tbuckley/cabot-search huggingface dataset:
In Vivo and in Vitro Chromosomal Damage Induced by LSD-25
Authors: Maimon M. Cohen, Kurt Hirschhorn, William A. Frosch
Journal: New England Journal of Medicine (1967)

THE induction of chromosomal aberrations by exogenous agents, such as viruses, radiation and chemicals, is an area of active cytogenetic investigation.1 Recently, the psychotomimetic hallucinogen, lysergic acid diethylamide (LSD-25), has been added to the list of chemicals capable of causing abnormalities in the chromosomes of human leukocytes.2 , 3 Such preliminary studies report the in vitro and in vivo chromosomal effects of LSD, and the present communication extends these observations to include additional in vitro findings and a significant sample of patients.Materials and MethodsIn Vitro StudiesPeripheral leukocyte cultures were initiated from 6 normal, healthy persons (3 males and 3 . . .
First-in Man, Phase 1 Study of CSL362 (Anti-IL3Rα / Anti-CD123 Monoclonal Antibody) in Patients with CD123+ Acute Myeloid Leukemia (AML) in CR at High Risk for Early Relapse
Authors: B. Douglas Smith, Gail J. Roboz, Roland B. Walter, Jessica K. Altman, Anna Ferguson, Tania J. Curcio, Kaysey F. Orlowski, Linda Garrett, Samantha J Busfield, Megan Barnden, Brad Sedgmen, Souravi Ghosh, Sarah Hosback, Roslyn Davis, Allison Dyson, Sue Dasen, Mark DeWitte, Debra M. Bensen-Kennedy, Andrew W. Roberts
Journal: Blood (2014)
Case 38-1992
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, C.H. Coggins, S. Meehan
Journal: New England Journal of Medicine (1992)

Presentation of CaseA 72-year-old woman was admitted to the hospital because of orthostatic hypotension with syncopal attacks and proteinuria.There was a long history of hypertension, which was managed initially with reserpine and thereafter with hydrochlorothiazide; in recent years the patient had discontinued her medications. She was well in other respects until about three months before admission, when she began to experience recurrent orthostatic lightheadedness, anorexia, and difficulty in swallowing dry foods. She reported having pain in the left arm on exertion, without chest pain or dyspnea. An upper gastrointestinal series with a small-bowel study was normal except for . . .
Effect of Ethamivan on Alveolar Ventilation in Patients with Chronic Lung Disease
Authors: Theodore Rodman, Joseph F. Fennelly, Albert J. Kraft, Henry P. Close
Journal: New England Journal of Medicine (1962)

