tbuckley/cabot-search huggingface dataset:
Clinical Manifestations and Therapy of<i>Isospora belli</i>Infection in Patients with the Acquired Immunodeficiency Syndrome
Authors: Jack A. DeHovitz, Jean W. Pape, Madeleine Boncy, Warren D. Johnson
Journal: New England Journal of Medicine (1986)

Isospora belli has recently been recognized as an opportunistic protozoan pathogen in patients with the acquired immunodeficiency syndrome (AIDS). Although I. belli rarely causes diarrhea in patients with AIDS in the United States, we have documented isosporiasis in 15 percent (20 of 131) of such patients in Haiti. The infection was associated with chronic watery diarrhea and weight loss that was clinically indistinguishable from disease caused by the related coccidia cryptosporidium. No demographic or laboratory data distinguished the patients with AIDS and isosporiasis from those with either cryptosporidiosis or other opportunistic infections. Neither I. belli nor cryptosporidium was detected in stool samples from 170 healthy siblings, friends, and spouses of the patients with AIDS. In all patients with isosporiasis, diarrhea stopped within two days of the beginning of treatment with oral trimethoprim-sulfamethoxazole. Recurrent symptomatic isosporiasis developed in 47 percent of the patients, but it also responded promptly to therapy with trimethoprim-sulfamethoxazole. We conclude that isosporiasis is common in Haitian patients with AIDS, and that it responds to therapy with trimethoprim-sulfamethoxazole but is associated with a high rate of recurrence.
Abstract 4407: Novel mitochondria-targeted Doxorubicin Prodrug for colorectal cancer and hepatocellular carcinoma: In vitro studies
Authors: Jemianne Jia, Minzhi Xing, Xiaoxi Ling, Mingfeng Bai, Hyun S. Kim
Journal: Cancer Research (2015)

Abstract Purpose: The 18-kDa translocator protein (TSPO) in mitochondria is proapoptotic and upregulated in several types of cancers, particularly in colorectal cancer (CRC). This study aimed to develop a mitochondria-targeted doxorubicin prodrug and to investigate its cytotoxicity in human CRC (TSPO positive) and HCC (TSPO negative) cell lines. Methods: Mitochondria-targeted Doxorubicin Prodrug was synthesized by conjugation of a functional TSPO ligand with doxorubicin via an enzyme-cleavable linkage. Fluorescence cell viability assays in HT29, HCT116, HepG2 and Hep3B cells incubated with 5, 10, 25 and 50μM of Prodrug vs. Doxorubicin alone were performed using the CellTiter-Glo® Luminescent Cell Viability Assay (Promega, Madison, MI, USA) at 6, 12, 24, 48, 60 and 72 hrs. T-tests were used for all comparisons (significance &amp;lt;.05). Results: Significantly decreased cell viability in TSPO positive CRC cell lines (HCT116 and HT-29) with both the prodrug and doxorubicin vs. controls was observed (p&amp;lt;0.05). In HCT116, 10 and 25μM prodrug demonstrated significantly higher cytotoxicity vs. doxorubicin at 48 and 60 hrs, with plateau in effect at 72 hrs; 50μM prodrug had significantly higher cytotoxicity vs. doxorubicin alone at all time points (p&amp;lt;.05 for all). In HT-29, 25 and 50μM prodrug had significantly higher cytotoxicity vs. doxorubicin at 48 and 60 hrs (p&amp;lt;.05). In TSPO negative HCC cell lines (Hep3B and HepG2), prodrug and doxorubicin vs. control showed significantly decreased cell viability at all time points except for 10μM at 24 hrs; 25 and 50μM prodrug demonstrated similar cytotoxicity vs. doxorubicin at all time points except at 60 hours (p&amp;lt;.05 for all). Conclusion: Our novel mitochondria-targeted doxorubicin prodrug demonstrated superior cytotoxicity compared to doxorubicin in human CRC cell lines. Citation Format: Jemianne Jia, Minzhi Xing, Xiaoxi Ling, Mingfeng Bai, Hyun S. Kim. Novel mitochondria-targeted Doxorubicin Prodrug for colorectal cancer and hepatocellular carcinoma: In vitro studies. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4407. doi:10.1158/1538-7445.AM2015-4407
How do we choose the best donor for T-cell-replete, HLA-haploidentical transplantation?
Authors: Ying-Jun Chang, Leo Luznik, Ephraim J. Fuchs, Xiao-Jun Huang
Journal: Journal of Hematology & Oncology (2016)

