tbuckley/cabot-search huggingface dataset:
Phase I evaluation of a 24-h infusion of TAS-106 every 3 weeks (wks) in patients (pts) with solid tumors
Authors: C. H. Takimoto, A. Ricart, M. Mita, A. C. Mita, Q. Chu, A. W. Tolcher, J. Sarantopoulos, A. Mita, E. K. Rowinsky
Journal: Journal of Clinical Oncology (2007)

2513 Background: The nucleoside 3’-C-ethynylcytidine (TAS-106) is metabolized in cancer cells to ethynylcytidine triphosphate (ECTP), an inhibitor of RNA polymerases I, II, and III. TAS-106 has potent anticancer activity in broad range of human tumor xenografts. In prior clinical studies, bolus intravenous (IV) TAS-106 caused reversible dose-limiting peripheral neuropathy and the recommended phase II dose (RP2D) was 4.21 mg/m 2 every 3 wks. Myelosuppression, asthenia, and mild nausea and vomiting were also common. In rats, 24-h TAS-106 infusions are better tolerated with equivalent efficacy. Therefore, a Phase I study of 24-h infusions of TAS-106 was initiated. Methods: Escalating doses TAS-106 infused over 24-h every 3 wks were administered to cancer patients with pharmacokinetic (PK) monitoring during the initial cycle. Toxicity and response were assessed using NCI CTC (v2) grade (gr) and RECIST, respectively. Plasma and urine TAS-106 concentrations were monitored using LC/MS/MS methods. Results: Overall, 33 pts were treated at the following dose levels: 2.82 (4 pts), 3.5 (5 pts), 4.38 (6 pts), 5.48 (4 pts) 6.85 (6 pts) and 8.56 mg/m 2 (8 pts). At 8.56 mg/m 2 , 2 of 5 pts experienced neutropenic DLTs (febrile neutropenia and gr 4 neutropenia lasting greater than or equal to 3 days) No neuropathy DLTs were observed. At 6.85 mg/m 2 , gr 3 peripheral neuropathy in cycle 1 was observed in 1 patient, but no other DLTs occurred in 5 patients. Other common drug related toxicities occurring in any cycle included gr 1–2 fatigue (13 pts), gr 3–4 neutropenia (10 pts), gr 1 hand/foot syndrome (9 pts), gr 2–3 anemia (9 pts) gr 1 rash/skin exfoliation (10 pts), and peripheral neuropathy gr 1–2 (5 pts). No objective responses were seen; although 3 pts with parotid, adenoid cystic, and breast cancers demonstrated stable disease for 5, 6, and 7 months, respectively. Plasma concentrations increased with increasing dose, and at 6.85 mg/m 2 , the Cmax was 77.4±7.3 ng/mL, AUC 1,892±54 ng·h/mL, CL 102±13 mL/h/kg, VDss 1.37±.05 L/kg, and t1/2 was 9.85±1.47 h. Over 48 h, 62.1% of the administered dose of TAS-106 was excreted into the urine. Conclusions: Compared with bolus dosing, 24-h infusions of TAS-106 are better tolerated with less peripheral neuropathy. The RP2D for TAS-106 infused over 24-h every 3 wks is 6.85 mg/m 2 . [Table: see text]
Potential Role of pNF-H, a Biomarker of Axonal Damage in the Central Nervous System, as a Predictive Marker of Chemotherapy-Induced Cognitive Impairment
Authors: Akina Natori, Toru Ogata, Masahiko Sumitani, Takamichi Kogure, Teruo Yamauchi, Hideko Yamauchi
Journal: Clinical Cancer Research (2015)

Chemotherapy-induced cognitive impairment (CICI) is a clinically significant problem. Previous studies using magnetic resonance imaging indicated structural changes in the cerebral white matter of patients with CICI. Phosphorylated neurofilament heavy subunit (pNF-H), a major structural protein in axons, was recently reported to be elevated in the serum of patients with some central nervous system disorders. We performed a cross-sectional analysis of neuropsychological test results and serum pNF-H levels in patients undergoing adjuvant chemotherapy for breast cancer. Our hypothesis was that CICI is accompanied by axonal damage that can be detected by elevated serum pNF-H levels.Seventy-six patients with early breast cancer in various phases of treatment (naïve to chemotherapy; after one, three, or seven cycles of chemotherapy; or with a history of chemotherapy) were assessed by self-administered neuropsychological tests and a single pNF-H measurement. The χ(2) and Mann-Whitney tests were used for statistical analysis.Increased pNF-H levels were observed in 28.8% of the patients who underwent chemotherapy, but in none of the chemotherapy-naïve patients or patients with a history of chemotherapy. The pNF-H-positive rate increased significantly in proportion to the number of chemotherapy cycles (one cycle, 5.0%; three cycles, 31.6%; seven cycles, 55.0%; P < 0.05). No significant differences in neuropsychological test results were observed among the groups.The serum pNF-H level in patients undergoing chemotherapy for breast cancer increased in a cumulative dose-dependent manner, suggesting its potential application as a biomarker of neural damage after chemotherapy.
Role of fibreoptic bronchoscopy in the diagnosis of mycobacterial diseases.
Authors: A Funahashi, G H Lohaus, J Politis, L J Hranicka
Journal: Thorax (1983)

