tbuckley/cabot-search huggingface dataset:
Prevention of Surgical Oliguria and Renal-Hemodynamic Suppression by Sustained Hydration
Authors: Kevin G. Barry, Richard I. Mazze, Franklin D. Schwartz
Journal: New England Journal of Medicine (1964)

ANESTHESIA and surgery in man is frequently associated with acute depression of renal function and is occasionally followed by oliguric renal failure.1 2 3 4 Previous attempts have been made to minimize these effects by water and electrolyte infusions varying in quantity, electrolyte composition and time given in relation to the operative procedure. No acceptable method was found.5 , 6 The precipitation of cardiocirculatory overload and water intoxication in some patients offered a rationale for the fluid restriction applied by most physicians.5 , 7 Oliguria has usually been accepted as an inevitable, if undesirable, accompaniment of anesthesia and surgery.We have undertaken studies to re-examine the relations . . .
Magnesium Dynamics and Sympathetic Nervous System Activity in Patients With Chronic Heart Failure
Authors: Hisanori Samejima, Kazuhiko Tanabe, Noriyuki Suzuki, Kazuto Omiya, Masahiro Murayama
Journal: Circulation (1999)

This study was undertaken in patients with heart failure to investigate the relation between plasma norepinephrine (NE) concentration and Mg dynamics. The study subjects comprised 16 patients with chronic heart failure (mean age 64.9±10.0 years). Cardiopulmonary exercise testing was performed on all patients, and anaerobic threshold (AT), peak oxygen uptake (peak VO2) and peak exercise time were measured. Resting and peak values of plasma NE concentration and serum and erythrocyte magnesium concentration were also measured. The results were as follows: the serum Mg concentration was increased significantly immediately after exercise (p<0.01), and the erythrocyte Mg concentration showed a tendency to decrease (p<0.1). The resting plasma NE level was inversely correlated with AT (p<0.05, r=-0.57), peak VO2 (p<0.05, r=-0.55) and peak exercise time (p<0.01, r=-0.62). When the plasma NE concentration at rest was analyzed in 2 groups of patients, ie, those with higher than average and those with lower than average concentrations, the resting erythrocyte Mg concentration was significantly lower in the high-NE group (2.2±0.3 mg/dl) than in the low-NE group (2.7±0.5 mg/dl) (p<0.05). The data indicate that patients with chronic heart failure associated with high NE levels at rest who showed low exercise tolerance have intracellular hypomagnesemia, which may be caused by Mg migration from intracellular to extracellular spaces. (Jpn Circ J 1999; 63: 267 - 273)
Case 5-2002
Authors: Craig A Hurwitz, William C Faquin
Journal: New England Journal of Medicine (2002)

Presentation of CaseA 15-year-old boy was admitted to the hospital because of a retro-orbital mass.The patient had been well until three weeks earlier, when he began to have right retro-orbital and frontal pain graded 2 to 3 on a scale of 1 to 10, with 10 indicating the worst possible pain. The episodes occurred two or three times weekly, lasted one or two hours, and were relieved by ibuprofen. The pain had no positional features, and there was no accompanying photophobia, nausea, vomiting, sensitivity to noise, weakness, numbness, or tingling; the pain tended not to occur in the . . .
PWE-160 Prognostic significance of diagnostic delay in patients diagnosed with upper gastrointestinal tract cancer
Authors: J Wheat, P Blake, A Karran, WG Lewis
Journal: Gut (2015)