In haploidentical stem cell transplantations (haplo-SCT), nearly all patients have more than one donor. A key issue in the haplo-SCT setting is the search for the best donor, because donor selection can significantly impact the incidences of acute and chronic graft-versus-host disease, transplant-related mortality, and relapse, in addition to overall survival. In this review, we focused on factors associated with transplant outcomes following unmanipulated haplo-SCT with anti-thymocyte globulin (ATG) or after T-cell-replete haplo-SCT with post-transplantation cyclophosphamide (PT/Cy). We summarized the effects of the primary factors, including donor-specific antibodies against human leukocyte antigens (HLA); donor age and gender; killer immunoglobulin-like receptor-ligand mismatches; and non-inherited maternal antigen mismatches. We also offered some expert recommendations and proposed an algorithm for selecting donors for unmanipulated haplo-SCT with ATG and for T-cell-replete haplo-SCT with PT/Cy.
Case 21-1997
Authors: Joseph P. Eder, Phuong L. Nguyen
Journal: New England Journal of Medicine (1997)

Presentation of CaseA 67-year-old woman was admitted to the hospital because of a progressive choreiform disorder.The patient had been well until 13 months earlier, when she became dizzy and restless, had difficulty grasping things, and had to hold on to objects to maintain her balance while walking. Ten months before admission, dysphagia developed. The results of an evaluation performed elsewhere, including a lumbar puncture, computed tomographic (CT) scanning, magnetic resonance imaging (MRI), and an MRI angiographic examination of the brain, were normal.One month later, she was admitted to another hospital, where a nodule was found in the . . .
Case 16-1997
Authors: Lawrence H. Cohn, Michael R. Pins
Journal: New England Journal of Medicine (1997)

Presentation of CaseA 42-year-old woman was admitted to the hospital because of a mass in the pulmonic valve.The patient had been in stable health until six weeks earlier, when she began to have a dry cough that occasionally produced white sputum, with fatigue and exertional dyspnea. An examination performed 36 days before admission showed a prominent closure sound of the pulmonic valve (P2), without a murmur. The anteroposterior chest diameter was increased, and the respiratory excursion was reduced. The lungs were clear. Radiographs of the chest showed a normal cardiac silhouette, clear lungs, and esophageal dilatation . . .
Serial Impedance Plethysmography for Suspected Deep Venous Thrombosis in Outpatients
Authors: Menno V. Huisman, Harry R. Böller, Jan W. ten Cate, Johan Vreeken
Journal: New England Journal of Medicine (1986)

Diagnosis of deep venous thrombosis by clinical signs and symptoms is unreliable, but contrast venography is relatively expensive and invasive. We therefore evaluated the use of impedance plethysmography as a noninvasive alternative in 426 consecutive outpatients with clinically suspected acute deep venous thrombosis. Four sequential impedance plethysmograms were obtained on days 1,2,5, and 10 of the study. In 289 patients (68 percent), the results of all four studies were normal, and these patients were not treated with anticoagulants. One of these patients may have had a minor pulmonary embolus during the 10-day study period. During a six-month follow-up of all patients, none of the 289 patients whose plethysmograms were normal died of venous thromboembolism or presented with suspected pulmonary embolism. In 137 patients (32 percent), the impedance plethysmograms were abnormal; 117 (85 percent) had the abnormal results on their first test, and 20 (15 percent) had them on subsequent tests. All patients with abnormal plethysmograms also underwent contrast venography, which confirmed the diagnosis of deep venous thrombosis in 92 percent. We conclude that the diagnostic accuracy of repeated impedance plethysmography compares favorably with that of venography and that the technique is a safe and effective noninvasive approach to the diagnosis and care of outpatients with clinically suspected acute deep venous thrombosis. (N Engl J Med 1986; 314:823–8.)
P60 Uptake and Quality of Health Surveillance for Occupational Asthma in the UK
Authors: D Fishwick, D Sen, P Barker, A Codling, D Fox, S Naylor
Journal: Thorax (2015)

