tbuckley/cabot-search huggingface dataset:
Changing patterns of colorectal cancer metastases: A 10-year retrospective review
Authors: M. L. Sundermeyer, N. J. Meropol, A. Rogatko, H. Wang, S. J. Cohen
Journal: Journal of Clinical Oncology (2004)

3548 Background: Therapeutic advances for patients (pts) with metastatic colorectal cancer (CRC) have prolonged survival. Historically, bone and brain metastases have been uncommonly reported (6% and 1%, respectively). This study was undertaken to test the hypothesis that expanded treatment options are associated with an increased incidence of unusual sites of metastasis. Methods: Patients with metastatic CRC evaluated between 1993–2002 at Fox Chase Cancer Center were identified through the Tumor Registry. Medical records were abstracted to obtain: date of diagnosis, date of metastasis, site of primary malignancy (colon vs. rectum), therapeutic agents received, survival, and sites of metastatic disease. Results: The records of 1,021 patients were reviewed. Incidences of bone and brain metastases were 10.4% and 3%, respectively. Bone metastases were more common among pts receiving >1 active systemic agent (fluoropyrimidines, irinotecan, oxaliplatin, EGFR antibody, bevacizumab) compared to ≤1 (13% vs. 8.3%, p=0.017), and 3–5 compared to ≤2 (16% vs. 9.1%, p=0.008). Pts receiving irinotecan were more likely to develop bone metastases (13.2% vs. 8.3%, p=0.01), as were pts receiving oxaliplatin (16.9% vs. 9%, p=.003). Pts with rectal cancer were more likely to develop bone metastases than patients with colon cancer (16% vs. 8.6%, p=.001). Lung metastases were more common in patients with bone (64% vs. 38.7%, p<.0001) or brain (78.8% vs. 40.1%, p<.0001) involvement than in pts without. However, pts with bone or brain metastases were less likely to have liver metastases (67% vs. 81.3%, p<0.0001 for bone, 60.6% vs. 80.5%, p=0.01 for brain). Pts developing bone or brain metastases had a longer mean time from diagnosis to development of metastases (17.8 vs. 10.3 months, p<0.0001 for bone, 18.9 vs. 10.8 months, p=0.0036 for brain). Conclusions: These data demonstrate that the incidence of bone and brain metastases in pts with CRC is more common than previously reported, and is associated with receipt of multiple systemic treatments. As survival improves for this patient population, clinicians should be aware of the potential for metastasis in previously unusual sites. No significant financial relationships to disclose.
Carboxypeptidase-G2 (CPDG2) and leucovorin (LV) rescue with and without addition of thymidine (Thd) for high-dose methotrexate (HDMTX) induced renal dysfunction
Authors: P. C. Adamson, F. M. Balis, M. Boron, A. Shalabi, M. O’Brien, M. Eby, N. Jayaprakash, D. E. Cole, P. Ivy, B. C. Widemann
Journal: Journal of Clinical Oncology (2005)

