tbuckley/cabot-search huggingface dataset:
Cellular Reactivity to Altered Glomerular Basement Membrane in Glomerulonephritis
Authors: Howard M. Fillit, Stanley E. Read, Raymond L. Sherman, John B. Zabriskie, Ivo van de Rijn
Journal: New England Journal of Medicine (1978)

Glomerular basement membrane may be altered during glomerulonephritis, exposing antigens that are recognized as foreign. Immunochemical studies suggest that removal of peripheral glycopeptides from the basement membrane with glycosidase mimics this pathogenetic event. To examine these hypotheses, we studied 24 patients with biopsy-proved glomerulonephritis by means of the lymphocyte-blast-transformation assay. Three preparations of normal glomerular basement membrane were used: two mimicked the native state for the peripheral glycopeptides, and one was altered by glycosidases. Results showed minimal differences in responses to native glomerular basement-membrane preparations among patients with glomerulonephritis and control groups. However, patients with glomerulonephritis had a significant blastogenic response to the glycosidase-treated glomerular basement membrane as compared to patients with nonglomerular renal disease and normal controls (P less than 0.0005). These studies suggest that cellular reactivity to altered glomerular basement-membrane antigens can be detected in certain forms of progressive glomerulonephritis.
P231 A prospective cohort study of integrated palliative care of cystic fibrosis (CF)
Authors: SJ Bourke, R Mackley, Z Booth, S Doe, A Anderson, S Rice, AD Gascoigne, R Quibell
Journal: Thorax (2015)

<h3></h3> There are 140 deaths in the UK each year from CF, often on a transplant waiting list and often without specialist palliative care. A palliative physician and nurse joined our team in 2011, providing palliative care in parallel with standard CF care. We undertook a prospective study documenting symptoms and outcomes, the views of the CF team and the experience of the palliative specialists. Over 3 years, 28 (10%) of 282 patients at our Centre had palliative input; their mean age was 31 (range 18–47) years and mean FEV1 was 0.86 L (24%); 17 (61%) died - 6 were on a transplant waiting list, 10 were unsuitable, and one died post transplantation; 4 have had transplantation and no longer need palliative input, 7 are in on-going care; 15 (88%) of deaths were on the CF ward and 2 at home. All patients who died had had palliative care. The main symptoms were breathlessness, cough, pain, vomiting, fatigue and low mood. The mean palliative assessment score was high at 2.9, indicating that life was dominated by symptoms. Palliative interventions included opioid, benzodiazepine, anti-emetic and anti-depressant medications and non-pharmacological interventions included relaxation techniques, massage, acupuncture and cognitive therapy. A survey was completed by 16 members of the CF team: all felt that palliative specialists should be part of the team and rated the model of care highly with a mean score of 4.1 (scale 1–5); 11 thought that patients had found input very helpful and 5 helpful; one patient declined a palliative consultation. The palliative specialists had increased their knowledge of CF, found it useful to meet patients earlier and had no difficulty in providing palliation in parallel with standard CF care. Their workload was high and they identified additional needs of bereavement counselling and managing the effects of deaths on other CF patients. This integrated model was successful in overcoming barriers to specialist palliative care. Palliative specialists have improved their knowledge of CF and the CF team have learnt palliative skills.
The Syndrome of Alveolar Hypoventilation and Diminished Sensitivity of the Respiratory Center
Authors: Tor Richter, John R. West, Alfred P. Fishman
Journal: New England Journal of Medicine (1957)

IN the normal subject, an increment in the partial pressure of carbon dioxide (Pco2) in arterial blood of only a few millimeters of mercury suffices to double or even triple minute and alveolar ventilation. However, analysis of this relation in terms of a simple stimulus-response pattern is complicated by several factors: changes in blood pH accompany the changes in blood Pco2; intracellular buffers are interposed between the arterial blood and the respiratory center; and the magnitude of the ventilatory response seems to be conditioned, in some obscure way, by factors such as the level of total-body . . .
Case 14-1968
Authors: David G. Nathan, James M. Gibson
Journal: New England Journal of Medicine (1968)

