tbuckley/cabot-search huggingface dataset:
Complete Correction of the Wiskott-Aldrich Syndrome by Allogeneic Bone-Marrow Transplantation
Authors: Robertson Parkman, Joel Rappeport, Raif Geha, James Belli, Robert Cassady, Raphael Levey, David G. Nathan, Fred S. Rosen
Journal: New England Journal of Medicine (1978)

Two patients with the Wiskott-Aldrich syndrome had complete donor lymphoid and hematopoietic engraftment after successful allogeneic bone-marrow transplantation. One patient had had only a temporary donor T-lymphocyte graft after a previous transplantation, for which he had been prepared with cytarabine and cyclophosphamide; the patient's own T lymphocytes returned six months later. A repeat transplant, for which the patient was prepared with anti-human thymocyte serum, total-body irradiation and procarbazine, resulted in complete donor engraftment. The second patient underwent a successful transplantation after similar preparation, except that procarbazine was omitted. At 11 and five months after transplantation both had normal hematopoiesis and no evidence of graft-versus-host disease. This treatment of the Wiskott-Aldrich syndrome may be a model for the correction of other genetically determined immune and hematologic bone-marrow disorders.
Cerebral Thrombosis in Young Adults
Authors: Louis Berlin, Bernard Tumarkin, Herbert L. Martin
Journal: New England Journal of Medicine (1955)

THAT premature vascular degeneration leads to coronary occlusion in young adults is recognized. However, there is a great reluctance to accept a similar etiology for the apoplectic development of focal cerebral signs in young adults. The sudden development of such focal signs as hemiplegia and aphasia in a young patient warrants procedures for detection of a tumor, vascular anomaly, a source of emboli, infectious causes of endarteritis, hematologic disorders or other systemic diseases capable of producing vascular lesions. This investigation is often fruitless. Although there should be a search for all possible etiologic factors that give rise to apoplectic phenomena, . . .
Factors Predisposing to Bacteriuria during Indwelling Urethral Catheterization
Authors: Richard A. Garibaldi, John P. Burke, Marion L. Dickman, Charles B. Smith
Journal: New England Journal of Medicine (1974)

Of 405 hospitalized patients with temporary closed sterile urinary-catheter drainage, 95 (23 per cent) acquired bacteriuria. The risk was significantly greater for patients who were female, elderly or critically ill (p<0.005 for each with appropriate comparison group). The patients who received systemic antimicrobial agents acquired bacteriuria less frequently than the patients who did not (16 versus 32 per cent —p<0.001). However, the apparent protective effect of antimicrobials occurred only during the first four days in which catheterization was in progress. Breaks in the closed drainage system or improper care of the drainage bag occurred frequently (121 of 405 systems studied) and predisposed to bacteriuria. Bacterial contamination of the drainage bag preceded onset of bacteriuria in 18 per cent of cases. Strict adherence to aseptic care of closed sterile drainage systems can be expected to reduce rates of hospital-acquired, catheter-associated bacteriuria. (N Engl J Med 291:215–219, 1974)
Distinguishing Homozygous and Heterozygous Cystic Fibrosis Fibroblasts from Normal Cells by Differences in Sodium Transport
Authors: Jan L. Breslow, Joseph McPherson, J. Epstein
Journal: New England Journal of Medicine (1981)

We have found that cultured fibroblasts from patients with cystic fibrosis (CF) accumulate less 22Na in the presence of ouabain than do normal cells. After equilibration with 22Na in ouabain-exposed cells to that in unexposed cells, after five hours of incubation, was 2.34 +/- 0.14 (mean +/- S.D.) in 13 fibroblast strains from normal subjects and 1.33 +/- 0.08 in eight strains from patients with CF. Cells from eight different obligate CF heterozygotes (parents of children with CF) had a ratio of 1.38 +/- 0.07; those from three unaffected siblings (who have a two-thirds chance of carrying the disease) had a ratio of 1.27 +/- 0.04. The differences between CF homozygotes or heterozygotes and normal subjects were highly significant (P < 0.001), but there was considerable overlap between CF homozygotes and heterozygotes. This abnormality of sodium transport provides an unequivocal in vitro test that distinguishes normal cells from cells derived from CF homozygotes or heterozygotes. It should be useful for the identification of carriers of the CF gene.
Staphylococcal Scalded Skin Syndrome
Authors: L A Schenfeld
Journal: New England Journal of Medicine (2000)

