tbuckley/cabot-search huggingface dataset:
S26 Is the “time spent with saturations below 90%” on sleep study helpful in identifying Obesity Hypoventilation Syndrome in the Sleep Clinic?
Authors: GM Probert, B Prudon, SD West
Journal: Thorax (2015)

<h3>Introduction</h3> Obesity Hypoventilation Syndrome (OHS) is defined as sleep disordered breathing, obesity, and daytime hypercapnia, without another cause of ventilatory impairment.<sup>1</sup> Recent studies have shown that a raised base excess (≥2) or raised venous bicarbonate without daytime hypercapnia, represents a subgroup with OHS without overt respiratory failure.<sup>2</sup> A readily available sleep study parameter indicating the presence of OHS rather than requiring biochemistry would be ideal. We assessed the use of time spent with oxygen saturations ≤90% from standard sleep study data and its relationship with a biochemical diagnosis of OHS. <h3>Methods</h3> We prospectively collected data on sleep clinic patients referred for assessment of possible obstructive sleep apnoea. Patients underwent sleep studies as per standard practice, and the%time spent with saturations &lt;90% was noted (more or less than 30% of the night). Venous bicarbonate or arterial blood gas was checked. Those with evidence of OHS on blood testing had assessment to exclude co-existent respiratory disease. <h3>Results</h3> Data was collected from 190 patients, 71% male, average age 31 (10.8, range 25–75) and mean BMI 39 kg/m<sup>2 </sup>(8.7, 25–76). There was biochemical evidence of OHS in 54 patients (22%) (Venous bicarbonate<i> &gt;27,</i> BE≥2, pCO<sub>2</sub> ≥6kPa). Four patients were excluded: COPD (2), Myasthenia gravis (1) and thoracic scoliosis (1). Table 1 shows the results. Saturations of ≤90% for ≥30% of night had a sensitivity for diagnosing OHS of 59%, specificity 47%. The positive predictive value was 31% and negative predictive value was 74%. <h3>Conclusions</h3> The parameter of “time spent with saturations below 90%” on sleep study is not particularly sensitive or specific for identifying patients with OHS in isolation. We cannot find other literature which has assessed this variable. It does not seem that it can replace blood biochemical measurement in the diagnosis of OHS. This condition still has many unanswered questions remaining including best method of diagnosis and management. <h3>References</h3> 1 Mokhlesi B, Tulaimat A. Recent advances in obesity hypoventilation syndrome.<i> Chest</i> 2007;<b>132</b>(4):1322–36 2 Manuel A, Hart N, Stradling J. Is a raised bicarbonate, without hypercapnia, part of the physiological spectrum of obesity-related hypoventilation? <i>Thorax</i> 2014;<b>69</b>(Suppl 2): A29
Diet and Smoking in the Epidemiology of Cancer of the Cervix&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: J R Marshall, S Graham, T Byers, M Swanson, J Brasure
Journal: JNCI Journal of the National Cancer Institute (1983)

This study of 513 white cervical cancer patients and 490 white hospitalized controls considered, with adjustment for marital history and parity, the effects of smoking and dietary characteristics on the relative risk of developing cervical cancer. Although smoking was shown to be positively associated with risk, no dose-response relationship was evident. The frequency of consumption of cruciferous vegetables was positively associated with risk. Respondent reports of the frequency of prior ingestion of several food items were used in constructing crude indices of exposure to basic nutrients; the index of beta-carotene exposure was negatively associated with risk, whereas the index of fat consumption was positively associated with risk.
Controlling Health Expenditures — the Canadian Reality
Authors: Robert G. Evans, Jonathan Lomas, Morris L. Barer, Roberta J. Labelle, Catherine Fooks, Gregory L. Stoddart, Geoffrey M. Anderson, David Feeny, Amiram Gafni, George W. Torrance, William G. Tholl
Journal: New England Journal of Medicine (1989)