<h3>Introduction</h3> Statutory periodic health surveillance (HS) of workers can identify early cases of occupational asthma. Information about its uptake in the UK, and its content when carried out, are lacking. <h3>Methods</h3> A telephone survey of employers, and their occupational health professionals, was carried out in three sectors with the potential for producing exposures, which may result in the development of occupational asthma (bakeries, wood working, motor vehicle repair). <h3>Results</h3> 457 organisations participated (31% response rate); 77% employed less than 10 people, 17% between 10 and 50 and 6% more than 50. Risk assessments were common (67%) and 14% carried out any form of occupational asthma HS, rising to 19% if only organisations reporting asthma hazards and risks were considered. HS was carried out by both in-house (31%) and external providers (69%). Organisational policies were often used to define surveillance approaches (80%), but shared with the occupational health provider only in one third of cases. Occupational health providers described considerable variation in practice, with differing approaches seen for information sharing and workplace visits. Record keeping was universal, but worker-held records were not reported. Health surveillance tools, such as a questionnaire, were generally developed in-house. Lung function was commonly measured, but only limited interpretation was evident. The referral of workers to local specialist respiratory services was variable. <h3>Conclusions</h3> This study has provided new insights into the real world of health surveillance for occupational asthma in the UK. We consider that future work could and should define more practical, evidence based and simple approaches to HS, by working with the end users to develop interventions that meet their needs. This will ensure maximal uptake of high quality HS approaches and consistency.
Replicated psychometric correlates of schizophrenia
Authors: S O Moldin, I I Gottesman, J P Rice, L Erlenmeyer-Kimling
Journal: American Journal of Psychiatry (1991)

The authors' goals are to use scales from the MMPI hypothesized in their previous research to be correlates of liability to schizophrenia to differentiate DSM-III schizophrenia from bipolar and unipolar affective illness and to cross-validate these correlates in an independently ascertained sample of patients with Research Diagnostic Criteria (RDC) schizophrenia or affective disorder.The criterion sample consisted of 83 patients consecutively admitted to a state-operated community mental health center. Diagnosis of schizophrenia; bipolar disorder, manic; and major depression were assigned by using DSM-III. The replication sample consisted of 60 adults with RDC diagnoses of schizophrenia, schizoaffective disorder, bipolar disorder, and unipolar disorder who were parents of children in two samples collected for a study of offspring at high risk for schizophrenia and other psychopathology. After the patients in the criterion sample were classified by logistic regression analysis, the results were used to classify patients in the replication sample.The MMPI indicators had adequate sensitivity, specificity, and predictive power for classifying schizophrenia, and there was a moderately high rate of diagnostic agreement between the MMPI and DSM-III. Cross-validation in the replication sample was successful. Overall, the MMPI index was an adequate inclusion and exclusion criterion not only for DSM-III-defined but also for RDC-defined schizophrenia.A psychometric index composed of the paranoid schizophrenia, psychoticism, and manifest hostility scales from the MMPI would be a cost-effective measure to increase diagnostic efficacy in future schizophrenia research and clinical practice.
Aromatase Inhibitors in Breast Cancer
Authors: Alexander R.W. Forrest
Journal: New England Journal of Medicine (2003)

