tbuckley/cabot-search huggingface dataset:
Efficacy and toxicity of dose-adjusted EPOCH-rituximab in adults with newly diagnosed Burkitt lymphoma
Authors: K. Dunleavy, B. R. Healey Bird, S. Pittaluga, N. Grant, M. Shovlin, R. Little, R. Yarchoan, S. Steinberg, E. S. Jaffe, J. Janik, W. H. Wilson
Journal: Journal of Clinical Oncology (2007)

8035 Background: Burkitt Lymphoma (BL) is a rare and highly aggressive lymphoma, characterized by a high tumor proliferation rate. While the standard therapy of BL is highly effective, it involves intensive, multi-agent chemotherapy that is associated with considerable treatment-related toxicity and mortality, especially in older patients. We hypothesized that the regimen DA-EPOCH may be effective in BL, based on the observation that it overcomes the adverse effect of high proliferation in diffuse large B-cell lymphoma. Methods: We investigated DA-EPOCH-rituximab (R) in untreated BL in an attempt to maintain the high cure rates of standard therapy with minimal treatment related toxicity. Eligible patients had a diagnosis of untreated BL and could be HIV negative or positive with HIV negative patients (n=13) receiving 6 cycles of DA-EPOCH-R as previously described (Blood 99: 2685, 2002) and HIV positive (n=6) patients receiving 3–6 cycles of DA- EPOCH-R for 1 cycle beyond CR for a minimum of 3 cycles. All patients received intrathecal methotrexate prophylaxis and outpatient therapy where possible. Results: The characteristics of 19 enrolled patients are: median age (range) 29 (18–66) and ECOG PS 1(1–3); stage III/IV 10 (53%); LDH &gt; N 11 (61%); male sex 15 (79%); extranodal sites 13 (68%) and ileocecal disease 13 (68%). No patients so far had CNS involvement at diagnosis. Response is CR/CRu in 100% of patients with one patient receiving consolidative radiotherapy to a site of residual disease. OS and PFS are both 100% and EFS 93.3% at a median potential follow-up time of 29 months. Toxicities were fever/neutropenia in 16%, grade 4 neutropenia in 47% and grade 3/4 thrombocytopenia in 22% of cycles. There was one case of tumor lysis syndrome and no treatment related deaths. Conclusions: DA-EPOCH-R is highly effective in BL. It appears to be associated with much lower toxicity compared to standard high-dose regimens and may significantly advance the therapeutic index of BL treatment. Accrual continues. No significant financial relationships to disclose.
Denervation of the Abdominal Viscera for the Treatment of Traumatic Shock
Authors: C. Palmerio, B. Zetterstrom, J. Shammash, E. Euchbaum, E. Frank, J. Fine
Journal: New England Journal of Medicine (1963)

HYPERACTIVITY of the sympathetic nervous system is a pronounced characteristic of all types of traumatic shock. The generalized increase in vasoconstrictor activity can be beneficial in certain circumstances, such as acute hypovolemia. But if it is excessively intense and prolonged it may cause the shock to become refractory to all known methods of therapy. This is demonstrated by the observation that an antiadrenergic agent (for example, dibenamine) can prevent the development of the state of irreversibility to transfusion in hemorrhagic shock.1 2 3 The refractory state of shock produced by endotoxin may also be the result of excessive adrenergic activity, for it . . .
Duplication of the Cystic and Common Hepatic Ducts, Lined with Gastric Mucosa
Authors: C. Marshall Lee
Journal: New England Journal of Medicine (1957)

STRUCTURAL variations of the extrahepatic biliary tract are extremely common and have been extensively described, tabulated and diagrammed, in an effort to reduce the number of technical accidents during operations on this region of the body.True developmental anomalies of the biliary tract are much more unusual, and, with the possible exception of congenital atresia, major congenital malformations of the extrahepatic bile system can only be described as rare, at least in human beings. They are much more common in certain domestic animals, notably in cats and cattle, but they occur frequently enough in human subjects to have received substantial . . .
Clinicopathological characteristics of squamous cell carcinoma of the lung with programmed cell death ligand 1 (PD-L1) protein expression.
Authors: Tiffany Huynh, Anthony Chi, Vicente Morales Oyarvide, Justin F. Gainor, Aaron N. Hata, Michael Lanuti, Eugene J Mark, Jeffrey A. Engelman, Mari Mino-Kenudson
Journal: Journal of Clinical Oncology (2015)

