tbuckley/cabot-search huggingface dataset:
Effects of Chlorothiazide on the Pancreas
Authors: Allen L. Cornish, James T. McClellan, David H. Johnston, Bernice Bright
Journal: New England Journal of Medicine (1961)

Since its introduction into clinical use in 1958 chlorothiazide has gained widespread acceptance as an effective diuretic and hypotensive agent. Because it is effective when taken by mouth, patients have found its use both convenient and economical. In addition, many patients report that by taking chlorothiazide daily as a diuretic they have become free of the "ups and downs" of intermittent mercurial therapy.With careful administration to avoid electrolyte depletion, the toxic effects of the drug have been rare. There have been scattered reports of chlorothiazideinduced papular skin rashes,1 exfoliative dermatitis,2 purpura3 and jaundice.4 In addition to such untoward reactions . . .
The Depressant Effect of Cigarette Smoke on the in Vitro Antibacterial Activity of Alveolar Macrophages
Authors: Gareth M. Green, Diana Carolin
Journal: New England Journal of Medicine (1967)

CIGARETTE smoking has been recognized as "... the most important of the causes of chronic bronchitis. ..."1 Although knowledge of the pathogenic mechanisms of this relation is incomplete it is clear that cigarette smoke produces a variety of morphologic and physiologic changes in the lung. The association of both cigarette smoking and an increased susceptibility to bacterial infection with chronic bronchitis suggests that cigarette smoke directly inhibits antibacterial mechanisms of the bronchopulmonary tree.Defense of the lung against inhaled bacteria is achieved by the mechanism of bacterial clearance.2 A heavy dose of cigarette smoke inhibits bacterial clearance in mice.3 The . . .
Disease prevalence, tumour stage, and results of testing in the pilot phase of a service for cervical cancer screening and diagnosis in northern Tanzania
Authors: P. Serra, N. Masalu, L. Bucchi, J. Kahima, L.F. Kiyesi, R. Maltoni, O. Nanni, S. Sarti, M. Botteghi, D. Amadori
Journal: Annals of Oncology (2015)
Phase I pharmacokinetic and pharmacodynamic study of the heat shock protein 90 inhibitor AT13387 in patients with refractory solid tumors.
Authors: G. Shapiro, E. L. Kwak, B. J. Dezube, D. P. Lawrence, J. M. Cleary, S. Lewis, M. Squires, V. Lock, J. F. Lyons, M. Yule
Journal: Journal of Clinical Oncology (2010)

3069 Background: AT13387 is a highly potent heat shock protein 90 (HSP90) inhibitor (IC50 0.7 nM) derived from Astex fragment chemistry platform, Pyramid. AT13387 suppresses client proteins for greater than 7 days in tumor cells, making it the longest acting agent reported to date. Methods: In this phase I dose escalation trial, AT13387 was administered as a 1-hr intravenous infusion on days 1, 4, 8, 11, 15 and 18 of a 28-day cycle in a standard “3+3” design in order to determine MTD. Secondary endpoints included PK, PD and tolerability. Results: Between May 2008 and December 2009,21 patients with median age 57 (r 28-77) were treated with AT13387 over 5 dose levels, including 10, 20, 40, 80 and 120 mg/m2 twice weekly. No dose-limiting toxicities have been observed. The most frequent toxicities reported in the first eighteen patients were diarrhea (11/18, 61%) and fatigue (5/18, 28%) of mild or moderate severity. At the 120 mg/m2 dose level, reversible grade 1 visual changes were common, including blurred vision, flashes and delayed light dark/accommodation, occurring at day 11 or later. Evidence of HSP90 inhibition, manifest as an increase in HSP70 in PBMCs, was detected at all dose levels and exhibited dose dependence. Reductions in the expression of CDK4, raf-1 and phospho-AKT were also detected in PBMCs in a proportion of patients. PK parameters determined on days 1 and 18 of cycle 1 demonstrated exposure proportional to dose administered, without significant plasma accumulation with repeated administration. Clearance of AT13387 was independent of dose (mean 25 ml/min/kg). The best response in this heavily pre-treated population has been stable disease that persisted for at least six months in two patients (follicular cell carcinoma of the thyroid and metastatic uveal melanoma). Conclusions: Single-agent AT13387, administered as a twice-weekly infusion three weeks out of four, is well- tolerated at doses up to 120mg/m2. No hepatotoxicity has been observed. Favorable pharmacokinetics and expected pharmacodynamic endpoints have been demonstrated. Further schedule refinement may involve evaluation of twice-weekly dosing two weeks out of every three, as well as weekly administration. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Astex Therapeutics Astex Therapeutics Astex Therapetics, Astex Therapeutics Astex Therapeutics
Carcinoma and Thyroid Nodules
Authors: J. Martin Miller
Journal: New England Journal of Medicine (1955)

