tbuckley/cabot-search huggingface dataset:
Case 39-2011
Authors: Nagagopal Venna, R. Gilberto Gonzalez, Lawrence R. Zukerberg
Journal: New England Journal of Medicine (2011)

A woman in her 90s came to the ER because of acute unilateral ptosis. During the next 8 weeks, weakness of the neck, fatigue, choking, and difficulty breathing developed, progressing to respiratory failure and death. An autopsy was performed.
Expression of CD44 Splice Variants in Human Transitional Cell Carcinoma
Authors: Shingo Takada, Mikio Namiki, Kiyomi Matsumiya, Namcheol Park, Nobuyuki Kondoh, Kinya Uchida, Masaya Kitamura, Shiro Takahara, Tsuneharu Miki, Akihiko Okuyama
Journal: European Urology (1996)
Correlation of Expression of H/Le<sup>Y</sup>/Le<sup>B</sup>Antigens with Survival in Patients with Carcinoma of the Lung
Authors: Masayuki Miyake, Toshihiko Taki, Shigeki Hitomi, Sen-itiroh Hakomori
Journal: New England Journal of Medicine (1992)

The level of expression of H/Ley/Leb antigens is high in various histologic types of lung cancer, a feature that may be related to deletion of A and B blood-group antigens. We evaluated the possibility that expression of this antigen, which can be defined by the monoclonal antibody MIA-15–5, might be of prognostic value, as suggested by our previous observation that MIA-15–5 inhibits tumor-cell motility and metastasis.
Phase II trial of intracerebral administration of CpG oligonucleotide for patients with recurrent glioblastoma
Authors: R. Ursu, A. Carpentier, P. Metellus, M. Barrie, Y. Meng, F. Laigle-Donadey, A. Tibi, O. Chinot, A. F. Carpentier
Journal: Journal of Clinical Oncology (2009)

2043 Background: CpG-ODN are immunostimulating oligodeoxynucleotides containing CpG motifs. When injected locally, they can induce tumor rejection in animal models. In a phase I clinical trial, intra-tumoral infusions of CpG-ODN in glioblastoma patients were well tolerated at doses up to 20 mg. This multicenter phase II trial was designed to study the efficacy and tolerance of a local treatment by CpG-ODN in patients with recurrent glioblastoma. Methods: Patients with recurrent GBM occurring at least three months after radiotherapy and previously treated with one at least regimen of chemotherapy received 20mg CpG- ODN (CpG-28) by convection-enhanced delivery. The percentage of patients without tumour progression at 6 months after inclusion was the primary endpoint. Secondary endpoints were tolerance, survival, and radiological response. Results: Thirty-four patients were enrolled in two centers and thirty-one patients received the treatment. The 6-months progression free survival (PFS) was 19%. One partial response and 3 minor responses were observed. Eight patients (24%) were alive after 1 year, and 5 patients (15%) were alive 2 years after inclusion. The median overall survival was 28 weeks.Treatment was usually well tolerated. Among 6 patients studied, the pharmacokinetic profile of CpG-28 in the blood was heterogeneous. CpG-28 reached up to 79 ng/mL at the end of infusion in one patient. Return to baseline concentration occurred at around 70 hours after the start of infusion. Half-life estimates were variable ranging from 3 to 24 hours. The mean area under the plasma concentration-time curve (AUC) ranged from 0.07 to 0.65 μg x hr/ml. Conclusions: CpG-28 induced a few cases of radiological reponses, but the impact on the 6-months PFS was minimal in this population. However, the presence of long-term survivors suggest that this treatment might have been beneficial in some patients, whose molecular or clinical characteristics remain to be defined. [Table: see text]
Prognostic values of lung resistance protein (LRP) and P53 in patients with multiple myeloma (MM)
Authors: W. H. Elsawy, M. Abdel Kader, A. F. Gharib, M. M. Elnemr, S. A. Eltarhony, A. Y. Gendia, M. Abdullah, Y. T. Dorgham
Journal: Journal of Clinical Oncology (2007)