<h3>Introduction</h3> Recent public awareness campaigns for symptoms of cancer aim to improve outcomes by diagnosing cancer at an earlier stage. Whilst it is known that stage of disease at diagnosis predicts survival, the prognostic significance of delays in diagnosis and treatment of upper GI cancer is hitherto unknown. <h3>Method</h3> A prospective study of 150 consecutive upper GI cancer patients [median age 70 yr, 96 male, 102 oesophageal, 48 gastric cancer] presenting to a UK cancer network was performed. Duration of symptoms prior to patient presentation, and times between referral, investigations, diagnosis, and treatment commencement were recorded. Deprivation scores were obtained from the Welsh Indices of Multiple Deprivation (WIMD). Outcome measures were whether potentially curative therapy was possible at time of decision to treat (DTT), and overall survival. <h3>Results</h3> Median time from onset of symptoms to DTT was 18 weeks (3–143). There was no significant correlation between length of time from symptom onset to DDT and potentially curable disease (Chi<sup>2</sup>6.809, p = 0.146). There was no significant difference in overall survival according to length of time from onset of symptoms to DDT (Chi<sup>2</sup>4.209, p = 0.378). On multivariable analysis, gender (HR 3.600, 95% CI 1.659–7.811, p = 0.001) and overall deprivation rank (HR 1.001, 95% CI 1.000–1.001, p = 0.012) were significantly and independently associated with length of time from symptom onset to DDT. <h3>Conclusion</h3> Whilst diagnostic and treatment delays can be lengthy, there is no significant overall effect on rates of potentially curable disease or survival. <h3>Disclosure of interest</h3> None Declared.
Concurrent chemo radiotherapy followed by intraluminal brachytherapy in non-metastatic carcinoma esophagus
Authors: V. A. P. Reddy, P. K. Karanam, V. Biyani, P. Sunkesula
Journal: Journal of Clinical Oncology (2004)

4201 Background: The results of the treatment of Ca. of oesophagus have been poor inspite of advances in various treatment modalities. A high tumor dose is needed to achieve adequate local control, which is possible by an intraluminal boost following teletherapy. Methods: In this study, we report our experience with 85 patients of non-metastatic, histologically proven Sq. cell Ca. of the esophagus treated between July, 1993 and Feb' 2003 with concurrent chemotherapy (day 1 and Day 21, Inj. Cisplatin 70–100 mg. I.V. and Inj. Bleomycin 15 mg I.V.) and external Beam Radiotherapy (5040cGy at 180 cGy/frs.). This was followed by Intraluminal Brachytherapy with Syed's applicator, LDR (2000 cGy) or MDR-Selectron after loading applicator (500 cGy x 3 applications) at 0.5 cm from surface of applicator. U.G.I. endoscopic evaluation were done at the end of concurrent Chemo-radiotherapy, at the time of Brachytherapy, at 6 Weeks after completion of treatment and on follow up every two months thereafter. Results: At first follow up, i.e., at the end of 6 weeks following Intraluminal radiotherapy, 52/85 patients had complete relief of dysphagia, 23/85 patients had partial relief and 10/85 patients had minimal or no relief. Endoscopic evaluation showed no disease in 64/85 (75.3 %) patients and 21/85 (24.7 %) patients had residual disease. At the time of this analysis the median follow up of the patients was 54 months (Mean-50 months, Range- 6–120 months) and 38/85 (44.7%) patients are disease free and 46/85 (57.7%) are alive. Conclusions: Our study shows that Intraluminal Brachytherapy is an effective adjuvant to Teletherapy to facilitate high tumoricidal dose and along with concurrent combination chemotherapy can achieve excellent local control rate and disease free survival with acceptable toxicities. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Apollo Cancer Hospital
Case 48-1976
Authors: Richard C. Cabot, Robert E. Scully, James J. Galdabini, Betty U. McNeely, William B. Seaman, James J. Galdabini
Journal: New England Journal of Medicine (1976)