Figure 1 A six-year-old boy was hospitalized with a rash and fever. He had been well until two days before admission, when general pruritus developed. That evening, small water blisters developed at the base of his nose and face. During the next two days, the lesions spread despite treatment with cephalexin, which had been initiated one day before admission. The child's temperature was 38.3°C on admission. He appeared extremely uncomfortable but not acutely ill. He had numerous flaccid bullae on his face, neck, axilla, perianal region, upper back, and thighs. Nikolsky's sign was present (ready separation of the outer layer of epidermis from the basal layer), and a biopsy of a skin specimen revealed that the level of cleavage was at the granular layer. The boy was treated with intravenous nafcillin, and his condition improved over the next few days. He was discharged after seven days, with almost complete resolution of his rash. Figure 1 A six-year-old boy was hospitalized with a rash and fever. He had been well until two days before admission, when general pruritus developed. That evening, small water blisters developed at the base of his nose and face. During the next two days, the lesions spread despite treatment with cephalexin, which had been initiated one day before admission. The child's temperature was 38.3°C on admission. He appeared extremely uncomfortable but not acutely ill. He had numerous flaccid bullae on his face, neck, axilla, perianal region, upper back, and thighs. Nikolsky's sign was present (ready separation of the outer layer of epidermis from the basal layer), and a biopsy of a skin specimen revealed that the level of cleavage was at the granular layer. The boy was treated with intravenous nafcillin, and his condition improved over the next few days. He was discharged after seven days, with almost complete resolution of his rash. Louis A. Schenfeld, M.D.Conemaugh Memorial Medical Center, Johnstown, PA 15905
ATCT-18PHASE II STUDY OF MIPSAGARGIN (G-202), A PSMA-ACTIVATED PRODRUG TARGETING THE TUMOR ENDOTHELIUM, IN ADULT PATIENTS WITH RECURRENT OR PROGRESSIVE GLIOBLASTOMA
Authors: David Piccioni, Tiffany Juarez, Bradley Brown, Lara Rose, Victoria Allgood, Santosh Kesari
Journal: Neuro-Oncology (2015)

BACKGROUND: To overcome the challenges of blood-brain barrier penetration with toxic agents in patients with glioblastoma (GBM), we are investigating a soluble, cell cycle-independent prodrug targeted to the tumor vasculature. Mipsagargin is an analog of thapsigargin coupled with a PSMA-directed masking/targeting peptide that inhibits its biologic activity until proteolytic cleavage at the tumor site. PSMA is expressed selectively on some tumor types and on tumor vasculature, including tumor endothelium from human glioblastoma tissues. A Phase I study in patients with advanced solid malignancies suggests mipsagargin may induce disease stabilization in some patient populations. The primary objective of this Phase II study is evaluation of 6-month progression-free survival in patients with advanced GBM. Secondary outcomes include safety, efficacy, effects of mipsagargin on blood flow metrics, pharmacokinetics of mipsagargin in CSF and blood, and molecular response correlates. METHODS: This institutional, open label, phase II trial is ongoing in adult patients with recurrent/progressive GBM following 1-4 prior therapies (accrual goal 34 efficacy-evaluable). Mipsagargin is administered intravenously on Days 1, 2 and 3 of a 28-day treatment cycle; two dosing regimens have been evaluated: 40 mg/m2 on Days 1, 2 and 3 and 40 mg/m2 on Day 1 and 66.8 mg/m2 on Days 2 and 3. Based on tolerability in this patient population, the lower dosing regimen was selected for further evaluation. RESULTS: To date, 13 patients have been enrolled, with nine patients evaluable for efficacy. Two patients (22%) have experienced disease stabilization. Adverse events, mostly Grade 1 or 2, attributed to mipsagargin administration include reversible creatinine elevation, fatigue, rash, nausea/vomiting, headache, infusion-related reaction, upper abdominal pain, GERD, fever, itching, and intermittent body aches. CONCLUSIONS: Preliminary results suggest mipsagargin is well-tolerated and may induce disease stabilization in patients with advanced/recurrent GBM. The study remains open to enrollment and results will be updated.
ATNT-17EVALUATION OF THE SAFETY AND BENEFIT OF PHASE I ONCOLOGY TRIALS FOR PATIENTS WITH PRIMARY CENTRAL NERVOUS SYSTEM TUMORS
Authors: Lakshmi Nayak, Mrinal Gounder, Solmaz Sahebjam, Alona Muzikansky, Armando Sanchez, Serena Desideri, Xiaobu Ye, Percy Ivy, L. Burt Nabors, Michael Prados, Stuart Grossman, Lisa DeAngelis, Patrick Wen
Journal: Neuro-Oncology (2015)
Physiologic Observations in Human Cross Circulation
Authors: J. W. Eschbach, R.B. Epstein, J. M. Burnell, E. D. Thomas
Journal: New England Journal of Medicine (1965)