7554 Background: PD-L1 expression by immunohistochemistry (IHC) reportedly predicts patient response to anti-PD-1/PD-L1 therapies in early phase clinical trials for solid tumors. However, there is limited data on the patient/tumor characteristics associated with PD-L1 expression in squamous cell carcinoma of the lung (SqCC). Methods: PD-L1 (E1L3N, 1:200, Cell Signaling Technology), PTEN, and CD8 IHC were performed on tissue microarrays of resected SqCCs (n = 162). Subsets of patients underwent clinical molecular (SNaPshot) and FISH testing. Cases with 10% or more tumor cells exhibiting negative or reduced PTEN expression were considered to have PTEN loss. PD-L1 expression in tumor cells and CD8 expression in tumor infiltrating lymphocytes (TILs) were semiquantitatively evaluated. PD-L1 expression, defined as 5% or more of the tumor cells exhibiting membranous staining, was correlated with clinicopathological and molecular features as well as patient outcomes. Results: The study cohort consisted of 96 Stage I, 41 Stage II, 22 Stage III, and 3 Stage IV cases. Of those, 43 (27%) exhibited PD-L1 expression, which was associated with large tumor size (p = 0.001), advanced pathologic stage (Stage II or higher vs. Stage I, p = 0.041), nodal metastasis (p = 0.014), increased CD8+ TILs (grade 2-3 vs. 0-1, p < 0.001), and PTEN loss (p = 0.019) by univariate analysis. In multivariate analysis, large tumor size (p = 0.048) and increased CD8+ TILs (p < 0.001) remained significant. A Cox proportional-hazards model revealed a borderline significance of PD-L1 expression with shorter progression free survival (PFS) (p = 0.063), while advanced pathologic stage was associated with shorter PFS (p = 0.02) and increased CD8+ TILs with longer PFS (p = 0.01). Conclusions: As reported in other tumors, PD-L1 expression is significantly associated with CD8+ TILs in SqCC, and it may predict unfavorable patient outcomes. Interestingly, it is also associated with PTEN loss. There are currently limited targeted therapy options for SqCC, but blockade of the PD-1/PD-L1 pathway may offer promising treatment options for SqCC patients with PD-L1 expression.
The teaching of clinical oncology in Italian medical schools. A survey among teachers and students
Authors: R. Cellerino, F. Graziano, A. Piga, V. Ghetti
Journal: Annals of Oncology (1993)

Oncologists, health care workers and health organizations consider well-performed teaching programs in clinical oncology a fundamental step in cancer control. The aim of our study was to assess the views of teachers and students on the present status of oncology teaching in Italian medical schools and on the most common shortcomings in cancer education.A survey was carried out among teachers and students of 17 Italian medical schools using two different questionnaires. Six hundred forty-seven students of Northern, Central and Southern Italy in the final two years (5th and 6th) of their medical curriculum and 87 professors of pathology, surgery, internal medicine and medical oncology completed the questionnaires.Doctor/patient relationships and integration among disciplines were the most unsatisfactory aspects of oncology teaching, according to students. Biology, epidemiology, radiotherapy, and medical treatment were felt to be insufficiently treated, whilst diagnostic aspects, clinical management and surgery were rated sufficient. The median number of cancer patients to whom each student had access during his/her training was limited, averaging only 13 patients; however, a high degree of variability was noted. A larger number of patients was generally observed in smaller, less crowded medical schools, with notable exceptions. Although the majority of teachers had clinical practices related to their disciplines, only a small number of students underwent a period of clinical training. Traditional methods of teaching were preferred to innovative methods, while interaction among disciplines was uncommon.This survey emphasizes the dualism between students' expectations and teachers' ideas about cancer teaching. Doctor/patient relationships and poor attention to practical clinical problems seem the most critical issues for clinical oncology training in Italian medical schools.
Hyperhomocysteinemia: An Independent Risk Factor for Vascular Disease
Authors: Robert Clarke, Leslie Daly, Killian Robinson, Eileen Naughten, Seamus Cahalane, Brian Fowler, Ian Graham
Journal: New England Journal of Medicine (1991)

Hyperhomocysteinemia arising from impaired methionine metabolism, probably usually due to a deficiency of cystathionine β-synthase, is associated with premature cerebral, peripheral, and possibly coronary vascular disease. Both the strength of this association and its independence of other risk factors for cardiovascular disease are uncertain. We studied the extent to which the association could be explained by heterozygous cystathionine β-synthase deficiency.
Induction of Circulating Activated Suppressor-like T Cells by Methimazole Therapy for Graves' Disease
Authors: Thomas H. Tötterman, F. Anders Karlsson, Mats Bengtsson, Ib Mendel-Hartvig
Journal: New England Journal of Medicine (1987)