ACUTE respiratory acidosis is being recognized with increasing frequency in patients with chronic lung disease. It is a life-threatening complication demanding immediate and vigorous treatment, which often involves tracheostomy and mechanically assisted ventilation. The therapeutic regimen is both complex and protracted, and the mortality, even under optimal conditions, is appreciable.1 Potent pharmacologic agents, particularly respiratory stimulants, have therefore been sought in the hope of reducing the mortality and simplifying therapy. Recently ethamivan (diethylaminovanillic acid) has been made available for intravenous and oral administration and has been recommended for use in patients with chronic lung disease as a potent specific stimulant . . .
FRI0156 Pharmacokinetics of ABT-122, A Dual TNF- and IL-17A-Targeted DVD-IG™, After Single Dosing in Healthy Volunteers and Multiple Dosing in Subjects with Rheumatoid Arthritis
Authors: G.F. Ahmed, S. Goss, P. Jiang, H. Mansikka, R.J. Padley, A.A. Othman
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> ABT-122 is a novel dual-variable domain immunoglobulin that specifically neutralizes both TNF alpha and interleukin-17A, with the dual neutralization aimed to achieve greater clinical response in immune-mediated inflammatory diseases than blocking either cytokine alone. <h3>Objectives</h3> This work characterized the pharmacokinetics of ABT-122 after single [Intravenous (IV), subcutaneous (SC)] ascending doses in healthy volunteers or multiple SC ascending doses in subjects with rheumatoid arthritis (RA). <h3>Methods</h3> ABT-122 pharmacokinetics was evaluated in three Phase 1 studies for up to 92 days. In Study 1, single- ascending IV (0.1, 0.3, 1, 3 and 10 mg/kg) and SC (0.3, 1 and 3 mg/kg) doses were evaluated in healthy volunteers. In Studies 2 and 3, multiple ascending SC doses (1 mg/kg biweekly, 0.5 to 3 mg/kg weekly for 8 weeks) were evaluated in subjects with RA on stable methotrexate (MTX) therapy. ABT-122 pharmacokinetic parameters were estimated using non-compartmental analyses. <h3>Results</h3> Pharmacokinetic data were available from 48 healthy and 31 RA subjects with median body weights of 78 (range; 52 – 98) and 79 (range; 47 – 111) kg, respectively. ABT-122 pharmacokinetic profile showed multi-exponential disposition with more than dose-proportional exposure at the lower doses (0.1 – 1 mg/kg) and approximately dose-proportional exposure at doses &gt;1 mg/kg. With SC dosing, ABT-122 absolute bioavailability was approximately 50% and maximum serum concentrations were reached 3 – 4 days after dosing. After the last dose, ABT-122 AUC accumulation ratio was 3.8 to 5.6 with steady-state appearing to be achieved by 5 weeks of SC dosing. ABT-122 C<sub>max</sub> to C<sub>trough</sub> ratio was 2.6 and 1.3 for biweekly and weekly dosing, respectively (corresponding effective half-life of 10 days with biweekly dosing and 18 days with weekly dosing). In most of the subjects, anti-drug antibodies detected had no detectable impact on pharmacokinetics, safety or tolerability profile of ABT-122. <h3>Conclusions</h3> ABT-122 is characterized by a pharmacokinetic profile favorable for biweekly subcutaneous administration. The results from these three phase 1 studies supported advancing ABT-122 to Phase 2 testing in subjects with rheumatoid and psoriatic arthritis. <h3>Disclosure of Interest</h3> G. Ahmed Shareholder of: AbbVie, Employee of: AbbVie, S. Goss Shareholder of: AbbVie, Employee of: AbbVie, P. Jiang Shareholder of: AbbVie, Employee of: AbbVie, H. Mansikka Shareholder of: AbbVie, Employee of: AbbVie, R. Padley Shareholder of: AbbVie, Employee of: AbbVie, A. Othman Shareholder of: AbbVie, Employee of: AbbVie
Sequential Infection with Common Pathogens Promotes Human-like Immune Gene Expression and Altered Vaccine Response
Authors: Tiffany A. Reese, Kevin Bi, Amal Kambal, Ali Filali-Mouhim, Lalit K. Beura, Matheus C. Bürger, Bali Pulendran, Rafick-Pierre Sekaly, Stephen C. Jameson, David Masopust, W. Nicholas Haining, Herbert W. Virgin
Journal: Cell Host & Microbe (2016)
. . . And a Diagnostic Test Was Performed
Authors: Robert Greenwald
Journal: New England Journal of Medicine (2005)

To the Editor: At a recent case conference with a distinguished visiting professor, a fellow in allergy and immunology presented the case of an infant with diarrhea; an unusual rash (“alligator skin”); multiple immunologic abnormalities, including low T-cell function; tissue eosinophilia (of the gastric mucosa) as well as peripheral eosinophilia; and an apparent X-linked genetic pattern (several male relatives died in infancy). The attending physicians and house staff discussed several diagnostic possibilities, but no consensus was reached. Finally, the visiting professor asked the fellow if she had made a diagnosis, and she reported that she had indeed and mentioned a . . .
Laryngeal carcinoma in Sub Saharan Africa
Authors: A. A. Adeyemo, G. M. Mohammed
Journal: Journal of Clinical Oncology (2008)