Presentation of Case First admission. A twenty-one-year-old Italian man entered the hospital because of intermittent jaundice of long duration and recent dyspnea and ankle edema.For many years he had been aware of a yellow tint of his skin but had noticed no discoloration of the urine or stools. One month before entry there was the onset of swelling of the ankles and dyspnea on exertion.The patient's father had died as a result of leukemia. The diagnosis of thalassemia trait in his mother was subsequently made on the basis of typical blood morphology and an elevation of A2 . . .
Decreased Lymphocyte Beta-Adrenergic-Receptor Density in Patients with Heart Failure and Tolerance to the Beta-Adrenergic Agonist Pirbuterol
Authors: Wilson S. Colucci, R. Wayne Alexander, Gordon H. Williams, Robert E. Rude, B. Leonard Holman, Marvin A. Konstam, Joshua Wynne, Gilbert H. Mudge, Eugene Braunwald
Journal: New England Journal of Medicine (1981)

We compared the initial and long-term effects of the beta-adrenergic agonist pirbuterol in 12 patients with chronic congestive heart failure. The drug's initial effect was a 35 per cent increase in cardiac index, but there was no significant change in heart rate or mean arterial pressure. After one month of therapy, the mean cardiac index and ejection fraction had returned to base-line values, and no clinical effect was evident in most patients. This apparent tolerance was not accompanied by changes in heart rate, blood pressure, or body weight, and it occurred in the presence of therapeutic drug levels during long-term therapy. The density of beta-adrenergic receptors on lymphocytes from patients treated with pirbuterol was significantly depressed as compared with that of patients with heart failure of comparable severity but not treated with pirbuterol. We conclude that tolerance to the hemodynamic and clinical effects of pirbuterol develops during long-term administration; this tolerance may be related to a decrease in myocardial or vascular beta-adrenergic receptors or both.
PTH-027 Diagnostic yield of chromoendoscopy for dysplastic lesions is better than standard colonoscopy in patients with ulcerative colitis: a meta-analysis of prospective studies
Authors: V Subramanian, J Mannath, K Ragunath, C J Hawkey
Journal: Gut (2010)

<h3>Introduction</h3> Dysplasia in ulcerative colitis (UC) is often multifocal and flat, making it easy for significant lesions to be overlooked. Dye spraying the mucosal surface is believed to enhance visualisation of subtle mucosal abnormalities. Despite studies suggesting that chromoendoscopy could improve surveillance yields in patients with UC, the technique continues to be underutilised both in Europe and North America. <h3>Aims</h3> To compare the diagnostic yield of dysplastic lesions in patients with ulcerative colitis undergoing surveillance colonoscopy between chromoendoscopy (CE) and standard white light (WLE). <h3>Design</h3> Meta-analysis of randomised trials or prospective cohort studies. <h3>Methods</h3> We searched electronic databases for full journal articles published after 1990 reporting on chromoendoscopy in patients with IBD compared to standard white light endoscopy. We hand searched the reference lists of all retrieved articles. We carried out random effects meta-analysis, checked for bias using Funnel plots and calculated Cochran9s Q and the I<sup>2</sup> statistic to assess for heterogeneity. <h3>Results</h3> A total of 5 studies involving 1220 patients provided data on a total number of lesions detected by each method. The difference in yield between CE and WLE was 14% (95% CI 8% to 20%) with an NNT of 7.1. A total of five studies involving 1124 patients provided data on the number of targeted lesions detected by each method. The difference in yield of CE over WLE was 13% (7–19%) with an NNT of 7.7. A total of four studies involving 1128 patients provided data on number of flat lesions detected by either method. The difference in yield of CE over WLE was 13% (4–22%) with an NNT of 7.7. There was significant heterogeneity between the studies (I<sup>2</sup>&gt;50%) mainly due to the different populations of UC enrolled in the studies. Sensitivity analysis done by leaving each study out in turn did not affect the significance of the findings. <h3>Conclusion</h3> CE is significantly better than WLE in detecting dysplasia in patients with UC. This holds true for all lesions, number of targeted lesions and number of flat lesions detected. An average of 7–8 patients needs to have CE in order to detect an additional dysplastic lesion.
Case 30-2010
Authors: Hensin Tsao, Kenneth K. Tanabe, Donald P. Lawrence, Adriano Piris
Journal: New England Journal of Medicine (2010)