Thyrostatic drug treatment of Graves' disease suppresses excessive thyroid hormone synthesis and causes a parallel decrease in serum thyroid autoantibody levels. The mechanism of this immunosuppression is unknown. We studied methimazole-induced immunoregulatory effects prospectively in 14 patients with Graves' disease treated for up to six months. The numbers of circulating activated, HLA-DR-positive T helper/inducer cells decreased gradually, from 8.3+1.7 percent (+SD) to 1.0+1.7 percent (P less than 0.001). HLA-DR-positive T suppressor/cytotoxic cells increased transiently at one month, from 2.0+1.9 percent to 12.6+6.4 percent (P less than 0.001), and returned to 2.9+3.7 percent at six months. Methimazole did not alter the HLA-DR expression of T cells in vitro. In two patients, the helper activity of T cells in inducing autoantibody secretion in vitro was substantially reduced after one month of methimazole treatment. Before treatment, large proportions of thyroid-infiltrating T-cell subsets expressed the activation markers HLA-DR, interferon-gamma, and interleukin-2 receptors, which were partially lost during therapy. Methimazole treatment was accompanied by a gradual reduction in circulating levels of thyrotropin-receptor, microsomal, and thyroglobulin autoantibodies. These results are compatible with the view that methimazole-induced immunoregulation in Graves' disease is mediated by a direct inhibitory effect on thyrocytes. This inhibition is in turn accompanied by marked changes in the proportions of activated T helper-like and T suppressor-like cells. This altered T-cell activation profile reflects, at least in part, the functional suppression of autoantibody production observed in methimazole-treated patients with Graves' disease.
New methods in cross-cultural psychiatry: psychiatric illness in Taiwan and the United States
Authors: W M Compton, J E Helzer, H G Hwu, E K Yeh, L McEvoy, J E Tipp, E L Spitznagel
Journal: American Journal of Psychiatry (1991)

Cross-cultural psychiatric research has suffered from many methodological shortcomings. To answer some of these shortcomings, the present study compared rates of psychiatric disorders in Taiwan and the United States by combining data from both countries into a single data set.Results from large, community-based surveys in the United States and Taiwan, the National Institute of Mental Health (NIMH) Epidemiologic Catchment Area survey and the Taiwan Psychiatric Epidemiological Project, were combined into a single data set. This integration of the data sets was possible because both surveys used the NIMH Diagnostic Interview Schedule to ascertain cases. The integrated data sets were then analyzed with identical algorithms to generate lifetime prevalence rates of psychiatric disorders according to DSM-III criteria for both the United States and Taiwan.Lifetime prevalence rates of psychiatric illness in Taiwan were generally lower than U.S. rates. The rates of any disorder were 21.56% in Taiwan and 35.55% in the United States (Z = 22.34, p less than 10(-109]. The rates of most specific disorders were lower in Taiwan, and none of the rates was higher in Taiwan.While a culturally determined response bias may have lowered the rates in Taiwan somewhat, the results appear to be valid. Implications for the future use of structured diagnostic interviews in cross-cultural research are discussed.
Targeting notch signaling and estrogen receptor pathways in human breast cancer stem cells
Authors: N. S. Luraguiz, T. Yong, H. Yin, A. Sun
Journal: Journal of Clinical Oncology (2008)

22066 Background: Breast cancer stem cells have been identified as ESA+CD44+CD24-Lin- cells, which may account for disease relapse and metastasis. Deregulation in stem cell self-renewal pathways such as Notch, Wnt and Hedgehog signaling have been implicated in mammary transformation. In humans, high levels of Notch1 are associated with reduced patient survival. Inhibition of Notch signaling has been proposed as a potential strategy in treating breast cancer. Tamoxifen, a modulator of estrogen receptor (ER), is currently used for the treatment of both early and advanced ER+ breast cancer. It is unclear whether ER+ breast cancers originate from ER+ or ER- mammary stem/progenitor cells. Here, we investigate the molecular mechanisms of Notch signaling and ER interaction in breast cancer stem cells, and evaluate Notch inhibition and estrogen antagonist in targeting breast cancer stem cells. Methods: CD44+CD24- breast cancer stem cells are isolated by flow cytometry sorting of (1) human breast cancer cell line MDA-MB-231, (2) primary cells from invasive breast cancer lesions and (3) primary cells from benign breast tissues. Real-time PCR is performed to determine the expression of stem cell genes including genes in Notch pathway. IHC is performed to determine the ER and PR status of the cells. Stem like and non-stem like cells are treated with GSI (a Notch inhibitor) and tamoxifen. The effects of the treatments on cell proliferation and apoptosis are determined by BrdU and Tunnel Assays. Results and Conclusion: Previously we have shown that GSI alone effectively induced apoptosis in ER- MDA-MB-231 cells. Tamoxifen alone had substantial killing effects on ER+ MCF7 cells, but enhanced killing in both cell types were observed when treatments were combined. Stem like, non stem-like and unsorted cells were treated with GSI, tamoxifen and combination of GSI and tamoxifen. Proliferation was determined at 24 and 72 hours of treatment by BrdU assay. Stem-like cells exhibited significant sensitivity to GSI killing In addition, an enhanced effect was observed when GSI was combined with tamoxifen, suggesting that chemotherapy that targets both Notch signaling and estrogen receptor pathways in breast cancer stem cells may be an effective strategy in treating breast cancer. No significant financial relationships to disclose.
Esophageal and Gastric Cancers With Metastases Induced in Dogs by N -Ethyl- N ′-nitro- N -nitrosoguanidine 2
Authors: Koji Sasajima, Takashi Kawachi, Tomono Sano, Takashi Sugimura, Yukio Shimosato, Akiro Shirota
Journal: JNCI Journal of the National Cancer Institute (1977)