17022 Background: Early stage laryngeal carcinoma is curable, however reports from sub Saharan Africa showed that many patients presents with advanced disease requiring radical treatment with considerable morbidity and mortality. We reviewed our management of patients who presented with symptoms of laryngeal tumor and discussed the possible causes of late presentation. Methods: The bio data, presenting complaints and its duration and TNM stage of the lesion at presentation were retrieved from the records of patients who presented with symptoms of laryngeal tumor at the University College Hospital, Ibadan, Nigeria between 1999 and 2007. Results: There were a total of 114 patients seen but only 47 patients with complete records were included in this study, 42 males and 5 females; (M: F, 8.4:1). The age range was 28years to 84 years with a mean age of 57.5 years. Hoarseness was the commonest presentation (87%) with duration of 1year to 4years before presentation. Thirty- nine patients (82.9%) had T3/ T4 lesions at presentation. Five patients (10.6%) presented with T2 lesions while 3 patients (6.4%) presented with T1 lesions. Conclusions: An inefficient referral system, prevailing poor economic climate and poor outcome of radical treatment operates in a vicious circle to deter early presentation of patients with laryngeal carcinoma. To reverse the trend a coordinated public enlightenment programme and provision of subsidised health care delivery to indigent patients is required to gain an upper hand in the battle against laryngeal cancer. No significant financial relationships to disclose.
Randomized phase II study of gabapentin alone versus gabapentin plus tramadol for the management of oxaliplatin-induced peripheral neuropathy.
Authors: H. Shim, J. Yoon, J. Hwang, W. Bae, S. Cho, I. Chung
Journal: Journal of Clinical Oncology (2010)

TPS315 Background: Peripheral neuropathy is a representative side effect of oxaliplatin. Oxaliplatin-induced peripheral neuropathy (OXLIPN) related symptoms have negative effects on both quality of life and treatment outcomes. Tricyclic antidepressants and antiepileptics are currently used in clinical practice to treat OXLIPN; however, the results are minimally effective. This study is designed to compare the efficacy of gabapentin alone and combination of gabapentin and tramadol in patients (pts) with OXLIPN. Methods: Pts with duration ≥ 1 month symptomatic OXLIPN, a grade ≥ 2 on the NCI- CTC neuropathy are eligible. Pts are ineligible if they have preexisting symptomatic neuropathy because of other causes. This trial is designed to have 30 pts in each arm to provide 90% power to detect (with a two-sided αof 0.05) a one point change in pain intensity on a scale from 0 to 10, which is regarded as a clinically signigicant change. Considering drop-out rates of 10%, the total accrual pts will be 66. This study accepts crossover design consisting of two 4-week phases separated by 2-week washout period. Eligible pts are randomly assigned to 1 of 2 arms, either gabapentin (G group) or gabapentin with tramadol (G/T groups). The target dose of gabapentin in G group is 2,700 mg/day. The target doses of gabapentin and tramadol in G/T group are 2,400 mg/day and 200 mg/day, respectively. If toxic events occur, the dose is reduced to a previously well-tolerated dose level. During the first 3 weeks of each treatment period, the dose is escalated toward a maximal tolerated dose or the target ceiling dose, whichever is reached first. In the fourth week of each period, each pts will receive their maximal tolerated dose for the particular treatment, pts undergo a four-day dose tapering and an 11-day complete washout. Primary endpoint is the mean intensity of pain (NRS, 0-10) which pts rate three times daily. Secondary endpoints are NCI-CTC neuropathy grade, adverse effect, and quality of life. Primary outcome and adverse effects will be evaluated at baseline and then weekly. Other secondary outcomes will be evaluated at baseline and then every other week. No significant financial relationships to disclose.
Monoclonal Antibody Defining Fibroblasts Appearing in Fetal and Neoplastic Tissues&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: A H Bartal, C Lichtig, C C Cardo, C Feit, E Robinson, Y Hirshaut
Journal: JNCI Journal of the National Cancer Institute (1986)