MOST of the numerous articles on nodular goiter and thyroid cancer are written by surgeons and presumably for surgeons1 2 3 4 5 6 7; the papers of Crile8 9 10 are a notable exception. Internists and general practitioners see most of the nodular goiters, and the majority of patients are never referred to the surgeon. The suspicious thyroid glands, however, are submitted for surgical scrutiny, as are the glands that are easily identifiable as cancer on physical examination. These not undesirable circumstances contribute measurably to the unintentional distortions in some surgical statistics. Time has produced little unanimity of opinion between the two groups. The figures of . . .
Association of Epstein–Barr Virus with Leiomyosarcomas in Young People with AIDS
Authors: Kenneth L. McClain, Charles T. Leach, Hal B. Jenson, Vijay V. Joshi, Brad H. Pollock, Richard T. Parmley, Frederick J. DiCarlo, Ellen Gould Chadwick, Sharon B. Murphy
Journal: New England Journal of Medicine (1995)

Children with the acquired immunodeficiency syndrome (AIDS) have an unusually high incidence of smooth-muscle tumors (leiomyomas and leiomyosarcomas) in addition to malignant lymphomas. We tested the hypothesis that the smooth-muscle tumors in these children are associated with the Epstein–Barr virus (EBV).
68Ga-PSMA PET/CT Imaging and 153Sm-EDTMP Bone Pain Palliation Therapy
Authors: Arun Sasikumar, Ajith Joy, Raviteja Nanabala, M.R.A. Pillai, Boben Thomas
Journal: Clinical Nuclear Medicine (2016)

Ga-labeled prostate-specific membrane antigen (PSMA) is a potential tool in the imaging of recurrent prostate cancer. Ga-PSMA imaging is also useful for radiotherapy planning and in targeted therapy with Lu-PSMA. A few case reports regarding the use of Ga-PSMA in nonprostate cancer malignancies are also reported. We describe the use of Ga-PSMA imaging before Sm-EDTMP bone pain palliation therapy in a 58-year-old hormone refractory prostate cancer patient with extensive bone metastases.
Abstract 463: Successful generation of tumor infiltrating lymphocytes from human non-small cell lung cancer specimens
Authors: Kyoung-Hee Kim, Julia Kargl, Sylvia Lee, McGarry Houghton
Journal: Cancer Research (2015)

Abstract Tumor infiltrating lymphocytes (TILs) are naturally occurring cancer-fighting T cells found within malignant tumors. After decades of research, patient-derived TIL populations have been successfully re-infused into melanoma subjects, and have produced impressive treatment effects in a subset of cases. To date, the successful generation and usage of TIL populations for non-small cell lung cancer (NSCLC) patients has not been reported. Generating TILs from NSCLC tissue presents several challenges, as immune cell populations residing within the lungs are constantly exposed to numerous inhaled antigens and other particulate matter. Here, we report the successful generation of TILs from three NSCLC specimens from subjects undergoing surgical resection for curative intent. Six distinct lung cancer tissue fragments were cultured in the presence of IL-2 for each of the three cases. Each fragment yielded a TIL population, although their proliferative rates differed substantially. Each TIL population was subjected to flow cytometry to identify the cellular subtypes, and these results were compared to the lymphocyte subset content measured in the original in vivo tumor specimen. Preliminary findings suggest that the ability to generate CD8+ enriched TILs is dependent upon the CD8+ content present in vivo. Low CD8+ content was associated with an abundance of either Tregs or NK cells. Greater than 70% of the CD8+ populations generated displayed an effector phenotype (CCR7-CD45RA+), regardless of the overall cellular composition of the specimen. However, these cells displayed heterogeneous levels of exhaustion markers (PD1, Tim3), which inversely correlated with proliferative rates. Our results show that TIL populations can be successfully generated from primary human NSCLC specimens. Although the relative cellular content differed for each tissue fragment, we were able to generate at least one CD8+ effector population with low levels of exhaustion for each case. In vitro and in vivo studies to determine the tumor killing capacity of these TIL populations are currently underway. Note: This abstract was not presented at the meeting. Citation Format: Kyoung-Hee Kim, Julia Kargl, Sylvia Lee, McGarry Houghton. Successful generation of tumor infiltrating lymphocytes from human non-small cell lung cancer specimens. [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 463. doi:10.1158/1538-7445.AM2015-463
Case 2-1996
Authors: J.M. Jessup, F.M. Graeme-Cook
Journal: New England Journal of Medicine (1996)

