tbuckley/cabot-search huggingface dataset:
Pharmacologically based dosing of etoposide: a means of safely increasing dose intensity.
Authors: M J Ratain, R Mick, R L Schilsky, N J Vogelzang, F Berezin
Journal: Journal of Clinical Oncology (1991)

We have previously demonstrated that individualized dosing of etoposide (VP16) by 72-hour infusion is feasible and that the extent of leukopenia is a function of plasma concentration, pretreatment WBC (WBCp), albumin (ALB), performance status (PS), and bone marrow function (based on transfusion requirements). In the current study, 45 patients were randomized between a fixed dose of VP16 (125 mg/m2/d) versus individualized dosing to a target WBC nadir (WBCN) of 1,700/microL. The total dose was increased by an average of 22% in the latter patients (459 +/- 130 mg/m2 v 375 mg/m2, P = .002). This was associated with a decrease in both the mean WBCN (1,510 +/- 950 v 2,500 +/- 1,420/microL, P = .013) and in the variability of the WBCN (P = .039). The VP16 clearance (mL/min) was not correlated with body surface area. Partial responses were observed in one patient each with hepatoma and non-Hodgkin's lymphoma. We conclude that pharmacologically based dosing may be a means of increasing dose intensity without increasing the incidence of life-threatening toxicity due to a decrease in variability around a target WBC.
Lower respiratory tract infections in the European GRACE primary care network: Bacterial causes or do viruses also matter?
Authors: Margareta Ieven, Katherine Loens, Frank Coenjaerts, Christine Lammens, Anouk Vanderstraeten, Theo Verheij, Paul Little, Herman Goossens, Eric Claas, Anton van Loon
Journal: European Respiratory Journal (2011)

Especially the role of the newly recognised viruses is not well known in adult lower respiratory tract infections in the community (LRTI). We investigated the role of  S. pneumoniae  ( S.pn ),  Haemophilus  spp ( H .spp) and viruses in LRTI in the GRACE primary care network (PCN) using culture and real-time nucleic acid amplification tests (RT-NAATs) From 10/2007-04/2010 3102 patients with LRTI were enrolled in a prospective study in 16 PCNs in 12 EU countries. Nasopharyngeal swabs (NPS) and sputa for culture of  S.pn  and  H .spp were collected and frozen until transport to the central lab for nucleic acid (NA) extraction. Aliquots of NA extracts were sent to the LUMC and UMC-U for detection of influenzaviruses (INF) A/B, parainfluenzavirus (PIV)1-4, human rhinoviruses (HRV), human metapneumovirus (hMPV), respiratory syncytial virus (RSV), adenovirus (HAdV), Bocavirus (BOCA), coronaviruses (HCoV) OC43, NL-63, 229E, polyomaviruses KI and WU by in-house RT-PCR.  In 3082/3102 patients a NPS was collected. An aetiologic agent was detected in 77% of patients:  S.pn  and  H. spp in 9.1% and 14.9% respectively; a respiratory virus in 53.1%: HRV 18.6%, INF 11.1%, HCoV 7.4%, hMPV 4.4%, RSV 4.4%, polyomaviruses 2.8%, PIV 2.5%, HAdV 1.4%, BOCA 0.5%. For most viruses no significant differences were observed in prevalence between the 3 winters. In   This is the largest aetiologic study on LRTI in PCNs: in ±80% of the patients a microbial aetiology was found, over 50% were viral infections: HRV9s account for the majority. Use of RT-NAATs results in a significant improvement of the aetiologic diagnosis LRTI.
Prognosis in Chronic Lymphocytic Leukemia—Reply
Authors: Chadi Nabhan, Gordana Raca, Y. Lynn Wang
Journal: JAMA Oncology (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Is our preoperative TNM staging reliable
Authors: Marta Inchausti, Larraitz Garcia, Maria Alfonso, Ruth Diez, Amaia Urrutia, Amaia Sagarna, Estibaliz Perez, Unai Jimenez, Pedro Ansola
Journal: European Respiratory Journal (2011)

