tbuckley/cabot-search huggingface dataset:
The Emergence of Drug-Resistant Tuberculosis in New York City
Authors: Thomas R. Frieden, Timothy Sterling, Ariel Pablos-Mendez, James O. Kilburn, George M. Cauthen, Samuel W. Dooley
Journal: New England Journal of Medicine (1993)

In the past decade the incidence of tuberculosis has increased nationwide and more than doubled in New York City, where there have been recent nosocomial outbreaks of multidrug-resistant tuberculosis.
Use of Plasma Pharmacokinetics to Predict and Prevent Methotrexate Toxicity
Authors: Ronald G. Stoller, Kenneth R. Hande, Samuel A. Jacobs, Steven A. Rosenberg, Bruce A. Chabner
Journal: New England Journal of Medicine (1977)

To correlate the pharmacokinetics and toxicity of methotrexate, we measured the drug's clearance from plasma after 395 high-dose, six-hour infusions given to 78 patients. After 375 infusions, 48 hour methotrexate levels fell within 2 standard deviations of the mean for nontoxic infusions, and myelosuppression did not occur. Methotrexate concentrations exceeded the range for nontoxic patients (mean +/- 2 standard deviations) after 20 infusions. Serious myelosuppression occurred after six of these 20 infusions, including five of 12 infusions associated with 48-hour drug concentrations above 9 X 10(-7) M. In seven patients with 48-hour concentrations above 9 X 10(-7) M, the absence of toxicity could be attributed to subsequent rapid clearance of the drug; four of these patients also received large doses of supplemental leucovorin (50 to 100 mg per square meter every six hours). Determination of methotrexate concentration in plasma thus identified patients at high risk of toxicity, a group that may benefit from supplemental leucovorin rescue.
Prevalence of the Human Immunodeficiency Virus among University Students
Authors: H D Gayle, R P Keeling, M Garcia-Tunon, B W Kilbourne, J P Narkunas, F R Ingram, M F Rogers, J W Curran
Journal: New England Journal of Medicine (1990)

To estimate the magnitude of the human immunodeficiency virus (HIV) epidemic among university students, we conducted a blinded HIV-seroprevalence survey at 19 universities throughout the United States. HIV-antibody testing was performed on blood collected for routine medical purposes at the student health centers of the participating institutions. At each campus, from 250 to 1000 blood specimens were collected consecutively and tested for HIV antibodies by enzyme-linked immunosorbent assay and Western blot analysis. Nonidentifying demographic data were linked with the test results.
CSIG-13INVESTIGATING THE ROLE OF Fn14 IN EGFRvIII-DRIVEN GLIOBLASTOMA
Authors: Alison Roos, Zach Mayo, Michael Pineda, Jeffrey A. Winkles, Michael E. Berens, Nhan L. Tran
Journal: Neuro-Oncology (2015)

Glioblastoma Multiforme (GBM) is the most common malignant brain tumor in adults. Most GBM patients succumb to the disease less than one-year post diagnosis due to the highly invasive nature of the tumor, which prevents complete surgical resection and gives rise to tumor recurrence. The invasive phenotype also confers radio-and chemoresistant properties to the tumor cells; therefore, there is a need to develop new therapeutics that target drivers of GBM invasion. Amplification of EGFR is observed in over 50% of GBM tumors, of which half concurrently overexpress the variant EGFRvIII, and expression of both receptors confers a worse prognosis. EGFR and EGFRvIII cooperate to promote tumor progression and invasion, in part, through activation of the JAK/STAT-signaling pathway. Here we report that GBM cells expressing EGFRvIII show increased expression of a previously established mediator of glioma cell invasion and survival, fibroblast growth factor-inducible 14 (Fn14), at the mRNA and protein level. Treatment with a STAT3, STAT5, or JAK inhibitor decreased Fn14 mRNA and protein expression. Finally, knockdown of Fn14 levels in the EGFRvIII-expressing glioma cells decreased both cell survival after temozolomide (TMZ) treatment and cell invasion, which suggests that Fn14, in part, mediates the oncogenic phenotypes conferred by EGFRvIII signaling. Since EGFR inhibitors display limited therapeutic efficacy in GBM patients, we hypothesize that Fn14-targeted therapies could potentially limit invasiveness and chemoresistance in these tumor subtypes.
A Double-Blind Trial of a 16-Hour Transdermal Nicotine Patch in Smoking Cessation
Authors: Philip Tonnesen, Jesper Norregaard, Kåre Simonsen, Urbain Säwe
Journal: New England Journal of Medicine (1991)