Presentation of CaseA 32-year-old woman was admitted to the hospital because of left subcostal pain, bouts of fever, and a mass in the left hepatic lobe.The patient had been well until four years earlier, when she began to have progressive, constant left subcostal pain, with an intermittent increase in the temperature to 39.4°C, anorexia, and nausea. The episodes occurred approximately every six months and lasted for a week or two; they had recently begun to occur every four months.Three months before admission an evaluation elsewhere included an ultrasonographic examination, a computed tomographic (CT) scan of the abdomen, . . .
Beta-Galactosidase Deficiency in the Hurler Syndrome
Authors: Monica MacBrinn, Shintaro Okada, Marjorie Woollacott, Vimal Patel, Mae Wan Ho, A. L. Tappel, J. S. O'Brien
Journal: New England Journal of Medicine (1969)

A deficiency of β-galactosidase (pH 5.0) was found in frozen tissues (brain, liver, kidney and spleen) from 10 patients with Hurler's syndrome (Types 1–3). The diminished activity of this enzyme was demonstrated with the use of nitrophenyl-galactosides as well as ganglioside GM1 and a "keratan sulfate-like" mucopolysaccharide. Mixing experiments demonstrated that soluble endogenous inhibitors are not responsible for the lowered β-galactosidase activity. Activities of related hydrolases, including acid phosphatase, α-glucosidase, β-glucosidase, β-xylosidase, β-N-acetyl-galactosaminidase, β-N-acetyl-glucosaminidase, α-mannosidase, β-glucuronidase and cathepsins A-D, were increased two to five times. Deficiency of β-galactosidase may prove to be the primary enzymic defect in the Hurler syndrome.
Chlorpropamide-Induced Immune Hemolytic Anemia
Authors: Gerald L. Logue, Aubrey E. Boyd, Wendell F. Rosse
Journal: New England Journal of Medicine (1970)

Acute intravascular hemolysis developed while a patient was taking the oral sulfonylurea, chlorpropamide. An IgG antibody was present in the patient's serum that in the presence of chlorpropamide and fresh serum, brought about the lysis of complement-sensitive red cells from patients with paroxysmal nocturnal hemoglobinuria. The antibody was found to cross-react with other sulfonylureas but not with sulfisoxazole. Red cells from some patients with paroxysmal nocturnal hemoglobinuria were not lysed by this "innocent-bystander" reaction.
Studies on the Mechanism of Hypotensive Action of Chlorothiazide
Authors: D. Aleksandrow, W. Wysznacka, J. Gajewski
Journal: New England Journal of Medicine (1959)

MANY observations point to a relation existing between arterial hypertension and body sodium metabolism. Some clinical forms of hypertension (such as Cushing's syndrome and toxemia of pregnancy) are constantly accompanied by a marked sodium retention. Substitution of sodium chloride solution for drinking water leads to experimental hypertension in rats.1 In human subjects prolonged heavy salt intake also seems to increase the occurrence of hypertension.2 Chronic salt depletion in dogs prevents the development of experimental renal hypertension.3 A similar preventive effect of a diet containing a high ratio of potassium to sodium has been observed in rats.4 The hypotensive effect of . . .
Increased Frequencies Of Myeloid-Derived Suppressor Cells and Regulatory T-Cells Decrease Response To Donor Lymphocyte Infusions, Independent Of Graft Versus Host Disease In Multiple Myeloma
Authors: Laurens E. Franssen, Maarten E. Emmelot, Niels W.C.J. van de Donk, Henk Lokhorst, Tuna Mutis
Journal: Blood (2013)
Ocular Lesions in Rheumatoid Arthritis and Related Disorders with Particular Reference to Retinopathy
Authors: Arthur L. Scherbel, Allen H. Mackenzie, James E. Nousek, Martin Atdjian
Journal: New England Journal of Medicine (1965)

Original Article from The New England Journal of Medicine — Ocular Lesions in Rheumatoid Arthritis and Related Disorders with Particular Reference to Retinopathy — A Study of 741 Patients Treated with and without Chloroquine Drugs
Influence of Age and of Iodine Intake on the Production of Thyroid Tumors in the Rat&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: H. Isler, Ph.D., C. P. Leblond, M.D., Ph.D., A. A. Axelrad, M.D., Ph.D.
Journal: JNCI Journal of the National Cancer Institute (1958)

