tbuckley/cabot-search huggingface dataset:
Persistent Chromosomal Aberrations Following Radioiodine Therapy for Thyrotoxicosis
Authors: S. J. Cantolino, R. D. Schmickel, M. Ball, C. F. Cisar
Journal: New England Journal of Medicine (1966)

PRESENT evidence indicates that human chromosomes are at risk whenever exposed to ionizing radiation. Chromosomal aberrations have been demonstrated after accidental,1 2 3 therapeutic4 , 5 and diagnostic6 7 8 exposures. Initially, such defects were noted after high-level radiation exposure. Incriminated early were such forms of exposure as x-ray therapy, for ankylosing spondylitis,4 , 5 prodigious doses of radioiodine (131I) for carcinoma of the thyroid gland9 , 10 and accidental gamma and neutron irradiation.1 In some cases these aberrations have been observed twenty years after exposure.5 More recently, low-level radiation exposure in the form of certain diagnostic x-ray procedures has been demonstrated to cause less severe but significant chromosomal . . .
Beta-adrenergic receptor function in affective illness
Authors: G N Pandey, M W Dysken, D L Garver, J M Davis
Journal: American Journal of Psychiatry (1979)

In a study of beta-adrenergic receptor sensitivity, the authors determined the response of cyclic AMP synthesis to in vitro addition of norepinephrine (NE) and isoproterenol (IP) in leukocytes of patients with affective illness and schizophrenia and of normal controls. IP-stimulated increase in 3H-cyclic AMP synthesis in depressed patients was significantly lower than in normal subjects and schizophrenic patients. These results suggest that beta-adrenergic receptor sensitivity is reduced in depressive illness.
Phase I/II study of PTK787/ZK 222584 (PTK/ZK), a novel, oral angiogenesis inhibitor in combination with FOLFIRI as first-line treatment for patients with metastatic colorectal cancer (CRC)
Authors: T. Trarbach, N. Schleucher, M. Tewes, S. Seeber, U. Junker, D. Laurent, U. Vanhoefer, E. Masson, D. Lebwohl
Journal: Journal of Clinical Oncology (2005)

3605 Background: Vascular endothelial growth factors (VEGF-A, -B, -C, D and -E) are potent angiogenesis factors secreted by many solid tumors. PTK/ZK is a novel, oral, small molecule angiogenesis inhibitor that blocks all known VEGF receptor tyrosine kinases, important mediators in the formation of new blood and lymph vessels that contribute to tumor growth and metastasis. Method: The goal of this trial is to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of once-daily oral PTK/ZK in combination with infusional 5-fluorouracil (5-FU)/leucovorin (LV) plus irinotecan (FOLFIRI) as first-line treatment in patients (Pts) with metastatic CRC. PTK/ZK was administered in doses of 500, 1,000, 1,250, and 1,500 mg/day (d) to cohorts of 3 to 7 Pts. FOLFIRI was administered every 2 weeks (wks) as irinotecan (180 mg/m2, day 1) plus LV (200 mg/m2, 2-hour infusion) and 5-FU (400 mg/m2 bolus followed by 600 mg/m2 as a 22-hour infusion) on days 1 and 2. Results: To date, 21 Pts are enrolled; 6 at the 500 mg/d dose, 7 at 1,000 mg/d, 5 at 1,250 mg/d, and 3 at 1,500 mg/d. PTK/ZK was well tolerated. There was 1 DLT at 500 mg/d (grade [Gr] 3 fatigue) and 1 at 1,000 mg/d (Gr 3 hypertension); both resolved within 2 wks of PTK/ZK discontinuation. The pharmacokinetics of PTK/ZK was unaffected by FOLFIRI. Coadministration of 1,250 mg/d PTK/ZK with FOLFIRI had minor effects on irinotecan exposure but lowered the AUC of SN38 in serum by ∼40%; clinical relevance is under investigation. Best response by SWOG criteria for 17 evaluable Pts include 7 (41%) partial responses, 8 (47%) with stable disease, and 2 (12%) with progressive disease. Median PFS for 17 Pts was 7.1 months (95% CI = 6.2, 11.7 months). Median OS for 19 intent-to-treat Pts was 24.3 months (95% CI = 18.0, unknown months). Conclusion: The results suggest that the combination of PTK/ZK with FOLFIRI is safe, well tolerated, and has activity in Pts with metastatic CRC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis, Schering AG
An Unusual Case of Chloroma Without Marrow Involvement Demonstrated on Ga-67 Scintigraphy
Authors: THOMAS EADE, BENG TAN, ROBERT MANSBERG, JOHN M. ROBERTS
Journal: Clinical Nuclear Medicine (2002)

