tbuckley/cabot-search huggingface dataset:
Overview of Combined Modality Therapies for Head and Neck Cancer
Authors: I. W. Dimery, W. K. Hong
Journal: JNCI Journal of the National Cancer Institute (1993)

The survival rate is 40% for patients with advanced squamous cell carcinoma of the head and neck whose tumors are completely resected and 20% for those with unresectable tumors treated with radiotherapy alone. During the past 10 years, combined modality approaches have been developed in an effort to enhance locoregional disease control, reduce distant metastases, and preserve anatomic function. They include the following: (a) neoadjuvant chemotherapy followed by standard therapy with surgery and/or radiation, (b) adjuvant chemotherapy after surgery or radiotherapy with or without neoadjuvant chemotherapy, and (c) neoadjuvant chemotherapy concurrent with radiotherapy. Even early studies of cisplatin plus fluorouracil (5-FU) reported 50%-90% overall response rates, and this is the main drug combination used in clinical trials. In the Veterans Affairs Cooperative Study Program, 5-FU and cisplatin followed by radiotherapy achieved a 49% complete response rate and preservation of the larynx in 64% of the patients. These results supported the findings of other nonrandomized trials that sequential induction chemotherapy and radiotherapy results in laryngeal preservation without compromising overall survival. The Head and Neck Cancer Intergroup Trial compared adjuvant postoperative cisplatin plus 5-FU prior to radiotherapy with postoperative radiotherapy. Survival at 4 years was 44% with radiotherapy alone and 48% with chemotherapy and radiotherapy. Biochemical modulation of 5-FU with leucovorin and biologic response modifiers such as interferon has achieved complete response rates as high as 66%, but severe mucositis continues to be the dose-limiting toxic effect. Standard radiotherapy for advanced nasopharyngeal carcinoma--a unique type of head and neck cancer--resulted in 5-year survival of 10%-40%, but neoadjuvant chemotherapy plus radiotherapy has achieved overall complete response rates greater than 80% with median survival of 5 or more years. We conclude that curability of nasopharyngeal carcinoma with a combined modality approach appears to be an achievable goal, but adequate evaluation in large-scale randomized trials is hampered by low accrual to clinical trials. In summary, neoadjuvant therapy for squamous cell head and neck carcinoma results in complete response rates of 22%-66%, but addition of adjuvant therapy may be necessary for a survival advantage over standard therapy. Although concurrent chemoradiotherapy has produced increased survival, additional trials are needed to determine optimal dosages.
SOME FACTS ABOUT VACCINATION.
Authors: HEMAN SPALDING
Journal: JAMA (1902)

Owing to a lack of exact knowledge from absolutely reliable sources on the subject of vaccination, there is a good deal of misapprehension in the public mind as to the efficacy of vaccination as a protection against smallpox, and the constant inquiry is made: "When shall we vaccinate?" "How long does it protect?" and "How often should we be vaccinated?" Many members of the medical profession, busy with other things to do and not compelled to face the epidemic horrors of a hundred years ago and not exact in their knowledge on the subject of vaccination, have a halting, uncertain, confused state of mind on the subject, which goes far to create doubt in the public. There are doctors, and good ones, too, who have had so little experience with vaccination that they do not know what constitutes a successful vaccination. I visited a neighboring town where a reputable physician
Phase II study of avatrombopag in thrombocytopenic patients with cirrhosis undergoing an elective procedure
Authors: Norah A. Terrault, Tarek Hassanein, Charles D. Howell, Shobha Joshi, John Lake, Linda Sher, Hugo Vargas, Joe McIntosh, Shande Tang, Tim M. Jenkins
Journal: Journal of Hepatology (2014)
Unnatural Deaths in a National Cohort of People Diagnosed With Diabetes
Authors: Roger T. Webb, Paul Lichtenstein, Marie Dahlin, Navneet Kapur, Jonas F. Ludvigsson, Bo Runeson
Journal: Diabetes Care (2014)

