tbuckley/cabot-search huggingface dataset:
C5a-Inhibitor Deficiency in Peritoneal Fluids from Patients with Familial Mediterranean Fever
Authors: Yaacov Matzner, Amnon Brzezinski
Journal: New England Journal of Medicine (1984)

Normal peritoneal fluid contains an inhibitor of neutrophil chemotaxis that acts by antagonizing the complement-derived chemotactic anaphyllatoxin C5a. The inhibitor resembles a substance previously described in synovial fluids and is a protein with a molecular weight of approximately 40,000 as determined by gel filtration. In contrast, levels of inhibitory activity in peritoneal fluids from five patients with familial Mediterranean fever were decreased to less than 10 per cent of those found in normal subjects. Gel filtration of peritoneal and synovial fluids from these patients did not yield any fraction with inhibitory activity. We suggest that C5a-inhibitor deficiency in joint and peritoneal fluids from patients with familial Mediterranean fever may have a role in the pathogenesis of the inflammatory attacks characteristic of this disease.
IMPACT trial: Predictive factors for maintenance therapy with MGN1703 in patients with metastatic colorectal carcinoma.
Authors: Jorge Riera-Knorrenschild, Werner Scheithauer, Hendrik Kröning, Frank Mayer, Dieter Nitsche, Reinhard Ziebermayr, Johannes Andel, Dirk Arnold, Burghardt Wittig, Hans-Joachim Schmoll
Journal: Journal of Clinical Oncology (2014)

3615 Background: The immunomodulator MGN1703, a TLR-9 agonist, has shown good safety profile in patients with metastatic solid tumors. The IMPACT trial was conducted to assess clinical efficacy, safety, and immunological effects of MGN1703 as maintenance therapy twice weekly. Methods: The international randomized (2:1) double-blind placebo-controlled phase 2 IMPACT trial in mCRC patients with disease control after 1st-line chemotherapy by FOLFOX/XELOX or FOLFIRI +/- bevacizumab. After randomization of 59 out of 129 planned patients (43 MGN1703, 16 placebo) the trial was prematurely closed due to slow recruitment. Results: A superior effect of MGN1703 compared to placebo was shown: HR for the primary endpoint PFS on maintenance was 0.55 (p=0.041) by local and 0.56 (p=0.070) by independent assessment. For PFS from start of induction therapy the HR was 0.50 (p=0.022) and 0.49 (p=0.030), respectively. Notably, at time of study closure 4 MGN1703 patients were still free of PD and continued in compassionate use. A possible predictive effect was identified by Cox regression analyses: HR of 0.07 (p<0.0001) for patients with normal CEA and 0.39 (p=0.005) for patients with an objective response. Evaluation of biological activity via cell populations and chemokine serum levels confirmed immune system activation in MGN1703 patients. Cox regression and ROC analyses identified of activated NKT-cells (CD3+/CD56+/CD69+) at baseline as potentially predictive for a benefit from MGN1703 treatment (HR: 0.27, p=0.007). Study treatment was well tolerated: 32.6% vs. 18.8% of patients (MGN1703 vs. placebo) had drug-related AE and in only 1 patient per arm it was of grade 3 (MGN1703: sensory polyneuropathy, placebo: papular exanthema). Seven SAEs were reported of which only 1 was possible drug-related (moderate atypical pneumonia). Conclusions: Following induction chemotherapy, MGN1703 maintenance in mCRC patients is associated with improved PFS and an activation of the innate and adaptive immune system. Treatment was safe and well tolerated. There is preliminary evidence that CEA levels, tumor response, and activated NKT cells before start of MGN1703 therapy allow for identification of benefitting patients. Clinical trial information: NCT01208194.
Lesson of the week : Unusual case of choriocarcinoma occurring 12 months after delivery
Authors: A. Todd, E. Newlands, M. Palazzo
Journal: BMJ (1998)