EADE, THOMAS M.B.,Ch.B.; TAN, BENG M.B.B.S., F.R.A.C.R.; MANSBERG, ROBERT M.B.B.S., F.R.A.C.P.; ROBERTS, JOHN M. M.B.B.S., F.R.A.C.P. Author Information
Tackling obesity among the medical profession
Authors: S. Kenwright
Journal: BMJ (2014)

McCartney confuses the issue—being fat is not related to being a “good” or “bad” doctor.1 I have known excellent doctors who were fat, smoked, or whose judgment could be trusted even when tipsy. Equally, being obese does not make advice on weight reduction more effective, and the obese doctor who has lost weight can be unduly …
Effects of the Novel Long-Acting GLP-1 Agonist, Albiglutide, on Cardiac Function, Cardiac Metabolism, and Exercise Capacity in Patients With Chronic Heart Failure and Reduced Ejection Fraction
Authors: John J. Lepore, Eric Olson, Laura Demopoulos, Thomas Haws, Zixing Fang, April M. Barbour, Michael Fossler, Victor G. Davila-Roman, Stuart D. Russell, Robert J. Gropler
Journal: JACC Heart Failure (2016)
Commentary: Biomarkers in Occupational Cancer Epidemiology: Considerations in Study Design
Authors: Richard B. Hayes
Journal: Environmental Health Perspectives (1992)

Epidemiologic studies of occupational groups have been central to the identification of human carcinogens.The incorporation of a biochemical component into occupational studies of cancer can expand the possibilities for identifying human carcinogens and for understanding the disease process.Two epidemiologic studies of occupation and cancer which include evaluation of biomarkers are described.The association of acetylator phenotype with bladder cancer risk was studied in benzidine-exposed workers.The association of benzene- related leukopenia with leukemia is being studied in benzene-exposed workers.These investigations illustrate issues in the use of biomarkers in epidemiologic studies of cancer risk.Such studies require the identification and characterization of the population at risk.Disease susceptibility factors are amenable for inclusion in these studies and can be statistically modeled as exposure-effect modifiers.Biomarkers of exposure are mainly of importance in short-term longitudinal and cross-sectional studies of exposure and intermediate outcomes and for validation of other data sources.Several sources of error can affect the results of molecular epidemiologic studies.Aside from minimizing laboratory error, consideration must be given in the design and execution of these studies to potential problems in subject selection and field collection ofbiologic samples and other relevant data.
Withdrawal Reaction after Long-Term Therapeutic Use of Benzodiazepines
Authors: Usoa Busto, Edward M. Sellers, Claudio A. Naranjo, Howard Cappell, Martha Sanchez-Craig, Kathy Sykora
Journal: New England Journal of Medicine (1986)