To examine risk of unnatural death among people diagnosed with diabetes irrespective of disease type.We conducted a matched cohort study of the entire Swedish population using interlinked national registers. From the National Diabetes Register we identified 252,191 people diagnosed with diabetes (type 1 or 2) during 1996-2009. Each cohort member was matched for age, sex, and county of birth to five unaffected individuals randomly sampled from the Total Population Register. Mortality was examined with complete ascertainment, and risk ratios (RRs) for all unnatural deaths and for specific causes (suicide, accident, homicide, and iatrogenic effects) were estimated using conditional fixed-effects Poisson regression.Risk of any unnatural death was elevated versus the general population: 77.3 versus 32.1 per 10,000 (RR 2.2 [95% CI 2.1-2.4]), and these deaths occurred at a younger age in the diabetes cohort. Risk was increased for suicide (RR 3.4 [95% CI 3.0-3.8]), accident (RR 2.0 [95% CI 1.9-2.1]), homicide (RR 3.1 [95% CI 1.6-6.1]), and iatrogenic effects (RR 2.4 [95% CI 1.9-3.2]). It was greatly elevated for fatal poisoning from a variety of agents, including psychotropic drugs and "other and unspecified medication," as well as narcotics, alcohol, and carbon monoxide. Almost 9% of all fatal poisoning cases in the diabetes cohort were identified as overdoses of insulin or oral hypoglycemic drugs.Various causes of unnatural death, in particular deliberate and accidental poisonings, occur more frequently among diabetic patients. Before preventive strategies can be implemented, a deeper understanding of the risk factors and causal mechanisms explaining the marked elevations in risk is needed.
A common mutation (G-455--&gt; A) in the beta-fibrinogen promoter is an independent predictor of plasma fibrinogen, but not of ischemic heart disease. A study of 9,127 individuals based on the Copenhagen City Heart Study.
Authors: A Tybjaerg-Hansen, B Agerholm-Larsen, S E Humphries, S Abildgaard, P Schnohr, B G Nordestgaard
Journal: Journal of Clinical Investigation (1997)

A common mutation (G-455--> A) in the promoter region of the beta-fibrinogen gene has been associated with elevated plasma fibrinogen levels. Whether fibrinogen genotype affects plasma fibrinogen levels and risk of ischemic heart disease in the general population has not been studied. We investigated the association between fibrinogen genotype, plasma fibrinogen levels, and ischemic heart disease in a general population sample (n = 9,127). The A-allele (relative frequency, 0.20) was associated with elevated plasma fibrinogen levels in both genders (P < 0.001). While the effect of the A-allele on fibrinogen level was additive in men, the effect was dominant in postmenopausal women. The A-allele raising effect appeared to be two- to threefold greater in individuals with ischemic heart disease than in those without. An increase of 1 SD in plasma fibrinogen increased the odds ratio for ischemic heart disease by approximately 20% (P < 0.01 for women and < 0.005 for men). However, the frequency of the A-allele was similar in those with and without ischemic heart disease, and genotype was not a predictor of disease. These results demonstrate that the (G-455--> A) mutation in the promoter region of the beta-fibrinogen gene is associated with an increase in plasma fibrinogen in both genders in the general population. This increase does not appear to cause ischemic heart disease.
Catheters and Urinary Tract Infection
Authors: Frank Naso
Journal: JAMA (1973)

<h3>To the Editor.—</h3> Referring to the article "Prevention of Catheter-Associated Urinary Tract Infection" (221:1270, 1972), I would like to comment: Although the catheter is associated with a high incidence of urinary tract infection, with proper management, the sequelae may be minimized. In our field of rehabilitation medicine, the indwelling catheter on a long-term basis is necessary in some patients with spinal cord injury, since they may have an incompletely emptying bladder, high residual urine volumes, associated sepsis, and pyelonephritis. In these cases, the indwelling catheter is a necessary evil. With proper management, the prognosis in chronic paraplegia is good since the 20-year mortality for chronic renal disease is 7%.<sup>1</sup> Proper management of the patient with an indwelling catheter is relatively simple. Promoting an acidic urine will inhibit bacterial growth.<sup>2</sup>Furthermore, Andriole has clearly demonstrated water diuresis was associated with sterilization of the experimentally infected rat renal medulla.<sup>3</sup>
Prenatal lead exposure, delta-aminolevulinic acid, and schizophrenia.
Authors: Mark G A Opler, Alan S Brown, Joseph Graziano, Manisha Desai, Wei Zheng, Catherine Schaefer, Pamela Factor-Litvak, Ezra S Susser
Journal: Environmental Health Perspectives (2004)