<h3>Abstract</h3> <b>Choriocarcinoma should be considered in women of childbearing age with acute haemorrhage occurring even years after a normal birth</b> Choriocarcinoma is a malignant tumour that arises from trophoblastic epithelium; it has an incidence of 0.05 to 0.23 per 1000 live births.1 The most important risk factor, a history of hydatidiform mole, is present in only half of cases, and many cases occur after a normal full term pregnancy.2 We report the case of a young woman with choriocarcinoma who presented with an intraperitoneal haemorrhage from splenic metastases. She also developed multiple pulmonary tumour emboli and haemorrhage from tumour infiltration. She is the first patient in the United Kingdom, so far as we are aware, to survive ventilation for this disease.
Muscle weakness is a significant problem in older patients receiving chemotherapy
Authors: M. Extermann, I. Boler, E. O’Neill, R. Brown, J. Defelice, R. Levine, E. Lubiner, P. Reyes, F. Schreiber, G. H. Lyman, L. Balducci
Journal: Journal of Clinical Oncology (2006)

8545 Background: Accurate prediction of toxicities from chemotherapy in the elderly could lead to improved decision making and supportive care. Methods: A large prospective multicentric cohort study of older cancer patients undergoing chemotherapy is underway to document the occurrence of chemotherapy toxicity and to develop a predictive score: the CRASH score (Chemotherapy Risk Assessment Score for High Age patients). Toxicity, including muscle weakness, is assessed using the Common Toxicity Criteria v.3.0. Results: An analysis of the first 200 patients entered in the study revealed an infrequently highlighted side effect: muscle weakness. Twenty patients were not evaluable for this analysis. Muscle weakness was reported by 22 patients. This represented 12.2% of the patients, of whom 13 (7.2%) had grade 3 muscle weakness. There was no grade 4 muscle weakness. This side effect appears to be independent from fatigue: only 4/22 patients reported concomitant severe (grade 3–4) fatigue, and among the 24 patients with severe fatigue, only 4 reported any muscle weakness. Muscle weakness occurred fairly early during the treatment: median 30 days (range 6–126 days). The muscle weakness was predominantly of two types: a generalized muscle weakness, or a weakness affecting the lower extremities. It was accompanied by falls in two patients. That weakness was present across tumor types, chemotherapy types, individual physicians, and oncology centers. Like the rest of the study population, the majority of these patients had advanced disease. Other frequent severe side effects were: grade 4 neutropenia 31.7%; grade 3–4: hypokalemia 8.8%, hyperglycemia 8.3%, hyponatremia 7.2%, febrile neutropenia 7.2%, diarrhea 7.2%, infection with neutropenia 6.7%. Conclusion: Muscle weakness is a frequent and clinically significant side effect of chemotherapy in the elderly, distinguishable from fatigue. This could be targeted by a preventive physical therapy intervention to prevent muscle deconditioning. [Table: see text]
Case 32-1966
Authors: Wyland F. Leadbetter, Austin L. Vickery
Journal: New England Journal of Medicine (1966)

Presentation of CaseA fifty-eight-year-old woman entered the hospital because of a fracture.Four hours previously she had sustained a fracture of the left femur in a fall down a stairway. She had had diabetes for twenty years and had adhered rigidly to a regimen of a 1300-calorie diet and 20 units of lente insulin daily, with careful tests of the urine and frequent supplemental doses of crystalline insulin for + or ++ glycosuria. She had had numerous hypoglycemic reactions, sometimes leading to convulsive seizures. There was no history of diabetic ketoacidosis.For several months before admission she had experienced . . .
Relationship of Industry Sponsorship to Results of Cost-effectiveness Analyses of Drugs Used in Breast Cancer Treatment
Authors: Xiulu Ruan, Gary W. Bumgarner, Alan David Kaye
Journal: JAMA Oncology (2016)

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
Low Molecular Weight Heparins as Extended Prophylaxis Against Recurrent Thrombosis in Cancer Patients
Authors: Cocav A. Engman, Leo R. Zacharski
Journal: Journal of the National Comprehensive Cancer Network (2008)

