tbuckley/cabot-search huggingface dataset:
M3 Anxiety and Depression in Patients with Breathing Pattern Disorders or Chronic Respiratory Disease
Authors: SD Naylor, J Haines, A Vyas, SJ Fowler
Journal: Thorax (2015)

<h3>Background</h3> Patients that have chronic respiratory disease (CRD) and breathing pattern disorders (BPD) have a higher prevalence of anxiety and depression than the general population. These patients have worse respiratory health outcomes and in addition, their psychological problems are often left undiagnosed and untreated. Little is known about how anxiety and depression varies between CRD and BPD. <h3>Methods</h3> This prospective study involved screening patients attending secondary and tertiary respiratory clinics over an eight-week period. Patients were asked to complete the Hospital Anxiety and Depression Scale (HADS), Short Form-12 (SF-12) and St. George's Respiratory Questionnaire (SGRQ). Demographical data and spirometry were also collected. Our primary outcome measure was the difference in these scores between patients with CRD (asthma, bronchiectasis and chronic obstructive pulmonary disease) compared to BPD (vocal cord dysfunction and dysfunctional breathing). <h3>Results</h3> 43 patients (21 with CRD and 22 with BPD) completed questionnaires; mean (SD) age 55 (17) yrs, 32 female. The overall prevalence of borderline anxiety was 17% and clinically significant anxiety 37%. The overall prevalence of borderline depression was 15% and clinically significant depression 29%. Of the patients with CRD, 29% had anxiety and 29% depression. In the BPD cohort, anxiety and depression were found in 45% and 30% of patients respectively. The difference between these groups was not statistically significant (anx: <i> P = 0 </i>.42; dep <i> P = 0 </i>.19). Independent predictors for anxiety and depression were higher SGRQ (anx: <i> P = 0 </i>.001; dep: <i> P &lt; 0 </i>.0001), lower SF-12 Mental (anx: <i> P &lt; 0 </i>.0001; dep: <i> P &lt; 0 </i>.0001) and Physical (anx: <i> P = 0 </i>.042; dep: <i> P = 0 </i>.0027) Health Composite Scores, and lower FEV<sub>1</sub>% predicted (anx: <i> P = 0 </i>.0043; dep: <i> P = 0 </i>.016). <h3>Conclusions</h3> Anxiety and depression are present in a significant numbers of individuals in both CRD and BPD, with no difference between these groups, so efforts should be made to screen for psychological problems in patients with both CRD and BPD. Worse respiratory function and more symptoms are important contributing factors to patients' risk of anxiety and depression.
Of Nicks and Time
Authors: Brahmajee K. Nallamothu, Sanjay Saint, Theodore J. Kolias, Kim A. Eagle
Journal: New England Journal of Medicine (2001)

A 32-year-old man with a history of asthma and "crack" cocaine use presented to the emergency department after an episode of syncope. Earlier that evening, he had smoked crack cocaine several times. Shortly after his last use, he began to have sharp chest pain, which radiated to his shoulders and was associated with dizziness and diaphoresis, followed by a sudden loss of consciousness. His wife, who witnessed the event, described him as "foaming at the mouth" and having involuntary trembling of his arms and legs. He was brought immediately to the emergency department.The patient reported no shortness . . .
Uterine Cancer: Its Early Detection by Simple Screening Methods
Authors: Daniel J. McSweeney, Donald G. McKay
Journal: New England Journal of Medicine (1948)

UNTIL the cause of and a specific cure for cancer have been found, successful treatment must depend on early diagnosis. Since symptoms suggestive of cancer may not appear until the disease is well advanced, early diagnosis must be made by a process of "screening" whereby symptom-free persons are examined at frequent intervals and studies made to detect malignant lesions.The most frequent cancers in women are those of the uterus, both cervix and corpus, which comprise about 30 per cent of all malignant tumors in women, lesions of the cervix predominating over those of the corpus about 5:1. Early malignant . . .
Effect of Continuous Intravenous Infusion of Zidovudine (AZT) in Children with Symptomatic HIV Infection
Authors: Philip A. Pizzo, Janie Eddy, Judy Falloon, Frank M. Balis, Robert F. Murphy, Howard Moss, Pam Wolters, Pim Brouwers, Paul Jarosinski, Marc Rubin, Samuel Broder, Robert Yarchoan, Arturo Brunetti, Mary Maha, Sandra Nusinoff-Lehrman, David G. Poplack
Journal: New England Journal of Medicine (1988)