We conducted a double-blind, placebo-controlled trail in which 40 patients who had undergone long-term therapy with benzodiazepines were switched to placebo or to diazepam in a dose approximately equivalent to their usual dose of the benzodiazepine; the dose of diazepam was then tapered during an eight-week period. Patients were assessed clinically and psychologically and had weekly sessions of behavioral therapy. The subjects who received placebo had more symptoms, assessed their symptoms as more severe, and stopped taking the study drug at a higher rate than those receiving the tapering doses of diazepam. The subjects in the placebo group also had symptoms shortly after being switched to placebo, whereas those in the diazepam group had symptoms much later. Some withdrawal symptoms were distinct from those of anxiety (e.g., tinnitus, involuntary movement, and perceptual changes). Withdrawal symptoms occurred earlier in patients who had received short-acting benzodiazepines than in those who had received long-acting benzodiazepines. Symptoms gradually disappeared over a four-week period in both the placebo and the diazepam groups. Serial determination of plasma benzodiazepine concentrations was a useful way to assess compliance, treatment outcome, and relapse during withdrawal. We conclude that a clinically important, mild, but distinct withdrawal syndrome occurs after discontinuation of long-term therapeutic use of benzodiazepines.
SP0087 Taking Charge Patient Power
Authors: A. Higginbottom
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> My personal story on learning to live and self-manage my condition of Fibromyalgia. After many years of uncertainty the importance to finally receive a diagnosis. The awful realisation of being unable to work for many years and how my illness has affected my family, my whole life. Then being able to attend a Pain Management Programme at the local Rheumatology Hospital. Learning new techniques, skills and self-management that has now changed my life for the better. Which then gave me the confidence to work part time for a year to see how I managed, especially with the fatigue part of the condition. Then resulted in me being offered a part time permanent paid position <h3>Disclosure of Interest</h3> None Declared
Case 36-2008
Authors: Steven D. Brass, Marlene L. Durand, John H. Stone, John W. Chen, James R. Stone
Journal: New England Journal of Medicine (2008)

A 59-year-old man was admitted to this hospital with a 6-month history of chronic daily headache, fever, and myalgia. Dry mouth, polydipsia and polyuria, and pain in the jaws on chewing developed. Neuroimaging studies showed diffuse thickening and enhancement of the dura, extending to the pituitary stalk. Computed tomography revealed calcified nodules in the lungs and spleen. A diagnostic procedure was performed.
Importance of timing of PET scan after therapy in oncology
Authors: N. Mullai, W. Baker, L. Simons
Journal: Journal of Clinical Oncology (2007)

13014 Background: Growth factors are routine after systemic chemotherapy both as primary and secondary prophylaxis. Similarly PET scan is increasingly used for initial staging and follow-up of response. Timing of both is important since false positive results are noted due to high sensitivity of the test. Methods: Records of four patients with super positive PET scan with diffuse uptake in the axial skeleton were analyzed for the timing of administration of white cell growth factor before imaging and confirmation of bone finding with a follow- up bone scan to rule out mets. Results: Two patients were treated for stage IIIB/IV non-small cell lung cancer, one patient with breast cancer was receiving adjuvant treatment for stage IIIA breast cancer, and the last patient was treated for metastatic pancreatic cancer. All had negative scans for bone mets before the start of treatment. PET scan was done for staging in one patient and evaluation of abnormal CT scan in another, and follow-up of response in two patients. It was inadvertently obtained 10–14 days after the filgrastim/pefilgrastim administration. Based on the unusual uptake in bony skeleton, bone scan was ordered to rule out bone mets in all four patients. Since their bone scans were negative for metastatic disease they were continued on their treatment plan as scheduled. Conclusions: PET scan has been sparingly used until 1990’s due to high cost. Currently Medicare has approved it for wider indications. PET scan in general has high sensitivity and low specificity and false positive results are more common from metabolically active infection and inflammation. Granulocyte colony stimulating factor used with cancer treatments can increase the FDG uptake in PET scan. Diffuse increased uptake in bone marrow by PET scan can be seen in reactive marrow following growth factor therapy. Usually FDG uptake is modest with SUV of less than 3, uniform and diffuse if due to growth factor stimulation in contrast to greater intensity with SUV around 6 with non uniform distribution. Awareness of this pitfalls associated with PET scan allows image interpretation accurately. PET-CT fusion may increase the diagnostic specificity. However timing of the scan in relation to growth factor administration may also help to avoid the unnecessary anxiety and further follow up testing which adds to the health care costs. No significant financial relationships to disclose.
ATPS-97TEMOZOLOMIDE RESISTANT GLIOBLASTOMA (GBM) CELLS AND XENOGRAFTS ARE ESPECIALLY SENSITIVE TO PARP-INHIBITION
Authors: Alice Yuan, Lori Maxwell, Shahana Safdar, Xuiqing Lun, Ngoc Ha Dang, Donna Senger, Steve Robbins, Michael Blough, Gregory Cairncross
Journal: Neuro-Oncology (2015)