Cancer has been shown to be an independent risk factor for the development of venous thromboembolism (VTE; deep vein thrombosis and pulmonary embolism). Thromboprophylaxis reduces the incidence of VTE in patients with cancer; however, active cancer places patients at high risk for recurrent VTE, necessitating extended prophylactic regimens. Extended prophylaxis in patients with cancer can be problematic because of increased risk for bleeding. Oral anticoagulants, such as warfarin, have been the standard of care for extended prophylaxis, but maintaining a clinically effective level of anticoagulation can be difficult because of a wide range of drug interactions, a narrow therapeutic window, and an increased risk of bleeding complications, particularly in patients with cancer. Recent evidence indicates that long-term prophylaxis with low-molecular-weight heparins (LMWHs) is an effective and safe alternative to oral anticoagulation in patients with VTE and cancer, reducing the risk for recurrent VTE by up to 52%. LMWHs can also be seen as cost-effective for long-term prophylaxis, because higher drug acquisition costs are offset by the potential for reduced hospital stays, reduced need for coagulation monitoring, and fewer bleeding complications. Some studies suggest that LMWHs may also have direct antitumor effects and improve survival rates, most notably in patients with non-metastatic disease. Further clinical research is needed to evaluate the potential survival benefits of LMWH therapy in patients with cancer.
Case 29-2011
Authors: Noopur S. Raje, David J.R. Steele, Tara M. Lawrimore, Amer M. Johri, Aliyah R. Sohani
Journal: New England Journal of Medicine (2011)

Cardiac and renal failure developed in a 66-year-old woman. Echocardiography suggested infiltrative cardiomyopathy, lytic bone lesions were seen on imaging, and elevated serum free light chains were detected. A diagnostic procedure was performed.
Lung tumor exosomes induce a pro-inflammatory phenotype in mesenchymal stem cells via NFκB-TLR signaling pathway
Authors: Xiaoxia Li, Shihua Wang, Rongjia Zhu, Hongling Li, Qin Han, Robert Chunhua Zhao
Journal: Journal of Hematology & Oncology (2016)

In tumor microenvironment, a continuous cross-talk between cancer cells and other cellular components is required to sustain tumor progression. Accumulating evidence suggests that exosomes, a novel way of cell communication, play an important role in such cross-talk. Exosomes could facilitate the direct intercellular transfer of proteins, lipids, and miRNA/mRNA/DNAs between cells. Since mesenchymal stem cells (MSCs) can be attracted to tumor sites and become an important component of the tumor microenvironment, there is an urgent need to reveal the effect of tumor exosomes on MSCs and to further explore the underlying molecular mechanisms. Exosomes were harvested from lung cancer cell line A549 and added to MSCs. Secretion of inflammation-associated cytokines in exosome-treated MSCs were analyzed by RT-PCR and ELISA. The growth-promoting effect of exosome-treated MSCs on lung tumor cells was evaluated by in vivo mouse xenograft model. Signaling pathway involved in exosomes-treated MSCs was detected by PCR array of human toll-like receptor signaling pathway, RT-PCR, and Western blot. Data showed that lung tumor cell A549-derived exosomes could induce a pro-inflammatory phenotype in MSCs named P-MSCs, which have significantly elevated secretion of IL-6, IL-8, and MCP-1. P-MSCs possess a greatly enhanced ability in promoting lung tumor growth in mouse xenograft model. Analysis of the signaling pathways in P-MSCs revealed a fast triggering of NF-κB. Genetic ablation of Toll-like receptor 2 (TLR2) by siRNA and TLR2-neutralizing antibody could block NF-κB activation by exosomes. We further found that Hsp70 present on the surface of lung tumor exosomes contributed to the induction of P-MSCs by A549 exosomes. Our studies suggest a novel mechanism by which lung tumor cell-derived exosomes induce pro-inflammatory activity of MSCs which in turn get tumor supportive characteristics.
Case 2-2003
Authors: Peter M. Yurchak, Vikram Deshpande
Journal: New England Journal of Medicine (2003)

Presentation of CaseA 60-year-old man was admitted to the hospital because of dyspnea and pulmonary vascular congestion.The patient had reportedly been well until seven days earlier, when he began to have dyspnea during moderate exertion. Four days before admission, he felt a nonradiating, “heavy” discomfort in the lower retrosternal and epigastric areas when he stooped, bent over, or walked short distances. There was no orthopnea, sweating, nausea, or edema.Two days before admission, he entered another hospital. The blood pressure was 150/70 mm Hg. The pulse was 80 to 90 beats per minute and irregular. Inspiratory crackles were . . .
Hyperaldosteronism and Renal Sodium Loss Reversed by Drug Treatment for Malignant Hypertension
Authors: John R. Gill, Jack M. George, Alan Solomon, Frederic C. Bartter, Delores McBirney
Journal: New England Journal of Medicine (1964)