Abstract Canada and the United States have conducted a large-scale social experiment on the effects of alternative ways of funding expenditures for health care. Two very similar societies, with (until recently) very similar systems of providing health care, have adopted radically different systems of reimbursement. The results of this experiment are of increasing interest to Americans, because the Canadian approach has avoided or solved several of the more intractable problems facing the United States. In particular, overall health expenditures have been constrained to a stable share of national income, and universality of coverage (without user charges) eliminates the problems of uncompensated care, individual burdens of catastrophic illness, and uninsured populations. The combination of cost control with universal, comprehensive coverage has surprised some American observers, who have questioned its reality, its sustainability, or both. We present a comparison of the Canadian and American data on expenditures, identifying the sectors in which the experience of the two nations diverges most, and describing the processes of control. In any system, cost control involves conflict between providers and payers. Political processes focus this conflict, whereas market processes diffuse it. But the stylized political combat in Canada may result in less intrusion on the professional autonomy of the individual physician than is occurring in the United States. (N Engl J Med 1989; 320:571–7.)
Chemotherapy alternating gemcitabine and cisplatin concomitant with radiotherapy in locally advanced (LA) squamous cell carcinoma of the head and neck (SCCHN)
Authors: E. Tellez Bernal, J. L. Aguilar, J. Cruz, M. Granados, F. Maldonado, A. Moran, J. Martinez, G. Cabrera, H. Martinez-Said, M. Frias-Mendivil, A. Herrera
Journal: Journal of Clinical Oncology (2006)

15514 Background: In the Pignon’s meta-analysis, the OS benefit was 8% with chemoradiation in LA SCCHN. Unfortunately it is still unclear what scheme is the best, cisplatin (CDDP) being the most widely used drug. Other drugs such as gemcitabine (GMZ) has promising results, although toxicity has been severe but tolerable. We have published an initial study using GMZ and radiotherapy (ann oncol. 2004;15:301). In the present study we wished to determine if a scheme in which GMZ is alternated with CDDP and concomitant radiotherapy reduced toxicity yet maintains our previously described therapeutic effectiveness. This is a preliminary report with a short follow-up period. Methods: Inclusion criteria: patients with SCCHN (EC: III, IVa and IVb ) or with recurring disease, and no sytemic metastases or patients rejection of surgery between 03/2003 and 09/2004. Chemotherapy scheme consisted of GMZ at 100 mg/m 2 once a w, ws 1, 3, 5, 7 and CDDP at 50 mg/m 2 once a w, ws 2, 4, y 6. Radiotherapy consisted of 2 Gy/day, for a total of 70 Gy during the 7 ws. Toxicity evaluation focused on mucositis, xerostomia, dysphagia y leukopenia. Results: 28 patients were treated. 7 (25%)/ stage III, 11 (39.3%) IVa, 10 (35.7%) IVb. The tumor sites distribution was as follows: 9 patients with oropharynx and larynx disease (32.1%), 6 patients with oral cavity disease (21.4%), 3 patients with paranasal sinus disease (10.7%), and 1 hypopharinx (3.5%). A CCR was observed in 21 patients (75%), a partial response was observed in 5 patients (17%). Organ preservation was achieved in 68% of the patients. Toxicity: mucositis Grade 3–4 was in 42% of patients, leucopenia grade III in 29%, dysphagia in 19% and xerostomia in 10%. 40%of the patients stopped treatment for one or two weeks due to toxicity without affecting the doses of both treatments. Conclusions: The scheme with alternating GMZ and CDDP concomitant with radiotherapy is safe and effective. We observed a lower incidence in mucositis and few systemic toxic effects. Our findings support further studies in which alternating chemotherapeutic schemes are utilized given that tumor response is increased without an increment in toxicity. No significant financial relationships to disclose.
5FU-leucovorin (5FU/LV) with or without irinotecan (CPT-11) in stages II-III rectal cancers: Preliminary safety analysis of the French Intergroup R98 phase III trial
Authors: P. Piedbois, T. André, J. Y. Douillard, P. Rougier, A. Zawadi, M. Ychou, T. Muron, E. Achille, M. Buyse, E. Magherini
Journal: Journal of Clinical Oncology (2004)