2076 Background: We previously demonstrated that CPDG2, which rapidly hydrolyzes MTX to inactive metabolites, when combined with LV and Thd, effectively rescues patients (pts) with HDMTX-induced nephrotoxicity. This study assessed the role of Thd administration in these pts. Methods: Pts (n=100) with HDMTX-induced renal dysfunction and significantly delayed MTX clearance received 1–3 doses of CPDG2, 50 U/kg IV, and standard LV rescue. In the initial cohort pts (n=35) also received 8 g/m2/d of Thd by continuous IV infusion. Subsequently, Thd was restricted to pts with prolonged (> 96 hours) exposure to MTX or with severe MTX toxicity at study entry (n=9). Plasma MTX concentrations (available in 75 pts), MTX associated toxicities, and outcome were compared in pts who did (Thd+) vs. did not (Thd-) receive Thd. Results: CPDG2 was administered at a median of 96 and 66 hours after start of the MTX infusion in Thd+ (n=44) or Thd- (n=54) pts, respectively. Median plasma MTX concentrations measured by HPLC pre CPDG2 were 28.2 μM (range 0.37–849μM) and 26.7 μM (range 0.76–835μM), in Thd+ pts or Thd- pts, and decreased within 15 minutes after CPDG2 by a median of 98.7% (88–99.2%) and 98.8% (86.1–99.5%), respectively. Grade 3 or 4 mucositis developed in 31% of Thd+ pts and 21% of Thd- pts. In pts with osteosarcoma who received HDMTX as a single chemotherapy agent, there was no significant difference in the nadir absolute neutrophil count or platelet count between the Thd+ pts (n=19) and Thd- pts (n=23) (p=0.31 Mann-Whitney U). Five deaths were directly attributed to irreversible MTX toxicity. In these pts, CPDG2/LV/Thd rescue was instituted late (median 8 days after the start of MTX) compared with surviving pts (n=88) who were rescued with CPDG2 at a median of 3 days after start of MTX (p<0.003 Mann-Whitney U). Conclusions: Thd did not interfere with MTX hydrolysis by CPDG2. CPDG2/LV without Thd, if administered within 96 hours of start of HDMTX-infusion, effectively rescues patients who develop HDMTX-induced renal dysfunction. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Protherics
Response to a Physiologic Dose of Pyridoxine in Type I Primary Hyperoxaluria
Authors: Edmund R. Yendt, Moussa Cohanim
Journal: New England Journal of Medicine (1985)

We measured urinary oxalate and glycolate excretion before and during pyridoxine administration (2 to 200 mg per day) in four patients with primary hyperoxaluria. In two patients with Type I primary hyperoxaluria, urinary oxalate and glycolate excretion fell markedly in response to a physiologic dose of pyridoxine of 2 mg per day and became completely normal when the dose was increased to 25 mg per day. In the other two patients, who had a different type of primary hyperoxaluria (normal urinary glycolate excretion), there was no response to 2 mg of pyridoxine per day. In one of these patients, doses of 25 and 50 mg per day were also ineffective, but a moderate reduction in oxalate excretion took place with 200 mg per day; in the other patient there was a moderate reduction in oxalate excretion with 25 mg of pyridoxine per day. Our findings suggest that the degree of hyperoxaluria in this disorder may be only slight or moderate if the patient has been ingesting a pyridoxine-hch diet or multivitamin tablets containing small amounts of pyridoxine. Our results also suggest that smaller doses of pyridoxine than those heretofore employed should be tried in patients with primary hyperoxaluria. (N Engl J Med 1985; 312:953–7.)
Ragweed Immunotherapy in Adult Asthma
Authors: Peter S. Creticos, Charles E. Reed, Philip S. Norman, Jane Khoury, N. Franklin Adkinson, C. Ralph Buncher, William W. Busse, Robert K. Bush, Jyothi Gadde, James T. Li, Hal B. Richerson, Richard R. Rosenthal, William R. Solomon, Paul Steinberg, John W. Yunginger
Journal: New England Journal of Medicine (1996)

Although allergen immunotherapy is effective for allergic rhinitis, its role in treating asthma is unclear.
Twelve Years' Experience with National Sharing of HLA-Matched Cadaveric Kidneys for Transplantation
Authors: Steven K. Takemoto, Paul I. Terasaki, David W. Gjertson, J. Michael Cecka
Journal: New England Journal of Medicine (2000)

In October 1987, the United Network for Organ Sharing (UNOS) established a national kidney-sharing program to increase the number of HLA-matched transplantations. Since then, over 7500 cadaveric kidneys have been shipped to centers in 48 states for transplantation to HLA-matched patients. We evaluated the efficacy of the program during its first 12 years of operation.
Segmental basal cell naevus syndrome caused by an activating mutation in <i>smoothened</i>
Authors: Z. Khamaysi, R. Bochner, M. Indelman, L. Magal, E. Avitan‐Hersh, O. Sarig, E. Sprecher, R. Bergman
Journal: British Journal of Dermatology (2016)