To the Editor: Smith and Dowsett (June 12 issue)1 do not mention the possible abuse of aromatase inhibitors by bodybuilders and others who may misuse anabolic steroids. Misuse of testosterone and other androgens by male bodybuilders may be associated with the development of gynecomastia due to the synthesis of estrogens from exogenous androgen precursors.2 Tamoxifen and other estrogen-receptor blockers, as well as the aromatase inhibitor aminoglutethimide, may be used to prevent gynecomastia associated with androgen misuse.3,4 A possible additional benefit of aminoglutethimide is that it may block the cortisol response to exercise. The use of aminoglutethimide in this context . . .
Role of Ploidy, Chromosome 1p, and Schwann Cells in the Maturation of Neuroblastoma
Authors: Ingeborg M. Ambros, Andrea Zellner, Borghild Roald, Gabriele Amann, Ruth Ladenstein, Dieter Printz, Helmut Gadner, Peter F. Ambros
Journal: New England Journal of Medicine (1996)

Neuroblastoma is a heterogeneous disease, with manifestations ranging from spontaneous regression to lethal spread. Sometimes the tumor spontaneously differentiates toward a benign ganglioneuroma (maturing neuroblastoma). The prognosis is frequently related to ploidy, deletions in the short arm of chromosome 1, and amplifications of the N-myc oncogene. Maturing neuroblastomas consist of both neuronal cells and Schwann cells. We investigated the genetic composition of both cell types in maturing neuroblastomas, to determine the relation between genetic abnormalities and maturation.
Union Health Department Act
Authors: Autino Fiore
Journal: New England Journal of Medicine (1950)

ON AUGUST 10, 1949, Governor Paul A. Dever signed an act authorizing the organization of union health departments in Massachusetts. The act has been described as the most far-reaching health legislation passed in many years, and physicians in the Commonwealth will undoubtedly wish to be thoroughly acquainted with it. They should study its provisions carefully, analyze its possible effect on medical practice and finally form an opinion of its value and effectiveness in improving local public-health administration. Many physicians now accept civic responsibility and are actively interested in the affairs of local, state and federal government. However, Dr. Edward L. . . .
Safety and efficacy of brigatinib (AP26113) in advanced malignancies, including ALK+ non–small cell lung cancer (NSCLC).
Authors: D. Ross Camidge, Lyudmila Bazhenova, Ravi Salgia, Corey J. Langer, Kathryn A. Gold, Rafael Rosell, Alice Tsang Shaw, Glen J. Weiss, Narayana I. Narasimhan, David J. Dorer, Victor M. Rivera, Timothy Piers Clackson, Maureen G Conlan, David Kerstein, Frank G. Haluska, Scott N. Gettinger
Journal: Journal of Clinical Oncology (2015)