Presentation of CaseA 67-year-old man was admitted to the hospital because of abdominal pain.For many years he had had attacks of nausea and vomiting, without pain. Ten years before admission his wife died, and he suffered a prolonged grief reaction thereafter. Five years before entry abdominal pain and steatorrhea developed. A peroral intestinal biopsy disclosed a flattened mucosa consistent with celiac disease. A gluten-free diet was prescribed; the abdominal pain and steatorrhea disappeared, and he felt improved.Six months before admission he began to experience fatigue and malaise in a setting of overwork. Two months before entry dull, . . .
ATNT-26PHASE I/II STUDY OF DIANHYDROGALACTITOL IN PATIENTS WITH RECURRENT MALIGNANT GLIOMA
Authors: Kent Shih, Mahish Patel, Nicholas Butowski, Jeffrey Bacha, Dennis Brown, Anne Steino, Richard Schwartz, Sarath Kanekal, Lorena Lopez, Howard Burris
Journal: Neuro-Oncology (2015)

ATNT-26. PHASE I/II STUDY OF DIANHYDROGALACTITOL IN PATIENTS WITH RECURRENT MALIGNANT GLIOMA Kent Shih1,2, Mahish Patel1,3, Nicholas Butowski4, Jeffrey Bacha5, Dennis Brown5, Anne Steino5, Richard Schwartz5, Sarath Kanekal5, Lorena Lopez5, and Howard Burris1,2; Sarah Cannon Research Institute, Nashville, TN, USA; Tennessee Oncology, Nashville, TN, USA; Florida Cancer Specialists & Research Institute, Florida, USA; University of California San Francisco Division of NeuroOncology, San Francisco, CA, USA; DelMar Pharmaceuticals, Vancouver, BC, Canada Glioblastoma multiforme (GBM) is the most common brain cancer. Front-line systemic therapy with temozolomide is often ineffective due to O-methylguanine-DNA-methyltransferase (MGMT)-mediated resistance. Dianhydrogalactitol (VAL-083) is a bi-functional DNA N cross-linking agent that crosses the blood-brain barrier and demonstrated cytotoxic activity independent of MGMT in vitro. The main goal of this clinical trial was to determine an appropriate dose for Phase II/III trials in refractory GBM. METHODS: Open-label, single-arm Phase I/II dose-escalation study in patients with histologically-confirmed GBM, previously treated with radiation and must have failed both temozolomide and bevacizumab, unless contraindicated. The study utilized 3 + 3 dose-escalation design. Patients received VAL-083 on days 1, 2, 3 of a 21-day cycle. RESULTS: 30 GBM patients were enrolled across 8 dose cohorts ranging from 1.5 to 50mg/m/d. No drug-related severe adverse events were reported, and myelosuppression was mild at doses ≤40mg/m/d. Dose limiting toxicities (DLT) consisting of thrombocytopenia were observed at 50mg/m/d. Platelet nadir occurred around day 20, and DLT-related symptoms resolved rapidlyand spontaneously without concomitant treatment. Pharmacokinetic analyses show dosedependent linear systemic exposure with a short 1-2h plasma terminal halflife; Cmax ranged 739-1130ng/mL (5.1-7.7 mM) at 40mg/m/d resulting in calculated CNS concentrations within the IC50 range observed for multiple GBM cell-lines in vitro. Preliminary analysis shows increasing dose-dependent median survival with median OS 1⁄4 9.0 months at doses ≥30mg/m/d vs. 4.4 months at doses ,10mg/m/d. An expansion cohort of up to 14 patients has been initiatedat40mg/m/d.Asmall cohort (n 1⁄4 3) atan interim 45mg/m/d dose will also be studied, and the expansion cohort may be continued at this higher dose if safety data warrant. CONCLUSIONS: VAL-083 dosing appears limited by myelosuppression; however, 40mg/m/d dose exhibited favorable safety profile, with a trend toward improved survival vs. lower doses. Updated safety and efficacy data from the expansion cohort will be presented. ClinicalTrials.gov Identifier NCT01478178. Neuro-Oncology 17:v10–v17, 2015. doi:10.1093/neuonc/nov205.26 Published by Oxford University Press on behalf of the Society for Neuro-Oncology 2015.
Phase I pharmacokinetic (PK) and pharmacodynamic (PD) study of HDM-2 antagonist JNJ-26854165 in patients with advanced refractory solid tumors
Authors: J. Tabernero, L. Dirix, P. Schoffski, A. Cervantes, J. Capdevila, J. Baselga, L. van Beijsterveldt, H. Winkler, S. Kraljevic, S. H. Zhuang
Journal: Journal of Clinical Oncology (2009)