SOME patients with renal disease, with1 and without2 hypertension, cannot conserve sodium normally. The loss of sodium leads to an increased production of aldosterone, but the relation of the increased aldosterone production to the defective sodium conservation is not always clear, for the hyperaldosteronism may persist even when large amounts of sodium are given.2 , 3 This could be explained if the high sodium intake did not produce and maintain a normal volume of extracellular fluid in such patients. It could also be explained if the hyperaldosteronism were caused by a condition other than "sodium wasting."It has been suggested that malignant . . .
Cell growth and topoisomerase IIα inhibitory activity of the bacterial metabolites kinamycin C and kinamycin A
Authors: Xing Wu, Gary Dmitrienko, Valerie Goodfellow, Adedayo Otunola, Radek S. Laufer, Jack C. Yalowich, Brian Hasinoff
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

2392 

The antibiotics kinamycin C (KC) and kinamycin A (KA) are naturally occurring bacterial metabolites isolated from Streptomyces murayamaensis that contain an unusual and potentially reactive diazo side chain. Although the antimicrobial activity of the kinamycins has been described, the mechanism of inhibition of cell growth by these compounds is unknown. Our results show that KC and KA strongly inhibit the growth of the human erythroleukemic K562 cells ( IC 50 of 0.2 and 0.3 μM, respectively). A short drug treatment of the cells also resulted in strong growth inhibition indicating a rapid onset of action. KC rapidly induced apoptosis in K562 cells as measured by flow cytometry using annexin V-FITC staining and PI staining of DNA content. When synchronized CHO cells were treated with KA, the cells were able to exit G0 and traverse the first G2/M phase, but were not able to enter the second G2/M phase. KC and KA also inhibited the catalytic activity of purified human DNA topoisomerase IIα (topo II), but not that of topoisomerase I. Preincubation of KC with topo II reduced topo II activity, indicating that KC may have inhibited topo II through a direct reaction. The inhibitory activities of KC and KA were modulated by the presence of dithiothreitol (DTT) in the assay mixture as an increase in the DTT concentration (from 0.1 to 250 μM) in the reaction mixture increased the IC 50 of KC from 9 to 108 μM, and of KA from 8 to 66 μM. Based on the ability of DTT to partially protect topo II from inhibition by these compounds, the possibility that these compounds inhibit by reacting with critical thiol groups on topo II is being explored. Neither KC nor KA were able to cross-link DNA, nor did they bind to DNA, which indicated that these compounds did not act directly on DNA. KA and KC were also examined for their ability to stabilize a DNA-topo II covalent complex and act as a topoisomerase IIα poison by measuring their ability to cleave pBR322 DNA to produce linear DNA. Neither KA nor KC induced DNA cleavage and, thus, it was concluded that they did not act as topo II poisons. Also the growth inhibitory effects of KC and KA on K562 and K/VP.5 cells (containing one-fifth the topo II content of the parental K562 cells) were not significantly different, a result that is also consistent with these compounds exerting their activity by mechanisms distinct from topo II poisoning. In summary these results indicate that even though KC and KA inhibited topo II catalytic activity, this may not be the mechanism by which they inhibited cell growth. Support: CIHR and a Canada Research Chair in Drug Development to BH, NSERC through a Discovery Grant to GID and ROI CA90787 to JCY.
Serum Potassium Levels in Diabetic Coma
Authors: Richard H. Sinden, James L. Tullis, Howard F. Root
Journal: New England Journal of Medicine (1949)

THE clinical importance of variations in the serum potassium level during treatment of diabetic coma has been emphasized by the reports of Holler,1 Martin and Wertman,2 Nicholson and Branning,3 Frenkel, Groen and Willebrands4 and Nadler, Bellet and Lanning.5 They reported low potassium values in certain patients undergoing treatment for diabetic coma, with fatal results unless suitable potassium solutions were administered promptly. On the other hand, studies of serum potassium levels in conditions of shock, cardiac or renal failure indicate that if potassium is given as a therapeutic measure to patients with impending or actual renal failure, a dangerously high level . . .
Myeloproliferative and Lymphoproliferative Disorders in Tasmania, 1972–80: Occupational and Familial Aspects&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Graham G. Giles, Ph.D., J. Norelle Lickiss, M.D.
 4, Margaret J. Baikie, M.B.B.S., Raymond M. Lowenthal, M.D., Jean Panton
Journal: JNCI Journal of the National Cancer Institute (1984)