Schizophrenia is a severe mental disorder of unknown etiology. Recent reports suggest that a number of environmental factors during prenatal development may be associated with schizophrenia. We tested the hypothesis that environmental lead exposure may be associated with schizophrenia using archived serum samples from a cohort of live births enrolled between 1959 and 1966 in Oakland, California. Cases of schizophrenia spectrum disorder were identified and matched to controls. A biologic marker of lead exposure, delta-aminolevulinic acid (delta-ALA), was determined in second-trimester serum samples of 44 cases and 75 controls. delta-ALA was stratified into high and low categories, yielding 66 subjects in the high category, corresponding to a blood lead level (BPb) greater than or equal to 15 micro g/dL, and 53 in the low category, corresponding to BPb less than 15 micro g/dL. Using logistic regression, the odds ratio (OR) for schizophrenia associated with higher delta-ALA was 1.83 [95% confidence interval (CI), 0.87-3.87; p = 0.1]. Adjusting for covariates gave an OR of 2.43 (95% CI, 0.99-5.96; p = 0.051). This finding suggests that the effects of prenatal exposure to lead and/or elevated delta-ALA may extend into later life and must be further investigated as risk factors for adult psychiatric diseases.
HIF-1α is required for hematopoietic stem cell mobilization and 4-prolyl hydroxylase inhibitors enhance mobilization by stabilizing HIF-1α
Authors: C E Forristal, B Nowlan, R N Jacobsen, V Barbier, G Walkinshaw, C R Walkley, I G Winkler, J P Levesque
Journal: Leukemia (2015)

Many patients with hematological neoplasms fail to mobilize sufficient numbers of hematopoietic stem cells (HSCs) in response to granulocyte colony-stimulating factor (G-CSF) precluding subsequent autologous HSC transplantation. Plerixafor, a specific antagonist of the chemokine receptor CXCR4, can rescue some but not all patients who failed to mobilize with G-CSF alone. These refractory poor mobilizers cannot currently benefit from autologous transplantation. To discover alternative targetable pathways to enhance HSC mobilization, we studied the role of hypoxia-inducible factor-1α (HIF-1α) and the effect of HIF-1α pharmacological stabilization on HSC mobilization in mice. We demonstrate in mice with HSC-specific conditional deletion of the Hif1a gene that the oxygen-labile transcription factor HIF-1α is essential for HSC mobilization in response to G-CSF and Plerixafor. Conversely, pharmacological stabilization of HIF-1α with the 4-prolyl hydroxylase inhibitor FG-4497 synergizes with G-CSF and Plerixafor increasing mobilization of reconstituting HSCs 20-fold compared with G-CSF plus Plerixafor, currently the most potent mobilizing combination used in the clinic.
Effect of CAL-101, a PI3Kδ inhibitor, on ribosomal rna synthesis and cell proliferation in acute myeloid leukemia cells
Authors: L X T Nguyen, A Sesay, B S Mitchell
Journal: Blood Cancer Journal (2014)