3514 Background: JNJ-26854165 is a novel first-in-clinic oral Human Double Minute-2 (HDM-2) ubiquitin ligase antagonist. It increases the level of HDM-2 client proteins (e.g. p53) by inhibiting the association of HDM-2-client protein complex with the proteosome. Preclinical studies have demonstrated potent anti-proliferative and apoptosis-inducing activity of JNJ-26854165 in a broad range of p53 wild type and mutant tumor models. Methods: A 3+3 dose escalation study with the primary objectives to determine the adverse event (AE) profile, dose limiting toxicities (DLT) and maximum tolerated dose of JNJ-26854165 is ongoing. Secondary objectives include evaluation of PK and PD activity. Eligible patients have ECOG PS≤2 and adequate hematological, renal and hepatic function. JNJ-26854165 is administered orally once daily on a continuous schedule (21-day cycles). Sequential skin and tumor biopsies are taken, and evaluations for HDM-2, p53 and other pathway related markers are performed, including further molecular analyses for HDM-2 activity. Results: 37 pts have been treated at 9 dose levels (DL), 4–300 mg qd. AEs included nausea, vomiting, fatigue, anorexia, insomnia, electrolyte disturbances, liver function tests and creatinine elevations, and asymptomatic QTc prolongation, mostly grade 1–2. A DLT, grade 3 QTcF prolongation, was observed in one patient at DL 9. The patient was asymptomatic and the QTc prolongation recovered after treatment discontinuation. PK data showed dose-proportionality. After dosing at 300 mg, steady state Cmax and AUC0–24h were 2–3 μg/mL and ≈50 μg.h/mL, respectively, well exceeding the expected effective exposure modeled by preclinical studies. PD data showed engagement of the targeted pathway such as dose-dependent p53 upregulation in skin, upregulation of HDM-2 levels in tumors after treatment, and an increase in plasma MIC-1 levels. No objective responses have been observed so far. Conclusions: JNJ-26854165 was well tolerated at doses beyond the expected effective exposure modeled by preclinical studies. PD activity was observed at the 150–300 mg dose levels. The trial continues with cohort expansion at 300 mg. Updated results will be presented. [Table: see text]
Ponatinib versus imatinib for newly diagnosed chronic myeloid leukaemia: an international, randomised, open-label, phase 3 trial
Authors: Jeffrey H Lipton, Charles Chuah, Agnès Guerci-Bresler, Gianantonio Rosti, David Simpson, Sarit Assouline, Gabriel Etienne, Franck E Nicolini, Philipp le Coutre, Richard E Clark, Leif Stenke, David Andorsky, Vivian Oehler, Stephanie Lustgarten, Victor M Rivera, Timothy Clackson, Frank G Haluska, Michele Baccarani, Jorge E Cortes, François Guilhot, Andreas Hochhaus, Timothy Hughes, Hagop M Kantarjian, Neil P Shah, Moshe Talpaz, Michael W Deininger
Journal: The Lancet Oncology (2016)
High levels of plasma catecholamines in dexamethasone-resistant depressed patients
Authors: R F Barnes, R C Veith, S Borson, J Verhey, M A Raskind, J B Halter
Journal: American Journal of Psychiatry (1983)

Of nine depressed patients given the dexamethasone suppression test, the four dexamethasone-resistant patients had significantly higher plasma norepinephrine and epinephrine levels than the five patients with normal suppression. These results suggest greater sympathetic function in dexamethasone-resistant depressed patients.
Value of Cordotomy for the Relief of Pain
Authors: Saul A. Frankel, James D. Prokop
Journal: New England Journal of Medicine (1961)