A 15-year-old boy was seen in the outpatient cancer center because of a skin lesion that had recurred 13 months after excision. The recurrent lesion was excised, and a diagnosis of an atypical melanocytic lesion with features of melanoma was made.
Treatment of Diffuse Proliferative Lupus Nephritis with Prednisone and Combined Prednisone and Cyclophosphamide
Authors: James V. Donadio, Keith E. Holley, Richard H. Ferguson, Duane M. Ilstrup
Journal: New England Journal of Medicine (1978)

To evaluate the effectiveness of cyclophosphamide in the treatment of lupus nephritis, we designed a prospective study of patients with diffuse proliferative lupus nephritis. Twenty-six patients received prednisone (average dose, 40 mg per day) and 24 combined prednisone (average dose, 29 mg per day) and cyclophosphamide (average dose, 107 mg per day) for six months. Thereafter, all patients received maintenance doses of prednisone. Most of the patients improved (84 per cent) after six months of initial treatment with either program. Early progression of disease, ending mainly in end-stage renal disease, was equally frequent in the two treatment groups in patients with already advanced disease. In a four-year follow-up study there was a higher incidence (P approximately 0.04) and average rate (P approximately 0.02) of clinical recurrence of nephritis in the group initially given only steroid than in the group initially given both drugs. However, the proportion of patients alive after four years with stable or improved renal function was similar in the two treatment groups.
Cytotoxicity of bevacizumab is enhanced by β-glucan in tumors expressing membrane-bound VEGF
Authors: C. Salvador, B. Li, R. Hansen, D. Cramer, J. Yan
Journal: Journal of Clinical Oncology (2007)

3060 Background: Bevacizumab (B-Mab) is a murine-derived monoclonal antibody with human IgG1 framework against vascular endothelial growth factor (VEGF). Soluble PGG β -glucan functions with complement activation product iC3b to activate complement receptor 3 (CR3) and recruit neutrophils and macrophages leading to CR3 (iC3b-receptor)-dependent cytotoxicity of tumors coated with iC3b. In mouse xenograft models, PGG β-glucan has a synergistic effect with human anti-tumor antibodies. Consequently, we hypothesized that the IgG1 antibody B-Mab is capable of binding surface VEGF (sVEGF) on tumor cells thereby activating complement, and synergizing with PGG β-glucan to elicit CR3-dependent cytotoxicity. Methods: SCID mouse xenografts with SKOV-3 human ovarian carcinoma cells were established in groups treated intravenously as follows: PBS treated as control (C), PGG β-glucan alone (B), B-Mab alone (A) and combination PGG β-glucan + B-Mab (B+A), twice weekly for 4 weeks. After implantation, tumors were allowed to grow until they were 300 mm 3 before treatment. Results: SKOV-3 tumors in SCID mice showed sVEGF expression and had a complement deposition after B-Mab treatment. In vitro CR3-dependent cytotoxicity assay of B-Mab alone and B-Mab plus active moiety of β-glucan resulted in 0.2% and 19% cytotoxicity respectively. Tumor-bearing SCID mice treated with combination (A+B) showed significant difference in tumor growth inhibition and long-term survival as compared to the other treated groups. Moreover, neutrophil infiltration was markedly increased in the combination (A+B) group compared to the other groups. Conclusions: We have shown that combination treatment with bevacizumab and β -glucan imparts synergistic tumor cytotoxicity that achieves growth inhibition of VEGF-expressing tumor in vivo. Combination therapy should be considered as a potential therapeutic approach in patients with sVEGF positive tumors. (Supported by NIH grant RO1 CA86412 and gift research fund from Biothera, Inc.) No significant financial relationships to disclose.
Two Mechanisms of Erythrocyte Destruction in Penicillin-Induced Hemolytic Anemia
Authors: Robert O. Kerr, Joseph Cardamone, Agustin P. Dalmasso, Manuel E. Kaplan
Journal: New England Journal of Medicine (1972)

Antiglobulin testing revealed IgG, C3, C4 and C5 on the erythrocytes in a case of penicillin-induced, immune hemolytic anemia. When no penicillin was in the patient's serum, the survival times of autologous and of normal erythrocytes, measured concomitantly, were both shortened (half-time of 21 days). Antibody specific for penicillin was eluted from patient erythrocytes. On addition of eluate to a mixture of normal B cells coated with penicillin and O cells in the presence of complement, C3, but not IgG, was bound to the O cells. Addition of eluate and complement to a mixture of O erythrocytes treated with 2-amino-ethylisothiouronium bromide and penicillin-coated B cells resulted in hemolysis of the O cells. Two mechanisms of erythrocyte destruction are possible: the IgG, complement-binding, antipenicillin antibody causes destruction of patient erythrocytes coated in vivo with penicillin; and, in the absence of detectable serum penicillin, normal erythrocytes may be destroyed because they bind activated complement components.
The Radiographic Resolution of<i>Streptococcus pneumoniae</i>Pneumonia
Authors: Stephen J. Jay, Waldemar G. Johanson, Alan K. Pierce
Journal: New England Journal of Medicine (1975)