THE application of cross circulation to the treatment of patients with organ failure has previously been described.1 , 2 The technic is relatively simple and easily regulated.3 By this means patients with hepatic, renal or bone-marrow failure were treated for periods of two to fifty hours.2 This report describes observations made during four and a half months of daily cross circulation between a patient with leukemia and bone-marrow failure and a patient with renal failure. This symbiotic relation allowed each patient to derive benefit from and to provide support for the partner.Case SummariesJ.H., a 15-year-old girl, had acute myeloblastic leukemia, . . .
A Preliminary Study of Growth Hormone in the Treatment of Dilated Cardiomyopathy
Authors: Serafino Fazio, Domenico Sabatini, Brunella Capaldo, Carlo Vigorito, Arturo Giordano, Raffaele Guida, Francesco Pardo, Bernadette Biondi, Luigi Saccà
Journal: New England Journal of Medicine (1996)

Cardiac hypertrophy is a physiologic response that allows the heart to adapt to an excess hemodynamic load. We hypothesized that inducing cardiac hypertrophy with recombinant human growth hormone might be an effective approach to the treatment of idiopathic dilated cardiomyopathy, a condition in which compensatory cardiac hypertrophy is believed to be deficient.
A low‐cost, user‐friendly electroencephalographic recording system for the assessment of hepatic encephalopathy
Authors: Sami Schiff, Mariella Casa, Valeria Di Caro, Daniele Aprile, Giuseppe Spinelli, Michele De Rui, Paolo Angeli, Piero Amodio, Sara Montagnese
Journal: Hepatology (2016)

Electroencephalography (EEG) is useful to objectively diagnose/grade hepatic encephalopathy (HE) across its spectrum of severity. However, it requires expensive equipment, and hepatogastroenterologists are generally unfamiliar with its acquisition/interpretation. Recent technological advances have led to the development of low‐cost, user‐friendly EEG systems, allowing EEG acquisition also in settings with limited neurophysiological experience. The aim of this study was to assess the relationship between EEG parameters obtained from a standard‐EEG system and from a commercial, low‐cost wireless headset (light‐EEG) in patients with cirrhosis and varying degrees of HE. Seventy‐two patients (58 males, 61 ± 9 years) underwent clinical evaluation, the Psychometric Hepatic Encephalopathy Score (PHES), and EEG recording with both systems. Automated EEG parameters were calculated on two derivations. Strong correlations were observed between automated parameters obtained from the two EEG systems. Bland and Altman analysis indicated that the two systems provided comparable automated parameters, and agreement between classifications (normal versus abnormal EEG) based on standard‐EEG and light‐EEG was good (0.6 &lt; κ &lt; 0.8). Automated parameters such as the mean dominant frequency obtained from the light‐EEG correlated significantly with the Model for End‐Stage Liver Disease score ( r = −0.39, P &lt; 0.05), fasting venous ammonia levels ( r = −0.41, P &lt; 0.01), and PHES ( r = −0.49, P &lt; 0.001). Finally, significant differences in light‐EEG parameters were observed in patients with varying degrees of HE. Conclusion: Reliable EEG parameters for HE diagnosing/grading can be obtained from a cheap, commercial, wireless headset; this may lead to more widespread use of this patient‐independent tool both in routine liver practice and in the research setting. (H epatology 2016;63:1651‐1659)
Intraventricular Rupture of a Cerebral Abscess
Authors: D M McKalip, S K Gudeman
Journal: New England Journal of Medicine (1996)

Figure 1. Cerebral imaging studies were performed in a 53-year-old man with a one-week history of headache, ataxia, and disorientation that culminated in right hemiparesis and coma. He had a remote history of dental abscesses. Magnetic resonance imaging with gadolinium enhancement (Panel A) shows a left frontal lesion (arrow) in communication with the left lateral ventricle. Purulent material containing Streptococcus anginosus was obtained by ventriculostomy, and both intrathecal and intravenous antibiotics were given. A contrast-enhanced computed tomographic scan obtained after four weeks of treatment (Panel B) shows loculation of the left lateral ventricle (arrowheads) and transependymal edema (arrows). The patient . . .
Neovascularization: Upregulating Hif-1α by Hydrogel Nanofibrous Scaffolds for Rapidly Recruiting Angiogenesis Relative Cells in Diabetic Wound (Adv. Healthcare Mater. 8/2016)
Authors: Hao Chen, Peng Jia, Hui Kang, Hongbo Zhang, Yi Liu, Peilang Yang, Yufei Yan, Guilai Zuo, Lei Guo, Min Jiang, Jin Qi, Yuanyuan Liu, Wenguo Cui, Hélder A. Santos, Lianfu Deng
Journal: Advanced Healthcare Materials (2016)