CORDOTOMY for the relief of intractable pain was first performed by Martin in 1911 and is now a well established procedure.1 2 3 4 5 6 7 8 9 10 11 12 Unfortunately, many patients are denied its benefits because of a lack of understanding of what may be expected from this operation. Both patients and physicians have a natural tendency to regard surgery as a radical step, and especially surgery on the central nervous system. Those who have had any experience with cordotomy are also aware that there is a certain incidence of failure and of complications of varying severity. To make the decision to take a specific therapeutic step . . .
SAT0349 Patient-Reported Outcomes from a Phase 3 Study of Baricitinib in Patients with Rheumatoid Arthritis (RA) and an Inadequate Response to Tumor Necrosis Factor Inhibitors: Table 1
Authors: J.S. Smolen, J. Kremer, C. Gaich, A.M. DeLozier, D. Schlichting, L. Xie, M.C. Genovese
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> In ph 2 studies, baricitinib (bari) improved disease activity with an acceptable safety profile in pts with active RA naïve to biologic DMARDs (bDMARDs).<sup>1,2</sup> <h3>Objectives</h3> To report patient-reported outcomes (PRO) from a ph 3 study of bari in pts with active RA on 1 or 2 conventional DMARDs (cDMARDs) and an inadequate response or intolerance to ≥1 TNF inhibitors. <h3>Methods</h3> Pts were randomized 1:1:1 to placebo (PBO) or bari (2 or 4 mg) QD for 24 wks. PROs are listed in the table. Analyses included ANCOVA, logistic regression, and nonparametric methods and compared bari 2 or 4 mg vs. PBO. <h3>Results</h3> 527 pts were randomized. Assessment of PROs at baseline revealed severe impairment of physical function (HAQ-DI: 1.7-1.8) and QoL. Bari 2 and 4 mg resulted in statistically significant improvements from baseline vs. PBO in most PROs at 24 wks (Table). <h3>Conclusions</h3> In this ph 3 study of pts with active RA on cDMARDs and an inadequate response to bDMARDs, bari was associated with significant improvement in most PROs through 24 wks compared to PBO. <h3>References</h3> Keystone et al. Ann Rheum Dis 2015;74:333-340. Tanaka et al. Arthritis Rheum 2013;65(S10):S765. <h3>Disclosure of Interest</h3> J. Smolen Grant/research support from: Abbvie, Janssen, MSD, Pfizer, Roche, UCB, Consultant for: Abbvie, Amgen, Astra-Zeneca, Astro, Celgene, Glaxo, Janssen, Lilly, Medimmune, MSD, Novartis-Sandoz, Pfizer, Roche, Samsung, Sanofi, UCB, J. Kremer Grant/research support from: Abbvie, Amgen, BMS, Genentech, Lilly, Pfizer and UCB, Employee of: Part time employment with Corrona, C. Gaich Employee of: Eli Lilly and Company, A. DeLozier Employee of: Eli Lilly and Company, D. Schlichting Employee of: Eli Lilly and Company, L. Xie Employee of: Eli Lilly and Company, M. Genovese Grant/research support from: Abbvie, Astellas, Eli Lilly and Company, Galapagos, Pfizer, and Vertex
Evaluation of Antibodies to Hepatitis C Virus in a Study of Transfusion-Associated Hepatitis
Authors: Juan I. Esteban, Antonio González, José M. Hernández, Luis Viladomiu, Carmen Sánchez, Juan C. López-Talavera, David Lucea, Carmen Martin-Vega, Xavier Vidal, Rafael Esteban, Jaime Guardia
Journal: New England Journal of Medicine (1990)