3549 Background:The optimal adjuvant treatment of stages II-III rectal cancers is still debatable. When administered, postoperative chemotherapy is usually a 5FU-leucovorin (5FU/LV) regimen. CPT-11 + 5FU/LV has been shown to improve the outcome of patients (Pts) with metastatic disease. Methods: R98 trial compares postoperative 5FU/LV (control arm) to 5FU/LV + CPT-11. Primary endpoint is DFS. The trial, designed to include 600 Pts, was initiated in February 1999 by AERO, joined by three French groups (GERCOR in June 2000, FFCD and FNCLCC in December 2003). RT was recommended preoperatively. Centers were asked to choose the control arm, as either Mayo-Clinic regimen (A: LV 20 mg/m2, 5FU 425 mg/m2 bolus days 1–5, repeated at d29, d57, d92, d127 and d162) or LV5FU2 regimen (A': LV 200 mg/m2 over 2-hour, 5FU 400 mg/m2 bolus and 600 mg/m2 22-hour infusion, d1–2, Q2W for 12 cycles). Experimental arm (B) consisted of LV5FU2 + CPT-11 180 mg/m2 d1 of every cycle. Data were reviewed by an IDMC, which approved release of the present analyses. Results: Toxicity data from the first 154 Pts entered by 53 centers before 01/01/02 is analyzed. Pretreatment characteristics were well balanced between the groups; median age 64 years, stage II in 32% of Pts. 69% of Pts received RT, and 79% had sphincter conservation. 95% arm A and A', and 75% arm B Pts received more than 75% of planned chemotherapy dose. No toxic deaths were reported. G3–4 toxicity per Pt was as follows (A, A', B): neutropenia 28%, 0%, 34%; diarrhea 8%, 11%, 15%; nausea-vomiting 0%, 0%, 5%; mucositis: 8%, 0%, 0%; infection: 8%, 0%, 1%; other G3–4 toxicities <5%. Statistically significant differences in G3–4 toxicity profiles between the control and experimental arms indicated a higher incidence of mucositis in arm A (P=0.01), and a lower incidence of neutropenia in arm A' (P<0.0001). RT was not associated with a higher risk of diarrhea. Conclusions:5FU/LV + CPT-11 has an acceptable safety profile in Pts with resected rectal cancer compared to 5FU/LV. No major, unexpected toxicities were observed. Pt accrual is still ongoing. Study supported by Aventis Oncology, France Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis Aventis Aventis
Drug Response Indicator Test (DRIT) as a predictive test for treatment outcomes in advanced breast cancer patients (ABC)
Authors: K. H. Tkaczuk, N. S. Tait, O. Ioffe, M. Tan, M. Mohiuddin, S. Chumsri, D. A. VanEcho, M. J. Sutula, S. Lesko, S. Deamond, P. Ts'o
Journal: Journal of Clinical Oncology (2009)

1119 Background: There are limited options for selecting an optimal treatment regimen for ABC patients (pts). DRIT is a platform technology that provides a profile of a patient's tumor's sensitivity or resistance to commonly used chemotherapeutic, hormonal, or biological agents as a basis for individualized anticancer treatment approach. DRIT may allow physicians to choose more effective drug treatments before initiation of therapy and improve the efficacy and toxicity profile of cancer therapies. Methods: DRIT analysis is based on fluorescent dye-labeled monoclonal antibody staining followed by computer-assisted microscopy to quantitatively measure expression levels in tumor sections. The interpretation of DRI expression levels results in classification of tumors as sensitive or resistant to treatment with a mechanistically related drug. This study utilized the following drug/DRI combinations: hormonal therapy/estrogen receptor; capecitabine/thymidylate synthase; docetaxel, paclitaxel, abraxane/β-tubulin isoform III; trastuzumab/HER-2; gemcitabine/ribonucleotide reductase. DRIT was performed on the tumor tissue of consented study participants with ABC who were then deemed to be sensitive or resistant to a given agent/agents. We then analyzed retrospectively clinical treatment outcomes (clinically sensitive to therapy defined as-stable disease+partial response+complete response or resistant to therapy-no response to therapy) for 91 treatment interventions in 71 pts with the DRIT tissue data. Results: We found that the DRIT sensitivity was 0.99, with specificity of 0.59, positive predictive value of 0.88, negative predictive value of 0.93 and overall predictive value of 88% for treatment outcomes for this cohort of ABC pts. Conclusions: This study suggests that DRIT can provide more accurate prediction of treatment outcomes for ABC pts than the standard of care approach and therefore has a potential to avoid unnecessary ineffective drug treatment exposure. Prospective study in ABC pts is currently conducted at the UMGCC. [Table: see text]
Recurrent Military Tuberculosis
Authors: James J. Leonard, Sol Katz, Georges McCormick
Journal: New England Journal of Medicine (1957)

A DECADE ago acute Military tuberculosis was probably a universally fatal disease. This fact has come to be appreciated only in retrospect since the Military calcifications of healed disseminated histoplasmosis were at that time looked upon as examples of a spontaneous cure of Military tuberculosis.About the time that it became apparent that Military tuberculosis rarely, if ever, healed spontaneously new and potent antituberculous drugs were discovered. The characteristic common to all these drugs is their efficacy in the treatment of acute exudative forms of tuberculosis. The prototype of pure exudative disease is the Military tubercle.Now for the first . . .
A Comparison of Immediate with Deferred Zidovudine Therapy for Asymptomatic HIV-Infected Adults with CD4 Cell Counts of 500 or More per Cubic Millimeter
Authors: Paul A. Volberding, Stephen W. Lagakos, Janet M. Grimes, Daniel S. Stein, James Rooney, Tze-Chiang Meng, Margaret A. Fischl, Ann C. Collier, John P. Phair, Martin S. Hirsch, W. David Hardy, Henry H. Balfour, Richard C. Reichman
Journal: New England Journal of Medicine (1995)