Acute myeloid leukemia (AML) accounts for B80% of all adult leukemias and the majority of patients will relapse and die from this disease, indicating an unmet need for new therapies. 1,24][5] The overall survival of AML patients whose blasts demonstrated Akt activation was significantly shorter than that of patients without Akt activation, suggesting that this pathway could represent an important therapeutic target. 3,6ctivation of Akt is mediated by PI3K Class I p110 isoforms.The PI3K p110d catalytic subunit is consistently expressed at high levels in AML blasts. 7][10][11] Although recent studies demonstrated that CAL-101, which is 400-fold more selective for class I PI3K than for related kinases, exhibits far greater effects against B-ALL and CLL cells as compared with AML and myeloproliferative neoplasm cells, 11 we have recently shown that Akt directly regulates rRNA synthesis activity in AML, resulting in enhancement of cell proliferation. 12We have therefore asked whether CAL-101 could suppress rRNA synthesis by reducing Akt phosphorylation in AML cells with the goal of determining whether this approach might be therapeutically useful in this group of diseases.We first examined the expression of the PI3Kd isoform in 14 AML patient samples and 5 leukemic cell lines by western blot.The properties of the patient samples are shown in Supplementary Table 1. Figure 1a shows that PI3Kd is variably expressed in patient samples and cell lines.We then examined the effects of CAL-101 on Akt phosphorylation.Treatment with CAL-101 suppresses Akt phosphorylation in K562 cells and in combined lysates from 10 primary AML cells in a dosedependent manner (Figure 1b and Supplementary Figures 1a andb), as does the Akt inhibitor AZD8055.The molecular biomarkers of P70S6K and GSK3 phosphorylation are commonly used as indicators of PI3K pathway activity.The decrease in Akt phosphorylation induced by CAL-101 occurs concomitantly with a decrease in p-P70S6K and p-GSK3 (Figure 1b and Supplementary Figures 1a andb), further suggesting that CAL-101 suppresses PI3K/Akt downstream signaling pathways in AML cells.To determine whether the suppression of Akt signaling by CAL-101 impairs cell proliferation, we treated K562 cells with CAL-101 or AZD8055 and examined cell proliferation over time.
Radionuclide Scintigraphy of the Brain and Ultrasound Studies in Tubercular Meningitis
Authors: A M SAMUEL, A S VIDVANS
Journal: Clinical Nuclear Medicine (1987)

The present study was undertaken to assess the usefulness of brain scintigraphy and ultrasound evaluation of changes described in tuberculous meningitis. Brain scans were done with Tc-99m DTPA in 127 cases of tuberculous meningitis (TBM) and ultrasound studies in 41 cases with open anterior fontanelles. The data show that 54/127 (42.5%) of cases had abnormal brain scans, of which 33/54 had cerebrovascular infarcts and 14/54 had tuberculomas, while the remaining cases had either subdural effusions or generalized increased activity. The cerebrovascular infarcts were more frequent in patients with acute onset of TBM with associated hemiplegias. The ultrasound studies indicated that 80% of all cases of TBM had a mild to severe dilatation of the ventricles. About 55% of cases had a dilatation of only the lateral ventricles while the remaining cases had a block of aqueduct or beyond the fourth ventricles. Increased intracranial pressure changes were associated with a higher incidence of severe ventricular dilatation. Noninvasive detection methods in the study of TBM are important not only from the point of view of diagnosis but also to understand and evaluate the pathological changes occurring in vivo during the disease process and to judge the progress and response to treatment. A combination of ultrasound and brain scans offers diagnostic accuracy comparable to CT. Apart from cost, the larger radiation doses resulting from CT studies preclude its routine use in pediatric subjects.
The Rise of the Medical Scribe Industry
Authors: George A. Gellert, Ricardo Ramirez, S. Luke Webster
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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
Mesotheliomas and asbestos type in asbestos textile workers: a study of lung contents.
Authors: J C Wagner, G Berry, F D Pooley
Journal: BMJ (1982)

The asbestos contents of the lungs of former employees of an asbestos textile factory were determined at necropsy using a transmission electron microscope. Those who had died of mesothelioma were compared with a matched sample of those who had died of other causes. The predominant fibre processed in the factory was chrysotile, but crocidolite had also been used. The lung content was consistent with the known exposure to chrysotile, but the crocidolite content was also high, being about 300 times that of the general population of the United Kingdom. The lungs of those with mesothelioma did not contain more of either chrysotile or crocidolite than the lungs of the controls, so no particular type of asbestos could be implicated in causing the mesotheliomas. The evidence of substantial exposure to crocidolite means that the mesotheliomas that occurred in this factory could not be attributed with any certainty to the exposure to chrysotile.
Role of Stress in Heart Disease
Authors: Hamilton B. Webb
Journal: JAMA (1975)