The use of nicotine chewing gum combined with psychological support improves the success rate in quitting smoking. We studied the safety and efficacy of a transdermal nicotine patch in smoking cessation.
Case 22-1994
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Dennis J. Beer, Eugene J. Mark
Journal: New England Journal of Medicine (1994)

Presentation of CaseA 57-year-old man was referred to the hospital because of extensive bilateral air-space disease and a lung-biopsy specimen that showed alveolar filling, interpreted as pulmonary alveolar proteinosis.The patient had been in excellent heath until four months earlier, when fever, myalgia, and a dry cough developed. Two and a half months before entry he began to experience increasing exertional dyspnea while playing tennis.Two weeks later, the cough increased and became productive of thick green sputum. X-ray films of the chest showed “extensive cannon-ball-type lesions” throughout both lungs, with diffuse infiltrates. Erythromycin was taken for several weeks. . . .
Are Bilateral Breast Cancers and Breast Cancers Coexisting with Ovarian Cancer Different from Solitary Tumors? a Pair-Matched Immunohistochemical Analysis Aimed at Intrinsic Tumor Phenotype
Authors: E. Senkus, J. Szade, B. Pieczyńska, A. Zaczek, M. Świerblewski, W. Biernat, J. Jassem
Journal: Annals of Oncology (2014)
A potential contribution of antimicrobial peptide LL-37 to tissue fibrosis and vasculopathy in systemic sclerosis
Authors: T. Takahashi, Y. Asano, K. Nakamura, T. Yamashita, R. Saigusa, Y. Ichimura, T. Toyama, T. Taniguchi, A. Yoshizaki, Z. Tamaki, Y. Tada, M. Sugaya, T. Kadono, S. Sato
Journal: British Journal of Dermatology (2016)

LL‐37 is an antimicrobial peptide with pleiotropic effects on the immune system, angiogenesis and tissue remodelling. These are cardinal pathological events in systemic sclerosis (SSc). To elucidate the potential role of LL‐37 in SSc. The expression of target molecules was evaluated by immunostaining and quantitative reverse‐transcription real‐time polymerase chain reaction in human and murine skin. The mechanisms regulating LL‐37 expression in endothelial cells were examined by gene silencing and chromatin immunoprecipitation. Serum LL‐37 levels were determined by enzyme‐linked immunosorbent assay. In SSc lesional skin, LL‐37 expression was increased in dermal fibroblasts, perivascular inflammatory cells, keratinocytes and, particularly, dermal small vessels. Expression positively correlated with interferon‐α expression, possibly reflecting LL‐37‐dependent induction of interferon‐α. In SSc animal models, bleomycin‐treated skin exhibited the expression pattern of CRAMP, a murine homologue of LL‐37, similar to that of LL‐37 in SSc lesional skin. Furthermore, Fli1+/− mice showed upregulated expression of CRAMP in dermal small vessels. Fli1 binding to the CAMP (LL‐37 gene) promoter and Fli1 deficiency‐dependent induction of LL‐37 were also confirmed in human dermal microvascular endothelial cells. In the analysis of sera, patients with SSc had serum LL‐37 levels significantly higher than in healthy controls. Furthermore, serum LL‐37 levels positively correlated with skin score and the activity of alveolitis and were significantly elevated in patients with digital ulcers compared with those without. LL‐37 upregulation, induced by Fli1 deficiency at least in endothelial cells, potentially contributes to the development of skin sclerosis, interstitial lung disease and digital ulcers in SSc.
The Doctor of Tomorrow and Federal Medical Services
Authors: Robert Collier Page
Journal: New England Journal of Medicine (1952)

GENERAL MARSHALL, as Secretary of Defense, has stated that the Government is thinking in terms of a possible ten-year tension — a prolonged tension rather than a full-fledged war. What does this mean to the medical profession?Thirteen thousand physicians will be continually needed for active military duty, which means that for every 11.5 doctors who are engaged in private practice 1 doctor will be in uniform. Other governmental agencies presently engage the full-time professional services of 6.776 doctors. As of December 1950, there was 1 physician out of every 15.75 in the United States in governmental service of one . . .
Lymphocyte Mediators and Cellular Hypersensitivity
Authors: Philip R. Steinmetz, Christine Balko, John R. David
Journal: New England Journal of Medicine (1973)