All cases in a population-based series of myeloproliferative and lymphoproliferative (LP) disorders diagnosed in usual residents of Tasmania between 1972 and 1980 were asked for occupational histories and the occurrence of similar diseases in their close relatives. Occupational risks were observed for males who had farmed, mined, or worked in foundries and for women who had farmed or had been hairdressers. For individual diagnoses, the risk to farmers was seen to vary with age at diagnosis, sex, and region. With regard to familial risks, the LP and MP groups seemed to breed true, relatives being affected with a disorder from the other group not more often than would be expected by chance. The risks were of two kinds: Those to siblings and that between parent and child, particularly between mother and son. Occupational risks for the familial cases were limited to farming particularly in males diagnosed at 65 years of age or older. Females possessed elevated risks for the LP group only, and their highest relative risk was for those diagnosed before age 65. This evidence suggests that familial clustering of these disorders partly may be due to common environmental exposures in males from rural kindreds.
P28 Real World MDT Diagnosis of Idiopathic Pulmonary Fibrosis
Authors: M Hanley, C Leonard, N Chaudhuri
Journal: Thorax (2015)

<h3></h3> Idiopathic pulmonary fibrosis (IPF) is the commonest idiopathic interstitial lung disease (ILD). The diagnosis is determined by a usual interstitial pneumonitis (UIP) pattern on high resolution computed tomography (HRCT). Current guidelines advocate lung biopsy in patients with diagnostic uncertainty though biopsy can afford significant morbidity and mortality. We aimed to evaluate our practice in diagnosing IPF in relation to these guidelines. <h3>Methods</h3> We evaluated our experiences in a multidisciplinary team (MDT) setting in a UK tertiary referral centre of 104 patients referred with a presumed diagnosis of IPF between November 2012 and July 2014. <h3>Results</h3> After MDT discussion, 48.5% patients had definite UIP and 51.4% had possible UIP or fibrotic non-specific interstitial pneumonitis (NSIP) based on ATS/ERS criteria. Of the fifty-three patients with possible UIP/NSIP, fifteen (28%) patients had a lung biopsy. Twelve out of fifteen patients had UIP on biopsy (80%). One patient died and one suffered with chronic pain post-biopsy (13%). In the remaining thirty-eight (72%) patients, biopsy was not possible due to comorbidities or patient choice. Of the thirty-eight patients with radiological diagnosis of possible UIP/NSIP, thirteen (34%) patients were deemed to have a clinical diagnosis of probable IPF after MDT discussion based on disease progression and age. Two (5%) patients were subsequently diagnosed as having a connective tissue disease and twenty-three (60%) patients were clinically diagnosed as NSIP based on response to immunosuppression and stability of lung function. <h3>Conclusions</h3> Surgical lung biopsy is considered the gold standard within the diagnostic work-up when there is diagnostic uncertainty. However in our clinical practice over two thirds of patients are not suitable for biopsy due to comorbidities and patient choice. Our clinical experience of a high yield of UIP after biopsy in patients with a radiological diagnosis of possible UIP/NSIP and concerns regarding morbidity and mortality has altered our practice. We increasingly utilise clinical data regarding progression and failed response to immunosuppressive therapies to aid in the MDT diagnosis of IPF when there is diagnostic uncertainty. In the subsequent year, 8.7% of patients underwent biopsy versus 14.6%, reflecting a change in practice.
How<i>Escherichia coli</i>Infects the Urinary Tract
Authors: Gary K. Schoolnik
Journal: New England Journal of Medicine (1989)

Urinary tract infections are a common cause of morbidity, especially among otherwise healthy women of childbearing age. Antibiotic therapy will cure the infection in approximately 80 percent of such women; additional episodes occur in the rest. Most recurrent infections are not due to inadequate treatment of the original infection. Instead, they are new infections with different bacterial strains, which occur in women without demonstrable structural or neurologic abnormalities of the urinary tract. Such women are considered to be "infection-prone." In 80 to 90 percent of such cases a single bacterial species, Escherichia coli, is the responsible pathogen.Prospective studies . . .