To determine the characteristics of the radiographic resolution of bacteremic Streptococcus pneumoniae pneumonia we examined serial chest roentgenograms in 72 patients. Consolidation disappeared in all patients by eight to 10 weeks; volume loss (9 per cent), pleural disease (9 per cent), and stranding (19 per cent) often persisted beyond eight weeks. Resolution occurred earlier in patients less than 50 years old (P < 0.05) and in the absence of alcoholism and underlying airways disease regardless of age (P < 0.05). Delayed clearing occurred when these complicating factors were present in patients over 50. Lung cancer was not responsible for delayed resolution of pneumonia. We conclude that an appropriate interval for serial radiographic examinations after therapy for pneumococcal pneumonia is six weeks. (N Engl J Med 293:798–801, 1975)
The Angiotensin-Infusion Test
Authors: Norman M. Kaplan, Jack G. Silah
Journal: New England Journal of Medicine (1964)

THE recently increased awareness of renovascular disease as a cause of hypertension has given rise to a major diagnostic dilemma. Renovascular disease is present in a relatively small but significant proportion of the hypertensive population. It is usually curable by surgery, but if unrecognized, may become irreversible.1 It should therefore be considered in every patient with hypertension, but there is no safe and simple screening procedure applicable to the entire hypertensive population to identify those with functionally important renovascular disease.2 Clinical guides have been proposed to separate those who are most likely to have renovascular disease,3 but recent reports have . . .
Clinical update on the SHELTER study: A phase I/II trial of the HDAC inhibitor resminostat in patients with sorafenib-resistant hepatocellular carcinoma (HCC).
Authors: M. Bitzer, M. Horger, T. Ganten, M. P. Ebert, M. A. Woerns, M. M. Dollinger, A. Mais, B. Hauns, B. Hentsch, U. Lauer
Journal: Journal of Clinical Oncology (2011)

275 Background: Resminostat (4SC-201) is a novel oral pan-HDAC inhibitor in clinical development in a variety of cancer indications. The aim of the SHELTER study is to evaluate safety, tolerability, and efficacy in patients (pts) with HCC exhibiting progressive disease under sorafenib first-line therapy. Methods: Sorafenib-refractory pts with advanced HCC, BCLC B or C are included in a multicenter, open-label, two-arm parallel group trial. Resminostat is administered orally on three dose levels of 200 (DL1), 400 (DL2), and 600 mg (DL3) once daily, in combination with 400 mg sorafenib (arm A) or as mono therapy (600 mg, arm B). For arm A, a precedent dose escalation of resminostat and sorafenib is performed to determine the MTD. Resminostat is administered in a “5+9” dosing schedule, consisting of 5 consecutive treatment days (D1-5) followed by a 9-day rest period resulting in 14 day cycles. In arm A sorafenib is given twice daily throughout the treatment period. Primary objective is to determine progression-free survival rate after 12 weeks (6 cycles). Secondary objectives include safety and tolerability, tumor response, estimation of TTP, OS, assessment of PK, and biomarkers. Results: To date, 14 pts were treated either with 600 mg resminostat alone or on DL1-3 in combination with 400 mg sorafenib. The majority of AE observed so far include gastrointestinal disorders such as nausea and vomiting. Plasma exposure to resminostat increased dose-dependently on D1 (cycle 1) with mean AUC 0-6 h values of 10.5 h*mg/L (600 mg mono) and 9.01 h*mg/L (DL3). No major changes in PK characteristics of resminostat were found with or without co-administration of sorafenib. A considerable portion of patients showed stabilization of their disease (SD): 9 out of 12 pts and 4 out of 5 pts examined after 6 and 12 weeks, respectively, displayed SD. In one patient treated on DL2, SD persisted for 36 weeks along with good long-term tolerability. Conclusions: Preliminary clinical data confirmed the favorable oral drug profile of resminostat either in mono or in combination treatment with sorafenib. Initial data on therapeutic activity to overcome resistance to sorafenib are promising. [Table: see text]
The Effects of Hemorrhage on Body Composition
Authors: Francis D. Moore
Journal: New England Journal of Medicine (1965)

