tbuckley/cabot-search huggingface dataset:
Phase I Trial Results of Iodine-131–Labeled Antitenascin Monoclonal Antibody 81C6 Treatment of Patients With Newly Diagnosed Malignant Gliomas
Authors: Ilkcan Cokgor, Gamal Akabani, Chien-Tsun Kuan, Henry S. Friedman, Allan H. Friedman, R. Edward Coleman, Roger E. McLendon, Sandra H. Bigner, Xiao-Guang Zhao, Ana M. Garcia-Turner, Charles N. Pegram, Carol J. Wikstrand, Timothy D. Shafman, James E. Herndon, James M. Provenzale, Michael R. Zalutsky, Darell D. Bigner
Journal: Journal of Clinical Oncology (2000)

PURPOSE: To determine the maximum-tolerated dose (MTD) of iodine-131 ( 131 I)–labeled 81C6 antitenascin monoclonal antibody (mAb) administered clinically into surgically created resection cavities (SCRCs) in malignant glioma patients and to identify any objective responses with this treatment. PATIENTS AND METHODS: In this phase I trial, newly diagnosed patients with malignant gliomas with no prior external-beam therapy or chemotherapy were treated with a single injection of 131 I-labeled 81C6 through a Rickham reservoir into the resection cavity. The initial dose was 20 mCi and escalation was in 20-mCi increments. Patients were observed for toxicity and response until death or for a minimum of 1 year after treatment. RESULTS: We treated 42 patients with 131 I-labeled 81C6 mAb in administered doses up to 180 mCi. Dose-limiting toxicity was observed at doses greater than 120 mCi and consisted of delayed neurotoxicity. None of the patients developed major hematologic toxicity. Median survival for patients with glioblastoma multiforme and for all patients was 69 and 79 weeks, respectively. CONCLUSION: The MTD for administration of 131 I-labeled 81C6 into the SCRC of newly diagnosed patients with no prior radiation therapy or chemotherapy was 120 mCi. Dose-limiting toxicity was delayed neurologic toxicity. We are encouraged by the survival and toxicity and by the low 2.5% prevalence of debulking surgery for symptomatic radiation necrosis.
The Memorial Sloan Kettering Cancer Center (MSKCC) experience of systemic therapy in mucosal melanoma.
Authors: Christiana Bitas, Alexander Noor Shoushtari, Mark J. Bluth, Gauri Bhuchar, Robert Harrison Hester, Jacqueline Romero, Laura Fitzpatrick, Robert A Lefkowitz, Katherine Panageas, Gary K. Schwartz, Margaret K. Callahan, Michael Andrew Postow, Jedd D. Wolchok, Paul B. Chapman, Richard D. Carvajal
Journal: Journal of Clinical Oncology (2014)

9073 Background: Mucosal melanoma (MM) is a molecular and clinical subset of melanoma distinct from cutaneous melanoma (CM). The activity of systemic therapy (tx) in MM has not been rigorously evaluated. We performed a retrospective, single center analysis of MM patients (pts) treated with systemic tx. Methods: Using institutional databases, we identified pts with MM who were 1) treated at MSKCC between 1998-2012; 2) developed unresectable or metastatic disease (dz); 3) received ≥1 non-adjuvant systemic tx; 4) had scans available for blinded central radiology review using RECIST 1.1. Pt demographics and clinical outcomes were extracted. Results: 61 pts met inclusion criteria. Median age at diagnosis 64 years (range, 35-84); 71% female; primary site: 28 anorectal, 19 vulvovaginal, 13 head/neck, 1 gallbladder. Mutation (mut) status: 8/35 KIT mut (7 exon 11; 1 exon 13); 3/33 BRAF mut (all non V600mut); 3/33 NRAS mut. At time of 1st tx, 55 had metastatic dz (10 M1a, 6 M1b, 39 M1c) and 6 had locally advanced dz. Pts received 106 1st or 2nd-line systemic tx: 81 cytotoxic (24 single-agent alkylators [eg. TMZ, DTIC]; 47 alkylator-based combinations [eg. Cisplatin/Vinblastine/TMZ]; 10 other combinations); 11 immunotherapy [7 ipilimumab, 2 high-dose IL-2, 2 other]; 9 targeted [8 KIT inhibitors, 1 BRAF inhibitor]; 4 biochemotherapy; 1 other investigational tx. Overall response rate (RR) rate to 1st and 2nd-line tx was 16% and 13%, respectively, with no complete responses. 24-week (wk) dz control rate with 1st and 2nd-line tx was 20%, and 9%, respectively. RR in either 1st or 2nd-line to single-agent and combination alkylator tx was 8% (2/24), and 15% (7/47), respectively (p=0.71). RR to targeted tx and immunotherapy was 33% (3/9), and 9% (1/11), respectively. Median time to treatment failure (earlier of date of progression or change in therapy) was 11 wks (95% confidence interval [CI] 8-14 wks) for both 1st and 2nd line tx. Median overall survival (OS) from initiation of 1st-line tx was 11 mo (95% CI 8-13 mo). Conclusions: The efficacy of systemic tx in MM is modest and appears similar to that seen in CM. Clinical outcomes for this pt population are poor. Further investigation into the biology and treatment of MM is needed.
Case 26-1996
Authors: Jed B. Gorlin, Judith A. Ferry
Journal: New England Journal of Medicine (1996)

