tbuckley/cabot-search huggingface dataset:
The prognostic value of the cell cycle proteins p27/Kip1 and Ki67/MIB1 immunohistochemical expression in patients with surgically treated localized prostate cancer
Authors: C. D. Petraki, M. M. Vaslamatzis, K. Revelos, A. K. Gregorakis, K. D. Petraki, E. Theophanus, E. Katikos, C. Meristoudis, P. Stassinopoulou, M. Koutsilieris
Journal: Journal of Clinical Oncology (2004)

4686 Background: The assessment of the cyclin-dependent kinase inhibitor p27/Kip1 & the cell proliferation marker Ki67/MIB1 immunohistochemical (IHC) expression (E) as predictive indicators of prostate cancer (PC) biochemical failure (BF) after radical prostatectomy (RP). Methods: Included in the study were 130 consecutive patients - median age 66 (47–76) years & with median preoperative serum PSA 9.23 (2.5–45) ng/ml - who underwent RP for localized PC, between 01/1994 & 12/2001. Follow-up information was available for 94 patients. The median follow-up period was 28 (1–97) months. A cutoff value of 0.2 ng/ml of serum PSA was established as a BF threshold. The IHC method of streptavidin biotin peroxidase was performed on paraffin tissue sections, using antibodies against p27/Kip1 & Ki67/MIB1. Results: A statistically significant inverse correlation was observed between p27/Kip1 IHCE & (i) seminal vesicles invasion (SVI) [P=0.009], (ii) tumor volume [P=0.025] & (iii) preoperative serum PSA [P=0.002]. A statistically significant positive correlation was observed between Ki67/MIB1 IHCE & pelvic lymph nodes metastasis (PLNM) [P=0.006]. No statistically significant correlation was found between the studied markers & Gleason score (GS), periprostatic tissue infiltration (PTI), surgical margins infiltration, the presence of PIN & prostate weight. BF was observed in 35/94 (37%) patients. Kaplan-Meier survival curves showed that low p27/Kip1 & high Ki67/MIB1 IHCE, as well as the synchronous IHCE of low p27/Kip1 & high Ki67/MIB1 were significant predictors of BF (P=0.0005, P=0.0040 & P=0.0011 respectively). GS, PTI, SVI & PLNM were significant predictors for BF as well (P=0.044, P=0.001, P=0.000 & P=0.005 respectively). However, in the multivariate analysis (Cox Regression) SVI, PLNM & MIB1 IHCE were the only independent prognostic factors for BF (P=0.001, P=0.007 & P=0.020 respectively). Conclusions: The cell proliferation index assessed by Ki67/MIB1 IHCE may be a useful marker for BF prediction & decision management in patients with clinically localized PC after RP. No significant financial relationships to disclose.
Diagnosis of Human Lymphoma with Monoclonal Antileukocyte Antibodies
Authors: Roger A. Warnke, Kevin C. Gatter, Brunangelo Falini, Phyllis Hildreth, Rita-Elizabeth Woolston, Karen Pulford, Jacqueline L. Cordell, Brian Cohen, Christiane De Wolf-Peeters, David Y. Mason
Journal: New England Journal of Medicine (1983)

Two monoclonal antibodies have been produced that react with antigens present on human white cells. These reagents differ from other monoclonal antibodies of similar specificity in that the antigens they recognize are resistant to conventional tissue-fixation and embedding procedures. These reagents can therefore be used in immunocytochemical staining of paraffin-embedded tissue sections. We assessed the practical usefulness of this technique in the histopathological diagnosis of human lymphoid neoplasms by staining a wide range of routine surgical biopsy specimens of normal and neoplastic tissue (gathered from five institutions), using an indirect immunoperoxidase technique. In all 40 cases of non-Hodgkin's lymphoma, positive labeling of neoplastic cells was obtained with one or both antibodies. In contrast, no staining of neoplastic cells was observed in 60 samples of nonlymphoid neoplasms. We conclude that many of the difficulties encountered by histopathologists in distinguishing between lymphoid and nonlymphoid neoplasms may be overcome by immunohistologic labeling with monoclonal antibodies such as the ones we have studied.
A Familial Syndrome of Arterial Dissections with Lentiginosis
Authors: Wouter I. Schievink, Virginia V. Michels, Bahram Mokri, David G. Piepgras, Harold O. Perry
Journal: New England Journal of Medicine (1995)

