tbuckley/cabot-search huggingface dataset:
Case 52-1964
Authors: William Dameshek, Sanford I. Roth
Journal: New England Journal of Medicine (1964)

Presentation of Case First admission. A sixty-three-year-old woman entered the hospital because of anemia.Thirty-eight years previously she had rheumatic fever, with painful swelling of multiple joints that persisted for a year. Twenty-eight years later she was informed that she had a heart murmur and was given digitalis. Edema and exertional dyspnea were present for several years before entry. Eighteen months before admission she was referred to the Cardiac Clinic, where the murmurs of aortic stenosis, mitral stenosis and mitral regurgitation were heard. Digitalis was continued, and a diet low in sodium was prescribed. She complained of nausea when given . . .
A cost analysis of treatment with bevacizumab plus cisplatin and gemcitabine (BCG) versus cetuximab plus vinorelbine and cisplatin (CVC) in patients with advanced or recurrent non-small cell lung cancer (NSCLC) in Germany
Authors: D. F. Heigener, C. Wiesner, R. Aultman
Journal: Journal of Clinical Oncology (2009)

e17553 Background: Although new treatment options for advanced NSCLC can offer improved survival over standard treatment with chemotherapy (CT) they should also offer value for money. Bevacizumab (BEV), a humanized monoclonal antibody (MAb) directed against vascular endothelial growth factor when combined with CT increases overall survival (median 13.6 months in the AVAiL study) and progression-free survival (PFS) in patients with advanced NSCLC when compared with CT alone. Cetuximab (CTX), an IgG1 MAb which targets the epidermal growth factor receptor achieved a median survival time of 11.3 months when combined with CT in the FLEX study and marketing authorization is anticipated in 2009. The aim of this study was to compare the costs of treating NSCLC with BCG or CVC in Germany. Methods: A Markov model was used to compare drug and administration costs associated with treating advanced or recurrent NSCLC with either BCG or CVC. The model assumes patients move from non-progressive to progressed disease prior to death, according to transition probabilities derived from an indirect comparison of the efficacy of BCG and CVC in terms of PFS using data from the respective pivotal trials and appropriate indirect comparison methodology. Cost data were derived from local sources. Drug costs assumed CT was given for up to 6 cycles, that CTX was administered at an initial dose of 400 mg/m 2 followed by 250 mg/m 2 weekly until progression and that BEV was administered at 7.5 mg/kg until progression. The model estimated average drug and administration costs per patient treated with either BCG or CVC. Results: The mean total cost of BCG treatment was €4713 less per patient when compared with CVC (€28342 vs. €33055). The addition of BEV to CT was less costly than the addition of CTX to CT (€18796 vs. €29502) and the administration costs were also lower (€391 vs. €1179). Conclusions: Targeted therapy using BEV is less costly than CTX in Germany and thus, from a budget perspective, offers the best value for money strategy for improving outcomes in patients with advanced NSCLC. Furthermore, costs savings with BCG in Germany are likely to be increased when gemcitabine comes off-patent in 2009. [Table: see text]
Environmental Factors in the Etiology of Rhabdomyosarcoma in Childhood&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: S Grufferman, H H Wang, E R DeLong, S Y Kimm, E S Delzell, J M Falletta
Journal: JNCI Journal of the National Cancer Institute (1982)

In a case-control study of childhood rhabdomyosarcoma (RMS), families of 33 cases and 99 controls were interviewed. A relative risk (RR) of 3.9 was found associated with fathers' (but not mothers') cigarette smoking (P = 0.003). Cases had had fewer immunizations than controls, particularly smallpox vaccination (RR = 0.2; P = 0.001), and conversely had more preventable infections. An RR of 3.2 (P = 0.03) was found associated with exposure to chemicals and and RR of 3.7 (P = 0.004) was found associated with diets that included organ meats. Mothers of cases were more likely to be over age 30 years at subject's birth, to have used antibiotics preceding or during pregnancy, and to have had an overdue and/or assisted delivery. Other findings suggest that low socioeconomic status is associated with an increased risk of RMS. These aggregate findings imply that environmental factors may play an important role in the etiology of childhood RMS.
Case 32-2006
Authors: Iain P. Fraser, Christine M. Cserti, Walter H. Dzik
Journal: New England Journal of Medicine (2006)