INTRODUCTION: Poly (ADP-ribose) polymerase (PARP) inhibitors, which are helpful for subsets of patients with ovarian and breast cancer, may have the potential to augment the beneficial effects of temozolomide (TMZ) chemotherapy and ionizing radiation (IR), DNA-damaging therapies that prolong the survival of patients with glioblastoma (GBM). Here, we tested the effects of PARP-inhibition alone and PARP-inhibition in combination with TMZ and IR in GBM-derived brain tumour initiating cells (BTIC) and xenografts. METHODS: BTIC lines (n = 14) from patients with newly diagnosed or recurrent GBMs were treated with the PARP inhibitor, ABT-888 (10uM), either alone or in combination with TMZ (10ug/mL), IR (8 Gy), or TMZ plus IR; viability was measured using the AlamarBlue assay. Using BTICs that grew well in vivo, mice that harbored orthotopic xenografts were treated with ABT-888 alone, TMZ alone, or ABT-888 plus TMZ, and survival measured. RESULTS: ABT-888 was ineffective against all BTICs when administered as a single agent. BTICs that were sensitive to TMZ (i.e., newly diagnosed, methylated) were not sensitized further by ABT-888. However, BTICs that were either intrinsically resistant to TMZ (i.e., newly diagnosed, unmethylated) or had become resistant (i.e., recurrent, methylated or unmethylated) were rendered sensitive to TMZ by ABT-888 co-treatment. All lines were sensitive to IR and to the combination of TMZ and IR; ABT-888 did not enhance or negate sensitivity to IR in any of the combinations tested. Identical patterns of response to ABT-888 were seen in vivo. CONCLUSIONS: In a BTIC model of GBM, PARP inhibition with ABT-888 potentiates the cytotoxic effects of TMZ in BTICs and xenografts that are either inherently resistant to TMZ by virtue of MGMT expression or have acquired resistance through prior treatment. ABT-888 had little effect on TMZ-sensitive lines and xenografts. These observations warrant consideration as human trials of PARP-inhibitors are developed.
PCSM-09PSYCHOSOCIAL AND SYMPTOMATIC SCREENING AMONG PATIENTS WITH CENTRAL NERVOUS SYSTEM TUMORS
Authors: Jazmin Sevilla, Cheryl Abe, Pia Banerjee, Nanette Fong, Albert Lai, Timothy Cloughesy, Phioanh Nghiemphu
Journal: Neuro-Oncology (2015)

BACKGROUND: Identifying psychosocial and symptomatic issues among patients with central nervous system tumors is essential to their care. In this study, a brief questionnaire is used to improve our overall knowledge of general distress experienced by these patients, while specifically evaluating the frequency of psychosocial and symptomatic issues that they may encounter upon onset of diagnosis. METHODS: The questionnaire was completed by 366 patients at every visit at the UCLA neuro-oncology clinic. Among these, 104 patients completed the questionnaire more than once. Patients completed a depression screening using the PHQ-2 and a screen for suicidal ideation derived from the PHQ-9. The remainder of the questionnaire consisted of a list of psychosocial and symptomatic features in which patients were instructed to select if applicable. RESULTS: For the depression screening, 61% denied having little interest or pleasure in doing things over the past 2 weeks, while only 7% reported that they experienced this feeling nearly every day. When they were asked if they have been feeling down, depressed, or hopeless over the past 2 weeks, 61% denied these feelings, while 5% stated that they felt this way nearly every day. Of these, 4% of patients report of having suicidal thoughts. The most common psychosocial concerns were feelings of anxiety (33%), how their family is coping (29%), and their quality of life (25%). Among these patients, most reported that they needed assistance with finances (10%), transportation (8%), disability benefits (7%), and care at home (7%). When asked about symptoms, patients reported of significant cognitive changes (32%), fatigue (42%), and numbness/weakness/falls/imbalance (29%). CONCLUSION: The questionnaire emphasized the needs of the patients in the neuro-oncology clinic. This has served as a vital tool to reveal where intervention is indicated among these patients.
Case 23-2003
Authors: A. Razzaque Ahmed, Mathew M. Avram, Lyn M. Duncan
Journal: New England Journal of Medicine (2003)