Arterial dissection occurs when blood enters a vessel wall through an intimal tear and a false lumen of blood is formed within the media.1,2 The artery most commonly affected by dissection is the aorta,1 followed by the renal3,4 and extracranial internal carotid2,5 arteries. The pathogenesis of arterial dissection is incompletely understood, but a primary arteriopathy is frequently suspected, especially in younger patients. The possibility of a genetic predisposition to such an arteriopathy is supported by the familial occurrence of arterial dissections6–9 and their association with various heritable connective-tissue disorders.10,11 In our experience with cervical-artery dissections, . . .
Case 32-1990
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Henry L. Dorkin, Eugene J. Mark
Journal: New England Journal of Medicine (1990)

Presentation of CaseA day-old boy was admitted to the hospital because of a mass in the left hemithorax and respiratory distress.The child was born to a gravida-7 mother 24 years of age after a 37-week gestation. The pregnancy was complicated by hypertension of unknown degree and uncertain treatment and by the administration of an unknown agent for a urinary tract infection; the mother denied use of alcohol, other drugs, or tobacco during the pregnancy. Labor was induced at another hospital by oxytocin, with artificial rupture of membranes, followed by vaginal delivery. The Apgar scores were 6 at one . . .
SURG-10TRANSCRANIAL TOCA 511 FOLLOWED BY TOCA FC IN SUBJECTS WITH RECURRENT HIGH GRADE GLIOMA (HGG)
Authors: Manish Aghi, Michael A. Vogelbaum, Tim Cloughesy, George Kaptain, Jana Portnow, Derek Ostertag, Mary Rose Keller, Andreas Niethammer, Alice Chu, Santosh Kesari
Journal: Neuro-Oncology (2015)

Recurrent HGG remains a deadly cancer with survival from 7.2-8.1 months. Viral infection and killing of tumor cells has been demonstrated to stimulate antitumor immune responses pre-clinically. A Phase 1 study using a retroviral replicating vector (RRV), Toca 511, with oral Toca FC (extended-release 5-FC) is nearing completion. In this ongoing study (NCT 01156584) escalating doses of Toca 511 using 2 delivery methods are evaluated for safety and efficacy. Toca FC is administered in monthly cycles starting 4 weeks after injection and doses are escalated. Forty subjects have been treated (38 efficacy evaluable -received Toca 511/Toca FC). Toca 511 to 1.5 x 10^9 TU (3 mL) and Toca FC to 220 mg/kg/day have been safe and well tolerated with no DLTs. Related grade ≥3 adverse events for Toca 511 and Toca FC are infrequent (5.0%, 5.4%) and no subjects have discontinued Toca FC for toxicity. Blood tests show most subjects have no detectable virus - in those that do, clearance of virus occurs. Observed viral RNA signals are below the limit of detection after 2 cycles of Toca FC and viral DNA signal observed 4 weeks after virus injection are below the limit of detection after 3 months in the continuation study. Median survival is 13.8 months (95%CI 7.1, 22.2) using biopsy needle (N = 21); 10.6 months (95%CI 4.3, 13.1) with CED and real-time MRI-guidance (N = 17, p = 0.0276). In multivariate analysis biopsy needle delivery, tumor grade and number of recurrences are significant. Landmark survival is 45% OS12 and 10.5% OS24. Independent radiology review reveals a 3% PR rate (1/35) with clinical benefit rate (PR + SD) of 46%. This study confirms the feasibility and safety of transcranial delivery of RRV without resection. Survival compares favorably to historical data. Additional cohorts will use biopsy needle or intravenous delivery with higher doses of Toca FC.
Effectiveness of footwear and foot orthoses for calcaneal apophysitis: a 12-month factorial randomised trial
Authors: Alicia M James, Cylie M Williams, Terry P Haines
Journal: British Journal of Sports Medicine (2016)