VIF3 is a hybridoma-derived mouse IgG monoclonal antibody (MoAb) generated in a fusion with the use of a malignant fibrous histiocytoma as the immunizing agent and shown to recognize a 70-kilodalton antigen expressed within connective tissues. Of 55 human tissue culture cell lines tested by indirect immunofluorescence, VIF3 was shown to bind to 20 of 35 (57%) sarcomas, 4 of 9 (44%) normal fibroblasts, and none of 11 carcinomas and other neoplasm-derived cell lines. A panel of over 259 human frozen tissue sections obtained from surgical pathology specimens, postmortem studies, and elective abortions was used to further determine the histopathologic specificity of VIF3. MoAb VIF3 was found to bind to 15 of 19 (79%) human sarcoma tissue sections tested. It was also shown to recognize an antigen expressed on a subset of fibroblasts dispersed within the stroma of carcinomas obtained from all 46 patients tested, as well as a subset of cells within 3 of 10 benign hyperplastic tissues (30%). VIF3-positive cells were detected in all 60 fetal tissues tested including amniotic membranes, placentas, and umbilical cords. In contrast, fibroblasts of normal adult tissues tested stained infrequently (22/97 or 23%) with this reagent. The results confirm that this MoAb is directed against a human connective tissue-specific marker. VIF3 detects a marker appearing on fetal fibroblasts that is typically not present in normal adult tissues, but reappears in association with neoplastic diseases. MoAb VIF3 therefore defines a fibroblast-oncofetal antigen and as such may serve as a probe for immunopathologic studies.
Pure Red-Cell Aplasia Associated with Clonal Expansion of Granular Lymphocytes Expressing Killer-Cell Inhibitory Receptors
Authors: Rupert Handgretinger, Andreas Geiselhart, Arnaud Moris, Roger Grau, Oliver Teuffel, Wolfgang Bethge, Lothar Kanz, Paul Fisch
Journal: New England Journal of Medicine (1999)

Killer-cell inhibitory receptors inhibit cytolysis when natural killer cells encounter cells bearing HLA class I molecules.1,2 This phenomenon explains the preferential killing by natural killer cells of tumor cells with reduced expression of HLA class I molecules.3 This finding is the basis of the “missing self” model, in which the HLA class I allele lost by the tumor cells is not available to inhibit the killer cell's lytic machinery. Different types of killer-cell inhibitory receptors have distinct specificity for HLA-A, B, C, and E antigens.1,4 In addition, some natural killer cells also possess receptors that induce lysis of . . .
Detection of Malignant Tumors
Authors: Eric T. Fossel, Justine M. Carr, Jan McDonagh
Journal: New England Journal of Medicine (1986)

A sensitive and specific blood test for cancer has long been sought. The water-suppressed proton nuclear magnetic resonance (NMR) spectrum of plasma is dominated by the resonances of plasma lipoprotein lipids. We measured the mean line widths of the methyl and methylene resonances, which were found to be correlated with the presence or absence of malignant tumors. Values for the average line width were lower in patients with cancer. We analyzed plasma from 331 people (normal controls, patients with malignant and benign tumors, patients without tumors, and pregnant patients); NMR analysis and measurement of line widths were blinded to diagnosis or patient group. The mean line width for 44 normal controls (+/- SD) was 39.5 +/- 1.6 Hz. For 81 patients with untreated cancer, demonstrated by biopsy, the line width was 29.9 +/- 2.5 Hz. Patients with malignant tumors were reliably distinguished from normal controls by this method (P less than 0.0001), and differed from patients with diseases that did not involve tumors (line width, 36.1 +/- 2.6 Hz; P less than 0.0001). Patients with benign tumors (e.g., those of the breast, ovary, uterus, and colon) had line widths of 36.7 +/- 2.0 Hz and were different from those with malignant tumors (P less than 0.0001). However, pregnant patients and those with benign prostatic hyperplasia had line widths consistent with the presence of malignant tumors. The narrowing of lipoprotein-lipid resonances with cancer is consistent with the response of a host to tumor growth. We conclude that these preliminary results demonstrate that water-suppressed proton NMR spectroscopy is a potentially valuable approach to the detection of cancer and the monitoring of therapy.
Neoadjuvant biweekly dose-dense chemotherapy with fluouracil, epirubicin, and cyclophosphamide (FEC 90), followed by docetaxel in patients with HER2-neu negative primary breast cancer
Authors: D. Rodriguez-Abreu, A. Murias, M. García, V. Vega, C. Garcia, M. Mori, B. Báez-Acosta, A. Diez, J. Almenarez
Journal: Journal of Clinical Oncology (2009)