Three 6-month-old male beagle dogs were given a solution of 150 microng N-ethyl-N'-nitrosoguanidine (ENNG)/ml to drink ad libitum for 9 months. They all developed esophageal squamous cell carcinomas and gastric adenocarcinomas. The stomach adenocarcinomas were mostly in the antrum along the lesser curvature and were either well differentiated or poorly differentiated, with or without signet ring cells. The well-differentiated adenocarcinomas metastasized to the liver, and the poorly differentiated ones metastasized to the lymph nodes. The gastric mucosa in the antrum was atrophic, and the muscularis mucosae was fibrotic. Esophageal lesions were multicentric moderately differentiated squamous cell carcinomas, and they developed without diffuse hyperplastic changes of the epithelium. One dog with a large ulcerated carcinoma of the esophagus had metastases in the lung, liver, peritoneum, and abdominal lymph nodes. One dog also had a hemangiosarcoma with hepatic metastasis and spindle cell sarcoma in the stomach and duodenum, respectively.
Tardive dyskinesia in young adults
Authors: D Tarsy, R Granacher, M Bralower
Journal: American Journal of Psychiatry (1977)

The authors describe two cases of tardive dyskinesia in which severe axial dystonia and intense facial grimacing produced marked discomfort as well as social and physical disability. Both patients experienced the onset of psychiatric symptoms as young adults, showed a prompt response to antipsychotic drug therapy, and were subsequently left on maintenance treatment for indefinite periods. The severity of this frequently irreversible and disabling condition warrants careful consideration in the use of long-term antipsychotic drug treatment in the young psychiatric outpatient population.
Thesaurosis Following Inhalation of Hair Spray
Authors: Martin Bergmann, I. Jerome Flance, Herman T. Blumenthal
Journal: New England Journal of Medicine (1958)

HAIR spray is currently one of the most widely used cosmetic preparations. Although the exact compositions of various brands of hair sprays are closely guarded trade secrets, it is generally known that they may contain, in addition to a Freon propellant, various synthetic and naturally occurring resins in aqueous or alcoholic solutions. Perfumes and small amounts of lanolin are other common ingredients. So far, neither consumers nor physicians appear to have questioned the innocuity of these products. However, our experience with the following cases and subsequent animal experiments suggest that hair sprays may not be altogether harmless.Case ReportsCase . . .
Patterns of Illness in Rhinovirus Infections of Military Personnel
Authors: B. R. Forsyth, H. H. Bloom, K. M. Johnson, R. M. Chanock
Journal: New England Journal of Medicine (1963)

IN the past two years a new group of respiratory viruses, recently designated as rhinoviruses, has been associated with mild upper respiratory disease in adults.1 2 3 4 5 6 7 8 9 Agents of this group were isolated from Marine Corps personnel under surveillance at Camp Lejeune, North Carolina, from December, 1960, to January, 1962, and were shown to be associated with mild nonepidemic upper respiratory illness.10 From January, 1960, to March, 1962, epidemics of upper respiratory disease associated with adenovirus Type 4 and Coxsackie virus Group A, Type 21, occurred in the same population.11 12 13 During the time of this study, the characteristics of the population and . . .
Three-weekly (q3w) trastuzumab (H) plus chemotherapy in HER2-positive recurrent breast cancer (RBC)
Authors: A. Ardavanis, A. Alexopoulos, G. Lainakis, G. Rigatos
Journal: Journal of Clinical Oncology (2004)