A 3-year-old girl was admitted to the hospital with fever, rigors, lethargy, nausea, vomiting, and parasitemia 5 days after returning from a trip to Nigeria. She had not received antimalarial prophylaxis. On admission, the patient had anemia and thrombocytopenia. Twelve hours later, she had a generalized tonic–clonic seizure and hypotension and acidosis developed with an increasing level of parasitemia. A therapeutic procedure was performed.
THE PERIOD OF INFECTIVITY AND SERUM PREVENTION OF CHICKENPOX
Journal: JAMA (1929)

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
Serum Immunoglobulin free light chains as markers of disease burden and response to treatment in patients with Waldenstrom’s macroglobulinemia
Authors: E. Hatjiharissi, B. T. Ciccarelli, L. Ioakimidis, R. Borok, J. D. Soumerai, R. J. Manning, Z. R. Hunter, L. Xu, C. J. Patterson, S. Alvin, S. P. Treon
Journal: Journal of Clinical Oncology (2008)

8617 Background: Waldenstrom’s macroglobulinemia (WM) is a B-cell malignancy characterized by the presence of a serum monoclonal IgM protein, which is used to monitor both disease burden and response to treatment. Serum free light chains (sFLC) have recently emerged as a reliable tool to assess disease activity in patients with plasma cell disorders. Methods: To determine the role of sFLC in WM, we retrospectively-assessed the baseline levels of sFLC in 145 untreated, asymptomatic, patients using the Freelite sFLC assay (The Binding Site Ltd. UK). We also correlated sFLC with response to treatment, and performed serial measurements on symptomatic patients who received treatment on a clinical trial with BDR [Bortezomib, Dexamethasone, Rituximab]. Results: Of the 145 WM patients evaluated, 114 (78.6%) had an IgM-k and 31 (21.4%) had an IgM-λ paraprotein. Of the 114 patients with IgM-k, 88 (77%) had an elevated free k-LC and 103 (90%) had an abnormal κ/λ ratio. In the remaining 31 patients with IgM-λ, 23 (74%) had an elevated free λ-LC while 18 (58%) had an abnormal κ/λ ratio. Baseline sFLC levels were lower in asymptomatic patients [mean k-LC 129.42 mg/L (n=34) and mean λ- LC 49.97 mg/L (n=6)] compared to those with symptomatic disease [mean k-LC 261.45 mg/L (n=62) and mean λ-LC 301.73 mg/L (n=19), but did not reach statistical significance. Serial measurements of FLCs and comparison to the changes in the corresponding IgM values demonstrated a significant decrease in 2/6 responders tested 10 and 46 days post-treatment (10 days: 55% vs. 18%, 46 days: 81% vs. 39%). Similarly, an earlier increase in sFLCs was observed in the 2/4 non-responder patients after the 2nd-course of therapy, with a 44% and 128% increase in k and l-FLC vs. a 16% and 17% decrease in IgM, respectively. Conclusion: These results demonstrate that sFLC are significantly-elevated in patients with WM. Higher levels were observed in symptomatic versus asymptomatic patients. Preliminary evidence also suggests that sFLC maybe a more-sensitive and a better marker of response to treatment and disease progression than the current standard of serum IgM. No significant financial relationships to disclose.
X-Linked Recessive Nephrolithiasis with Renal Failure
Authors: Paul A. Frymoyer, Steven J. Scheinman, Philip B. Dunham, David B. Jones, Paul Hueber, Edward T. Schroeder
Journal: New England Journal of Medicine (1991)

Nephrolithiasis may occur as a consequence of a number of hereditary disorders. We describe a large kindred from northern New York with hereditary nephrolithiasis accompanied by urinary concentrating defects, nephrocalcinosis, renal insufficiency, and renal wasting of potassium, phosphate, calcium, and uric acid. The pattern of inheritance was established by examining the patients and their records and interviewing family members. Selected members of the family were evaluated in detail, with measurements of erythrocyte cation fluxes and carbonic anhydrase (carbonate dehydratase) activity.
A phase I study of the oral mTOR inhibitor ridaforolimus (RIDA) in combination with the IGF-1R antibody dalotozumab (DALO) in patients (pts) with advanced solid tumors.
Authors: S. Di Cosimo, J. C. Bendell, A. Cervantes-Ruiperez, D. Roda, L. Prudkin, M. N. Stein, A. Leighton-Swayze, Y. Song, S. Ebbinghaus, J. Baselga
Journal: Journal of Clinical Oncology (2010)