Introduction:  Agreement between preoperative and surgical TNM staging is usually    Aim:  To compare our preoperative staging (cTNM) with surgical-pathological staging (pTNM).   Methods:  Cross-sectional study of patients with lung cancer surgically treated from 1-1-08 to 31-12-09, excluding relapses or neoadjuvant therapies. Preoperative staging based on: CT scan, positron emission tomography (PET-CT), endobronchial ultrasonography (EBUS), endoscopic ultrasonography (EUS), mediastinoscopy. Agreement between cTNM and pTNM (according to 1997 TNM classification) was analyzed.   Results:  166 cases (characteristics in table 1). In table 2, concordance between cTNM and pTNM.  cTNM and pTNM matched in 80 cases (48,2%), understaging occurred in 5 cases (3%) and overstaging in 81 (48,8%). But in most cases, this lack of agreement would not suppose changes in the therapeutic decision, just in 21 cases (12,5%) the cTNM carried out a wrong therapeutic procedure (18 N2 found in thoracotomy and 3 T4 unresectables). TC and PET-TC used in all cases, EBUS in 35, EUS in 2 and mediastinoscopy in 3. In N staging, PET-CT was cN0 in 133 cases (where 7 were pN2, 5,2%) and cN1 21 (8 pN2, 25,8%). We performed 35 EBUS (33 cN0, 2 cN1) and final pN was N2 in 3 cases (FN rate 8,5%).   Conclusions:  1. Low agreement between cTNM and pTNM (48,2%), but only in 12,5% of cases would suppose a change in the treatment. 2. 25% of pN2 when cN1 by PET-CT (EBUS should be done). 3. When EBUS negative for N2, only 8,5% pN2.
Phase I trial of buthionine sulfoximine in combination with melphalan in patients with cancer.
Authors: P J O'Dwyer, T C Hamilton, F P LaCreta, J M Gallo, D Kilpatrick, T Halbherr, J Brennan, M A Bookman, J Hoffman, R C Young, R L Comis, R F Ozols
Journal: Journal of Clinical Oncology (1996)

PURPOSE AND METHODS Resistance to alkylating agents and platinum compounds is associated with elevated levels of glutathione (GSH). Depletion of GSH by buthionine sulfoximine (BSO) restores the sensitivity of resistant tumors to melphalan in vitro and in vivo. In a phase I trial, each patient received two cycles as follows: BSO alone intravenously (i.v.) every 12 hours for six doses, and 1 week later the same BSO as cycle one with melphalan (L-PAM) 15 mg/m2 i.v. 1 hour after the fifth dose. BSO doses were escalated from 1.5 to 17 g/m2 in 41 patients. RESULTS The only toxicity attributable to BSO was grade I or II nausea/vomiting in 50% of patients. Dose-related neutropenia required an L-PAM dose reduction to 10 mg/m2 at BSO 7.5 g/m2. We measured GSH in peripheral mononuclear cells (PMN), and in tumor biopsies when available, at intervals following BSO dosing. In PMNs, GSH content decreased over 36 to 72 hours to reach a nadir on day 3; at the highest dose, recovery was delayed beyond day 7. The mean PMN GSH nadirs were approximately 10% of control at BSO doses &gt; or = 7.5 g/m2; at 13 and 17 g/m2, all but two patients had nadir values in this range. GSH was depleted in sequential tumor biopsies to a variable extent, but with a similar time course. At BSO doses &gt; or = 13 g/m2, tumor GSH was &lt; or = 20% of starting values on day 3 in five of seven patients; recovery had not occurred by day 5. We measured plasma concentrations of R- and S-BSO by high-performance liquid chromatography (HPLC) in 22 patients throughout the dosing period. Total-body clearance (CLt) and volume of distribution at steady-state (Vss) for both isomers were dose-independent. The CLt of S-BSO was significantly less than that of R-BSO at all doses, but no significant differences in Vss were observed between the racemates. Harmonic mean half-lives were 1.39 hours and 1.89 hours for R-BSO and S-BSO, respectively. CONCLUSION A biochemically appropriate dose of BSO for use on this schedule is 13 g/m2, which will be used in phase II trials to be conducted in ovarian cancer and melanoma.
Phenomenological and neurocognitive perspectives on delusions: A critical overview
Authors: Louis Sass, Greg Byrom
Journal: World Psychiatry (2015)