Objective Calcaneal apophysitis, is a relatively common cause of heel pain in children. Very few randomised studies have evaluated treatment options. This trial compared the effectiveness of currently employed treatment options for the relief of pain and disability associated with calcaneal apophysitis. Design Factorial 2×2 randomised comparative effectiveness trial with 1, 2, 6 and 12-month follow-up. Setting Participants were recruited from the caseload of podiatrists at Monash health and Peninsula Health. Participants Children aged 8–14 years with clinically diagnosed calcaneal apophysitis. Interventions Treatment factor 1: two different types of in-shoe orthoses: a heel raise or prefabricated orthoses. Treatment factor 2: footwear replacement or no footwear replacement. Outcomes Our primary outcome was functional disability, the secondary outcomes were pain and ankle dorsiflexion range. Results A total of 133 children and their parents responded to the recruitment advertisement, 124 participated in the trial. At the 1 and 2-month follow-up points, there was a main effect of the shoe insert (heel raise) in only the physical domain for the Oxford ankle foot questionnaire (p=0.04). At the 6 and 12-month follow-up points, there was no main effect or interaction effect for any outcome measure. Conclusion This trial indicates at the 2-month time point there is a relative advantage in the use of heel raises over prefabricated orthoses for the treatment for calcaneal apophysitis. At 12 months there was no relative advantage to any one of the investigated treatment choices over another. Therefore, if a physical impact is experienced for greater than 2 months, the selection of treatment choice may defer to clinical judgement, cost-minimisation and or patient preference. Trial registration number ACTRN12609000696291.
Half a Loaf
Authors: Robert Kreisberg
Journal: New England Journal of Medicine (1994)

A 27-year-old woman had severe hypertension and hirsutism during the last trimester of a normal pregnancy. In the six months after the delivery of her child, she noticed increasing skin pigmentation and continued weight gain, and insulin-requiring diabetes mellitus developed. Her prepregnancy weight was 160 lb (73 kg), and her weight six months after delivery was 240 lb (109 kg). Her previous health had been excellent, and she had no family history of obesity or endocrine disease. She was not a smoker.I see patients with hypertension, hirsutism, and diabetes mellitus associated with weight gain in my practice . . .
MEK and PI3K-AKT inhibitors synergistically block activated IL7 receptor signaling in T-cell acute lymphoblastic leukemia
Authors: K Canté-Barrett, J A P Spijkers-Hagelstein, J G C A M Buijs-Gladdines, J C M Uitdehaag, W K Smits, J van der Zwet, R C Buijsman, G J R Zaman, R Pieters, J P P Meijerink
Journal: Leukemia (2016)

We identified mutations in the IL7Ra gene or in genes encoding the downstream signaling molecules JAK1, JAK3, STAT5B, N-RAS, K-RAS, NF1, AKT and PTEN in 49% of patients with pediatric T-cell acute lymphoblastic leukemia (T-ALL). Strikingly, these mutations (except RAS/NF1) were mutually exclusive, suggesting that they each cause the aberrant activation of a common downstream target. Expressing these mutant signaling molecules-but not their wild-type counterparts-rendered Ba/F3 cells independent of IL3 by activating the RAS-MEK-ERK and PI3K-AKT pathways. Interestingly, cells expressing either IL7Ra or JAK mutants are sensitive to JAK inhibitors, but respond less robustly to inhibitors of the downstream RAS-MEK-ERK and PI3K-AKT-mTOR pathways, indicating that inhibiting only one downstream pathway is not sufficient. Here, we show that inhibiting both the MEK and PI3K-AKT pathways synergistically prevents the proliferation of BaF3 cells expressing mutant IL7Ra, JAK and RAS. Furthermore, combined inhibition of MEK and PI3K/AKT was cytotoxic to samples obtained from 6 out of 11 primary T-ALL patients, including 1 patient who had no mutations in the IL7R signaling pathway. Taken together, these results suggest that the potent cytotoxic effects of inhibiting both MEK and PI3K/AKT should be investigated further as a therapeutic option using leukemia xenograft models.
The Prevalence of Psychiatric Illness in a Medical Out-Patient Clinic
Authors: Bertram H. Roberts, Nea M. Norton
Journal: New England Journal of Medicine (1952)