3008 Background: RIDA is a non-prodrug rapamycin analog mTOR inhibitor, and DALO is a humanized monoclonal antibody targeting the IGF-1R receptor. In preclinical models, dual mTOR/IGF1-R inhibition results in synergistic antitumor activity and inhibits feedback AKT activation due to TORC1 inhibition by rapamycin analogs. Methods: Pts with advanced cancers who failed standard therapy received RIDA at escalating doses of 10-40 mg/day QD×5/week combined with DALO at 10 mg/kg/week or 7.5 mg/kg every other week. RIDA was administered for one week prior to starting DALO to enable PK/PD assessment with and without DALO. PD parameters were assessed from PBMCs, skin biopsies, and tumor biopsies. Two dose levels were expanded to determine the optimal dose for future study. Results: 62 pts have been enrolled. During dose escalation, only one pt experienced a DLT (prolonged G2 stomatitis at dose level 1). RIDA 40 mg plus DALO 10 mg/kg/week (recommended doses for RIDA and DALO as single agents) was declared MTD. In an expansion cohort at the declared MTD, 4 DLTs were observed in 9 DLT-evaluable patients (G3 stomatitis, 3 pts; G3 fatigue, 1 pt) and cumulatively 4 of 15 (27%) pts at the declared MTD had DLTs. A 2nd expansion cohort at the next lower dose level (RIDA 30 mg plus DALO 10 mg/kg/week) is being evaluated, and there was 1 DLT in 17 DLT-evaluable pts so far. The most frequent treatment-related adverse events included stomatitis, fatigue, and hyperglycemia, mostly grade 1-2. Efficacy signals included 3 confirmed PRs (2 breast cancer [BCa], 1 parotid adenocarcinoma), 2 partial metabolic responses (PMRs) on FDG-PET scan (2 BCa), 2 prolonged SD > 6 months (1 BCa and 1 endometrial ca), and 3 pts with ≥50% decline in CA-125 (2 ovarian and 1 endometrial Ca). Of 23 BCa pts enrolled by December 1, 5 pts had efficacy signals (2 PRs, 1 SD for 9 months, and 2 PMRs); all 5 pts were ER+, and 4 had high Ki67 breast tumors. PK/PD assessments are currently underway and will be presented at the meeting. Conclusions: The combination of ridaforolimus and dalotuzumab is tolerable and has promising antitumor activity in heavily pretreated advanced cancer, particularly in ER+/high proliferation breast cancer. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Merck Merck Merck Merck, Novartis
NIMG-45REAL-TIME PET IMAGING DEMONSTRATES TUMOR ACCUMULATION AND OXYGENATION BY OMX-4.80P, AN OXYGEN CARRIER ENGINEERED FOR THE TREATMENT OF GLIOBLASTOMA
Authors: Laura Serwer, Natacha Le Moan, Melanie Regan, Joseph Blecha, Andrew Davis, Kevin Tanaka, Tim Keating, Jamie Romero, Philberta Leung, Tina Davis, Catherine Bedard, Sarah Ng, Feng Yan, Raquel Santos, Tomoko Ozawa, Nicholas Butowski, Stephen Cary, Theodore Nicolaides, Youngho Seo, Jonathan Winger, Henry VanBrocklin, Ana Krtolica
Journal: Neuro-Oncology (2015)