<h3>To the Editor.—</h3> In the review article in MEDICAL NEWS, "Two Studies Trace Role of Stress in Heart Disease" (232:696, 1975), the argument advanced is based in part on two fallacies that I believe should not be perpetuated. Myocardial infarction as a disease was indeed virtually unknown before the 1920s, but it does not follow that it was virtually nonexistent. It had only been described about 1909 and was not well taught for many years thereafter. My grandfather and my father-in-law signed out such deaths as "acute indigestion," and this was accepted uncritically by the authorities of that period. There is no way to know the actual incidence of myocardial infarction in the over-40 population at the turn of the century, but the assumption that it was low is unwarranted and probably erroneous. The self-pitying complaint that life's stresses are much greater in modern times in the United States should
A lesson to be learned from Karl Marx: smoking triggers hidradenitis suppurativa
Authors: R. Happle, A. König
Journal: British Journal of Dermatology (2008)

Journal Article A lesson to be learned from Karl Marx: smoking triggers hidradenitis suppurativa Get access R. Happle, R. Happle Department of Dermatology, Philipp University of Marburg, 35033 Marburg, Germany E‐mail: happle@med.uni‐marburg.de Search for other works by this author on: Oxford Academic Google Scholar A. König A. König Department of Dermatology, Philipp University of Marburg, 35033 Marburg, Germany E‐mail: happle@med.uni‐marburg.de Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 159, Issue 1, 1 July 2008, Pages 255–256, https://doi.org/10.1111/j.1365-2133.2008.08604.x Published: 01 July 2008
Requirement of pp60c-src expression for osteoclasts to form ruffled borders and resorb bone in mice.
Authors: B F Boyce, T Yoneda, C Lowe, P Soriano, G R Mundy
Journal: Journal of Clinical Investigation (1992)

Targeted disruption of the c-src proto-oncogene in mice has shown that src expression is required for normal bone resorption, since the src-deficient mutants develop osteopetrosis. To evaluate the mechanisms by which src-deficiency affects osteoclast function, we treated src-deficient mice with the stimulants of bone resorption, IL-1, parathyroid hormone, and parathyroid hormone-related protein, and analyzed the effects by quantitative bone histomorphometry and electron microscopy. Increased numbers of multinucleated cells with the morphological characteristics of osteoclasts appeared on bone surfaces, but these cells did not form ruffled borders or normal resorption lacunae. To confirm these in vivo findings, we cultured src-mutant bone marrow cells on dentine slices in the presence of 1,25 dihydroxyvitamin D3. Increased numbers of multinucleated cells were formed, but unlike normal murine bone marrow cells, they did not form resorption pits. These results indicate that osteoclasts appear in the absence of pp60c-src, but that pp60c-src expression is required for mature osteoclasts to form ruffled borders and resorb bone.
THE EFFECT OF PLATELET REACTIVITY ON INFARCT RELATED ARTERY PATENCY IN PATIENTS WITH ST-ELEVATION MYOCARDIAL INFARCTION
Authors: Nicoline J. Breet, Carina ACM Pittens, Heleen J. Bouman, Jochem W. van Werkum, Jurrien M. ten Berg, Christian M. Hackeng
Journal: Journal of the American College of Cardiology (2010)
Effect of plasmapheresis therapy on circulating levels of pemphigus antibodies
Authors: Rosario Tan-Lim, Jean-Claude Bystryn
Journal: Journal of the American Academy of Dermatology (1990)

We determined the circulating levels of pemphigus antibodies in 11 patients with pemphigus treated with plasmapheresis, corticosteroids, and immunosuppressive drugs and in 11 patients treated with corticosteroids and immunosuppressive drugs alone. Three weeks after hospitalization, the average titer of pemphigus antibodies had decreased from admission levels by 83% in patients treated with plasmapheresis but by only 18% in the other group (p less than 0.05). These results suggest that plasmapheresis, in conjunction with high doses of corticosteroids and immunosuppressive drugs, reduces circulating levels of pemphigus antibodies more rapidly than conventional therapy.
Clinical significance and distribution of putative virulence markers of 116 consecutive clinical Aeromonas isolates in southern Taiwan
Authors: Chi-Jung Wu, Jiunn-Jong Wu, Jing-Jou Yan, Hsin-Chun Lee, Nan-Yao Lee, Chia-Ming Chang, None Hsin-I Shih, Hsiu-Mei Wu, Li-Rong Wang, Wen-Chien Ko
Journal: Journal of Infection (2006)