Aberrant sonic hedgehog signalling, mostly due to PTCH1 mutations, has been shown to play a central role in the pathogenesis of basal cell carcinoma (BCC), as well as in basal cell naevus syndrome (BCNS). Mutations in smoothened (SMO) encoding a receptor for sonic hedgehog have been reported in sporadic BCCs but not in BCNS. We report a case with multiple BCCs, pits and comedones in a segmental distribution over the upper part of the body, along with other findings compatible with BCNS. Histopathologically, there were different types of BCC. A heterozygous mutation (c.1234C>T, p.L412F) in SMO was detected in three BCCs but not in peripheral blood lymphocytes or the uninvolved skin. These were compatible with the type 1 mosaic form of BCNS. The p.L412F mutation was found experimentally to result in increased SMO transactivating activity, and the patient responded to vismodegib therapy. Activating mutations in SMO may cause BCNS. The identification of a gain‐of‐function mutation in SMO causing a type 1 mosaic form of BCNS further expands our understanding of the pathogenesis of BCC, with implications for the treatment of these tumours, whether sporadic or inherited.
Enhancement of Esophageal Carcinogenesis Induced in Rats by &lt;italic&gt;N&lt;/italic&gt;-Amyl-&lt;italic&gt;N&lt;/italic&gt;-methylnitrosamine in the Presence of 12-&lt;italic&gt;O&lt;/italic&gt;-Tetradecanoylphorbol-13-acetate
Authors: H Matsufuji, H Ueo, M Mori, H Kuwano, K Sugimachi
Journal: JNCI Journal of the National Cancer Institute (1987)

Journal Article Enhancement of Esophageal Carcinogenesis Induced in Rats by N-Amyl-N-methylnitrosamine in the Presence of 12-O-Tetradecanoylphorbol-13-acetate Get access Hidemasa Matsufuji, M.D., Hidemasa Matsufuji, M.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar Hiroaki Ueo, M.D., Hiroaki Ueo, M.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar Masaki Mori, M.D., Masaki Mori, M.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar Hiroyuki Kuwano, M.D., Hiroyuki Kuwano, M.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar Keizo Sugimachi, M.D., F.A.C.S. Keizo Sugimachi, M.D., F.A.C.S. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 79, Issue 5, November 1987, Pages 1123–1129, https://doi.org/10.1093/jnci/79.5.1123 Published: 01 November 1987 Article history Received: 28 January 1987 Accepted: 12 June 1987 Published: 01 November 1987
Warfarin-Induced Skin Necrosis in a Patient with a Mutation of the Prothrombin Gene
Authors: Yiping Yang, Kenneth M. Algazy
Journal: New England Journal of Medicine (1999)

To the Editor: Skin necrosis is a rare complication of warfarin therapy.1 The necrotic lesions usually appear in a distinct pattern, with a predilection for fatty tissues such as the breasts, buttocks, and thighs, three to six days after the initiation of warfarin therapy. The pathophysiology underlying warfarin-induced skin necrosis is not entirely understood. Hypercoagulability has been found in patients with necrosis and in some cases correlates with hereditary conditions such as deficiencies of protein C, protein S, and antithrombin III.2 We describe a case of warfarin-induced skin necrosis in a patient with a G20210A mutation of the prothrombin gene . . .
18F-FET-PET hypermetabolic brain lesions: A correlation study to MRI and histopathologic findings.
Authors: A. Muigg, M. Nowosielski, J. Schwetz, T. Gotwald, D. Putzer, H. Maier, G. Stockhammer, M. Hutterer
Journal: Journal of Clinical Oncology (2010)