There is considerable overlap between phenomenological and neurocognitive perspectives on delusions. In this paper, we first review major phenomenological accounts of delusions, beginning with Jaspers' ideas regarding incomprehensibility, delusional mood, and disturbed "cogito" (basic, minimal, or core self-experience) in what he termed "delusion proper" in schizophrenia. Then we discuss later studies of decontextualization and delusional mood by Matussek, changes in self and world in delusion formation according to Conrad's notions of "apophany" and "anastrophe", and the implications of ontological transformations in the felt sense of reality in some delusions. Next we consider consistencies between: a) phenomenological models stressing minimal-self (ipseity) disturbance and hyperreflexivity in schizophrenia, and b) recent neurocognitive models of delusions emphasizing salience dysregulation and prediction error. We voice reservations about homogenizing tendencies in neurocognitive explanations of delusions (the "paranoia paradigm"), given experiential variations in states of delusion. In particular we consider shortcomings of assuming that delusions necessarily or always involve "mistaken beliefs" concerning objective facts about the world. Finally, we offer some suggestions regarding possible neurocognitive factors. Current models that stress hypersalience (banal stimuli experienced as strange) might benefit from considering the potential role of hyposalience in delusion formation. Hyposalience - associated with experiencing the strange as if it were banal, and perhaps with activation of the default mode network - may underlie a kind of delusional derealization and an "anything goes" attitude. Such an attitude would be conducive to delusion formation, yet differs significantly from the hypersalience emphasized in current neurocognitive theories.
Anxiety and depression in patients referred for pulmonary rehabilitation
Authors: Karen Ingram, Jane Canavan, Ria Fowler, Phillipa Marns, Amy Clark, Claire Nolan, Michael Polkey, William Man
Journal: European Respiratory Journal (2011)

Introduction:  Psychological morbidity is well recognised in chronic respiratory disease, but the effect of uptake, completion and response to pulmonary rehabilitation (PR) is unknown.   Method:  In 302 consecutive patients referred to an 8-week outpatient PR program, the Hospital Anxiety and Depression Score (HADS) was used to assess symptoms of anxiety and depression. A HADS domain score of ≥11 identified patients with moderate levels of anxiety and depression. Subsequent uptake and compliance with PR was recorded. Pre- to post-PR changes in incremental shuttle walk (ISW) and self-reported Chronic Respiratory Disease Questionnaire (CRDQ) were compared between those with moderate anxiety (ANX) or moderate depression (DEP), and those without, defined as HADS ≤7 (NA and ND).   Results:  71 (23.5%) and 59 (19.5%) patients had evidence of moderate anxiety and depression respectively. 22 (31%) of ANX and 21 (36%) of DEP either failed to start or complete PR. Despite similar FEV1% predicted, ANX had significantly impaired baseline ISW (median 100 vs. 180 m; p   Conclusion:  Significant psychological morbidity is prevalent in patients referred to PR. Over 30% fail to start or complete PR. These patients also have impaired exercise capacity and quality of life, but completers respond normally to PR.
Prevalence of arterial hypertension in obstructive sleep apnoea (OSA) patients - Impact of diabetes and obesity
Authors: Robert Plywaczewski, Anna Czyzak-Gradkowska, Monika Targowska, Przemyslaw Bielen, Pawel Sliwinski
Journal: European Respiratory Journal (2013)

Untreated OSA is a risk factor for cardiovascular morbidity. Arterial hypertension is one of the most frequent OSA complications. The aim of study was to compare hypertensive OSA pts and subjects without arterial hypertension. We studied 1164 OSA pts, mean age = 56.4±10.4 years, with obesity (BMI = 34.2±6.4 kg/m2) and moderate to severe disease (AHI = 39.6±21.7). We found 307 normotensive OSA pts (26.4%) and 857 OSA pts with arterial hypertension (73.6%). Comparison of both groups is shown in the table.

View this table:



Logistic regression revealed that: diabetes (OR- 3.05; 95%CI – 1.88-4.95; p  30 vs ≤ 30 (OR- 2.34; 95%CI – 1.67-3.28;p  125 vs ≤ 125 pg/ml (OR – 1.85; 95%CI – 1.23-2.79; p=0.003), hyperuricaemia (OR-1.83; 95%CI – 1.28-2.63; p=0.0009) and nocturia ≥ 2 vs   30 vs ≤30, T90 >30 vs ≤ 30.

Conclusions: Arterial hypertension was very common in our group of OSA pts. The highest risk of arterial hypertension was related to diabetes and obesity.
Outcome of Reduced Intensity Allografts in Patients Aged Over 45 Years with Acute Myeloid Leukaemia: Initial Results of the MRC AML15 Trial.
Authors: Nigel H. Russell, Andrew J Howman, Keith Wheatley, Robert K Hills, Charles Craddock, Lars Kjeldsen, John AL Yin, Alan K. Burnett
Journal: Blood (2009)
&lt;italic&gt;N&lt;/italic&gt;-Nitroso-&lt;italic&gt;N&lt;/italic&gt;-methylurea Initiation in Multiple Tissues for Organ-Specific Tumor Promotion in Rats by Phenobarbital&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: B A Diwan, A E Palmer, M Ohshima, J M Rice
Journal: JNCI Journal of the National Cancer Institute (1985)