The clinical benefits of zidovudine remain unproved in patients with asymptomatic human immunodeficiency virus (HIV) infection when CD4 cell counts exceed 500 per cubic millimeter. We compared zidovudine therapy given immediately with deferred therapy in such subjects.
The Christchurch Chromosome (Gp–)
Authors: Richard C. Juberg, Barbara Jones
Journal: New England Journal of Medicine (1970)

An 18-month-old male infant with mongolism and erythremic myelosis had two cell lines in his bone marrow and peripheral blood: one cell line, with 47 chromosomes, had 2 Gp— chromosomes, and the other, with 51 chromosomes, had 3 Gp—chromosomes. He died of acute myeloblastic leukemia at 21 months of age. The Gp— chromosome was present in four generations of his family; his mother, his maternal grandmother and his maternal maternal great-grandmother were carriers and phenotypically normal. The Gp— chromosome has not previously been reported in a patient with erythremic myelosis, an uncommon disease in children. Review of all reported propositi and members of their families with the Gp— chromosome shows no consistent phenotypic effect of this deletion. However, among 37 progeny of 18 carriers of the Gp— chromosome, five have had mongolism with 47 chromosomes. The Gp— chromosome itself appears to segregate normally among the progeny of carriers.
Secretome Signature Identifies ADAM17 as Novel Target for Radiosensitization of Non–Small Cell Lung Cancer
Authors: Ashish Sharma, Sabine Bender, Martina Zimmermann, Oliver Riesterer, Angela Broggini-Tenzer, Martin N. Pruschy
Journal: Clinical Cancer Research (2016)

Ionizing radiation (IR) induces intracellular signaling processes as part of a treatment-induced stress response. Here we investigate IR-induced ADAM17 activation and the role of ADAM17-shed factors for radiation resistance in non-small cell lung cancer.Large-scale secretome profiling was performed using antibody arrays. Secretion kinetics of ADAM17 substrates was determined using ELISA across multiple in vitro and in vivo models of non-small cell lung cancer. Clonogenic survival and tumor xenograft assays were performed to determine radiosensitization by ADAM17 inhibition.On the basis of a large-scale secretome screening, we investigated secretion of auto- or paracrine factors in non-small cell lung cancer in response to irradiation and discovered the ADAM17 network as a crucial mediator of resistance to IR. Irradiation induced a dose-dependent increase of furin-mediated cleavage of the ADAM17 proform to active ADAM17, which resulted in enhanced ADAM17 activity in vitro and in vivo Genetic or pharmacologic targeting of ADAM17 suppressed IR-induced shedding of secreted factors, downregulated ErbB signaling in otherwise cetuximab-resistant target cells, and enhanced IR-induced cytotoxicity. The combined treatment modality of IR with the ADAM17 inhibitor TMI-005 resulted in a supra-additive antitumor response in vivo demonstrating the potential of ADAM17 targeting in combination with radiotherapy.Radiotherapy activates ADAM17 in non-small cell lung cancer, which results in shedding of multiple survival factors, growth factor pathway activation, and IR-induced treatment resistance. We provide a sound rationale for repositioning ADAM17 inhibitors as short-term adjuvants to improve the radiotherapy outcome of non-small cell lung cancer. Clin Cancer Res; 22(17); 4428-39. ©2016 AACR.
Quinoline: Conversion to a Mutagen by Human and Rodent Liver2
Authors: Monica Hollstein, Ronald Talcott, Eddie Wei
Journal: JNCI Journal of the National Cancer Institute (1978)

Journal Article Quinoline: Conversion to a Mutagen by Human and Rodent Liver Get access Monica Hollstein, Monica Hollstein Search for other works by this author on: Oxford Academic PubMed Google Scholar Ronald Talcott, Ronald Talcott Search for other works by this author on: Oxford Academic PubMed Google Scholar Eddie Wei Eddie Wei Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 60, Issue 2, February 1978, Pages 405–410, https://doi.org/10.1093/jnci/60.2.405 Published: 01 February 1978 Article history Received: 14 June 1977 Accepted: 10 August 1977 Published: 01 February 1978
Frequency of the Asymptomatic Lower Esophageal Contractile Ring
Authors: Philip Kramer
Journal: New England Journal of Medicine (1956)