THE actual prevalence of psychiatric illness in the general population has never been accurately determined. This is a pressing problem that must be faced by the psychiatrist and the public-health official. Of more pertinent importance to the medical practitioner is the prevalence of psychiatric symptoms among the patients seeking help in the physician's office or the out-patient department of the general hospital. Previous studies of the prevalence of mental disease in general hospitals have not dealt with the medical out-patient department.1 2 3 This department has a special importance in that it is here that the patient's total medical state is surveyed, . . .
Fatal Renal Insufficiency after Oral Cholecystography
Authors: Arlan Gottlieb, Harry Spiera, Enoch Gordis
Journal: New England Journal of Medicine (1962)

SINCE 1924, when Graham and Cole1 introduced tetrabromophenolphthalein for oral cholecystography, many safe and more effective compounds have been developed. Until the recent use of tri-iodinated aromatic compounds attempts at cholecystography in the jaundiced patient usually, but not invariably, failed.2 In the patient with delayed excretion due to liver or gallbladder disease the increased load of a potentially nephrotoxic compound presented to the kidney poses a serious clinical problem. In the case of impaired hepatic function reported below, acute renal failure followed the oral administration of a large dose of cholecystographic agent.Case ReportA 44-year-old female nightclub entertainer was . . .
A Controlled Trial of Two Nucleoside Analogues plus Indinavir in Persons with Human Immunodeficiency Virus Infection and CD4 Cell Counts of 200 per Cubic Millimeter or Less
Authors: Scott M. Hammer, Kathleen E. Squires, Michael D. Hughes, Janet M. Grimes, Lisa M. Demeter, Judith S. Currier, Joseph J. Eron, Judith E. Feinberg, Henry H. Balfour, Lawrence R. Deyton, Jeffrey A. Chodakewitz, Margaret A. Fischl, John P. Phair, Louise Pedneault, Bach-Yen Nguyen, Jon C. Cook
Journal: New England Journal of Medicine (1997)

The efficacy and safety of adding a protease inhibitor to two nucleoside analogues to treat human immunodeficiency virus type 1 (HIV-1) infection are not clear. We compared treatment with the protease inhibitor indinavir in addition to zidovudine and lamivudine with treatment with the two nucleosides alone in HIV-infected adults previously treated with zidovudine.
An Unusual Variant of Acute Idiopathic Polyneuritis (Syndrome of Ophthalmoplegia, Ataxia and Areflexia)
Authors: Miller Fisher
Journal: New England Journal of Medicine (1956)

THE purpose of this communication is to report 3 cases of an acute neurologic illness characterized among other features by total external ophthalmoplegia, severe ataxia and loss of the tendon reflexes. The clinical picture in all 3 cases was so similar as to constitute an easily recognizable syndrome. The presenting symptoms and signs were most alarming for the attending physician on each occasion — unnecessarily so, since the course of the illness appears to be benign. The cause of the syndrome was obscure until, in the most recent case, a great rise in the protein of the cerebrospinal fluid in . . .
Phase I study of daily administration of MGCD265 to patients with advanced malignancies (Study 265–101)
Authors: C. K. Kollmannsberger, H. Hurwitz, G. Vlahovic, C. Maroun, J. Dumouchel, G. Reid, R. Martell, G. Shapiro
Journal: Journal of Clinical Oncology (2009)