8113 Background: This study was undertaken to assess the significance of lung-resistance related protein (LRP) expression and p53 mutations in plasma cells from untreated multiple myeloma (MM) patients and to determine whether LRP expression and p53 deletions was associated with a poor response and survival in patients treated with a conventional dose of melphalan. Methods: We have studied LRP expression by immunocytochemistry and p53 deletions by interphase fluorescence in situ hybridization (FISH) with a DNA probe specific for the p53 locus at 17p13 in bone marrow plasma cells from 38 untreated patients with MM received conventional oral dose melphalan (0.25 mg/kg, day 1 to 4) combined with prednisone (MP). We also studied their association with both response to chemotherapy and survival of the patients. Results: By FISH, deletions of p53, were detected in 31.5% of patients and LRP was found positive in 36.8%. Patients with a p53 deletion were predominantly at stage III (p53 deletion in 83.4% of stage III patients vs. 8.3% of patients at stages I and II respectively; P = 0.04). Both p53 deletion and LRP expression were correlated with other laboratory and clinical parameters. The overall response rate of all of the evaluable patients was 63.2%. The response rate was 79.2% for patients without LRP expression but only 35.7% for patients with LRP expression (P = 0.01). Among the 12 patients with a p53 deletion by FISH, 25% responded compared with 75% of patients without p53 deletion (P = 0.001). With the exception of LRP expression and p53 deletions, there was no other prognostic variable sharing any correlation with response. The median survival of LRP-positive patients was 11 months (95%-Cl: 9 to 24), whereas the median survival duration of LRP negative patients was not reached (Cl: 26 to 82; P &lt; .002; hazard ratio [HR] = 2.9 (1.4–5.7). Patients with and without p53 deletions had significantly different overall survival times (median 13.9 months, 95%-CI: 8 to 26 and median not reached, CI: 24 to84, respectively; P &lt; .0001; hazard ratio [HR] = 2.6). Conclusions: For patients with MM who were treated with conventional-dose chemotherapy, LRP expression and p53 deletions provides prognostically relevant information in addition to that provided by standard prognostic factors. No significant financial relationships to disclose.
Identification of MYC-Dependent Transcriptional Programs in Oncogene-Addicted Liver Tumors
Authors: Theresia R. Kress, Paola Pellanda, Luca Pellegrinet, Valerio Bianchi, Paola Nicoli, Mirko Doni, Camilla Recordati, Salvatore Bianchi, Luca Rotta, Thelma Capra, Micol Ravà, Alessandro Verrecchia, Enrico Radaelli, Trevor D. Littlewood, Gerard I. Evan, Bruno Amati
Journal: Cancer Research (2016)

Abstract Tumors driven by activation of the transcription factor MYC generally show oncogene addiction. However, the gene expression programs that depend upon sustained MYC activity remain unknown. In this study, we employed a mouse model of liver carcinoma driven by a reversible tet-MYC transgene, combined with chromatin immunoprecipitation and gene expression profiling to identify MYC-dependent regulatory events. As previously reported, MYC-expressing mice exhibited hepatoblastoma- and hepatocellular carcinoma–like tumors, which regressed when MYC expression was suppressed. We further show that cellular transformation, and thus initiation of liver tumorigenesis, were impaired in mice harboring a MYC mutant unable to associate with the corepressor protein MIZ1 (ZBTB17). Notably, switching off the oncogene in advanced carcinomas revealed that MYC was required for the continuous activation and repression of distinct sets of genes, constituting no more than half of all genes deregulated during tumor progression and an even smaller subset of all MYC-bound genes. Altogether, our data provide the first detailed analysis of a MYC-dependent transcriptional program in a fully developed carcinoma and offer a guide to identifying the critical effectors contributing to MYC-driven tumor maintenance. Cancer Res; 76(12); 3463–72. ©2016 AACR.
Oral Cortisone Treatment of Infantile Eczema
Authors: Lewis Webb Hill
Journal: New England Journal of Medicine (1953)

THERE is no doubt that cortisone or adrenocorticotrophin (ACTH) often causes spectacular temporary improvement in infantile eczema.1 2 3 4 5 It is my opinion, however, that these agents when given parenterally and in a hospital, in spite of their great theoretical interest and undoubted temporary favorable action, have little place in the practical over-all management of the disease, for the eczema returns as soon as the treatment is discontinued, and the difficulties of keeping it up over a long period are formidable. The course of the disease is merely interrupted for a short time — it is doubtful if the results are worth . . .
Attitudes towards breast conservation in patients aged over 70 with breast cancer
Authors: L. Smith, S. Dayal, J. Murray, A. Lannigan
Journal: International Journal of Surgery (2015)

Background
The majority of breast conserving surgery (BCS) is performed in younger women. There is little published information about the views of women aged over 70 regarding BCS. The aim of this study was to investigate the attitudes of this age group towards BCS, and factors which may influence their treatment decision-making.
Transplantable Human Tumors in Experimental Chemotherapy: Effects of Actinomycins on H.S. #1 and H.Ep. #3 in the Rat2
Authors: M. N. Teller, P. C. Merker, J. E. Palm, G. W. Woolley
Journal: JNCI Journal of the National Cancer Institute (1962)