8062 Background: Brigatinib is an investigational oral tyrosine kinase inhibitor with preclinical activity against rearranged ALK and clinically identified crizotinib-resistant mutants. Methods: A phase (ph) 1/2 single-arm, open-label, multicenter study in patients (pts) with advanced malignancies is ongoing. Pts received brigatinib (30–300 mg/d total daily dose, ph 1; 90 mg/d, 180 mg/d, or 90 mg/d for 7 d followed by 180 mg/d, ph 2). Safety was evaluated in all 137 treated pts; efficacy was evaluated in all 79 ALK+ NSCLC pts. NCT01449461. Results: Median age: 57 y; 58% female. As of 4 Aug 2014, 47% of total pts and 71% of ALK+ NSCLC pts remained on study. Median and maximum time on treatment were 5.5 mo and 29 mo (ongoing), respectively. Most common treatment-emergent adverse events, generally grade 1/2, included: nausea 45%; diarrhea 36%; fatigue 36%; cough 26%; headache 26%. Early-onset pulmonary events, observed ≤7 d after starting treatment, included dyspnea, hypoxia, or new pulmonary opacities on chest computed tomography suggestive of pneumonia or pneumonitis and occurred in 13/137 (9%) pts (6/44 [14%] pts started at 180 mg qd [once daily]; 2/50 [4%] pts started at 90 mg qd [pts treated with 90 mg qd or 90 mg qd for 7 d followed by 180 mg qd]). Of 72 evaluable ALK+ NSCLC pts, 52 (72%) responded: 45/65 (69%) with prior crizotinib and 7/7 crizotinib-naive pts. Median duration of response: 49 wks. Median progression-free survival (PFS): 56 wks; 47 wks with prior crizotinib. In a post hoc independent radiological review of pts with baseline intracranial central nervous system metastases, 6/12 pts with lesions ≥10 mm had a brain response (≥30% decrease in sum of longest diameters of target lesions) and 8/26 pts with only nonmeasurable lesions had disappearance of all lesions. Median intracranial PFS for these pts: 97 wks. Conclusions: Brigatinib has promising antitumor activity in ALK+ NSCLC pts with and without prior crizotinib, including pts with brain metastases. Early-onset pulmonary events were observed less frequently with the 90-mg starting dose compared with higher doses. A randomized ph 2 trial of brigatinib 90 mg qd vs 90 mg qd for 7 d followed by 180 mg qd in crizotinib-resistant ALK+ NSCLC (ALTA) is underway. Clinical trial information: NCT01449461.
Maturity-Onset Diabetes of Youth in Black Americans
Authors: William E. Winter, Noel K. Maclaren, William J. Riley, Derrel W. Clarke, Michael S. Kappy, Rebecca P. Spillar
Journal: New England Journal of Medicine (1987)

Twelve of 129 black patients with youth-onset diabetes were identified as having an unusual clinical course, with apparent insulin dependence at the time of presentation followed by absence of dependence months to years later. This atypical form of diabetes was found in at least two generations in 9 of the 12 families of the propositi. Fourteen of the diabetic relatives, as well as the 12 propositi, were studied. Islet-cell autoantibodies were not found in any of the patients, and thyroid microsomal autoantibodies were found in only one. The frequencies of the insulin-dependent-diabetes–associated antigens HLA-DR3 and DR4 were not increased among the propositi, and diabetes did not cosegregate with HLA haplotypes in the informative families. Insulin secretion, as measured by C-peptide responses to a liquid mixed meal (Sustacal), was intermediate between secretion in nondiabetic controls and that in patients with classic insulin-dependent diabetes. Peripheral-blood monocytes expressed increased numbers of insulin receptors as well as decreased empty-site affinities. The atypical form of diabetes in black Americans can be distinguished from classically defined insulin-dependent diabetes and may be best classified as a form of maturity-onset diabetes of youth. (N Engl J Med 1987; 316:285–91.)
EPIG-14EPIGENOMIC (DNA METHYLATION AND EXPRESSION) SIGNATURES DEFINE SUBSETS OF BOTH IDHmut AND IDHwt GLIOMA WITH DISTINCT CLINICAL OUTCOMES
Authors: Tathiane Malta, Thaís Sabedot, Michele Ceccarelli, Floris Barthel, Stefano Pagnotta, Antonio Iavarone, Roel Verhaak, Houtan Noushmehr
Journal: Neuro-Oncology (2015)