From January 1976 to December 1981 mycobacteria were recovered for the first time from the respiratory tract of 179 patients. Twenty-three patients had undergone fibreoptic bronchoscopy during initial investigation after three or more expectorated sputum specimens were negative for acid-fast bacilli. Three of these patients had nodular lesions on the chest radiograph and the diagnosis of mycobacterial disease was made only after thoracotomy. In the remaining 20 patients bronchial brushings yielded a positive culture in 19, while bronchial brushing was negative in one patient in whom culture of sputum before bronchoscopy had been positive. In eight of these 19 patients (group A) bronchial brushing was the only source that gave a positive result from culture, while in 11 patients (group B) both bronchial brushing and prebronchoscopy sputum yielded positive cultures. When these two groups were compared no difference was seen in their clinical presentation or radiographic findings but there was a notable difference in the quality of the presentation or radiographic findings but there was a notable difference in the quality of the prebronchoscopy sputum. Six of eight patients in group A had poor prebronchoscopy sputum, while 10 of 11 in group B had good prebronchoscopy sputum. It is concluded that, if a patient is unable to produce sputum or is able to produce only a poor specimen, fibreoptic bronchoscopy may be a useful means of obtaining additional material for culture.
Airborne arsenic and urinary excretion of arsenic metabolites during boiler cleaning operations in a Slovak coal-fired power plant.
Authors: J W Yager, J B Hicks, E Fabianova
Journal: Environmental Health Perspectives (1997)

Little information is available on the relationship between occupational exposure to inorganic arsenic in coal fly ash and urinary excretion of arsenic metabolites. This study ws undertaken in a coal-fired power plant in Slovakia during a routine maintenance outage. Arsenic was measured in the breathing zone of workers during 5 consecutive workdays, and urine samples were obtained for analysis of arsenic metabolites--inorganic arsenic (Asi), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA)--prior to the start of each shift. Results from a small number of cascade impactor air samples indicated that approximately 90% of total particle mass and arsenic was present in particle size fractions >/= 3.5 micron. The 8-hr time-weighted average (TWA) mean arsenic air concentration was 48.3 microg/m3 (range 0.17-375.2) and the mean sum of urinary arsenic (SigmaAs) metabolites was 16.9 microg As/g creatinine (range 2.6-50.8). For an 8-hr TWA of 10 microg/m3 arsenic from coal fly ash, the predicted mean concentration of the SigmaAs urinary metabolites was 13.2 microg As/G creatinine [95% confidence interval (CI), 10.1-16.3). Comparisons with previously published studies of exposure to arsenic trioxide vapors and dusts in copper smelters suggest that bioavailability of arsenic from airborne coal fly ash (as indicated by urinary excretion) is about one-third that seen in smelters and similar settings. Arsenic compound characteristics, matrix composition, and particle size distribution probably play major roles in determining actual uptake of airborne arsenic.
VA Overhaul Bill Becomes Law
Authors: Tracy Hampton
Journal: JAMA (2014)

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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
What the Future Holds for Psychosomatic Medicine
Authors: Herbert Weiner
Journal: Psychotherapy and Psychosomatics (1984)