TUMOR, rubor, calor et dolor, cum functione laesa: since the times of the ancients these have been the cardinal signs of inflammation, diagnostic of a reaction by the organism that was detrimental to its well-being. In 1883, Rudolph Virchow, the founder of cellular pathology, advised Metchnikoff to proceed with his researches cautiously, since "most pathologists do not believe in the protective role of inflammation."1 Metchnikoff proceeded, although not with caution, and his life's work provided the basis for the recognition that cellular as well as humoral mechanisms participate in immunity and immunopathology. There is now substantial evidence that cellular . . .
Treatment of Acute Myelogenous Leukemia in Children and Adults
Authors: Howard J. Weinstein, Robert J. Mayer, David S. Rosenthal, Bruce M. Camitta, Felice S. Coral, David G. Nathan, Emil Frei
Journal: New England Journal of Medicine (1980)

We designed a protocol to address the problem of relapse from complete remission in acute myelogenous leukemia. Patients in remission were treated for 14 months; early and later intensification of chemotherapy, sequential drug combinations, and high-dose continuous infusions of cytarabine were included. Eighty-three consecutive patients under 50 years of age were entered into this study from February 1976 to October 1979. The rate of complete remission is 70 per cent. A Kaplan-Meier analysis predicts that 49 +/- 17 per cent of patients (mean +/- 2 S.D.) who entered complete remission will remain free of disease at two years. Durations of complete remission for patients in the 0 to 17-year and 18 to 50-year age groups are comparable.
Pathogenicity of IgG in patients with IgG4-related disease
Authors: Masahiro Shiokawa, Yuzo Kodama, Katsutoshi Kuriyama, Kenichi Yoshimura, Teruko Tomono, Toshihiro Morita, Nobuyuki Kakiuchi, Tomoaki Matsumori, Atsushi Mima, Yoshihiro Nishikawa, Tatsuki Ueda, Motoyuki Tsuda, Yuki Yamauchi, Ryuki Minami, Yojiro Sakuma, Yuji Ota, Takahisa Maruno, Akira Kurita, Yugo Sawai, Yoshihisa Tsuji, Norimitsu Uza, Kazuyoshi Matsumura, Tomohiro Watanabe, Kenji Notohara, Tatsuaki Tsuruyama, Hiroshi Seno, Tsutomu Chiba
Journal: Gut (2016)

<h3>Objective</h3> IgG4-related disease (IgG4-RD) is a systemic disease characterised by elevated serum IgG4 and IgG4-positive lymphoplasmacytic infiltration in the affected tissues. The pathogenic role of IgGs, including IgG4, in patients with IgG4-RD, however, is unknown. <h3>Design</h3> We examined the pathogenic activity of circulating IgGs in patients with IgG4-RD by injecting their IgGs into neonatal male Balb/c mice. Binding of patient IgGs to pancreatic tissue was also analysed in an ex vivo mouse organ culture model and in tissue samples from patients with autoimmune pancreatitis (AIP). <h3>Results</h3> Subcutaneous injection of patient IgG, but not control IgG, resulted in pancreatic and salivary gland injuries. Pancreatic injury was also induced by injecting patient IgG1 or IgG4, with more destructive changes induced by IgG1 than by IgG4. The potent pathogenic activity of patient IgG1 was significantly inhibited by simultaneous injection of patient IgG4. Binding of patient IgG, especially IgG1 and IgG4, to pancreatic tissue was confirmed in both the mouse model and AIP tissue samples. <h3>Conclusions</h3> IgG1 and IgG4 from patients with IgG4-RD have pathogenic activities through binding affected tissues in neonatal mice.
Comparing histopathology from patients with X-linked recessive ichthyosis and autosomal recessive congenital ichthyosis with transglutaminase 1 mutation: A report from the National Registry for Ichthyosis and Related Skin Disorders
Authors: Catherine S. Yang, Hyemin Pomerantz, Kathleen A. Mannava, Jessica Corwin, Martin A. Weinstock, Philip Fleckman, John J. DiGiovanna, Leslie Robinson-Bostom
Journal: Journal of the American Academy of Dermatology (2016)
A phase I study of YM155, a novel survivin suppressant, administered by 168 hour continuous infusion to patients with advanced solid tumors
Authors: A. W. Tolcher, S. Antonia, L. D. Lewis, A. Mita, J. Mahany, N. J. Reddy, E. Till, D. Buell, A. T. Keating
Journal: Journal of Clinical Oncology (2006)