TCGA Glioma working group recently performed comprehensive characterization studies of both low grade glioma (LGG) and primary glioblastoma (GBM), which independently identified strong heterogeneity in clinical diagnosis using genome-wide aberrant DNA methylation (Brennan et al Cell 2013 and TCGA NEJM 2015). By integrating the GBM and LGG DNA methylation data, we aimed to investigate the discordance among the clinical subtypes. We performed unsupervised clustering of DNA methylation profiles of 932 gliomas (516 LGG and 416 GBM) and identified 6 robust groups (LGm1-6). LGm1-3 can be characterized as enriched for IDHmut (451/454, 99%) and was mostly LGG (421/454, 92.7%). In contrast, LGm4-6 was IDHwt (477/478, 99.8%) and was predominantly GBM (383/478, 80%). LGm1-3 showed distinct hypermethylation across the whole genome compared to LGm4-6 clusters, however there were distinct methylation subtypes within the LGm1-3 that stratified the IDHmut into two subgroups. Interestingly, the previously identified high grade G-CIMP and IDHmut-non-codel LGG cases split into LGm1 and LGm2-3. A methylation signature was able to discriminate a subgroup of IDHmut samples, which can be characterized as hypomethylated, displays activated expression of a cell cycle/cell proliferation signature and is enriched with SOX2-binding sites in the hypomethylated elements. Interestingly, this group can be characterized by worse clinical outcome. Likewise, among the IDHwt cohort, we observed distinct methylation and clinical subtypes with a subset with hypomethylated signature, showed an increased overall survival relative to both LGG and GBM IDHwt. Interestingly, this subtype lack mutation and copy number alterations compared to other IDHwt cases, and share a strong epigenetic profile similar to pilocytic astrocytoma. Our analyses were confirmed using 4 independent non-TCGA data and therefore suggests that new relevant subtypes of both IDHmut with poor survival and IDHwt with good survival exist and should be studied further.
Quartan Malaria Occurring Subsequent to a Blood Transfusion
Authors: William J. H. Fischer, Charles L. York
Journal: New England Journal of Medicine (1946)

WITH the return of military personnel from areas where malaria is endemic, the problem of post-transfusion malaria is bound to assume greater importance than it has in the past. The following case deserves mention because of several unusual features.Case ReportE. M., a 40-year-old married woman, was admitted to the Rhode Island Hospital on February 25, 1946, complaining of chills and fever every 3rd day for the last several weeks. She had previously been seen at the hospital on September 19, 1945, when she was admitted in shock. At that time she gave a history of vaginal bleeding for . . .
Abstract 5388: Methionine S-adenosyltransferase 2A (MAT2A) inhibitors for cancer treatment
Authors: Wen Zhang, Vitaliy Sviripa, David Watt, Chunming Liu
Journal: Cancer Research (2015)

Abstract Methionine S-adenosyltransferase 2A (MAT2A) is the catalytic subunit for synthesis of S-adenosylmethionine (SAM), the principal methyl donor in many biological processes. MAT2A is up-regulated in many cancers, including liver cancer and colorectal cancer (CRC) and is a potentially important drug target. In normal liver, methionine S-adenosyltransferase 1 (MAT1), but not MAT2A is expressed. MAT2A is induced in liver cancer. We developed a family of fluorinated N,N-dialkylaminostilbene agents, called FIDAS agents, that inhibit the proliferation of CRC cells and liver cells in vitro and in vivo. Using a biotinylated FIDAS analog, we identified the catalytic subunit of MAT2A as the direct and exclusive binding target of these FIDAS agents. FIDAS agents do not bind MAT1A. MAT2B, an associated regulatory subunit of MAT2A, binds indirectly to FIDAS agents through its association with MAT2A. FIDAS agents inhibited MAT2A activity in SAM synthesis, and depletion of MAT2A by shRNAs inhibited CRC and liver cancer cell growth. FIDAS agents also inhibited specific histone methylation and repressed transcription of c-myc and other oncogenes. FIDAS agents delivered orally repressed CRC xenografts in athymic nude mice. Based on SAR and docking studies, new generations of FIDAS agents were synthesized and tested. An active in vivo metabolite of FIDAS was identified. PK/PD studies were performed. Our findings suggest that FIDAS analogs targeting MAT2A represent a family of novel and potentially useful agents for cancer treatment. Citation Format: Wen Zhang, Vitaliy Sviripa, David Watt, Chunming Liu. Methionine S-adenosyltransferase 2A (MAT2A) inhibitors for cancer treatment. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5388. doi:10.1158/1538-7445.AM2015-5388