In the recent past, the questions that face a comprehensive psychosomatic medicine have been defined. These questions refer to the context in which disease begins, the timing of the onset of the disease, the role of previous social experience in predisposing to disease, and the choice of the particular disease. It is suggested that a study of bereavement may be paradigmatic in answering these four questions: Bereavement has been cited as a factor in a large variety of disease. However, bereavement may produce discriminated responses of grief; helplessness, hopelessness, and giving-up; and pathological mourning. Pathological mourning in turn may be associated with autoimmune disease. There is evidence that separation and bereavement produces changes in immune function but there is as yet no evidence that it produces distortions of the immune process. There are many factors that affect the timing of disease onset, including maturational ones. Many social experiences have been shown to alter behavior and bodily function and predispose to disease. The question of the choice of disease is determined not only by the effects of bereavement and early experiences, and age, but also by a multiplicity of predisposing ones some of which have been specified.
Matrix Metalloproteinase Inhibitor COL-3 in the Treatment of AIDS-Related Kaposi's Sarcoma: A Phase I AIDS Malignancy Consortium Study
Authors: Mary Cianfrocca, Timothy P. Cooley, Jeannette Y. Lee, Michelle A. Rudek, David T. Scadden, Lee Ratner, James M. Pluda, William D. Figg, Susan E. Krown, Bruce J. Dezube
Journal: Journal of Clinical Oncology (2002)

PURPOSE: Matrix metalloproteinases (MMPs) are involved in tumor invasion and metastasis and are overexpressed in Kaposi’s sarcoma (KS) cells. The primary aim was to define the safety and toxicity of the MMP inhibitor COL-3 in patients with AIDS-related KS. Secondary aims were to evaluate tumor response, pharmacokinetics, and changes in blood levels of MMP-2, MMP-9, vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF). PATIENTS AND METHODS: COL-3 was administered orally once daily, and doses were escalated in cohorts of three to six subjects. Patients with symptomatic visceral KS or severe tumor-associated edema were excluded. Antiretroviral therapy was permitted but not required. Study end points were grade 3 or 4 toxicity or progressive KS. Serial blood specimens were obtained for pharmacokinetics and levels of MMP-2, MMP-9, VEGF, and bFGF. RESULTS: Eighteen patients received COL-3 in dosing cohorts of 25, 50, and 70 mg/m2/d. Prior KS therapy was reported by 17 patients (9...
LOBAR PNEUMONIA AS AN INFECTIOUS DISEASE
Authors: C. H. Whittle
Journal: BMJ (1928)

M-TN BRmJO 15&The caccuwn, ascending, transverse, and descending, colon, and rectum, were also empty and collapsed..Hcart.-The pericardial sac.contained about two ounces of.blood-stainied fluid.The heart showed no abnormality.The lungs were soft and congested.The condition was most
Haemoglobin Levels in Women's Auxiliary Air Force
Authors: S. Yudkin
Journal: BMJ (1944)

MEDICAL JOURNALthe drug was given for 7 days; then a 5-day interval was allowed to elapse before restarting it.It was only on the second occasion that the supposed intolerance became apparent.The only other instances of spaced dosage associated with pur- pura are recorded by Russell and Page (1940), Harries (1942), Werner (1942), Gorham et al. (1943), and Hurd and Jacox (1943).In 8 cases the administration was uninterrupted.Drug hypersensitivity may remain after recovery.Hurd and Jacox found that giving a small dose of sulphathiazole or sulphadiazine to their patient caused a marked fall in the platelet count with an increased bleeding time and, a positive tourniquet test.Rosenfeld and Feldman (1942), however, were able to give a later course to their patient with no further purpura.In the reported cases no member of the sulphonamide group of drugs seems exempt as a causative agent, and sulphanilamide, sulphapyriceine, sulphathiazole, and sulphadiazine have all been held responsible.The high mortality of this condition-8 out of 9 cases proved fatal-makes early recognition essential.The first clinical sign is nearly always epistaxis.If this or other spontaneous bleed- ing is discovered in a patient receiving sulphonamide drugs the administration should be stopped immediately and a bleeding time and capillary resistance test eone.Adequate transfusion of fresh blood is probably the best line of treatment.SummaryA. fatal case of acute purpura occurring in the course of sulpha- pyridine therapy in pneumonia is recorded.The pathogenesis of this condition is discussed.Vascular lesions as a basis for its causation are emphasized.In view of its high mortality a watch for extraneous bleeding should be made in all cases receiving sulphonamide drugs.
Enteropathogenic Escherichia coli
Authors: Richard L. Golden
Journal: JAMA (1961)