On page 907 Y. Liu, W. Cui, H. A. Santos, L. Deng and co-workers describe a novel water soluble desferrioxamine-loaded hydrogel nanofibrous scaffold designed to rapidly recruit angiogenesis relative cells. The scaffold promotes the healing process of diabetic wounds through up-regulating Hif-1α and its downstream genes. Furthermore, the degradation rate of the scaffold is effectively corresponding with the closing rate of the wound, leaving enough space for new epidermis formation.
OC-060 Analysis of unexpected non-colorectal lesional histopathology in 1252 resections for suspected crlm: Abstract OC-060 Table 1
Authors: D O’Reilly, J Hodson, R Marudanayagam, R Sutcliffe, P Muiesan, D Mirza, J Isaac, K Roberts
Journal: Gut (2015)

<h3>Introduction</h3> Resection is a safe and effective treatment for colorectal liver metastases (CRLM). Surgery is indicated by imaging findings with a history of synchronous or metachronous colorectal cancer. This study examined cases where patients were found to have non-colorectal lesions after resection for CRLM. <h3>Method</h3> Liver resections were identified from a prospective database. Additional data were retrieved from electronic records. Resections were divided into those where histology demonstrated CLRM or complete pathological response to chemotherapy (A) and those where an alternative pathology was detected (B). Univariate analyses with Mann-Whitney, Fisher’s exact and Kendall’s tau tests were performed. <h3>Results</h3> There were 1252 resections (2002–2012). Group A 1213 (96.9%), Group B 39 (3.1%). The groups did not differ in age, sex or synchronous/metachronous disease. Group B patients had significantly fewer tumours (p = 0.006), with significantly smaller maximum sizes (p &lt; 0.001). Group B patients also had significantly lower T (p = 0.031), N (p &lt; 0.001) and Dukes’ (p &lt; 0.001) stages. In addition to this, the CEA level was also significantly lower in group B patients (median A = 8.1, B = 1.8, p &lt; 0.001). Group B histopathology is shown in the Table 1. 25/31 in group B had preoperative MRI (data unavailable in 8). 32 resections were undertaken where the primary is known to have been T0N0 (Dukes’ A). Of these 5 (16%) were in group B; two of these had malignant pathology (HCC and cholangiocarcinoma). <h3>Conclusion</h3> Unexpected non-colorectal lesional pathology findings after resection for CRLM are rare, of the same order of frequency as mortality. In a small proportion of the cases there was some equivocation in the reports of preoperative imaging. However, all proceed on the basis they were CRLM. Haemangiomata, which were often hyalinised, were the most common finding. 9/39 had alternative malignant pathology. Current practice is to avoid lesional biopsy before liver resection because of the risk of tumour seeding. The present data support this. <h3>Disclosure of interest</h3> None Declared.
Palbociclib treatment of FLT3-ITD+ AML cells uncovers a kinase-dependent transcriptional regulation of FLT3 and PIM1 by CDK6
Authors: Iris Z. Uras, Gina J. Walter, Ruth Scheicher, Florian Bellutti, Michaela Prchal-Murphy, Anca S. Tigan, Peter Valent, Florian H. Heidel, Stefan Kubicek, Claudia Scholl, Stefan Fröhling, Veronika Sexl
Journal: Blood (2016)
Precision Medicine for Charcot-Marie-Tooth Disease
Authors: David Pleasure
Journal: JAMA Neurology (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
Synergistic inhibition of breast cancer cell lines with the combination of a dual inhibitor of EGFR/HER-2/neu and a Bcl-2 inhibitor
Authors: L. Witters, A. Witkoski, M. Planas-Silva, J. Viallet, M. S. Berger, A. Lipton
Journal: Journal of Clinical Oncology (2006)