596 Background: A primary goal of therapy for large early stage breast cancers is to achieve breast conserving surgery (BCS) through tumor mass reduction with neoadjuvant chemotherapy. In addition, induction of pathological complete response (pCR) is reported to prolong disease-free survival. Encouraged by results from recent studies of dose-dense chemotherapy in the adjuvant setting, we studied preoperative treatment with biweekly 5-fluorouracil, epirubicin, and cyclophosphamide followed sequentially by triweekly docetaxel. Methods: Eighty-one women with stage IIA to IIIB breast cancer were entered into this trial between August 2003 and April 2008. Patients received 5-fluorouracil 600mg/m 2 , epirubicin 90 mg/m 2, and cyclophosphamide 600 mg/m 2 (q2w x 4 cycles) followed by docetaxel 100 mg/m 2 (q3w x 4 cycles). Granulocyte colony-stimulating factor was administered each cycle to reduce the risk of neutropenic complication. After chemotherapy, patients underwent surgery, and received standard adjuvant radiotherapy and hormone therapy as usual clinical practice. The primary endpoint of this trial was pathological response rate and the secondary endpoints were BCS rate and toxicity. Results: A total of 79 patients were analyzed. The median age was 50y (28–74), the median tumour size was 4 cm. 50 patients (63.2%) were ER positive and/ o PR positive. 48 patients (60.7%) were pre-menopausal. Median follow-up was 36m, 64 patients had stage II (81%) and 15 had stage III (19%). Clinical response was seen in all cases. A pCR with no evidence of tumor in the breast and lymph nodes was confirmed in 21 patients (26.5%). BSC was performed in 61 patients (77.2%). Treatment was well tolerated, 8 patients (10.1%) had grade 3/4 hematological toxicity. Others adverse events including, anorexia, fatigue, nausea, vomiting, mucositis, myalgia, nail changes, peripheral neuropathy, hand-foot skin reactions were mild and manegeable. Conclusions: The neoadjuvant biweekly dose-dense chemotherapy with fluouracil, epirubicin and cyclophosphamide (FEC 90), followed by docetaxel is safe and demostrates a high pathological response rate (pCR) of 26.5% with an increase rate of BCS of 77.2%. No significant financial relationships to disclose.
Treatment of Penicillin-Resistant<i>Neisseria gonorrhoeae</i>with Oral Norfloxacin
Authors: Steven R. Crider, Steven D. Colby, Larry K. Miller, William O. Harrison, Sharon B. J. Kerbs, S. William Berg
Journal: New England Journal of Medicine (1984)

Norfloxacin, an orally administered quinoline carboxylic acid that is structurally related to nalidixic acid, has been shown to be highly active in vitro against penicillinase-producing Neisseria gonorrhoeae. Ninety-two men with culture-proved gonococcal urethritis, 46 per cent with penicillinase-producing N. gonorrhoeae, and 27 per cent with non-penicillinase-producing N. gonorrhoeae that was resistant to penicillin were given either 1200 mg of norfloxacin divided into two equal oral doses four hours apart (59 patients) or 2 g of spectinomycin intramuscularly (33 patients). All patients in both treatment groups were cured. No adverse reactions were reported in either group. We conclude that a two-dose, single-day regimen of orally administered norfloxacin is effective therapy for uncomplicated urethritis caused by penicillin-resistant strains of N. gonorrhoeae.
Barbiturates and Lung Cancer In Humans&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: Gary D. Friedman, M.D.
Journal: JNCI Journal of the National Cancer Institute (1981)