The influence of age and of iodine intake on the production of neoplastic thyroid nodules was investigated in 1-, 4-, and 14-month-old rats fed for 12 months on a low iodine diet with or without iodine supplement. After autopsy, the number and size of thyroid nodules was estimated in semiserial sections of the entire gland. While the thyroid glands of the animals given iodine supplement were grossly and histologically normal, those of iodine-deficient rats showed gross enlargement, hyperplasia, decreased colloid, and hyperemia. Nodules were observed and classified on the basis of histological appearance into two broad categories referred to as type-β and type-γ. Type-β nodules were found in 84 of the 135 iodine.deficient rats but in none of the 38 iodine-supplemented rats. Hence the formation of these nodules required the iodine deficiency and, presumably, the high level of circulating thyrotrophic hormone induced by this condition. The proportion of rats with type-β nodules, 74 percent, 52 percent, and 64 percent in the 1 -, 4-, and 14-month groups, respectively, was not increased by aging. Type-γ nodules were found in 3 of the iodine-supplemented rats and in 30 of the iodine-deficient rats. Hence iodine deficiency and presumably the resulting high level of circulating thyrotrophic hormone were not essential to, but facilitated the formation of, type-γ nodules. The incidence, 9 percent, 20 percent, and 42 percent in the 3 age groups, respectively, and the size of type-γ nodules increased with age.
Influence of Lung Function and Sleep-disordered Breathing on All-Cause Mortality. A Community-based Study
Authors: Nirupama Putcha, Ciprian Crainiceanu, Gina Norato, Jonathan Samet, Stuart F. Quan, Daniel J. Gottlieb, Susan Redline, Naresh M. Punjabi
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Rationale: Whether sleep-disordered breathing (SDB) severity and diminished lung function act synergistically to heighten the risk of adverse health outcomes remains a topic of significant debate.Objectives: The current study sought to determine whether the association between lower lung function and mortality would be stronger in those with increasing severity of SDB in a community-based cohort of middle-aged and older adults.Methods: Full montage home sleep testing and spirometry data were analyzed on 6,173 participants of the Sleep Heart Health Study. Proportional hazards models were used to calculate risk for all-cause mortality, with FEV1 and apnea–hypopnea index (AHI) as the primary exposure indicators along with several potential confounders.Measurements and Main Results: All-cause mortality rate was 26.9 per 1,000 person-years in those with SDB (AHI ≥5 events/h) and 18.2 per 1,000 person-years in those without (AHI <5 events/h). For every 200-ml decrease in FEV1, all-cause mortality increased by 11.0% in those without SDB (hazard ratio, 1.11; 95% confidence interval, 1.08–1.13). In contrast, for every 200-ml decrease in FEV1, all-cause mortality increased by only 6.0% in participants with SDB (hazard ratio, 1.06; 95% confidence interval, 1.04–1.09). Additionally, the incremental influence of lung function on all-cause mortality was less with increasing severity of SDB (P value for interaction between AHI and FEV1, 0.004).Conclusions: Lung function was associated with risk for all-cause mortality. The incremental contribution of lung function to mortality diminishes with increasing severity of SDB.
Radioactive Iodine (<sup>125</sup>I) Therapy for Thyrotoxicosis
Authors: I. R. McDougall, W. R. Greig, F. C. Gillespie
Journal: New England Journal of Medicine (1971)

131I therapy of thyrotoxicosis results in an increasing incidence of hypothyroidism with the passage of time. Conventional methods of reducing this phenomenon have led to slower rates of control or adjuvant drug therapy. The very short-range emissions of 125I have been shown in laboratory animals to disrupt thyroid-cell function more than division, suggesting the use of this isotope in the treatment of thyrotoxicosis in humans. Fifteen patients received a mean of 1008 μCi of 125I per gram of thyroid weight. Sixty per cent are euthyroid, 26.6 per cent hypothyroid, and 6.7 per cent thyrotoxic; they have been under review for 19.9 months. Of seventy-seven patients who received a mean of 589 μCi per gram of thyroid weight, 68.8 per cent are euthyroid, and 23.4 per cent hypothyroid; 5.2 per cent remain thyrotoxic after a mean follow-up period of 11.9 months. Of fifty-six given a mean of 382 μCi of 125I per gram of thyroid weight, 80.3 per cent are euthyroid, 12.5 per cent hypothyroid and 7.2 per cent thyrotoxic, 14.3 months after receiving therapy.
Use of Multinucleated Giant Cells to Diagnose a Viral Eruption
Authors: Frank C Koranda
Journal: New England Journal of Medicine (2004)