3014 Background: Survivin is one of the family of inhibitor of apoptosis proteins (IAP) that suppresses apoptosis through inhibition of caspases and procaspases. Survivin is selectively expressed in most solid tumors but not normal tissues. In a PC-3 cell model YM155 inhibited survivin mRNA transcription and survivin protein expression and showed potent (nM) anti-proliferative activity in preclinical models including tumor regressions. Methods: The objectives were to determine the maximum tolerated dose (MTD) of 168 hour continuous infusion of YM155 every 3 weeks, to evaluate toxicity, characterize the pharmacokinetics and observe anti-tumor activity. Standard 3+3 dose escalation scheme was utilized. Additional pts were added to fully characterize toxicities at the MTD. Pharmacokinetic sampling was performed during cycles 1 and 2. Results: 41 pts (M/F: 31/10, median age 61, range 28–78) with performance status of 0–2 were enrolled into 4 dose cohorts [1.8 mg/m 2 /day (N = 8), 3.6 (6), 6.0 (2) and 4.8 (25)]. Most common tumor types were prostate (9), NHL (5), and colorectal (5). 2/2 pts experienced DLTs at 6.0 (renal tubular necrosis with grade 3 mucositis and increased serum creatinine), thus the MTD was 4.8 mg/m 2 /day. The most frequent AEs were: pyrexia, arthralgia, nausea, fatigue and diarrhea. The most common grade 3 or 4 drug related AEs were: mucosal inflammation (N = 2, 4.9%) and increased INR (N = 2, 4.9%). At MTD, the median clearance was 47 L/hr with a median steady state concentration of 7.5 ng/mL and a median terminal half-life of 22 hours. Two pts with chemotherapy refractory intermediate grade NHL had marked reduction of lymph nodes including one that was durable (PR reviewed independently). This pt went onto BMT and was in remission at the time of this submission. Two HRPC pts exhibited PSA response (&gt; 50% reduction). Conclusions: YM 155, the first survivin inhibitor, was well tolerated, had a MTD of 4.8 mg/m 2 /day × 7 days and exhibited provocative anti-tumor activity in 4 pts that warrant broad phase II evaluation. No significant financial relationships to disclose.
Differential Serum Vitamin B<sub>12</sub>Concentrations in Mothers and Infants
Authors: William P. Boger, Gilbert M. Bayne, D. Wright, George D. Beck
Journal: New England Journal of Medicine (1957)

IN a previous communication,1 a steady decline in the serum vitamin B12 concentrations during pregnancy was reported. Even as early as the first trimester, the serum concentrations of vitamin B12 were found to be significantly lower than those for normal women of the same age. During the course of this study,1 a personal communication was received from Dr. Bacon Chow, of Johns Hopkins University School of Hygiene and Public Health, indicating that a difference in the serum vitamin B12 concentrations of mother and infant had been observed.2 Accordingly, the investigation reported here was undertaken to confirm and . . .
A randomized placebo-controlled trial of melatonin for poor appetite in advanced cancer patients.
Authors: E. Del Fabbro, S. Dalal, R. Dev, E. Bruera
Journal: Journal of Clinical Oncology (2010)

TPS319 Background: Although initially thought to be synthesized exclusively in the pineal gland and primarily involved as a circadian messenger of light and dark, melatonin is now recognized to have multiple actions and synthesized in various tissues including lymphocytes and the gastrointestinal tract. Melatonin supplementation stimulates appetite in animals, and its presence in the digestive tract is associated with intestinal transit and nutrient absorption. Altered levels of melatonin are found in patients with a range of cancers and preliminary nonrandomized studies in patients with advanced solid tumors suggest melatonin may attenuate weight loss, anorexia, fatigue, and depression. These studies are limited by a lack of blinding and the absence of placebo controls. Melatonin appears to be safe at doses up to 300 mg daily in noncancer patients and after prolonged use in normal volunteers. Methods: Eligibility criteria include patients with solid gastrointestinal tumors or lung cancer, a ≥ 5% involuntary weight loss within the last 6 months and anorexia > 3 (0 is best and 10 is worst) on the Edmonton Symptom Assessment Scale (ESAS). Patients with untreated endocrine dysfunction (hypoadrenalism and thyroid abnormalities) are excluded and nutritional impact symptoms such as nausea, diarrhea, mucositis, constipation, or clinical depression should be resolved or stable for ≥2 weeksat the time of inclusion. Design is a double-blind placebo-controlled trial of 20 mg melatonin vs. placebo for 4 weeks. At the end of 4 weeks, all study patients are given the opportunity to take 20 mg melatonin at night for an additional 4 weeks. The primary objective at 4 weeks is to determine whether melatonin improves appetite in patients with advanced lung cancer or gastrointestinal cancer as defined by a decrease of 1.5 in appetite score from baseline (on ESAS). The secondary objectives include body weight, lean body mass (by bioelectrical impedance and bone free arm muscle area), caloric intake (24 hour diet recall), resting energy expenditure (indirect calorimetry) and serum levels of C-reactive protein. Current accrual stands at 62 patients, and we anticipate enrolling 126. No significant financial relationships to disclose.
Rapid Access to Mental Health Professionals With Experience in Treating Cancer-Related Distress: The American Psychosocial Oncology Referral Helpline
Authors: Elizabeth Harvey, Lauren Rogak, Ruth Ford, Jimmie Holland
Journal: Journal of the National Comprehensive Cancer Network (2013)