In a hypothesis-generating study looking for possible carcinogenic effects of drugs in humans, each of three barbiturates (pentobarbital sodium, phenobarbital, and secobarbital sodium) showed a statistically significant association with the subsequent development of lung cancer, with relative risks ranging from 1.5 to 2.8. Further analysis showed that the association was not explained by the increased prescription of barbiturate drugs shortly before the diagnosis of lung cancer or by an association of barbiturate use with cigarette smoking. Much of the data did not support a causal relationship. Neither a relation of lung cancer to duration or intensity of use not one between barbiturate use and a specific histologic type could be demonstrated.
S99 Pulmonary Rehabilitation in Interstitial Lung Disease – a prospective, observational study
Authors: C Sharp, M McCabe, MJ Hussain, H Adamali, DL Smith, A Edwards, AB Millar
Journal: Thorax (2015)

<h3>Background</h3> Pulmonary rehabilitation (PR) is important in the management of interstitial lung disease (ILD), however it remains unclear how sustained the initial benefits in exercise capacity and quality of life are in this group of patients. An increasing number of ILD patients are participating in PR courses and it is vital that they be offered the most beneficial approach possible. <h3>Methods</h3> We have analysed prospectively gathered data from a well characterised population of ILD participants with &gt;24 months follow-up, from a well-established PR service. Participants completed incremental shuttle walk (ISWT) and chronic respiratory disease questionnaire (CRDQ) before PR, at course completion, 6 months and 12 months follow-up. These data were compared to establish changes over time compared to baseline. The ILD cohort was compared to a further group with chronic obstructive pulmonary disease (COPD). Semi-structured interviews were conducted with ILD participants to establish qualitative views on existing and possible future PR provision. <h3>Results</h3> Data were available for 79 participants with ILD. PR gave initial improvements in ISWT (29.5 m (95% CI 13.7 to 45.2 m)) and CRDQ (11.6 (95% CI 8.5 to 14.7)), however these benefits were not sustained at 6 months (ISWT change 0.0 m (95% CI -23.2 to 23.2 m), CRDQ change 2.5 (95% CI -2.4 to 7.4)) and 12 months (ISWT change -0.7 m (95% CI -37.3 to 35.9 m), CRDQ change 4.0 (95% CI -2.2 to 10.2)). In contrast, the COPD group demonstrated more durable benefit in exercise capacity (ISWT change at 6 months 35.7 m, 95% CI 10.76 to 60.68, p &lt; 0.01). A greater proportion of those who had continued with home exercise maintained an increase in walking distance above the MCID than those who had not (46.4% vs 10.5%, p = 0.01). Interview responses highlighted the value attached to PR by participants with ILD, but also suggested that this could be improved by increased course duration, ongoing supervised exercise following course completion and greater tailoring of content to those with ILD. <h3>Conclusions</h3> PR as currently delivered gives initial benefits to participants with ILD, however these are not sustained. More tailored approaches to this group are needed to improve the sustainability of response to PR.
Management of viral hepatitis in patients with haematological malignancy and in patients undergoing haemopoietic stem cell transplantation: recommendations of the 5th European Conference on Infections in Leukaemia (ECIL-5)
Authors: Vincent Mallet, Florian van Bömmel, Christopher Doerig, Sven Pischke, Olivier Hermine, Anna Locasciulli, Catherine Cordonnier, Thomas Berg, Darius Moradpour, Heiner Wedemeyer, Per Ljungman
Journal: The Lancet Infectious Diseases (2016)