Effects of phenobarbital [(PB) CAS: 50-06-6], a systemic tumor promoter, on carcinogenesis initiated by the broad-spectrum carcinogen N-nitroso-N- methylurea [(NMU) CAS: 684-93-5] were investigated in F344/NCr rats. Single and divided doses of NMU were evaluated for this purpose in 4-week-old rats of both sexes. Rats received iv injections of either 0.2 mmol NMU/kg (body wt) once or 0.05 mmol NMU/kg (body wt) for 4 weeks (1 injection/wk), followed by or concurrently with PB (0.05% in drinking water) that was continued until the termination of the experiment. Half the rats were killed at 52 weeks and survivors at 80 weeks. At 52 weeks, PB given subsequent to NMU or concurrently with divided doses of NMU significantly enhanced the incidence of thyroid follicular tumors only in male rats. This sex difference in thyroid tumorigenesis was somewhat less pronounced in animals killed at 80 weeks. Only 1 liver cell adenoma occurred in males and none in females given NMU alone. PB given concurrently with divided doses of NMU enhanced the yield of hepatocellular foci/cm2 but had no significant effect on hepatic tumor development. Subsequent exposure to PB, however, significantly promoted hepatocarcinogenesis in rats of both sexes given NMU in divided doses; 50% of males and 40% of females given NMU (0.05 mmol/kg, administered four times) followed by PB had hepatocellular adenomas and carcinomas by 80 weeks. PB did not affect the incidence of any other kind of neoplasms seen in NMU-initiated or control rats. These lesions included squamous cell neoplasms of the skin, oropharynx, and forestomach; nonsquamous epithelial tumors of mammary gland, pituitary body, intestinal mucosa, and urinary bladder; tumors of the central and peripheral nervous system; and mesenchymal tumors of the kidney. A sequence of multiple low doses of NMU appeared to be a convenient and useful systemic, multitissue, tumor-initiation regimen for systematic investigation of organ-specific tumor promotion in rats.
Induction of Malignant Tumors in the Rabbit by Oral Administration of Diethylnitrosamine
Authors: H. J. Rapp, J. H. Carleton, Crile Crisler, E. M. Nadel
Journal: JNCI Journal of the National Cancer Institute (1965)

Hepatic carcinomas developed in 13 of 13 rabbits receiving diethylnitrosamine in their drinking water (0.042 g/liter, 6 days a week) for periods ranging from 52 to 82 weeks. A hepatoma was found in 1 animal receiving diethylnitrosamine for 28 weeks; animals autopsied before 28 weeks had no tumors. Most tumors were a mixed type including trabecular, adenocarcinomatous, sarcomatous, and anaplastic patterns. The tumors invaded lymphatic and blood vessels and metastasized to the lymph nodes, omentum, lungs, kidneys, adrenals, spleen, heart, ovaries, and body wall. The only other tumor found was an adenocarcinoma of the lung. Some comparisons and differences of the diethylnitrosamine-induced tumors in rabbits and guinea pigs are discussed.
Factors influencing sputum conversion among smear-positive pulmonary tuberculosis patients in Morocco
Authors: Khalid Bouti, Karima Marc, Mouna Soualhi, Rachida Zahraoui, Jouda Benamor, Jamal Eddine Bourkadi, Ghali Iraqi
Journal: European Respiratory Journal (2013)

Background: Sputum smear positive pulmonary tuberculosis patients expel infectious viable bacilli for a period following commencement of treatment.  Objective: To determine the time to sputum smear conversion and study the factors influenceng it.  Design: A prospective study was undertaken at our hospital in Rabat over a six months period on a cohort of 119 sputum smear positive patients. Patients were followed up fortnightly. At each follow up, specimens were collected and processed for microscopy using standard protocol.  Results: 96.6% of our patients completed the study (4 deaths). Sputum conversion rate was 42% after two weeks, 73% after one month, and 95% after two months. Univariate and stepwise regression analysis showed that patients who had high smear grading, military, bilateral radiologic lesions were more likely to undergo delayed or non-conversion [P   Conclusion: Since viable bacilli continue to be expelled for up to two months, infection control measures should be maintained for such time. Patients with high smear grading, miliary, bilateral radiologic lesions need to be monitored more closely.
Primary Liver Carcinoma and Liver Cirrhosis in Atomic Bomb Survivors, Hiroshima and Nagasaki, 1961-75, With Special Reference to Hepatitis B Surface Antigen
Authors: M Asano, H Kato, K Yoshimoto, S Seyama, H Itakura, T Hamada, S Iijima
Journal: JNCI Journal of the National Cancer Institute (1982)