Presentation of CaseA seven-year-old boy was admitted to the hospital because of fever, lymphadenopathy, hepatosplenomegaly, and eosinophilia.The boy had been in good health until two months earlier, when fever and disorientation developed. He was taken to another hospital, where a seizure occurred. Meningoencephalitis was diagnosed, antibiotics were administered intravenously, and he received phenytoin and carbamazepine. He recovered and was discharged taking both agents; phenytoin was discontinued after one month.Two weeks before admission to this hospital, the fever recurred, particularly in the early morning hours; the temperature rose as high as 38.9°C, with anorexia. Eleven days before admission, . . .
Impaired Oxygenation in Surgical Patients during General Anesthesia with Controlled Ventilation
Authors: H. H. Bendixen, Hedley Whyte, M. B. Laver
Journal: New England Journal of Medicine (1963)

THE present study was undertaken to determine if the pattern of ventilation, by itself, may influence oxygenation during anesthesia and surgery. The hypothesis was examined that progressive pulmonary atelectasis, with increased shunting, may occur during constant ventilation whenever periodic hyperinflation (by deep breaths) is lacking, even though tidal ventilation is normal by the usual criteria, and that the impaired oxygenation, caused by atelectasis, is reversible by passive hyperinflation of the lungs.Normal tidal ventilation of the lungs serves the immediate requirements for adequate uptake of oxygen and elimination of carbon dioxide. Certainly, the maintenance of normal ventilation depends also on . . .
Comparative Analysis of Natural Killer Cell and Macrophage Recognition of Concanavalin A-Resistant Chinese Hamster Ovary Cells: Role of Membrane Oligosaccharides
Authors: B Pohajdak, K C Lee, I Sugawara, V Miller, J A Wright, A H Greenberg
Journal: JNCI Journal of the National Cancer Institute (1986)

As was previously shown, a mutation rendering Chinese hamster ovary (CHO) cells concanavalin A (Con A) resistant (Con AR) resulted in enhanced binding and susceptibility to lysis by natural killer (NK) cells. In the present study altered cell surface carbohydrate expression on the Con AR CR-7 cell line was demonstrated. This could be detected by flow cytometry with the use of fluorescein isothiocyanate-conjugated lectins Con A, wheat-germ agglutinin, and peanut agglutinin, and by a radiolabeled monoclonal antibody (49H.8) that recognizes a phenyl-P-galactose determinant. Two other independently selected Con AR CHO lines (BCR-2 and ECR-1) also exhibited increased NK cell reactivity, which suggests that a similar and, likely, a single mutation has altered the phenotype of these cells. Tunicamycin, an inhibitor of N-linked glycosylation, was able to reverse the binding to the CHO lines with the use of conditions that did not affect protein or DNA synthesis. The mutation rendering the CR-7 line Con AR and more sensitive to NK cell lysis and binding resulted in reduced killing and adhesion by activated bone marrow-derived macrophages from DBA/2J and CBA/CaJ mouse strains. Inhibition of macrophage and NK cell lysis by simple monosaccharides was demonstrated; however, macrophage killing was inhibited only by D-mannose, whereas NK cell lysis was reduced by all sugars tested. Neither macrophage nor NK cell adherence to tumor monolayers was affected by any of the monosaccharides. These results suggest that complex N-linked oligosaccharides are important for NK cell and macrophage binding and lysis.
RTRB-03SHORT DELAY IN INITIATION OF RADIOTHERAPY WITH CONCURRENT CHEMOTHERAPY FOR GLIOBLASTOMA: A SECONDARY ANALYSIS OF NRG ONCOLOGY/RTOG 0525 AND 0825
Authors: Deborah T. Blumenthal, Minhee Won, Benjamin W. Corn, Mark R. Gilbert, Paul Brown, Felix Bokstein, David G. Brachman, Maria Werner-Wasik, Grant K. Hunter, Egils Valeinis, Eric F. Kuehn, Kirsten Hopkins, Luis Souhami, H. Ian Robins, Peixin Zhang, Minesh P. Mehta
Journal: Neuro-Oncology (2015)