The hepatitis C virus (HCV) is now known to be the chief cause of transfusion-associated non-A, non-B hepatitis, but the prevalence of HCV among blood donors and the frequency of transmission by blood transfusion are unknown.To assess the sensitivity and specificity of a test for antibody to HCV, we tested serum samples from participants in a large study of transfusion-associated hepatitis. Samples were obtained prospectively from consecutive adults undergoing open-heart surgery in Spain, but were tested retrospectively, after the antibody enzyme immunoassay for anti-HCV became available.Of 280 transfusion recipients given a total of 1109 units of blood, 27 (9.6 percent) had transfusion-associated non-A, non-B hepatitis (mean follow-up, 52 weeks) and 24 of the 27 seroconverted to anti-HCV-positive, whereas only 2 (0.8 percent) of the remaining transfusion recipients seroconverted. Among the 1044 donor specimens available for testing, 16 (1.5 percent) had anti-HCV antibody. Only 1 additional seropositive donor was found when 44 implicated donors who had been seronegative were retested 9 to 12 months later. Of the 16 recipients of anti-HCV-positive blood, 14 (88 percent) had transfusion-associated hepatitis and seroconverted to anti-HCV-positive. The remaining two recipients had neither hepatitis nor anti-HCV antibody. Among 25 patients with non-A, non-B hepatitis for whom all transfused blood was tested, 14 had received blood positive for anti-HCV.About 90 percent of blood donors with antibody to HCV have infectious virus in their blood. The screening of blood donors for anti-HCV antibody should prevent about half the cases of transfusion-associated hepatitis, but the donors with infectious virus who are anti-HCV-negative may remain seronegative for prolonged periods.
Brief Report: Chlamydia Psittaci Endocarditis Diagnosed by Blood Culture
Authors: Daniel S. Shapiro, Shannon C. Kenney, Margaret Johnson, Carolyn H. Davis, Stephen T. Knight, Priscilla B. Wyrick
Journal: New England Journal of Medicine (1992)

THERE have been approximately a dozen reported cases of endocarditis due to Chlamydia psittaci, the etiologic agent of psittacosis (ornithosis, or parrot fever). It is not known whether this number reflects a truly low incidence of endocarditis associated with C. psittaci or whether cases are missed because of the difficulty of establishing this diagnosis. Although one study reported an association between exposure to pet birds and subsequent acquired valvular heart disease,1 this finding has not been widely accepted. We describe a woman who presented with culture-negative endocarditis. Despite treatment with a standard antibiotic regimen, the patient required mitral-valve replacement. . . .
Pneumococcal Peritonitis in Patients with Postnecrotic Cirrhosis
Authors: Murray Epstein, Frank M. Calia, George J. Gabuzda
Journal: New England Journal of Medicine (1968)

Six episodes of pneumococcal peritonitis in five patients with postnecrotic cirrhosis, portal hypertension and ascites are reported. This diagnosis must be considered when fever or abdominal complaints, especially with leukocytosis, occur in patients with postnecrotic cirrhosis with ascites. Onset may be insidious. Physical examination and gross characterization of ascitic fluid were not diagnostic. Cell counts and Gram-stained smears of ascitic fluid provided first evidence of bacterial peritonitis. Adequate bacteriologic studies of blood and ascitic fluid established definitive diagnosis. Bactericidal levels of penicillin were demonstrated in ascitic fluid after a relatively small intravenous dose. Therapeutic responses to parenteral penicillin were prompt and successful with respect to the pneumococcal peritonitis. However, in four patients the peritonitis occurred as a preterminal event or was followed by other complications that caused death.
The Polymorphism Of Base Excision Repair Gene, XRCC1 Arg399Gln Is Associated With The Therapy-Related Myelodysplastic Syndromes (MDS)
Authors: Batchimeg Norjmaa, Takayuki Saitoh, Atsushi Iwasaki, Yasuhiro Nitta, Yuta Masuda, Itsumi Suda, Ayaka Kaneko, Hiroaki Shimizu, Hiroshi Handa, Akihiko Yokohama, Norifumi Tsukamoto, Toru Sakura, Hirokazu Murakami
Journal: Blood (2013)
Alcohol as an Environmental Mortality Hazard
Authors: Andreas Heinz, Anne Beck, Michael A. Rapp
Journal: JAMA Psychiatry (2016)

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