To produce concentrations of zidovudine (AZT) in plasma and cerebrospinal fluid that would provide constant inhibition of the replication of human immunodeficiency virus (HIV), we gave AZT by continuous intravenous infusion to 21 children ranging in age from 14 months to 12 years who had acquired HIV infection through transfusions or perinatally. All patients were symptomatic before AZT treatment (Class P2 of the Centers for Disease Control); 13 (62 percent) had evidence of neurodevelopmental abnormalities. The mean CD4/CD8 ratio was 0.18; 11 patients had CD4 counts below 0.2 x 10(9) per liter. We administered AZT at four dose levels: 0.5, 0.9, 1.4, and 1.8 mg per kilogram of body weight per hour. The plasma drug concentrations achieved at the respective dose levels were 1.9 +/- 0.3, 2.8 +/- 1.4, 3.1 +/- 1.1, and 4.5 +/- 1.0 microM. The steady-state cerebrospinal fluid:plasma ratio was 0.24 +/- 0.07. The only evidence of toxicity was bone marrow suppression. Transfusion was required in 14 patients because of low levels of hemoglobin (5 mmol per liter [less than 8 g per deciliter]). Dose-limiting neutropenia (less than 0.5 x 10(9) polymorphonuclear leukocytes per cubic millimeter) occurred in most patients who received doses of 1.4 mg per kilogram per hour or more. Improvement in neurodevelopmental abnormalities occurred in all 13 children who had presented with encephalopathy before treatment. Serial measurements of IQ before therapy and after three and six months of continuous therapy with AZT showed that IQ scores, including those for verbal and performance IQ, rose in these 13 patients and in 5 other children who had no detectable evidence of encephalopathy before treatment. Most patients also had increased appetite and weight, decreased lymphadenopathy and hepatosplenomegaly, decreased immunoglobulin levels, and increased numbers of CD4 cells. In some patients the improvement in the features of encephalopathy occurred despite the absence of immunologic improvement. We conclude that AZT is beneficial in children with symptomatic HIV infection, especially those with encephalopathy (which may be subclinical), and that the optimal continuous intravenous dose of AZT in children is between 0.9 and 1.4 mg per kilogram per hour.
Sensitivity of myxoid-round cell liposarcoma (MRCL) to trabectedin (T) may be related to a direct effect on the fusion transcript
Authors: F. Grosso, C. Forni, R. Frapolli, A. Greco, A. Gronchi, J. Jimeno, R. Mantovani, M. D'Incalci, S. Pilotti, P. G. Casali
Journal: Journal of Clinical Oncology (2007)

10000 Background: Myxoid-round cell liposarcomas (MRCL) is a variant of liposarcoma, associated with t(12;16)(q13;p11) and the rarer t(12;22)(q13;q12) chromosomal translocation, resulting in the FUS-CHOP and EWS-CHOP fusion proteins, supposed to act as aberrant transcription factors. We reported the exceedingly high clinical efficacy of T against MRCL, which is a magnitude higher in comparison to other liposarcomas and sarcomas. Reasons thereof remain unknown, but a distinct mechanism of action of T in MRCL is suspected on clinical grounds. Methods: Tumor biopsies were taken from 9 MRCL patients (pts) before starting T, and the tumor was fully characterized by cytogenetic and molecular analysis. Primary cultures were set up, and tumor fragments were transplanted in scid mice, to develop an experimental model aimed at investigating the mechanism of action of T. Chromatin immunoprecipitation (ChIP) analysis on the 402–91 myxoid liposarcoma cell line was performed, to characterize the DNA binding capability of FUS-CHOP. Finally, in vivo ChIP analyses are currently ongoing, using tumor samples obtained before and after therapy with T. Tumor samples from 3 patients have been processed so far. Results: All patients had t(12–16) by FISH. Molecular characterization showed that 7 pts had the type II transcript, 1 had the type III, and 1 both type II and III. Primary cultures evaluated after the first 3 passages were morphologically, cytogenetically and molecularly consistent with the original tumor, as well as the 4 tumours grown in mice so far. In the myxoid liposarcoma cell line carrying the type I transcript, selective binding of FUS-CHOP to some promoters was seen. Impairment of this binding activity was observed after treatment with T at concentration 1–4 nM. Conclusions: There is in vitro evidence of a direct effect of T on the fusion protein's ability to bind to promoters. In vivo studies on the experimental model are ongoing, and results will be presented. No significant financial relationships to disclose.
Paroxysmal Nocturnal Hemoglobinuria
Authors: R. R. Merliss
Journal: New England Journal of Medicine (1952)