INTRODUCTION: We previously reported the unexpected finding that survival was significantly improved in patients with newly-diagnosed GBM when radiation was initiated later (>4 weeks post-op) compared to earlier (≤2 weeks post-op). That analysis included 2855 patients from 16 RTOG trials conducted prior to the era of concurrent temozolomide (TMZ) with RT. We now report on 1127 patients from two studies involving newly-diagnosed GBM, treated with RT + TMZ followed by adjuvant TMZ. Our hypothesis was that concurrent TMZ has a synergistic/radiosensitizing mechanism, making RT timing less significant. METHODS: Data from patients on both arms of RTOG 0525 and the placebo arm of RTOG 0825 were investigated. An analysis comparable to our prior study was performed to determine whether there was still an impact on survival by delaying RT in the RT + TMZ era. Overall survival was investigated using Cox proportional hazard model. Progression from diagnosis to 30 days after RT completion was analyzed using Chi-square test. RESULTS: 94.9% of the patients started RT 2-5 weeks post-op. Given the small number of patients who started RT early, comparisons were made between >4 and ≤4 weeks delay of radiation. There was no statistically significant difference for overall survival (p-value = 0.29; HR = 0.93; 95% CI: 0.80-1.07) after adjusting for RPA and MGMT methylation status. Similarly, the rate of early progression did not differ significantly (p-value = 0.59). CONCLUSIONS: We did not see a significant prognostic influence of delaying radiation within the range of 2-5 weeks post-op when given concurrently with TMZ for newly-diagnosed GBM. TMZ may level the playing field for patients treated with chemoradiation and offset the effect of RT delay that was seen when RT was given alone; however, the effects of early initiation of radiation tested previously could not be replicated. Supported by National Cancer Institute grants U10CA21661, U10CA180868, U10CA180822 and U10CA37422, Merck & Co. and Genentech.
Acid-Reflux Disorders
Authors: C E Pope
Journal: New England Journal of Medicine (1994)

In recent years, the concept of acid-reflux disorders has been broadened to include not only the effects of gastroesophageal reflux on the esophageal mucosa but also the role of acid reflux in laryngeal and pulmonary symptoms. This review discusses the effects of reflux on the esophagus, larynx, and lungs, emphasizing similarities and differences between gastrointestinal and respiratory manifestations of acid reflux.Esophageal RefluxPathophysiologyFor the past 20 years, it was assumed that the lower esophageal sphincter is the primary determinant of esophageal reflux. It is now recognized, however, that transient relaxation of the lower esophageal sphincter, not the resting . . .
Some Physiologic Aspects of Dermatologic Problems
Authors: Walter C. Lobitz
Journal: New England Journal of Medicine (1954)

THERE is an old saying that the study of clinical dermatology is the study of gross and microscopical pathology of the skin in the living. In recent years the physiology of the skin of the human being has become better understood. As a result the practice of modern clinical dermatology has become even more exciting because it encompasses not only the understanding and correlation of gross and microscopical structural changes of the skin but also the "applied physiology" of the skin.1 When the program chairman suggested that this discussion might include some physiologic approaches to the understanding of skin disorders, . . .
A Randomized Trial of the Discontinuation of Primary and Secondary Prophylaxis against<i>Pneumocystis carinii</i>Pneumonia after Highly Active Antiretroviral Therapy in Patients with HIV Infection
Authors: Juan C. Lopez Bernaldo de Quiros, Jose M. Miro, Jose M. Peña, Daniel Podzamczer, Juan C. Alberdi, Esteban Martínez, Jaime Cosin, Xavier Claramonte, Juan Gonzalez, Pere Domingo, Jose L. Casado, Esteban Ribera
Journal: New England Journal of Medicine (2001)

Prophylaxis against Pneumocystis carinii pneumonia is indicated in patients with human immunodeficiency virus (HIV) infection who have less than 200 CD4 cells per cubic millimeter and in those with a history of P. carinii pneumonia. However, it is not clear whether prophylaxis can be safely discontinued after CD4 cell counts increase in response to highly active antiretroviral therapy.
Everolimus versus sunitinib prospective evaluation in metastatic non-clear cell renal cell carcinoma (The ESPN Trial): A multicenter randomized phase 2 trial.
Authors: Nizar M. Tannir, Eric Jonasch, Emre Altinmakas, Chaan S. Ng, Wei Qiao, Pheroze Tamboli, Priya Rao, David F. McDermott, Christopher G. Wood, Toni K. Choueiri
Journal: Journal of Clinical Oncology (2014)