e14525 Background: MGCD265 is a novel multitargeted receptor tyrosine kinase (RTK) inhibitor that targets the mesenchymal epithelial transition (c-Met) and the vascular endothelial growth factor (VEGF) receptors (VEGFR1, VEGFR2, and VEGFR3). Additional RTK targets include Tie-2, and Ron. Those kinases are known to be involved in tumor development and angiogenesis. The objective of this Phase I study is to evaluate the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of daily administration of MGCD265 in patients with solid tumors. Methods: This is a multicenter, open-label, dose escalation study of oral MGCD265 administered as a continuous 21-day cycle. Cohorts of 3–4 patients were enrolled per dose level, initially with dose doubling between cohorts, followed by smaller increments once grade 2 drug-related toxicity is observed. Dose limiting toxicity (DLT) was defined as: grade 4 neutropenia; grade 4 thrombocytopenia; any &gt; grade 3 nonhematologic toxicity; severe/sustained hypertension; or any toxic effect leading to a patient missing &gt; 4 doses of MGCD265. Treatment would continue until disease progression or toxicity. Results: Ten patients with advanced solid tumors have been treated. Characteristics: age range 25–75; gender: 8 M/2F; ECOG: 0 (1 patient); 1 (9 patients). At dose levels of 24, 48 and 96 mg/m 2 , no DLTs nor grade 2 or greater drug-related AEs during cycle 1 have been reported. Eight patients received treatment for 2 cycles or more. Preliminary PK profile after the first dose of administration shows a dose dependent increase in AUC and C max with an approximate mean half-life of 23 hours (see Table below). At the 96 mg/m2 dose, exposure was in the range of the lower end of the efficacious exposure in certain xenograft models. PD markers including plasma HGF and VEGF and shed/soluble receptors s-Met and s-VEGFR2 have been evaluated. Conclusions: Daily oral administration of MGCD265 was found to be well tolerated at doses of 24, 48, and 96 mg/m 2 . Further dose escalation is underway. [Table: see text] [Table: see text]
Acid-Base Response to Chronic Hypercapnia in Man
Authors: Newton C. Brackett, Charles F. Wingo, Orhan Muren, Jose T. Solano
Journal: New England Journal of Medicine (1969)

To define "steady-state" chronic hypercapnia in man, we studied 20 patients with stable carbon dioxide tensions from 34 to 103 mm of mercury and with no apparent complicating disorders. The whole-body titration curve in chronic uncomplicated hypercapnia is characterized by a linear increase in estimated hydrogen ion activity as carbon dioxide tension increases. Over a range of carbon dioxide tensions from 34 to 103 mm of mercury the arterial-blood hydrogen ion activity increased by 0.24 nM per liter per millimeter of mercury increase in carbon dioxide tension. Thus, the whole-body defense of arterial-blood pH appears equally effective over the range of carbon dioxide tensions observed in this study. The physiologic response to chronic hypercapnia in man is defined by a zone that is approximately 11 nM per liter (0.10 pH unit) wide for hydrogen ion and 10 mEq wide for bicarbonate. These significance bands may be used to separate mixed acid-base disorders in patients with chronic hypercapnia.
Thy-1 Antigen on Normal and Neoplastic Rat Mammary Tissues: Changes in Location and Amount of Antigen During Differentiation of Cultured Stem Cells&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: P S Rudland, M J Warburton, P Monaghan, M A Ritter
Journal: JNCI Journal of the National Cancer Institute (1982)