<h3>To the Editor:—</h3> I would like to comment on the article by K. A. Mian appearing inThe Journal(<b>171</b>:1957-1961 [Dec. 5] 1959), entitled "Isolation of Enteropathogenic Escherichia Coli from Household Pets," and the subsequent correspondence by Dr. D. A. Price in the Nov. 26, 1960, issue ofThe Journal(<b>174</b>:1755). In support of Mr. Mian's report on the carrier status of household pets harboring enteropathogenic<i>Esch. coli</i>and the possible epidemiologic relationship to infantile diarrhea, I would like to refer to a group of 20 cases that I recorded in 1956.<sup>1</sup>Among these instances of pathogenic<i>Esch. coli</i>-induced infantile gastroenteritis, was noted the case of a 4-year-old girl from whom<i>Esch. coli</i>0 26:B6 was isolated and identified by seroagglutination. The same organism was recovered from the family dog. In analyzing the epidemiologic aspects of this new finding, I considered in my report the possibilities
COX-1–derived thromboxane A2 plays an essential role in early B-cell development via regulation of JAK/STAT5 signaling in mouse
Authors: Qiong Yang, Maohua Shi, Yujun Shen, Yingjiao Cao, Shengkai Zuo, Caojian Zuo, Hui Zhang, Dmitry I. Gabrilovich, Ying Yu, Jie Zhou
Journal: Blood (2014)
S108 A historical cohort study to determine the prevalence of common chronic respiratory diseases and medication use in drug misusers
Authors: F. Palmer, M. Jaffray, M. Moffat, C. Matheson, J. Haughney, A. Coutts
Journal: Thorax (2010)

Introduction and aim A local substance misuse study and anecdotal evidence from primary care, suggested many methadone patients have respiratory disease and/or prescriptions for respiratory preparations. Anecdotal evidence from clinical colleagues supports this. With little published literature in this area, this preliminary study aimed to explore the prevalence of respiratory diseases and prescriptions for respiratory medication in drug misusers. Method This exploratory study used a historical cohort design with matched controls. An analysis of Primary Care Clinical Informatics Unit (PCCIU) GP consultation data was conducted. The prevalence of common respiratory diseases (ever appearing in the patient's medical records) and commonly used respiratory prescriptions (in 2008) between drug misusers and matched controls (general population sample) was compared. Results The PCCIU data contained a cohort of 18 570 patients (9285 per group), of which, 64% (n=11885) were male and 75.7% (n=14060) were aged 31–59. Results revealed an increased prevalence of chronic respiratory disease in drug misusers versus controls. Drug misusers were more likely to be prescribed chronic respiratory diseases medications than controls. These results were still significant when adjusted for smoking status, where those who had never smoked were compared to those who had ever smoked (current and ex smokers) (See [Abstract S108 Table 1][1]). Median quantity of SABA and ICS prescriptions during 2008 were also statistically significantly higher in drug misusers*. The median quantity of SABA prescribed for drug misusers were 4 (IQR 2–8) vs 3 (IQR 1–7) in controls**. The median quantity of ICS prescribed for drug misusers were 4 (IQR 2–8) vs 2 (IQR 1–5) in controls**. *Median Prescription for patients on ≥1 prescription. **p<0.001 Mann–Whitney U. View this table: Abstract S108 Table 1 Comparisons using PCCIU SPICE data Conclusion These data suggest, drug misusers have a significantly higher prevalence of respiratory diseases and are prescribed significantly more respiratory medications than matched controls. Adjusting for smoking status, still revealed drug misusers have significantly increased odds of have a respiratory disease or being prescribed respiratory medication, indicating there may be more complex factors involved related to drug use needing further exploration. As a first stage exploratory study, we have set the scene for future work to begin to determine the potential reasons for this association. [1]: #T1
Venlafaxine, but Not Mirtazapine Lowers Retinol-Binding Protein 4 Serum Concentrations in Nondiabetic Depressed Patients
Authors: M. Deuschle, T. Angermeier, S. Westphal, F. Lederbogen, M. Gilles, P. Frankhauser, C. Schilling, V. Onken, B. Weber-Hamann, D. Kopf
Journal: Psychotherapy and Psychosomatics (2010)
Analysis of <i>Epidermal Growth Factor Receptor</i> Gene Mutation in Patients with Non–Small Cell Lung Cancer and Acquired Resistance to Gefitinib
Authors: Takayuki Kosaka, Yasushi Yatabe, Hideki Endoh, Kimihide Yoshida, Toyoaki Hida, Masahiro Tsuboi, Hirohito Tada, Hiroyuki Kuwano, Tetsuya Mitsudomi
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Non–small cell lung cancers carrying activating mutations in the gene for the epidermal growth factor receptor (EGFR) are highly sensitive to EGFR-specific tyrosine kinase inhibitors. However, most patients who initially respond subsequently experience disease progression while still on treatment. Part of this “acquired resistance” is attributable to a secondary mutation resulting in threonine to methionine at codon 790 (T790M) of EGFR. Experimental Design: We sequenced exons 18 to 21 of the EGFR gene to look for secondary mutations in tumors with acquired resistance to gefitinib in 14 patients with adenocarcinomas. Subcloning or cycleave PCR was used in addition to normal sequencing to increase the sensitivity of the assay. We also looked for T790M in pretreatment samples from 52 patients who were treated with gefitinib. We also looked for secondary KRAS gene mutations because tumors with KRAS mutations are generally resistant to tyrosine kinase inhibitors. Results: Seven of 14 tumors had a secondary T790M mutation. There were no other novel secondary mutations. We detected no T790M mutations in pretreatment specimens from available five tumors among these seven tumors. Patients with T790M tended to be women, never smokers, and carrying deletion mutations, but the T790M was not associated with the duration of gefitinib administration. None of the tumors had an acquired mutation in the KRAS gene. Conclusions: A secondary T790M mutation of EGFR accounted for half the tumors with acquired resistance to gefitinib in Japanese patients. Other drug-resistant secondary mutations are uncommon in the EGFR gene.
Disulfiram: An Unusual Side Effect
Authors: Sheldon I. Miller
Journal: JAMA (1977)