THE most accurate method of study of any disease is enlightened statistical analysis of a large number of cases. However, paroxysmal nocturnal hemoglobinuria is a rare blood dyscrasia; approximately 45 cases, not all of convincing authenticity, have appeared in the literature to this time.9 Consequently, no physician or group of physicians is likely to collect a number sufficient to be of statistical significance. Therefore, in this disease an older method, that of long-term observation of a few cases, must be relied on to add to the common stock of medical knowledge. This paper is based on clinical observation of two . . .
Prostate brachytherapy post implant dosimetry: Timing matters
Authors: K. J. Minehan, K. Furutani, K. McNamara, D. Groshek, E. Mitchell, M. Price, M. Emme, T. Harms
Journal: Journal of Clinical Oncology (2006)

14597 Background: Permanent seed implant (PSI) brachytherapy is a common treatment modality for low-risk prostate cancer. Post implant dosimetry (PID) is utilized to asses the quality of the implant. Significant prostate swelling occurs as a result of the implant procedure, and this swelling subsides over time. PID completed on Day 0 after the implant procedure captures the prostate swelling from the procedure. Conversely, PID completed one month later does not have this swelling. PID can therefore show great variation, depending on the timing of the analysis. It is hypothesized that PID completed on Day 0 demonstrates lower dosimetric parameters than PID completed one month later. Methods: Thirteen low risk prostate cancer patients, (Stage ≤ T2, PSA &lt; 13.9, Gleason Score ≤7) were implanted with 125 Iodine seeds, with a prescription dose of 145Gy to the prostate plus a 5mm margin. Computed Tomography (CT) PID was completed for each patient on day 0 and on average 33 days following the implant. The prostate was contoured on each axial CT image and the data was analyzed using commercially available PSI planning software. The dose which encompassed 90% of the prostate volume (D90) was calculated for day 0 and day 33 PID. Results: On average, the prostate volume contoured was larger on day 0 PID (Avg. 44.9 cc; range 19–97 cc) compared to day 33 PID (Avg. 38.9 cc; range 18–59 cc) (P = 0.068). The D90 values however, were significantly higher on day 33 PID (Avg.163.7 Gy; range 125–212 Gy) than on day 0 PID (Avg.149 Gy; range 112–166 Gy) (P = 0.003). This D90 relationship was even demonstrated paradoxically in two patients whose contoured prostate volume was larger on the day 33 PID as compared to the day 0 PID. Conclusions: Timing does matter in the analysis of post implant dosimetry for PSI brachytherapy. The D90 values were significantly greater on day 33 PID compared to Day 0 PID while the contoured prostate volumes were not. Future studies which use PID planning to evaluate implant quality should specify the timing of the PID, as this would facilitate cross study comparison. No significant financial relationships to disclose.
Faith Healing, Christian Science, and the Medical Care of Children
Authors: Rita Swan
Journal: New England Journal of Medicine (1983)

Christian Science was developed in the late 19th century as one of many drugless healing methods. Its founder, Mary Baker Eddy, repeatedly called it a system of medicine.1 , 2 She founded her Massachusetts Metaphysical College "for medical purposes,"3 and graduated "doctors of Christian Science."4 She recommended that doctors become Christian Scientists.5 She applauded when North Carolina law recognized Christian Science practitioners as professional healers and licensed them along with physicians.6 She protested when other licensing boards denied her practitioners rights to "the practice of medicine."7 The terminology of her system duplicates that of a medical health-care system. The church trains "nurses" . . .
Esophagitis Associated with the Use of Alendronate
Authors: Piet C. de Groen, Dieter F. Lubbe, Laurence J. Hirsch, Anastasia Daifotis, Wendy Stephenson, Debra Freedholm, Suzanne Pryor-Tillotson, Mitchel J. Seleznick, Haim Pinkas, Kenneth K. Wang
Journal: New England Journal of Medicine (1996)

Alendronate, an aminobisphosphonate and a selective inhibitor of osteoclast-mediated bone resorption, is used to treat osteoporosis in postmenopausal women and Paget's disease of bone. Aminobisphosphonates can irritate the upper gastrointestinal mucosa.
Extreme Hyperkalemia in Munchausen-by-Proxy Syndrome
Authors: Daniella Magen, Karl Skorecki
Journal: New England Journal of Medicine (1999)