4505 Background: In a single-arm phase II trial of sunitinib in non-clear cell RCC (nccRCC) we previously reported (Tannir et al. Eur Urol 2012), objective response rate [ORR] was 5% and median progression-free survival [PFS] was 2.7 months. Temsirolimus was previously shown to produce overall survival (OS) benefit in poor-risk RCC including nccRCC (Hudes et al. NEJM 2007). Methods: This is a randomized phase II trial of everolimus (E) vs. sunitinib (S) with crossover design in metastatic nccRCC. Primary endpoint was PFS in first-line (1L). Secondary endpoints were PFS in second-line (2L), safety, and OS. A sample size calculation of 108 pts (54/arm) was based on an assumption of improved median PFS from 12 weeks with S to 20 weeks with E. Pts were stratified by histology (papillary vs. others), and MSKCC risk groups. Kaplan-Meier curves were used to estimate unadjusted time-to-event distributions. Stratified log rank tests were used to compare each time-to-event variable between groups. Results: Seventy-three pts were enrolled. Sixty-eight pts were eligible and evaluable (median age 59, 43 males [63%], 52 pts [77%] had prior nephrectomy). Twenty-seven pts had papillary, 11 pts had chromophobe, 9 pts had unclassified, 7 pts had translocation, 13 pts had sarcomatoid, and 1 pt had oncocytic RCC. Thirty-five pts received E (good-risk 4, intermediate-risk 29, poor-risk 2). Thirty-three pts received S (good-risk 4, intermediate-risk 29). ORR with S in 1L was 12% (2 pts had chromophobe, 1 pt had papillary type 1 and 1 pt had 99% sarcomatoid); ORR with E in 1L was 0%. Median PFS in 1L with S was 6.1 mos (95% CI: 4.7, 10.8) and 4.1 mos with E (95% CI: 2.7, 7.4); p = 0.25. Thirty-eight pts received 2L therapy (S 19, E 19). Median PFS in 2L with S was 1.8 mos (95% CI: 1.5, NA) and 4.3 mos with E (95% CI: 1.4, NA). A total of 27 pts have died (8 had S and 19 had E). Median OS with E in 1L was 10.5 mos (95% CI: 7.4, NA); median OS with S in 1L was not reached; p=0.01. Toxicity was consistent with previous reports of E and S. Conclusions: Based on futility analysis for PFS and inferior OS with E compared to S in 1L, the DSMB recommended termination of further pt accrual on this trial. E cannot be recommended as 1L option in nccRCC.
Rates and Risks of Diethylstilbestrol-Related Clear-Cell Adenocarcinoma of the Vagina and Cervix
Authors: Sandra Melnick, Philip Cole, Diane Anderson, Arthur Herbst
Journal: New England Journal of Medicine (1987)

We reviewed 519 cases of clear-cell adenocarcinoma of the vagina and cervix identified by the Registry for Research on Hormonal Transplacental Carcinogenesis of the University of Chicago through June 30, 1985. In 60 percent of all cases the patient's mother had received diethylstilbestrol during pregnancy. An additional 12 percent of all mothers had been treated with another hormone or with an unidentified medication. Ninety-one percent of the cases in diethylstilbestrol-exposed women were diagnosed when the patient was between the ages of 15 and 27. The median age at diagnosis was 19.0 years. The risk that clear-cell adenocarcinoma will develop in an exposed female from birth through age 34 is 1 case per 1000 women. The temporal pattern of occurrence of clear-cell adenocarcinoma corresponds closely with that of the use of diethylstilbestrol for pregnancy support in the United States. The rarity of this tumor among exposed women suggests that diethylstilbestrol is not a complete carcinogen and that some other factor is also involved in the pathogenesis of clear-cell adenocarcinoma of the vagina and cervix.
A Young Woman With Bilateral Breast Cancer: Identifying a Genetic Cause and Implications for Management
Authors: Monique A. de Bruin, James M. Ford, Allison W. Kurian
Journal: Journal of the National Comprehensive Cancer Network (2013)