842 Background: The safety profile of weekly H is well known. However, recent studies have shown that H 6mg/kg q3w is as well tolerated and maintains therapeutic H levels over 21 days. Based on these data, we have investigated H q3w plus docetaxel (T), vinorelbine (N) or capecitabine (X). Methods: 31 patients (pts) with HER2-positive (23 IHC 3+, 8 IHC2+/FISH-positive) disease were enrolled. 20 pts were treated first line (prior adjuvant chemotherapy allowed). 11 patients had received prior therapy for RBC (1–3 regimens). Drug doses: H–8mg/kg loading, 6mg/kg q3w, day (d)1; T–100mg/m2, d1; N–25mg/m2, d1/8; X–2500 mg/m2, d1–14. Treatment was discontinued or cytotoxic changed upon disease progression. Results: H was combined with T, N or X in 11, 11 and 12 patients respectively. A total of 293 courses have been given (range 3–30, median 9.45). In 2 pts, N replaced X and in one pt X replaced N upon progression. In one pt, T was given after X and N. 2 pts received H/T plus carboplatin and one received H/N plus gemcitabine. In 2 IHC2+/FISH-positive pts, treatment was discontinued after FISH reassessment (these pts were included in the toxicity evaluation). Overall, the q3w H-containing regimens were well tolerated. The majority of toxicities observed were typical of the cytotoxics administered. Five pts displayed H infusion-related reactions. One H/X pt with previous anthracycline exposure displayed a grade 2 decrease in LVEF, associated with an intraventricular clot and persistant hypokalaemia. H, but not X, was discontinued and LVEF normalised 6 months later. One H/T pt with known lymhangitic pulmonary disease had transient post-infusion dyspnea. Although, given the heterogeneity of the study, efficacy of the q3w schedule cannot be evaluated, 18 clinical responses (3 CR, 15 PR), 8 cases of stable disease and 5 of progressive disease have been documented after ≥3 courses. Median time to progression, duration of response and survival have not yet been reached. Conclusion: In this small, heterogeneous group of pts, q3w H plus chemotherapy seems to be as well tolerated and active as weekly H. No significant financial relationships to disclose.
Serum Glucocorticoid–Regulated Kinase 1 Blocks CKD–Induced Muscle Wasting Via Inactivation of FoxO3a and Smad2/3
Authors: Jinlong Luo, Anlin Liang, Ming Liang, Ruohan Xia, Yasmeen Rizvi, Yun Wang, Jizhong Cheng
Journal: Journal of the American Society of Nephrology (2016)

Muscle proteolysis in CKD is stimulated when the ubiquitin-proteasome system is activated. Serum glucocorticoid–regulated kinase 1 (SGK-1) is involved in skeletal muscle homeostasis, but the role of this protein in CKD–induced muscle wasting is unknown. We found that, compared with muscles from healthy controls, muscles from patients and mice with CKD express low levels of SGK-1. In mice, SGK-1-knockout (SGK-1-KO) induced muscle loss that correlated with increased expression of ubiquitin E3 ligases known to facilitate protein degradation by the ubiquitin-proteasome, and CKD substantially aggravated this response. SGK-1-KO also altered the phosphorylation levels of transcription factors FoxO3a and Smad2/3. In C2C12 muscle cells, expression of dominant negative FoxO3a or knockdown of Smad2/3 suppressed the upregulation of E3 ligases induced by loss of SGK-1. Additionally, SGK-1 overexpression increased the level of phosphorylated N -myc downstream–regulated gene 1 protein, which directly interacted with and suppressed the phosphorylation of Smad2/3. Overexpression of SGK-1 in wild-type mice with CKD had similar effects on the phosphorylation of FoxO3a and Smad2/3 and prevented CKD–induced muscle atrophy. Finally, mechanical stretch of C2C12 muscle cells or treadmill running of wild-type mice with CKD stimulated SGK-1 production, and treadmill running inhibited proteolysis in muscle. These protective responses were absent in SGK-1-KO mice. Thus, SGK-1 could be a mechanical sensor that mediates exercise-induced improvement in muscle wasting stimulated by CKD.
Case 10-2003
Authors: Francine M. Foss, Suzanne L. Aquino, Judith A. Ferry
Journal: New England Journal of Medicine (2003)

Presentation of CaseA 72-year-old man was transferred to this hospital from another hospital because of rapidly progressive leukemia and multiorgan failure.The patient had lost an unknown amount of weight during the preceding two months, but he was considered to be in stable condition, with mild chronic renal failure (creatinine level, 1.9 mg per deciliter [168 μmol per liter] nine months before admission). Twenty-three days before admission, laboratory studies were performed at another hospital in preparation for an elective transurethral resection of the prostate gland (Table 1 and Table 2).Two weeks before admission, tolterodine was prescribed. About 10 days before . . .