To the Editor: A 20-month-old girl was admitted to the hospital because of a reported febrile convulsion. Her medical history included recurrent simple febrile convulsions and unexplained slight gynecomastia. Physical examination revealed a well-nourished and cheerful child, with normal vital signs and physical and psychomotor development, except for the slight gynecomastia. Repeated blood tests from different puncture sites sent in different test tubes to the hospital laboratory revealed extreme hyperkalemia, incompatible with life, and very high serum creatinine concentrations (Table 1, samples 1 through 3). The electrocardiogram showed no signs of hyperkalemia. Urine output was normal. The discrepancy between the . . .
In Search of Perverse Polymorphisms
Authors: Nadia Rosenthal, Robert S. Schwartz
Journal: New England Journal of Medicine (1998)

By the time the Beagle left the waters of the remote Galapagos Islands, Charles Darwin had still not realized that the natural variations within a species would provide the means for its evolution. Later, the Galapagos finches furnished ideal support for his theory of natural selection, because after a long separation from the finches of the rest of the world, they had become highly inbred. Geographic isolation had restricted their gene pool, so that the subtle differences Darwin saw among the island finches must have resulted from genetic changes, or polymorphisms, that arose spontaneously in individual birds and were then . . .
Depression in the Elderly
Authors: Dan Blazer
Journal: New England Journal of Medicine (1989)

DEPRESSION is a psychiatric syndrome frequently encountered by physicians who treat older adults. Depression is not one disease, but rather the presentation of multiple medical and psychiatric disorders, ranging from bereavement to hypothyroidism. Most older persons are satisfied with their lives and experience only transient fluctuations in mood. Persistent depressive symptoms in the elderly must therefore not be ignored or devalued but require a thorough diagnostic workup.In surveys of adults in the community, major depression is less prevalent among those 65 and older than in younger groups.1 There may be an increased prevalence of depression among those 85 years . . .
Maintenance pemetrexed plus best supportive care (BSC) versus placebo plus BSC: A phase III study
Authors: T. E. Ciuleanu, T. Brodowicz, C. P. Belani, J. Kim, M. Krzakowski, E. Laack, Y. Wu, P. Peterson, S. Adachi, C. C. Zielinski
Journal: Journal of Clinical Oncology (2008)

8011 Background: This multicenter phase III trial compared the efficacy and safety of pemetrexed (Pem) versus placebo (Plac) in pts with stage IIIB/IV NSCLC who had not progressed on four cycles of platinum-based induction chemotherapy. Per protocol, final analyses were completed for all outcomes except overall survival (OS). Sub-group analyses were based on results from prior studies. Methods: In this double-blind trial, pts were randomized (2:1 ratio; balanced for stage, ECOG PS, sex, response to induction therapy, non-platinum component of induction therapy, and brain metastases) to receive Pem (500 mg/m2, day 1) plus BSC or Plac plus BSC in 21-day cycles until disease progression. All pts received vitamin B12, folic acid and dexamethasone. The primary analysis of progression-free survival (PFS) was based on an unadjusted Cox HR (target n=660; alpha=0.05; power=85% to show HR<1.00 assuming 462 events and HR=0.75). Results: A total of 663 pts were enrolled (Pem=441; Plac=222). Pt characteristics were well balanced between arms: median age=61 years; 27% female; 39% PS 0, 60% PS 1; 19% Stage IIIB; 23% East Asian; 50% adenocarcinoma, 27% squamous cell, 3% large cell, and 20% other/indeterminate histology; 49% induction CR/PR; and 8% with brain metastases. Pem had better efficacy with respect to PFS (4.3 vs 2.6 mos [HR 0.502, 95% CI: 0.42–0.61, p <0.00001]) and tumor response (p <0.001), especially in non-squamous pts. With 55% censoring (all pts), preliminary OS was 13.0 mos with Pem and 10.2 mos with Plac (HR 0.798, 95% CI 0.63–1.01, p = 0.060). There were no significant toxicity differences between arms except for grade 3–4 anemia (Pem 4.5%, Plac 1.4%) and total SAEs due to drug (Pem 4.3%, Plac 0%). Conclusions: Post-induction maintenance therapy with Pem is well tolerated and offers superior PFS compared with Plac in pts with advanced NSCLC. This trial confirms that Pem has greater efficacy in patients with non-squamous histology. Median PFS (mos) HR p-value Objective Tumor Response (CR+PR+SD) p-value Pem Placebo Pem Placebo All patients 4.3 2.6 0.502 <0.00001 51.7 33.3 <0.001 Non-squamous (n=482) 4.5 2.6 0.444 <0.00001 57.7 32.7 <0.001 Adenocarcinoma (n=329) 4.7 2.6 0.452 <0.00001 61.0 33.0 <0.001 Large Cell (n=20) 3.5 2.1 0.400 0.109 45.5 33.3 0.670 Other (n=133) 4.2 2.8 0.433 0.0002 51.1 31.7 0.041 Squamous (n=181) 2.8 2.6 0.692 0.039 34.8 34.8 1.000 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Eli Lilly and Company Eli Lilly and Company Eli Lilly and Company Eli Lilly and Company Eli Lilly and Company
A new method for treating "headaches"
Authors: D Sherwin
Journal: American Journal of Psychiatry (1979)