Eighteen actinomycins and 2 actinomy-cin chromophores were tested for antineoplastic activity against transplantable human tumors H.S. #1 and H.Ep. #3 growing subcutaneously in the X-irradiated and cortisone-treated rat. Eight compounds, when given intra-peritoneally, inhibited the growth of H.S. #1. Five of these were inhibitory at doses which were occasionally toxic to the host, as indicated by weight loss and/or mortality. Fourteen compounds were inhibitory to H.Ep. #3; only 2 were toxic at or below doses that reduced tumor growth. Actinomycins C, J, and P5995-9, when given orally rather than intraperitoneally, inhibited tumor growth over a wider range of tolerated doses. Although the actinomycins are, in general, a toxic group of compounds, the comparatively higher Maximum Effective Dose/minimum effective dose indexes for actinomycins J and P5995-9, given per os, may be indicative of a greater potential for clinical usefulness.
Bereavement after sibling death: a population‐based longitudinal case‐control study
Authors: James M. Bolton, Wendy Au, Dan Chateau, Randy Walld, William D. Leslie, Jessica Enns, Patricia J. Martens, Laurence Y. Katz, Sarvesh Logsetty, Jitender Sareen
Journal: World Psychiatry (2016)

The objective of this study was to examine mental disorders and treatment use among bereaved siblings in the general population. Siblings (N=7243) of all deceased children in the population of Manitoba, Canada who died between 1984 and 2009 were matched 1:3 to control siblings (N=21,729) who did not have a sibling die in the study period. Generalized estimating equations were used to compare the two sibling groups in the two years before and after the index child's death on physician‐diagnosed mental disorders and treatment utilization, with adjustment for confounding factors including pre‐existing mental illness. Analyses were stratified by age of the bereaved (&lt;13 vs. 13+). Results revealed that, in the two years after the death of the child, bereaved siblings had significantly higher rates of mental disorders than control siblings, even after adjusting for pre‐existing mental illness. When comparing the effect of a child's death on younger versus older siblings, the rise in depression rates from pre‐death to post‐death was significantly higher for siblings aged under 13 (p&lt;0.0001), increasing more than 7‐fold (adjusted relative rate, ARR=7.25, 95% CI: 3.65‐14.43). Bereaved siblings aged 13+ had substantial morbidity in the two years after the death: 25% were diagnosed with a mental disorder (vs. 17% of controls), and they had higher rates of almost all mental disorder outcomes compared to controls, including twice the rate of suicide attempts (ARR=2.01, 95% CI: 1.29‐3.12). Siblings in the bereaved cohort had higher rates of alcohol and drug use disorders already before the death of their sibling. In conclusion, the death of a child is associated with considerable mental disorder burden among surviving siblings. Pre‐existing health problems and social disadvantage do not fully account for the increase in mental disorder rates.
Case 12-1990
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, D.R. Cave, C.C. Compton
Journal: New England Journal of Medicine (1990)

Presentation of CaseA 21-year-old man was admitted to the hospital because of chronic nausea, vomiting, diarrhea, progressive weakness, and suspected polyneuropathy.The patient was well until the age of 14 years, when he experienced the sudden onset of abdominal pain, nausea, and vomiting. An emergent laparotomy showed edema and hyperemia of the ileal mesentery; adhesions of several loops of small bowel were observed, and a small amount of pus was seen in the pouch of Douglas; all mesenteric lymph nodes were reported to be enlarged. A specimen of the lymph nodes was obtained; microscopical examination of the specimen revealed . . .
RTRB-10TYROSINE KINASE RECEPTOR TIE2 REGULATES DNA REPAIR THROUGH THE PROTO-ONCOGENE ABL1 IN BRAIN TUMOR STEM CELLS
Authors: Mohammad B. Hossain, Rehnuma Shifat, David G. Johnson, Mark T. Bedford, Mien-Chie Hung, Konrad Gabrusiewicz, Joy Gumin, Ravesanker Ezhilarasan, Erik P. Sulman, Frederick Lang, Jessica Tyler, Raymond Sawaya, W.K. Alfred Yung, Juan Fueyo, Candelaria Gomez-Manzano
Journal: Neuro-Oncology (2015)