Breast cancer is a common manifestation of an underlying genetic susceptibility to cancer, and 5% to 10% of all breast cancers are associated with a germline mutation in a known risk allele. Detection of mutations has implications for targeted screening and prevention strategies for probands, and for genetic counseling and testing of their family members. This report presents a case involving a 35-year-old woman with no family history of breast or ovarian cancer who presented with a palpable right breast lump. Imaging revealed multiple bilateral breast masses and right axillary adenopathy, and core needle biopsies showed invasive ductal carcinoma in both the right and left breast. This report discusses the appropriate genetics evaluation for a patient with bilateral breast cancer at a young age, including testing for mutations in BRCA1 and BRCA2, followed, if negative, by consideration of testing for mutations in TP53 (Li-Fraumeni syndrome). Given the specialized counseling and testing needs of patients with Li-Fraumeni syndrome, and the implications for targeted screening strategies if a mutation is found, referral to a cancer genetics expert is strongly recommended.
“A brownish depressed area”: a novel narrow band imaging colonoscopic finding of a depressed adenoma
Authors: K Fu, Y Tsujinaka, Y Hamahata, K Matsuo, O Tsutsumi
Journal: Gut (2008)

We read the article by East et al ( Gut 2007; 57 :65–70) with great interest. Their study included high yields of flat adenomas in the proximal colon using newly developed narrow band imaging (NBI). Other than their study, two others have reported that the use of NBI improves polyp detection;1 2 however, these studies did not include any depressed-type colorectal neoplasia which has been detected not only in Japan but also in Western countries. It is important to detect depressed-type neoplastic lesions during colonoscopy as they tend to invade …
CT scan abnormalities and outcome of chronic schizophrenia
Authors: A Vita, M Dieci, G M Giobbio, P Azzone, M Garbarini, E Sacchetti, B M Cesana, C L Cazzullo
Journal: American Journal of Psychiatry (1991)

The authors evaluated the relationship between brain morphological characteristics assessed by means of computerized tomography and the 2-year clinical and social outcomes of 18 patients with chronic schizophrenia. Cerebral structural abnormalities, especially cortical atrophy, were associated with a poorer outcome in several areas of clinical and social functioning.
Aregenerative Anemia Associated with Benign Thymoma
Authors: Bayard Clarkson, Darwin J. Prockop
Journal: New England Journal of Medicine (1958)

FOURTEEN cases of aregenerative anemia associated with benign thymoma have been reported to date in the medical literature.1 2 3 4 5 6 7 8 9 10 11 The present report adds 2 cases of the syndrome and describes an experimental attempt to produce anemia with an extract of the thymoma from 1 of the patients.The report of Humphreys and Southworth5 in 1945 first emphasized the fact that the association of thymoma and aregenerative anemia could not be ascribed to chance. They reported the case of a fifty-eight-year-old woman with a large mediastinal tumor that was unresponsive to irradiation. Two years after discovery of the tumor, a severe refractory . . .
Visceral hypersensitivity is associated with GI symptom severity in functional GI disorders: consistent findings from five different patient cohorts
Authors: Magnus Simrén, Hans Törnblom, Olafur S Palsson, Miranda A L van Tilburg, Lukas Van Oudenhove, Jan Tack, William E Whitehead
Journal: Gut (2017)

Our aim was to evaluate the association between visceral hypersensitivity and GI symptom severity in large cohorts of patients with functional GI disorder (FGID) and to adjust for psychological factors and general tendency to report symptoms.We included five cohorts of patients with FGIDs (IBS or functional dyspepsia; n=1144), who had undergone visceral sensitivity testing using balloon distensions (gastric fundus, descending colon or rectum) and completed questionnaires to assess GI symptom severity, non-GI somatic symptoms, anxiety and depression. Subjects were divided into sensitivity tertiles based on pain/discomfort thresholds. GI symptom severity was compared between sensitivity tertiles in each cohort and corrected for somatisation, and anxiety and depression.In all five cohorts, GI symptom severity increased gradually with increasing visceral sensitivity, with significant differences in GI symptom severity between the sensitivity tertiles (p<0.0001), with small to medium effect sizes (partial η2: 0.047-0.11). The differences between sensitivity tertiles remained significant in all cohorts after correction for anxiety and depression, and also after correction for non-GI somatic symptom reporting in all of the cohorts (p<0.05).A gradual increase in GI symptom severity with increasing GI sensitivity was demonstrated in IBS and functional dyspepsia, which was consistent across several large patient groups from different countries, different methods to assess sensitivity and assessments in different parts of the GI tract. This association was independent of tendency to report symptoms or anxiety/depression comorbidity. These findings confirm that visceral hypersensitivity is a contributor to GI symptom generation in FGIDs.