BACKGROUND: Hypoxia is a hallmark of glioblastoma (GB) and is correlated with tumor progression and decreased overall survival. OMX-4.80P is a protein oxygen carrier engineered for the treatment of GB in combination with radiotherapy. Prior studies in rodent GB models demonstrated that OMX-4.80P accumulates within intracranial tumors and reduces tumor hypoxia—as assessed by immunohistochemical and ELISA methods—and enhances tumor killing by radiotherapy. To support clinical evaluation of OMX-4.80P in patients, this report describes non-invasive positron emission tomography (PET) imaging to assess both OMX-4.80P tumor accumulation and oxygen delivery. METHODS: To assess its biodistribution, OMX-4.80P was labelled with 89Zr using a desferrioxamine (DFO) chelator. Either 89Zr-DFO-OMX-4.80P or free 89Zr was administered intravenously to both nude mice bearing H460 subcutaneous xenografts, as well as to Fischer rats bearing intracranial F98 tumors. OMX-4.80P distribution was assessed by PET, and by measuring radioactivity in major organs using a gamma counter. To assess OMX-4.80P-mediated changes in tumor hypoxia in the same tumor models, tumor:brain signal ratio of the hypoxia marker fluoromisonidazole (18F-FMISO) was assessed before and after treatment with OMX-4.80P by performing scans on two consecutive days. RESULTS: While free 89Zr was present mainly in the bones, 89Zr-DFO-OMX-4.80P was not, suggesting that the label is stable in vivo. As expected, 89Zr-DFO-OMX-4.80P accumulated in both subcutaneous and intracranial tumors, and in the clearance organs (liver, kidneys, spleen). Furthermore, 18F-FMISO levels, as measured by tumor:brain ratios, were decreased by >2 fold after either intravenous or intratumoral injection of OMX-4.80P, in both subcutaneous and intracranial tumors demonstrating OMX-4.80P-mediated tumor oxygenation activity. CONCLUSIONS: PET-based approaches are a feasible method for assessing OMX-4.80P distribution and oxygenation. These methods will be developed as biomarkers of OMX-4.80P activity in a planned Phase 1 clinical trial in newly diagnosed GB patients.
Protein-Sparing Therapy in Postoperative Patients
Authors: Gordon R. Greenberg, Errol B. Marliss, G. Harvey Anderson, Bernard Langer, William Spence, E. Bruce Tovee, Khursheed N. Jeejeebhoy
Journal: New England Journal of Medicine (1976)

In patients receiving hypocaloric total parenteral nutrition, protein sparing with infusions of amino acids alone is alleged to occur because low insulin levels allow mobilization of endogenous fat. Four groups of patients studied for their first four postoperative days received all their nutrition parenterally as: 150 g per day of glucose, protein (as amino acids, 1 g per kilogram per day) alone, protein plus 50 g per day of soybean-oil emulsion or protein plus 150 g per day of glucose. All groups of patients receiving protein had lesser negative nitrogen balance than patients receiving glucose alone. The addition of glucose to protein did not increase negative nitrogen balance. The protein-sparing effect of amino acids appears to be a function of the infused amino acids alone and is not related to the degree of endogenous fat mobilization. (N Engl J Med 294:1411–1416, 1976)
Clonality of Reed–Sternberg Cells in Hodgkin's Disease
Authors: Michael Hummel, Theresa Marafioti, Harald Stein
Journal: New England Journal of Medicine (1999)

To the Editor: In 1995 we reported in the Journal the results of a molecular analysis of single Reed–Sternberg cells in biopsy specimens from patients with Hodgkin's disease.1 Amplified immunoglobulin heavy-chain gene sequences bore the hallmarks of B cells, and in 6 of the 12 cases we studied, there was evidence of the presence of monoclonal Reed–Sternberg cells — that is, identical immunoglobulin-gene rearrangements in several different Reed–Sternberg cells. Unexpectedly, we also found polyclonal Reed–Sternberg cells (i.e., cells with unrelated immunoglobulin-gene rearrangements). Other groups have also found polyclonal Reed–Sternberg cells,2 but some investigators indicated that the cells in individual cases . . .
Immunological functions of liver sinusoidal endothelial cells
Authors: Percy A Knolle, Dirk Wohlleber
Journal: Cellular and Molecular Immunology (2016)