Presentation of CaseA 79-year-old woman with a gastric B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT) type was admitted to the hospital because of erosive mucosal and cutaneous lesions.The patient had been well until 14 months before admission, when she began to have cramping abdominal pain and to pass black, tarry stools. Endoscopic ultrasonographic examination of the upper gastrointestinal tract to the second part of the duodenum, performed 13 months before admission, revealed a large, submucosal, noncircumferential mass, 6 by 3 cm, involving the cardia and gastroesophageal junction, without associated bleeding or ulceration; the mass was well defined . . .
Comparative Observations of Reserpine and Syrosingopine
Authors: Bertram M. Winer, Bal M. Sahay
Journal: New England Journal of Medicine (1960)

IN animals, syrosingopine, a synthetic derivative of reserpine, has hypotensive activity equivalent to that of reserpine, but markedly less sedative effect.1 In man, syrosingopine has been reported to have hypotensive effects and virtually no side effects when administered orally in doses of 1 to 5 mg. a day.2 3 4 5 6 Our studies indicate that syrosingopine does not have hypotensive potency equivalent to that of reserpine when administered orally in human hypertensive subjects. The evidence suggests that in man syrosingopine is either poorly absorbed or inactivated in the gastrointestinal tract.Materials and MethodsThe effects of orally administered reserpine and syrosingopine were compared . . .
Polymorphisms in the Coagulation Factor VII Gene and the Risk of Myocardial Infarction
Authors: L Iacoviello, A Di Castelnuovo, P De Knijff, A D'Orazio, C Amore, R Arboretti, C Kluft, M Benedetta Donati
Journal: New England Journal of Medicine (1998)

High blood levels of coagulation factor VII are associated with a risk of ischemic vascular disease. Although factor VII levels may be genetically determined, the relation between genetic polymorphisms of factor VII, factor VII blood levels, and the risk of myocardial infarction has not been established.We performed a case-control study of 165 patients with familial myocardial infarction (mean [+/-SD] age, 55+/-9 years) and 225 controls without a personal or family history of cardiovascular disease (mean age, 56+/-8 years). The polymorphisms involving R353Q and hypervariable region 4 of the factor VII gene were studied. Factor VII clotting activity and antigen levels were also measured.Patients with the QQ or H7H7 genotype had a decreased risk of myocardial infarction (odds ratios, 0.08 [95 percent confidence interval, 0.01 to 0.9] and 0.22 [95 percent confidence interval, 0.08 to 0.63], respectively). For the R353Q polymorphism, the RR genotype was associated with the highest risk, followed by the RQ genotype and then by the QQ genotype (P<0.001). For the polymorphism involving hypervariable region 4, the combined H7H5 and H6H5 genotypes were associated with the highest risk, followed in descending order by the H6H6, H6H7, and H7H7 genotypes (P<0.001). Patients with the QQ or H7H7 genotype had lower levels of both factor VII antigen and factor VII clotting activity than those with the RR or H6H6 genotype. Patients with the lowest level of factor VII clotting activity had a lower risk of myocardial infarction than those with the highest level (odds ratio, 0.13; 95 percent confidence interval, 0.05 to 0.34).Our findings suggest that certain polymorphisms of the factor VII gene may influence the risk of myocardial infarction. It is possible that this effect may be mediated by alterations in factor VII levels.
Serum Concentrations of Penicillin Following the Administration of Crystalline Procaine Penicillin G in Oil
Authors: William L. Hewitt, Philip Whittlesey, Chester S. Keefer
Journal: New England Journal of Medicine (1948)

THE use of peanut oil and beeswax suspensions of amorphous calcium penicillin and of the sodium and potassium salts of crystalline penicillin G for delaying its absorption when injected intramuscularly is well known. The recent preparation of the crystalline procaine salt of penicillin G has afforded the opportunity for studying the absorption of a relatively insoluble salt.1 , 2 Procaine penicillin is a true salt derived by the stoechiometric combination of procaine hydrochloride and sodium penicillin G. Calculated on the basis of a potency for crystal-line sodium penicillin G at 1667 units per milligram, the theoretical potency of crystalline procaine penicillin G . . .