THE aqueous phase of body composition — the total body water and its solutes — includes as its prime component the great working mass of body cells, participating in energy exchange and substrate oxidation for work performance. The body-cell mass is surrounded, infiltrated and bathed by a second watery component, slightly smaller in volume, and concerned with the bulk movement of oxygen, carbon dioxide, metabolites and regulators, via the circulation: the extracellular fluid. Whatever other differences exist between these two reservoirs of body water, none is more clear cut than the fact that within cell water the predominant cation is . . .
Effect of Passive Smoking on Angina Pectoris
Authors: Wilbert S. Aronow
Journal: New England Journal of Medicine (1978)

The effect of passive smoking on exercis-induced angina in a well ventilated and in an unventilated room was evaluated in 10 patients with angina. Patients exposed to 15 cigarettes smoked within two hours in a well ventilated room or an unventilated room increased their resting heart rate, systolic and diastolic blood pressure, and venous carboxyhemoglobin and decreased their heart rate and systolic blood pressure at angina. Patients exposed to passive smoking in an unventilated room had a larger increase in resting heart rate, systolic and diastolic blood pressure, and venous carboxyhemoglobin and a greater reduction in heart rate and systolic blood pressure at angina. The duration of exercise until angina was decreased 22 per cent after passive smoking in a well ventilated room (P less than 0.001), and decreased 38 per cent after passive smoking in an unventilated room (P less than 0.001). Passive smoking aggravates angina pectoris.
Abstract 31: A new research solution for circulating cell free DNA with short amplicons allow accurate detection of 70 COSMIC mutations at 1% detection limit
Authors: Ann Mongan, Richard Chien, Antonio Martinez-Alcantara, Fiona Hyland
Journal: Clinical Cancer Research (2016)

Abstract Non-invasive determination of the resistance or recurrence of tumor development will allow for a safer, more cost effective method for cancer research. As circulating tumor DNA makes up only a small fraction of cell-free DNA (cfDNA) recovered from blood plasma, targeted sequencing offers an ideal tool for mutation detection. Furthermore, as cfDNA is more fragmented than genomic DNA, it presents new technical challenges. In particular, reports in the literature have shown that the majority of cfDNA fragment sizes fall between 120-200 bp, with a median length of 170 bp. Consistent with these reports, we observed an amplicon size dependent improvement in coverage with input samples containing high amounts of fragmented DNA (FFPE or cfDNA). To optimize for cfDNA selection, we have released an Ion AmpliSeq™ designer that offers amplicons of 100-140 bp in size. In this study we conducted a head-to-head comparison between short (100-140 bp) and long (135-175 bp) designs for the same set of targets. These two panels evaluate 1000 COSMIC hotspot mutations from 73 frequently mutated genes. We applied a protocol using magnetic beads to isolate cfDNA from one control (Coriel GM23485) and 3 cfDNA samples. We completed the molecular characterization of the isolated cfDNA using the multiplexing capabilities of Ion AmpliSeq™ library preparation and Ion PGM™ sequencer. Our results showed the short amplicon design led to an improvement of library yield that correlated with the amounts of fragmented DNA contained in the cfDNA samples. The shorter amplicon design also offered improved depth coverage and uniformity for fragmented DNA, while maintaining high performance with genomic DNA. Variant analysis of GM23485 with 70 known mutations at 1% allelic frequency showed &amp;gt;95% positive predictive value with no false negative. In short, the bead-based cfDNA isolation protocol and short amplicon designs offer a simple sample preparation workflow to facilitate rapid mutation detection for cfDNA in cancer research. Citation Format: Ann Mongan, Richard Chien, Antonio Martinez-Alcantara, Fiona Hyland. A new research solution for circulating cell free DNA with short amplicons allow accurate detection of 70 COSMIC mutations at 1% detection limit. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Integrating Clinical Genomics and Cancer Therapy; Jun 13-16, 2015; Salt Lake City, UT. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(1_Suppl):Abstract nr 31.