Liver sinusoidal endothelial cells (LSECs) line the liver sinusoids and separate passenger leukocytes in the sinusoidal lumen from hepatocytes. LSECs further act as a platform for adhesion of various liver-resident immune cell populations such as Kupffer cells, innate lymphoid cells or liver dendritic cells. In addition to having an extraordinary scavenger function, LSECs possess potent immune functions, serving as sentinel cells to detect microbial infection through pattern recognition receptor activation and as antigen (cross)-presenting cells. LSECs cross-prime naive CD8 T cells, causing their rapid differentiation into memory T cells that relocate to secondary lymphoid tissues and provide protection when they re-encounter the antigen during microbial infection. Cross-presentation of viral antigens by LSECs derived from infected hepatocytes triggers local activation of effector CD8 T cells and thereby assures hepatic immune surveillance. The immune function of LSECs complements conventional immune-activating mechanisms to accommodate optimal immune surveillance against infectious microorganisms while preserving the integrity of the liver as a metabolic organ.
Erythrocyte Transketolase Activity in Dialyzed Patients
Authors: E. T. Lonergan, M. Semar, R. B. Sterzel, G. Treser, M. A. Needle, L. Voyles, K. Lange
Journal: New England Journal of Medicine (1971)

Abstract Predialysis erythrocyte transketolase activity was depressed in 10 of 12 patients receiving chronic dialysis. Five patients had evidence of neuropathy. Dialysis effected a 43.0 per cent improvement in transketolase activity. Predialysis plasma inhibited normal activity by an average of 34.2 per cent, but post-dialysis plasma had little inhibiting effect. A low-molecular-weight (less than 501) substance, or substances, isolated from the dialysate of chronic uremics inhibited transketolase activity by 45.0 per cent. Two patients having the longest courses of dialysis had no neuropathy and showed no depression of activity, and their plasma failed to inhibit normal activity. Since transketolase has been shown to have an important role in myelin maintenance, it is suggested that accumulation of a low-molecular-weight toxin (or toxins) that depresses transketolase activity may lead to myelin-sheath degeneration, with subsequent neuropathy. Dialysis, by removing the inhibitor (or inhibitors) may permit ...
Long-term survival demonstrated with trastuzumab plus docetaxel: 24-month data from a randomised trial (M77001) in HER2-positive metastatic breast cancer
Authors: J.-M. Extra, F. Cognetti, D. Maraninchi, R. Snyder, L. Mauriac, M. Tubiana-Hulin, S. Chan, D. Grimes, A. Anton, M. Marty
Journal: Journal of Clinical Oncology (2005)

555 Background: Trial M77001 investigated trastuzumab (Herceptin; H) in combination with docetaxel (D) vs D alone as first-line treatment in HER2+ MBC and demonstrated significant clinical benefits, including prolonged survival, when H was added to taxane therapy. Here we report updated results 24 months after the last pt entered the trial. Methods: M77001 is a multicentre, randomised trial. Eligibility criteria included: HER2+ disease (95% had IHC 3+ and/or FISH+ disease); no prior chemotherapy for MBC; LVEF >50%. D was given as 100mg/m2 q3w x 6 cycles and H as 4mg/kg loading followed by 2mg/kg wkly until disease progression. Pts progressing on D alone could crossover to receive H. The primary endpoint was ORR, confirmed by an independent radiologist. Results: 94 pts were randomised to each arm (2 pts in the HD arm received no treatment and were excluded). The 24-month cut-off data are shown in the table below. Considerably more pts who received the HD regimen showed long-term survival at the 24-month cut-off analysis. 28 of the HD pts were alive for >3 yrs after randomisation, with 2 pts surviving for >4 yrs (14 and 1 pt, respectively, in the D only group; of the 14 pts who survived >3 yrs several had crossed over to H). H added little to the toxicity profile of D. There are no new safety concerns. The incidence of febrile neutropenia (23% vs 17%) and CHF (2% vs 0%) for HD vs D remains unchanged. Conclusion: In patients with HER2-positive MBC the combination of HD is highly effective and associated with significant clinical benefits over D alone. There is evidence of a long-term survival benefit following the addition of H to the D regimen. These sustainable data strongly support the first-line use of H + taxane in pts with HER2-positive MBC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis Aventis, Bristol-Myers Squibb, Elan Pharma, Eli Lilly, Italfarmaco Hoffmann-La Roche Roche, sanofi-aventis