<h3>To the Editor.—</h3> I have seen a side effect of disulfiram (Antabuse) that, to my knowledge, has not yet been reported. It occurred after the beginning of treatment and although it was not serious, it was sufficiently unpleasant to necessitate cessation of treatment with this drug. <h3>Report of a Case.—</h3> A 40-year-old man with a five-year history of increasing alcoholism had had a colostomy for many years as the result of ulcerative colitis. The patient had had no trouble with the colostomy for a long time and had learned what diet was necessary to maintain satisfactory functioning. His alcohol intake had never seriously affected the functioning of the colostomy, but emotional upsets did so. The only major problem that he had had with it over the years was the occasional occurrence of an unpleasant odor, usually resulting from dietary indiscretion. The patient agreed that disulfiram would be helpful in controlling
HIGH SYNTAX SCORE PREDICTS WORSE IN-HOSPITAL CLINICAL OUTCOMES IN PATIENTS UNDERGOING PRIMARY ANGIOPLASTY FOR ACUTE MYOCARDIAL INFARCTION
Authors: Seref Kul, Ozgur Akgul, Huseyin Uyarel, Mehmet Ergelen, Okkes T. Kucukdagli, Abdurrahman Tasal, Ercan Erdogan, Ahmet Bacaksiz, Osman Sonmez, Mehmet Gul, Nevzat Uslu, Omer Goktekin
Journal: Journal of the American College of Cardiology (2013)
Points from Letters: Accidental Injection of Potassium
Authors: R. A. Moorhouse, I. W. Marshall
Journal: BMJ (1974)

SIR,-A revealing point about the work load and remuneration of general practitioners was made by a delegate at the 1974 Annual Conference of Representatives of Local Medical Committees but was not mentioned in your summary.It is worthy of consider- ation by B.M.A. members generally.
Barriers to Improving Diabetes Care for Blacks
Authors: Robert M Anderson, William H Herman, Jacina M Davis, Ruth P Freedman, Martha M Funnel, Harold W Neighbors
Journal: Diabetes Care (1991)

Barriers to Improving Diabetes Care for BlacksIn the spring of 1989, the University of Michigan Diabetes Research and Training Center (MDRTC) convened a Task Force on Diabetes and the Black Population.This editorial is based on that task force report, which was issued on 15 January 1990.The mission of the task force was to identify potential barriers to the translation of scientific knowledge into improved health care and health for blacks with diabetes.Although it is known that diabetes affects a disproportionate number of black Americans, there is a paucity of information about the causes and effects of this burden.We hope this editorial contributes to a dialogue within the diabetes community that will lead to an increasingly articulated and tangible commitment to reducing the disproportionate burden that diabetes places on African Americans and other minorities in the United States.
Fluorodeoxyglucose PET in Relapsing Polychondritis
Authors: Frank De Geeter, Stefaan J. Vandecasteele
Journal: New England Journal of Medicine (2008)

The authors report on a case of fever of unknown origin in which 18F-fluorodeoxyglucose (FDG) positron-emission tomography (PET) was instrumental in depicting cartilage inflammation, which eventual...