The author describes a 10-week study designed to gain some understanding of how to treat patients who have suffered for a long time with headaches that have not been alleviated by many attempts at treatment. Fourteen patients whose chief complaint was this kind of headache were given varying amounts of perphanazine and amitriptyline with the direct suggestion that these drugs would be helpful. This treatment appeared successful for 10 of the 14 patients at 6-month and 3-year follow-up.
The Hidden Epidemic: Confronting Sexually Transmitted Diseases, by Institute of Medicine
Authors: M. Adler
Journal: BMJ (1997)

Institute of Medicine: National Academy Press, £32.95, pp 275 ISBN 0 309 05495 8

There is a tendency to look on AIDS and HIV and other sexually transmitted diseases as issues largely of the developing world, particularly sub-Saharan Africa and Southern and South East Asia. However, some rich industrialised countries, particularly the United States, have an epidemic of sexually transmitted diseases (about 12 million new cases annually, of which 3 million occur in teenagers), and no national coordinated control programme of education and clinical services.

The Hidden Epidemic is the report of a 16 member committee on prevention and control of sexually transmitted diseases set up by the Institute of Medicine to assess the current impact of such diseases and to “provide direction for future public health programmes, policy and research in STD prevention and …
Abstract 4499: Cytotoxicity, biochemical activity, and structural analysis of ONC201 and comparisons to a biologically inactive isomer
Authors: Jessica Wagner, Christina Leah Kline, Richard S. Pottorf, Bhaskara Rao Nallaganchu, Gary L. Olson, David T. Dicker, Joshua E. Allen, Wafik S. El-Deiry
Journal: Cancer Research (2015)

Abstract We previously identified TRAIL-inducing compound 10 (TIC10), also known as NSC-350625, as a small molecule being developed under the name ONC201 that has potent anti-tumor efficacy and a benign safety profile in preclinical cancer models. Further investigation of the preclinical profile of this drug candidate led in early 2014 to the FDA acceptance of the investigational drug application (IND) for oral ONC201 to treat patients with advanced cancer. The initially disclosed chemical structure of ONC201 provided by Stahle et. al in an expired patent was described as an imidazo[1,2-a]pyrido[4,3-d]pyrimidine derivative. Our first report of its anticancer activity by Allen et. al. included mass spectrometry and 1H NMR that indicated both were consistent with the structure depicted by Stahle et. al and the National Cancer Institute. A recent publication reported that the structure of ONC201 differs from the initial description and is in fact an angular [3,4-e] isomer of the previously depicted structure. Here, we report X-ray crystallography and other structural studies of ONC201 produced by Oncoceutics in a dihydrochloride salt form for clinical use that confirm the angular [3,4-e] structure and indicate that the material is not a mixture of the two isomers. Furthermore, we confirm that although fragmentation by mass spectrometry for the isomers is identical, the angular [3,4-e] isomer can be definitively identified as ONC201 by implementing specific various spectroscopy techniques to identify differences between ONC201 and the linear isomer. In accordance with our structural analysis, in vitro activity assays in cancer cells indicate that the previously disclosed anti-cancer activity and mechanism of action are indeed associated exclusively with the [3,4-e] structure and not the [4,3-d] linear isomer. Together these studies confirm the angular [3,4-e] structure of ONC201 as the highly active and pure anti-cancer drug candidate that was utilized in prior preclinical pharmacology studies and is now entering clinical trials in several oncology indications. Citation Format: Jessica Wagner, Christina Leah Kline, Richard S. Pottorf, Bhaskara Rao Nallaganchu, Gary L. Olson, David T. Dicker, Joshua E. Allen, Wafik S. El-Deiry. Cytotoxicity, biochemical activity, and structural analysis of ONC201 and comparisons to a biologically inactive isomer. [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 4499. doi:10.1158/1538-7445.AM2015-4499