University of Kansas Medical Center Kansas City, KS 66160 art of the differential diagnosis of a vesicular eruption must include smallpox. The characteristic smallpox lesions — papulovesicular pustules — develop two to four days after an influenza-like prodrome. The lesions progress from macules to papules to vesicular pustules. The eruption appears first on the face; spreads centrifugally to the scalp, upper chest, back, arms, and hands; and appears last on the abdomen, legs, and feet. The lesions are all in the same stage of development on a given area of the body. The differential diagnosis of the vesicular-pustule stage includes varicella (chickenpox), eczema herpeticum (disseminated herpes), and herpes zoster. One way of differentiating varicella, herpes simplex, and herpes zoster from smallpox is to identify multinucleated giant cells in a Tzanck smear from a fresh vesicle. Smallpox does not produce multinucleated giant cells. The features of the multinucleated giant cell include multinucleation, with molding of the nuclei as they are crowded together (Panel A; Giemsa, ¬400); peripheral margination of the chromatin; and a ground-glass appearance of the nuclei (Panel B; Giemsa, ¬400). The cell may also have a bizarre or atypical shape. The Tzanck preparation shown in Panel A is from a lesion in a 19-year-old woman with atopic dermatitis in whom eczema herpeticum developed from herpes simplex. The preparation in Panel B is from a 32-year-old man with varicella.
Case 38-2009
Authors: Steven D. Brass, Marc J. Dinkin, Ziv Williams, Kalpathy S. Krishnamoorthy, William A. Copen, Stefanie H. Freeman
Journal: New England Journal of Medicine (2009)

A boy was first seen in the pediatric neurology clinic at 16 years of age because of paroxysmal headaches and visual changes. Physical and neurologic examinations were normal, and imaging studies showed no intracranial abnormalities. Headaches persisted despite a variety of therapies and during the next 4 years were associated with transient weakness, loss of consciousness, obtundation, and back pain. Intermittent optic-disk edema was noted. When the patient was 21 years old, lumbar puncture revealed an opening pressure of 25 cm of water; several hours later, symptoms of cauda equina syndrome developed. A diagnostic procedure was performed.
Reported alcohol use in women with premenstrual syndrome
Authors: M B Tobin, P J Schmidt, D R Rubinow
Journal: American Journal of Psychiatry (1994)

Women with prospectively confirmed premenstrual syndrome (N = 21) reported greater alcohol use than comparison subjects (N = 16) in a longitudinal study. The difference in reported alcohol use was not confined to the premenstruum, nor did it correlate with dysphoric symptoms or cravings for food premenstrually.
Subcutaneous Icatibant for the Treatment of Acute Attacks of Hereditary Angioedema: Comparison of Self-Administration to Administration at a Medical Facility
Authors: Iris Otani, William R. Lumry, Huamin Henry Li, Chevy Chase, Timothy J. Craig, Marc A. Riedl, Bruce L. Zuraw, Aleena Banerji
Journal: Journal of Allergy and Clinical Immunology (2016)
151P: Outcomes of research biopsies in clinical trials of EGFR mutation-positive NSCLC patients pretreated with EGFR-TKIs
Authors: B.-C. Liao, Y.-Y. Bai, C.-C. Lin, S.-Y. Lin, Y.-F. Lee, C.-C. Ho, J.-Y. Shih, Y.-C. Chang, C.-J. Yu, J. Yang
Journal: Journal of Thoracic Oncology (2016)
Pathology of Esophageal Neoplasms and Associated Proliferative Lesions Induced in Rats by &lt;italic&gt;N&lt;/italic&gt;-Methyl-&lt;italic&gt;N&lt;/italic&gt;-benzylnitrosamine
Authors: Sherman F. Stinson, Robert A. Squire, Michael B. Sporn
Journal: JNCI Journal of the National Cancer Institute (1978)

Multiple squamous cell neoplasms of the esophagus were induced in 24 inbred F344 rats by sc injection of N-methyl-N-benzylnitrosamine at a dose level of 2.5 mg/kg weekly for 20 weeks. All of these rats also developed papillomas, 67% developed pedunculated papillary carcinomas, and 63% developed carcinomas that invaded the wall. Of 191 total neoplasms, 66% were papillomas, 17% were papillary carcinomas, and 17% were carcinomas that invaded the wall. The neoplasms were well differentiated with various degrees of keratinization. Anaplastic areas were found in most lesions, but were more common in carcinomas. Neoplasms that invaded the wall were sessile, with prominent intraluminal growth, or infiltrating, with predominant intramural growth. Penetration through the wall was observed, but neither metastases nor invasion of adjacent tissues was found. In addition to neoplasms, atypical endophytic proliferation of basal and spinous cells was observed in some of these rats. Proliferative or neoplastic changes were not observed outside the upper gastrointestinal tract.