WITHIN recent years several papers have identified a ringlike narrowing or constriction in the terminal portion of the esophagus as a cause of dysphagia1 2 3 (Fig. 1). Although this narrowing had been observed before these reports and described as an annular indentation in the phrenic ampulla, little clinical significance was attached to its presence.4 That the constriction is capable of producing symptoms was demonstrated by the feeding of a barium bread or barium-steak meal or barium-filled gelatin capsules to patients who did not have any obvious cause for their dysphagia but did have an annular constriction on x-ray study. After these . . .
Hemodynamic Assessment of Amrinone
Authors: Joseph R. Benotti, William Grossman, Eugene Braunwald, Dominick D. Davolos, Adawia A. Alousi
Journal: New England Journal of Medicine (1978)

Amrinone, a new bipyridine derivative, exerts a positive inotropic action in experimental preparations and is effective when administered orally to dogs. To assess its immediate effects in man, we studied by cardiac catheterization the hemodynamic responses to amrinone (1.85 to 3.5 mg per kilogram given intravenously) in eight patients with congestive heart failure already receiving full doses of digitalis. The following statistically significant (P<0.01) effects were noted: cardiac index increased from a mean±1 S.D. of 1.8±0.3 to 2.6±0.3 liters per minute per square meter; peak rate of left ventricular pressure rise rose from 849±233 to 1206±456 mm Hg per second; left ventricular end-diastolic pressure fell from 25±9 to 14±7 mm Hg; pulmonary-capillary pressure fell from 28±8 to 15±4 mm Hg; and right atrial pressure fell from 12±6 to 7±5 mm Hg. Mean heart rate was unchanged, and aortic mean pressure declined slightly (86±10 to 80±7 mm Hg, P<0.025). No toxicity was observed. Amrinone, whose mechanism of action has not yet been defined, warrants further study as a possible treatment for heart failure. (N Engl J Med 299:1373–1377, 1978)
Entry of Black and Other Minority Students into U.S. Medical Schools
Authors: Steven Shea, Mindy Thompson Fullilove
Journal: New England Journal of Medicine (1985)

BLACKS and other minorities continue to be underrepresented in medical schools in the United States. In 1980, 11.7 per cent of the population was classified as black, but blacks accounted for only 6.6 per cent of the total entering medical-school class, 2.6 per cent of practicing physicians,1 and 1.7 per cent of medical-school faculty.2 The problem of underrepresentation is in fact more severe than these national statistics indicate, since a third of the black students and a quarter of the black faculty members were concentrated in three predominantly black medical schools.In 1970 the Association of American Medical Colleges (AAMC), . . .
Metabolic and Cardiovascular Responses to Epinephrine in Diabetic Autonomic Neuropathy
Authors: Jannik Hilsted, Erik Richter, Sten Madsbad, Bente Tronier, Niels Juel Christensen, Per Hildebrandt, Meta Damkjær, Henrik Galbo
Journal: New England Journal of Medicine (1987)

Norepinephrine-induced vasoconstriction, which is mediated by alpha-adrenergic receptors, is accentuated in patients with autonomic neuropathy. In contrast, responses mediated by beta-adrenergic receptors, including vasodilatation and metabolic changes, have not been evaluated in these patients. To study these responses, we administered epinephrine in a graded intravenous infusion (0.5 to 5 μg per minute) to seven diabetic patients without neuropathy, seven diabetic patients with autonomic neuropathy, and seven normal subjects. Mean arterial pressure decreased significantly in the patients with autonomic neuropathy (P<0.01) but was unchanged in the other groups. Since cardiac output increased to a similar extent in the three groups, the decrease in blood pressure was due to a significantly larger decrease (P<0.01) in total peripheral vascular resistance in the patients with autonomic neuropathy. The heart rate increased significantly more during the infusions in the patients with neuropathy than in those without neuropathy. Epinephrine produced a greater increase in blood glucose, the glucose-appearance rate, lactate, glycerol, and free fatty acids in the patients with autonomic neuropathy than in the other groups (P<0.05). These findings indicate that several beta-receptor–mediated responses to epinephrine are enhanced in patients with diabetic autonomic neuropathy. The underlying mechanism remains to be elucidated. (N Engl J Med 1987; 317:421–6.)