelits did not sceiii the same natuire as thoso we hlad come wlheni we wem-e students or resi-dent hospital officers.TheIa the majority of the casesliad well-marked plhysical sigis, whlichll helped uLs to place themi in definite categories, wlhereas in maniy of ourI p.tieents in prii-ate, thlough tlley presented wealthl ofsymptoms, there were few if aiiyl physical signs, certaiilfy nonie of a giaoss nature, to cor roborate syn ptoms.Itmiiiglht, indeed, be said that the miiainstay imanyi' prac- tic'es consists of those patients wvlio do niot prcs3nt-physical signis.Tlhey-arenot confinied to one society, they are seatter(d tlhriou ho1ut all, and suspect there are plenty of them in the hospitals also, but they not he found muchielt in tlhe war-ds; they are pirobably seeni by ouit-patient physician, to wlhomii they come againi and again for the paper bearing tile magic words Thie conscientious (doctor wvith miiuclh industry 'exanmmics them all over, to discover what it is producing these e disabling syninptoms; he pasases in review their internal organs, thiei teeth, their eves tlieir nasal sinluses, nln(l what nlot; andl so fine are the rnodeiii miethods of diagnos
Application of Computer Techniques to Medical Data
Authors: D. F. Klein
Journal: JAMA (1965)

<h3>To the Editor:</h3> Breneman's stimulating communication, "Postoperative Thromboembolic Disease" (<b>193</b>:-576, 1965) raises a number of statistical and practical issues in the application of computer techniques to medical data and practice. Breneman first isolated seven preoperative variables (age, overweight, preanesthetic immobilization, etc) in which there were significant differences between patients who developed postoperative thromboembolic complications and those who did not. This in itself is a worthwhile contribution. This was followed by a multivariate analysis yielding an equation by which each patient's measures on these seven variables could be weighted and summed, producing an individual overall score. This score correlates maximally, for this sample, with the occurrence of complications, and is recommended to identify high-risk patients and initiate prophylactic measures. This application of relatively novel statistical techniques should require a cautionary discussion of the mathematical assumptions underlying the technique and their fulfillment in the case at hand. In this case the
Monkey business: reflections on testosterone
Authors: Tony Delamothe
Journal: BMJ (2012)

Why is it easier to believe in the effects of testosterone than it is to show them?



If ever there was a hormone whose discovery was a foregone conclusion it was testosterone. Almost a century before the steroid was isolated Arnold Berthold showed that transplanting testes into castrated roosters restored their characteristically rooster-like behaviour.1 After this, trapping the essence of masculinity in a bottle was only a matter of time.

Time and, for Adolf Butenandt, 25 000 L of urine donated by a Berlin police barracks.2 From this he extracted 50 mg of the weak androgen androsterone and went on to synthesise testosterone and win the Nobel prize for chemistry in 1939. “Dynamite, gentlemen, it is pure dynamite,” he told the Nobel committee (a joke at the expense of the explosive’s inventor).

Between Berthold and Butenandt, however, came the neurologist Charles-Edouard Brown-Sequard. At the age of 72 he delighted the world by announcing that he had rejuvenated himself by injecting aqueous extracts of testes from freshly killed guinea pigs and dogs. A placebo effect, say modern killjoys—little hormone would have dissolved in water. Nevertheless, soon many doctors were treating their male patients with organ extracts.1

In the 1920s …
A CASE OF EARLY ACUTE PANCREATITIS WITHOUT HEMORRHAGE.
Authors: H. H. GERMAIN
Journal: JAMA (1904)

Of the many cases of acute pancreatitis reported in the literature, most present quite advanced lesions. The largest number are examples of hemorrhagic or of necrotizing pancreatitis with extensive destruction of the organ. A few are cases of focal suppurative lesions. The study of these cases has not thrown great light on the etiology and histogenesis of the lesions, but our present knowledge of the condition has been gained mainly from animal experimentation. In animals the pancreas has been treated in a great variety of ways. Some of these, as injections of chromic acid, present conditions which manifestly play no part in the causation of the natural disease in man. Others, such as injections of digestive ferments (papain), bacteria, gastric juice or bile, imitate conditions that, to say the least, might occur in man. Of these the entrance of bile seems to offer the most satisfactory explanation of many of the cases
Concomitant Brucellosis and Tuberculosis
Authors: J. T. Sharp, H. J. Wheelwright, P. O. Nice
Journal: New England Journal of Medicine (1952)

THE following case is reported because the patient presented a baffling combination of clinical and laboratory evidences of severe acute disease and because the association of brucellosis and hematogenous tuberculosis has not, to our knowledge, been previously recorded.Case ReportM. A., a 36-year-old farmhand, was first seen at the White River Junction Veterans Administration Hospital on November 18, 1949, having arrived by ambulance from a farm some distance away in a comatose condition. A meager history was obtained by telephone from a brother, who stated that the patient had first complained of headache about 3 weeks before admission. This . . .
ADHD Drug Decreased Binge Eating
Authors: Anita Slomski
Journal: JAMA (2015)

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Arthritis of idiopathic haemochromatosis
Authors: E. B. D. Hamilton, A. B. Bomford, J. W. Laws, R. Williams
Journal: Annals of the Rheumatic Diseases (1983)

interrelationship between articular chondrocalcinosis, patellofemoral degeneration, and quadriceps calci- fication.Articular chondrocalcinosis is subcategorised into present at the knee and in joints other than the knee.Analysis of these figures shows that the prevalence of patellofemoral degeneration and quadriceps calcification is similar in patients with and without articular chondrocalcinosis.CONCLUSION
Straining Out Gnats
Authors: Robert M. Soule
Journal: JAMA (1982)

<h3>To the Editor.—</h3> A medical journal has, on two occasions,<sup>1,2</sup>recently devoted considerable space to warnings and discussions of the minuscule amounts of sugar in antacids. Calculating the actual number of calories involved shows that the "risk" to diabetics ranged up to 9.6 calories per dose or an average added caloric intake of 38.4 calories per day— calorically equal to one-half slice of bread. Whether the proved benefits of antacids for ulcers should be withheld for risk of adding 38.4 calories to the daily diet seems highly questionable. As a clinician I believe that today we may "Strain out a gnat while swallowing a camel" (Matthew 23:24). At a time when the American Heart Association states that there are 100,000 fewer deaths per year from heart disease and stroke, at a time when the American Cancer Society states that the cancer death rate for persons younger than 50 years
596 DOES FAL (FRACTIONAL ALLELIC LOSS) ANALYSIS PREDICT OUTCOME IN PRIMARY LIVER CANCER?
Authors: A.M. Tanase, P. Pineau, S. Dima, T. Dumitrascu, G. Oprisan, A. Marchio, S. Dinu, A. Dejean, I. Popescu
Journal: Journal of Hepatology (2010)