13100 Background: The epidermal growth factor receptor (EGFR; ErbB1) and HER-2/neu (ErbB2), members of the ErbB family of receptor tyrosine kinases, are overexpressed in a variety of human tumors and overexpression generally correlates with poor prognosis and decreased survival. Use of inhibitors of these receptors as monotherapies, e.g., trastuzumab, Iressa, and erlotinib, has led to advances in treatment, but many patients do not respond or develop resistance. The anti-apoptotic protein, Bcl-2, is also overexpressed in a number of human tumors. Inhibitors of Bcl-2 induce apoptosis and sensitize cancer cells to other therapies. This study assesses the effects of a combination of a reversible inhibitor of both EGFR and HER-2/neu that is similar to lapatinib (GW2974) and a pan inhibitor of the Bcl-2 family (GX15–070: Gemin X Biotechnologies, Inc.) on the growth of human breast cancer cells. Methods: The MCF-7 human breast cancer cell line transfected with a control vector, MCF/neo, and the HER-2/neu transfected MCF-7 cell line, MCF/18, were treated with various concentrations of GW2974 (0.25–10 μM) and/or the GX15–070 pan Bcl-2 inhibitor (50–500 nM). After a 3 day exposure, cell number was determined using the colorimetric MTT tetrazolium dye assay. Percent of control was normalized to corresponding concentrations of the solvent for both agents (DMSO). Results: Treatment with the GW2974 dual inhibitor or the GX15–070 pan Bcl-2 inhibitor resulted in dose-dependent growth inhibition in both the control and HER-2/neu transfected MCF-7 cell lines. The combination of both agents produced synergistic growth inhibition in both cell lines as confirmed by isobologram analysis. Conclusions: This study has demonstrated synergy with the combination of a dual inhibitor of EGFR and HER-2/neu and an inhibitor of Bcl-2 in control and HER-2/neu overexpressing MCF-7 human breast cancer cells. This finding warrants an evaluation of this combination in clinical trials for the treatment of patients with metastatic breast cancer. [Table: see text]
Abstract LB-241: HGF promotes resistance to MET inhibitor AMG337 in MET-amplified gastric cancer cells
Authors: Marcia Gordon, Alexandra Croft, Chi-Ming Li, Sean Taylor, Sean R. Caenepeel, Kim Quon
Journal: Cancer Research (2015)

Abstract The MET oncoprotein is a tyrosine kinase that is the only known receptor for its ligand, HGF (Hepatocyte Growth Factor). In approximately 5% of gastric cancers, MET is activated by focal amplification, rendering it constitutively active and ligand independent. MET-amplified cancer cell lines and xenografts are typically dependent on MET signaling for proliferation or survival. To test this dependency in patients, a number of small molecule MET inhibitors, including AMG337, are currently undergoing clinical evaluation for the treatment of MET-amplified tumors.Here we characterize resistance mechanisms to MET inhibitor AMG337 in vitro. We show that under standard culture conditions, resistance does not readily arise in MET-amplified gastric cell lines SNU620 and MKN45 treated with a therapeutic dose (&amp;gt;IC90) of AMG337. Surprisingly however, exogenous recombinant human HGF enables resistance to readily appear, with emergent cultures possessing resistance mutations in the MET activation loop at positions D1228 and Y1230. Phosphoprotein analysis shows that HGF increases autophosphorylation and activation of mutant MET sufficiently to drive cell proliferation even in the presence of AMG337.Notably, deep sequencing and clonal analysis of individually barcoded cells show that pre-existing mutant clones are likely present in cultures prior to drug treatment. However, such clones are unable to robustly proliferate in drug-containing media unless HGF is present. Based on copy number analysis, we propose that a single or small number of pre-existing mutant MET alleles in an individual cell is sufficient to drive resistance in the presence of exogenous HGF. In contrast, in HGF-negative media, a single mutant MET allele is insufficient and thus resistance does not readily arise unless gradual drug dose escalation protocols that select for increased mutant MET copy number are employed.Our results identify a key mechanism by which HGF can promote resistance to MET inhibitors in MET-amplified cancer cell lines. Because HGF is present in tumor microenvironments, combining anti-HGF antibodies with maximally-tolerated doses of small molecule MET inhibitors such as AMG337 may be beneficial in preventing resistance and in promoting durable responses. Citation Format: Marcia Gordon, Alexandra Croft, Chi-Ming Li, Sean Taylor, Sean R. Caenepeel, Kim Quon. HGF promotes resistance to MET inhibitor AMG337 in MET-amplified gastric cancer cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-241. doi:10.1158/1538-7445.AM2015-LB-241