Glioblastoma is the most common and aggressive primary brain tumor in adults with a median survival of 9-15 months. This tumor invariably recurs after therapy, which is largely caused by the striking radioresistance. In gliomas, we found the tyrosine kinase receptor TIE2 is overexpressed in brain tumor stem cells (BTSCs) and in human surgical glioma specimens in relation to malignancy. Here we find that ionizing irradiation (IR) treatment of mice bearing intracranial BTSCs-derived xenografts resulted in an unexpected TIE2 nuclear localization and increased level of its natural ligand, ANG1. These data was corroborated in BTSCs and glioma cultures upon IR or Ang1 stimulus, using immunofluorescence and confocal analysis, and subcellular fractionation followed by Western blot. Of clinical interest, nuclear TIE2 is associated with radioresistance of glioma cells, which was reverted by using Tie2 soluble receptor (which inhibits ANG1/TIE2 interaction) and after genetic Tie2 mutation of a newly discovered nuclear localization signal. At the molecular level, we also found that after IR treatment, TIE2 localized in the DNA-repair foci and complexed with gH2AX, suggesting a role of TIE2 in the DNA repair machinery. To validate our hypothesis, we used a fluorescent reporter construct in which GFP gene was reconstituted following a non-homologous end joining (NHEJ) event, and we observed that TIE2-expressing cells showed more efficient NHEJ repair than non-expressing TIE2 cells. Based on the recently reported role of ABL1 (cAbl) in the ATM and KAT5 mediated DNA damage repair, we explored the relationship between ABL1 and the TIE2-mediated radioresistance. Our data clearly showed that DNA repair efficiency significantly and specifically decreased by using ABL1 inhibitors or ABL1 siRNAs, but not after ABL2 inhibition. Collectively, our results should propel the development of preclinical studies on the combination of nuclear TIE2-targeting strategies and inhibition of ABL1 with radiotherapy for patients with glioblastomas.
P280 A Single Centre Experience Of Spontaneous Clearance Of Mycobacterium abscessus In Cystic Fibrosis Patients
Authors: HD Green, PJ Barry, R Bright-Thomas, AM Brennan, AK Webb, R Lord, A Horsley, AM Jones
Journal: Thorax (2015)

<h3>Introduction</h3> The <i>Mycobacterium abscessus</i> complex is an emerging group of pathogens, which pose significant management challenges in CF. Current guidelines specify treatment is indicated in patients with repeated sputum culture positivity alongside radiological or clinical deterioration. However, identifying NTM as the cause of deterioration in the polymicrobial CF lung is challenging. Additionally, <i>M. abscessus</i> complex isolates are usually multi-resistant, requiring lengthy and complex treatment regimens. Whether to treat patients based on culture results alone is contentious and approaches differ between centres. Here we analyse our experience of <i>M. abscessus</i> at a large UK adult CF centre. <h3>Methods</h3> All patients with 1 or more positive sputum culture for <i>M. abscessus</i> since 2010, and minimum of 1 mycobacterial culture and 1 year of follow-up since first positivity were included. Anti-mycobacterial treatment and culture results following first positivity were recorded. <i>M. abscessus</i> eradication was defined as 4 consecutive negative cultures spanning at least 1 year. <h3>Results</h3> 21 patients were included. Of these, 6 (29%) have received/are receiving, anti-mycobacterial therapy based on clinician diagnosis of <i>M. abscessus</i> pulmonary disease. All 6 currently remain culture positive. Of the 15 remaining patients, 6 are consistently culture positive (duration 12 months - 5 years), but do not have evidence of NTM pulmonary disease. Spontaneous clearance of <i>M. abscessus</i> from sputum has occurred in 7 patients (Table 1). Of these, 5 (71%) had ≥3 positive cultures including 1 patient with 5 positive samples spread over 2 years and 1 patient with 5 positive samples spread over 9 months. In 2 patients infection status cannot yet be confirmed as these patients have ≤4 mycobacterial culture results following their initial positive result. <h3>Conclusion</h3> Patients may spontaneously clear <i>M. abscessus</i> from their sputum, even with a history of multiple positive cultures over many months. If patients are treated on culture results alone there is a risk of initiating potentially unnecessary, lengthy and poorly tolerated treatment. Our results suggest that adhering to clinical guidelines of recognising clinical deterioration secondary to <i>M. abscessus</i> remains paramount before commencing treatment and assessment of treatment success without control data may be very misleading.
Chronic oral etoposide in small-cell lung cancer: Clinical and pharmacokinetic results
Authors: C. Sessa, M. Zucchetti, V. Torri, O. Pagani, M. D'Incalci, D. Gentili, G. Martinelli, J. DeJong, M. Alerci, F. Cavalli
Journal: Annals of Oncology (1993)
Occupational Risk for Primary Cytomegalovirus Infection among Pediatric Health-Care Workers
Authors: Meyer E. Dworsky, Kathryn Welch, George Cassady, Sergio Stagno
Journal: New England Journal of Medicine (1983)