With the use of immunofluorescent and immunocytochemical techniques on histologic sections of mammary glands from inbred WF rats, the thymocyte differentiation antigen (Thy-1) was identified partially on and immediately adjacent to the myoepithelial cells of ducts and alveoli. This antigen was absent from epithelial cells lining such structures. Some fibroblastic cells external to these structures also bore Thy-1. During glandular development the intensity of fluorescence due to the binding of Thy-1 antibodies increased as the myoepithelial cells matured. Similarly, mammary adenocarcinomas induced by 7,12-dimethylbenz[a]anthracene (DMBA) and N-methyl-N-nitrosourea contained elongated, presumptive myoepithelial cells that demonstrated varying degrees of Thy-1 immunofluorescence. This phenomenon was qualitatively mimicked by cultured cell lines from normal and DMBA-induced tumors. Elongated myoepithelial-like and fibroblast-like cells possessed Thy-1, whereas the cuboidal epithelial cell lines failed to express this antigen on the cell surface. Measurement of the relative number of Thy-1 molecules per cell by antiserum absorption techniques suggested that a neoplastic stem cell line, rat mammary (Rama) 25, contained about 3 X 10(5) Thy-1 molecules per cell in a form not directly accessible at the cell surface to anti-Thy-1 antibodies; the number of cryptic Thy-1 molecules was reduced when this cell line differentiated to alveolar-like cells in culture. However, when this cell line differentiated to myoepithelial-like cells, approximately 5 X 10(6) molecules per cell were exposed to anti-Thy-1 antibodies with a concomitant reduction of the cryptic pool. Morphologic maturation of elongated, myoepithelial-like cell line variants was also accompanied by increased surface Thy-1 fluorescence. Thus some of the myoepithelial cells in normal glands and tumors may arise by differentiation of epithelial stem cells and a spectrum of maturation states of the myoepithelial cell may exist as monitored by cellular morphology and surface Thy-1 expression.
GENO-19INTEGRATED GENOMIC ANALYSIS OF OLIGODENDROGLIAL TUMORS IDENTIFIES DISTINCT MOLECULAR SUBGROUPS WITHIN 1p/19q CO-DELETED OLIGODENDROGLIOMAS
Authors: Aurelie Kamoun, François Ducray, Caroline Dehais, Ahmed Idbaih, Nabila Elarouci, Eric Letouze, Dominique Figarella-Branger, Aurelien de Reyniès, Jean-Yves Delattre
Journal: Neuro-Oncology (2015)

BACKGROUND: Oligodendroglial tumors are a group of heterogeneous gliomas in terms of clinical, radiological, histological and molecular profiles. Current molecular classification of oligodendroglial tumors identifies 3 groups with distinct clinical outcomes based on two genetic events only: IDH mutation and 1p/19q co-deletion. Integrating data from additional molecular level contributes to refine further this classification and adapt clinical practice accordingly. METHODS: 156 tumors with an oligodendroglial component (Grade II(46), III(100), IV(10)) as well as 22 supportive samples (11 glioblastomas, 2 diffuse astrocytomas, 9 normal brain samples) were profiled transcriptionally (mRNA expression arrays and microRNA sequencing), genomically (SNP arrays) and epigenetically (DNA methylation arrays). Unsupervised consensus classification was performed for each omics separately and by integrating the different omics. RESULTS: A strong correlation was observed between the classification systems obtained from the different omics and 5 subgroups of tumors were robustly identified. The validity of these 5 classes was confirmed on public TCGA data from low grade gliomas (TCGA-LGG). Beyond the 3 well-known molecular classes (1p/19q co-deletion and IDH mutation, IDH mutation only, no IDH mutation and no 1p/19q co-deletion), our multi-omics classification reveals 3 additional subgroups within the group of 1p/19q co-deleted tumors. These 3 subgroups are associated with distinct genomic alterations, distinct expression patterns of cell differentiation markers (from oligodendroglial precursor cells, oligodendrocytes, or neuronal cells), and distinct expression of oncogenic pathways and immune signatures. Follow-up duration of our cohort was not long enough to highlight reliable associations with prognosis but the analysis of TCGA-LGG based on our new 3 subgroups shows a significant association with distinct survival outcomes independently from histologic grade. CONCLUSION: This work represents the first integrative multi-omics analysis of oligodendroglial tumors and enables the refining of their molecular classification. The new classification identifies for the first time distinct molecular subgroups within 1p/19q co-deleted oligodendroglial tumors.