During 1961-75, 128 cases of primary liver carcinoma (PLC) in the Radiation Effects Research Foundation life-span study extended sample and 301 cases of liver cirrhosis in the pathology study sample were observed. The presence of hepatitis B surface antigen (HBsAg) was assessed in all of the cases with the use of orcein and aldehyde fuchsin stains and was confirmed by the immunofluorescence technique. The incidence of PLC was two times higher in Nagasaki than in Hiroshima, which was statistically significant, but little difference was noted in the prevalence of cirrhosis in the two cities. Findings that might possibly explain the higher PLC incidence in Nagasaki were 1) the 2.3 times higher presence in Nagasaki than in Hiroshima of HBsAg in the livers of subjects without liver disease and 2) the two times higher prevalence in Nagasaki than in Hiroshima of cirrhosis with PLC. We believe that the higher incidence of PLC in Nagasaki is attributable to hepatitis B virus infection, although other factors (e.g., immunologic competence affected by radiation) cannot be excluded. In both cities, a suggestive relationship of radiation dose to cirrhosis prevalence, but not to PCL prevalence, was noted. To clarify possible radiation effects on cirrhosis prevalence, further follow-up of the populations of these two cities is necessary.
A phase II clinical trial of carboplatin infusion in high-risk acute nonlymphoblastic leukemia.
Authors: J A Martínez, G Martín, G F Sanz, A Sempere, I Jarque, J de la Rubia, M A Sanz
Journal: Journal of Clinical Oncology (1991)

Carboplatin (CBDCA) is a second-generation platinum drug that has been shown to be useful when used as a continuous infusion in treatment of refractory adult leukemia. We report on the effectiveness of continuous infusion CBDCA, 300 mg/m2/d x 5 days, as evaluated in nine patients with secondary acute nonlymphocytic leukemia (ANLL) (seven previous myelodysplastic syndrome and two treatment-associated ANLL), three ANLL patients in first relapse, six refractory ANLL, and nine patients with blastic phase of chronic myelogenous leukemia (BP-CML). All patients were considered assessable. The response rate was 44% (eight complete remissions [CRs], four partial remissions [PRs]). Median duration of postchemotherapy neutropenia was 36 days (range, 18 to 45). Therapy was well tolerated, and toxicity was mainly hematologic and nondose-limiting. Despite prolonged neutropenia, severe infections were rarely seen, and most patients were managed as outpatients. Twelve patients had nausea and vomiting, two had symptomatic hypomagnesemia, and one patient showed reversible ototoxicity. Because of substantial antileukemic activity and unusual extrahematologic toxicity, CBDCA appears to be an effective second-line agent in the treatment of ANLL and should be considered for upgrading to first-line treatment regimens.
Skeletal muscle impairment and proteomic profil in human pulmonary arterial hypertension
Authors: Francois Potus, Aude Pflieger, Simon Malenfant, Sébastien Bonnet, Steeve Provencher
Journal: European Respiratory Journal (2014)

Introduction: the most important symptom of pulmonary arterial hypertension (PAH) is exercise intolerance leading poor quality of life. Numerous observations suggest that exercise limitation in PAH is not solely due to pulmonary hemodynamic impairment, but that other determinants such as skeletal muscle abnormalities are involved. In order to better understand the origins of exercise limitation in PAH, we studied the proteomic signature of skeletal muscle impairment in patients with idiopathic PAH (iPAH). Methods and results: Muscle proteins from 4 iPAH patients and 4 sex and age matched controls were extracted following quadriceps muscle biopsy. Fractioned peptides were then tagged using isobaric Tags for Relative and Absolute Quantitation (iTRAQ, ABsciex) specific for each patient. Over 900 proteins were identified using iTRAQ analysis, among them, 9 were under-expressed and 7 were over-expressed in all iPAH patient quadriceps. In silico analysis revealed that more than 75% of the under-expressed proteins are involved in oxidative metabolism and most other highlighted proteins play a role in myogenesis. These findings were structurally associated with decreased mitochondrial density (citrate synthase assay) and impaired mitochondrial structure measured by electronic microscopy, while muscle fibers distribution was unchanged. Functionally, all these abnormalities resulted in decreases in oxidative metabolism Conclusions: For the first time in humans, we provide evidences that, as in lungs and the right ventricle, the impaired mitochondrial/metabolism function is also present in skeletal muscle suggesting that PAH might be considered as a global mitochondrial/metabolic disease.