The risk of acquiring cytomegalovirus (CMV) from infected infants concerns pediatric health-care workers, particularly those who may be pregnant. We determined the prevalence of CMV antibody, and thus of past infection, in groups of medical students and house staff, nurses, and physicians, and in groups of pregnant and nonpregnant young women in the community. Although age, sex, and race influenced the results, occupation did not. We then estimated the exposure of the health-care workers by determining the prevalence of CMV infection in three groups of asymptomatic infants for whom they provided care; CMV was shed in urine or saliva of 1.6 per cent of newborns, 13 per cent of premature infants hospitalized for over a month, and 5 per cent of older infants seen in outpatient settings. When we determined the incidence of primary infection in the adult groups by retesting the seronegative members about two years later, we found that the annual attack rates in the medical students (0.6 per cent), house staff (2.7 per cent), and nurses (3.3 per cent) were not higher than in young women in the community (2.5 per cent during pregnancy and 5.5 per cent between pregnancies). We conclude that although pediatric health-care workers frequently and unknowingly care for infants shedding CMV, this occupational contact confers no greater risk than that faced by young women in the community at large. (N Engl J Med 1983; 309:950–3.)
Evaluation of macrophage inflammatory protein-3 alpha (MIP-3a) as a serum marker for prognosis of colorectal cancer.
Authors: T. Iwata, K. Tanaka, Y. Inoue, Y. Toiyama, J. Hiro, S. Saigusa, Y. Mohri, C. Miki, T. Tabata, M. Kusunoki
Journal: Journal of Clinical Oncology (2010)

10585 Background: A significant difference in survival exists among metastatic colorectal cancer (mCRC) patients receiving multidisciplinary treatments including chemotherapy, radiofrequency ablation, and cytoreductive surgery. At present, no validated prognostic marker is available in mCRC. The aim of this study is to identify cytokine markers related to prognosis of mCRC patients and to assess their prognostic significance. Methods: Six patients with synchronous liver metastases receiving multidisciplinary treatments were selected. They were divided into longer survival group (n=3) and shorter survival group (n=3). Difference in serum cytokine expression between different prognosis groups was determined using the cytokine array. Macrophage inflammatory protein-3 alpha (MIP-3a) was identified consequently. Serum MIP-3a was measured using a commercially available enzyme-linked immunosorbent assay in 242 CRC patients to clarify the association of MIP-3a with clinical outcome. Results: The median MIP-3a level was 28.2 pg/ml (range, 0 to 1462). We use the median level of serum MIP-3a as a cutoff point. Patients with synchronous liver metastases had significantly higher serum MIP-3a (p<0.001). No association of MIP-3a with other clinicopathological variables was observed. Overall survival of the patients with high MIP-3a was significantly worse than that of the patients with low MIP-3 alpha (p<0.001). In univariate analysis, high MIP-3a was correlated with poor survival (p<0.001). Multivariate analysis showed that high serum MIP-3a was an independent prognostic factor in CRC patients (relative risk, 2.7; 95% CI, 1.61 to 4.76; p<0.001). In mCRC patients (n=62), high MIP-3a was associated with poor survival (p<0.05). Conclusions: Serum MIP-3a is an independent prognostic factor for colorectal cancer. This may provide a useful guide to decision making of mCRC patients. No significant financial relationships to disclose.
Case 37-1994
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Robert I. Parker, Phuong L. Nguyen
Journal: New England Journal of Medicine (1994)

Presentation of CaseA newborn boy was admitted to the hospital because of petechiae and massive splenomegaly.The infant was born in the 39th week of the sixth pregnancy of a woman 35 years old. The pregnancy was complicated only by a febrile illness with vomiting, diarrhea, and dehydration during the third month. There was no evidence of fetal distress, and the baby was vigorous; the Apgar score was 8 at both one minute and five minutes. The birth weight was appropriate for the gestational age. In the nursery abdominal distention and petechiae were observed. Hematologic studies were performed ( . . .
Non-Atopic Individuals Exhibit a Distinct Immune Reactivity Patterns in Response to Timothy Grass Pollen in and out-of-Season
Authors: Denise Hinz, Gregory Seumois, Jason Greenbaum, Brandie White, Veronique M. Schulten, David H. Broide, John Sidney, Carla Oseroff, Erik R. Wambre, Eddie A. James, William W. Kwok, Pandurangan Vijayanand, Bjoern Peters, Alessandro Sette
Journal: Journal of Allergy and Clinical Immunology (2016)