The new quality standard for cancer care established in 2008 by the Institute of Medicine requires that the psychosocial domain be integrated into routine cancer care. The American College of Surgeons Commission on Cancer has incorporated this standard in its accreditation requirements for 1500 cancer centers in the country, to be fully implemented by 2015. Oncology offices and clinics are developing procedures for quickly identifying distressed patients and referring them to appropriate mental health professionals. The American Psychosocial Oncology Society (APOS), the Association of Oncology Social Work, and the Oncology Nursing Society are currently drafting recommendations to assist clinics in complying with accreditation requirements. A critical component of this new quality standard is assuring that those who need mental health services are referred to the appropriate resource. A large disconnect exists in most communities between oncology and mental health professionals because they treat very different patient populations. Therefore, oncology staff may have difficulty identifying mental health professionals for patients in need of psychological help. This step can be simplified by use of the APOS Helpline. This article discusses the unique role of the APOS Referral Helpline in the context of this new era of psychosocial care for patients with cancer.
Case 35-2008
Authors: Kirk R. Daffner, Janet C. Sherman, R. Gilberto Gonzalez, Robert P. Hasserjian
Journal: New England Journal of Medicine (2008)

A 65-year-old right-handed man was transferred to this hospital because of the recent onset of confusion and memory loss. MRI scans of the brain showed symmetric abnormalities involving the temporal lobes, left basal forebrain, and insular regions. A CT scan of the chest disclosed an anterior mediastinal mass. A diagnostic procedure was performed.
Case 15-2012
Authors: Nagagopal Venna, Christina M. Coyle, R. Gilberto González, E. Tessa Hedley-Whyte
Journal: New England Journal of Medicine (2012)

A 48-year-old woman was admitted to the hospital because of diplopia, headaches, and papilledema. Imaging revealed cysts in the fourth ventricle and spinal canal. A diagnostic procedure was performed.
Abstract 18870: Impact of Atherectomy on Length of Stay and Cost of Care for Lower Extremity Arterial Intervention - A Cross-sectional US Experience
Authors: Nilay Patel, Shilpkumar Arora, Sopan Lahewala, Sidakpal S Panaich, Nileshkumar Patel, Chirag Savani, Abhishek Dave, Badal Thakkar, Achint Patel, Parth Bhatt, Sanskruti Patel, Samir V Patel, Rajesh Sonani, Kanishk Agnihotri, Aashay Patel, Vikas Singh, Sunny Jhamnani, Abhishek Deshmukh, Apurva O Badheka
Journal: Circulation (2015)

Background: There is lack of data regarding impact of atherectomy on the length of stay (LOS) and cost of hospitalization in lower extremity arterial revascularization. Methods: HCUP’s Nationwide Inpatient Sample (NIS) 2012 was queried using the ICD-9- CM code for peripheral vascular disease and procedural codes 39.90 (bare metal stent - BMS), 00.55 (drug eluting stent - DES), 17.56 (peripheral atherectomy) and 39.50 for angioplasty. Only procedures performed in patients ≥18 years of age were included. Hierarchical mixed effects linear regression models were generated to evaluate multivariate predictors of LOS and hospitalization costs. Results: A total of 13,206 (weighted: 66,030) lower extremity arterial revascularizations were identified (43.8% female &amp; 65.5% white). Out of these, atherectomy was utilized in 23.2%. Atherectomy utilization was associated with significant reduction in LOS (4.96 ± 0.11 days vs. 5.78 ± 0.07 days, p &lt;0.001) but higher hospitalization cost ($ 25196 ± 359 vs. $ 23408 ± 185, p &lt; 0.001). Multivariate analysis showed similar results with decrease in LOS (-0.71 days, -1.00 - - 0.43; p &lt; 0.001) but higher hospitalization cost (+1875 $, +811 - +2940; p = 0.001) with atherectomy, which was matched by propensity score analysis. Additionally, emergent/urgent &amp; weekend admissions and Charlson score ≥2 were further associated with increased LOS and hospitalization costs. (Figure) Conclusion: Our study demonstrates that atherectomy utilization is associated with significant reduction in length of stay, which was counterbalanced by a slight increase in hospitalization costs following lower extremity arterial revascularization.