2042 Background: Due to the specific incorporation of 18F-fluoroethyl-L-tyrosine (18F-FET) into glioma cells, a number of studies have proven the clinical value of 18F-FET-PET to identify brain lesions as gliomas and to determine the extent of the brain tumor for treatment planning and biopsy guidance. However, the specificity of 18F-FET-PET in brain tumor diagnosis is still unknown. Therefore, the aim of this study was to correlate 18F-FET-PET hypermetabolic brain lesions to histopathologic diagnosis and MRI findings. Methods: We retrospectively analysed pre- and post-operative 18F-FET-PET scans of 200 patients with suspected neoplastic brain lesions and compared the results to MRI and histopathologic findings. Results: Comparison of preoperative 18F-FET-PET metabolic active brain lesions with histopathologic findings revealed that not only glial tumors, but also other primary brain tumors, including anaplastic ependymoma, primitive neuroectodermal tumors, medulloblastoma, primary CNS lymphoma, pinealoblastoma, acoustic neuroma, anaplastic meningeoma, inflammatory multiple sclerosis and ADEM lesions were 18F-FET hypermetabolic. 18F-FET activity in inflammatory lesions was remarkably lower than in tumor lesions. In some cases after macroscopic total resection of a malignant glioma and no residual tumor on MRI, 18F-FET-PET clearly identified residual tumor burden. FET-PET was helpful to discriminate between post-radiation necrosis/pseudoprogression and tumor recurrence. Conclusions: 18F-FET-PET hypermetabolism is detectable in various neoplastic and inflammatory brain lesions limiting the specificity for glial tumors. After histopathologic diagnosis of a glial tumor 18F-FET-PET scans are sensitive to identify residual tumor after neurosurgical intervention, which should be implemented in radiotherapy planning. Pre- and postoperative 18F-FET-PET scans may also be helpful to guide stereotactic biopsy or surgery and to discriminate necrosis/pseudoprogression from tumor recurrence. No significant financial relationships to disclose.
Influence of Preimmunization Antibody Levels on the Specificity of the Immune Response to Related Polysaccharide Antigens
Authors: Carol J. Baker, Dennis L. Kasper, Morven S. Edwards, Gerald Schiffman
Journal: New England Journal of Medicine (1980)

We studied the influence of preimmunization antibody level on the immune response of adults to one of two structurally related yet immunologically distinct type-specific polysaccharides from Type III Group B streptococcus and Type 14 pneumonococcus. Four weeks after immunization with multivalent pneumococcal vaccine, 20 subjects with low levels of antibody to Type III Group B streptococcus antigen had no significant increase in antibody to this antigen (P greater than 0.05), but all volunteers with moderate to high preimmunization antibody levels who were immunized with Pneumovax had significant increases (P less than 0.01). However, the streptococcal antibody response to pneumococcal Type 14 antigen was weaker and briefer than that in 10 adults given Type III Group B streptococcus vaccine(P less than 0.05). Preimmunization antibody levels influenced the immune response to a structurally similar polysaccharide antigen, but specific Type III polysaccharide antigen appeared necessary to induce a primary antibody response in "nonimmune" adults. We conclude that immunization of mothers with pneumococcal vaccine is not likely to prevent neonatal Type III Group B streptococcal infection, despite immunologic similarities between the two organisms.
Cardiac Failure Associated with Acute Anemia
Authors: Thomas D. Kinney, G. Kenneth Mallory
Journal: New England Journal of Medicine (1945)

IT HAS long been known that anemia has a profound effect on the heart. In 1857, Bamberger1 pointed out that cardiac enlargement was found in many patients suffering from chronic anemia, a finding that has since been confirmed by many observers. In 1931, Ball,2 for the first time, demonstrated such enlargement by x-ray and showed that the diameter of the heart returned to within normal limits after the anemia had improved. This finding also has been confirmed by other investigators.3 , 4 In 1939, Ellis and Faulkner5 studied the hearts of 64 patients suffering from anemia. Of 38 cases examined by x-ray, . . .
Sequence variations in HCV core-derived epitopes alter binding of KIR2DL3 to HLA-C∗03:04 and modulate NK cell function
Authors: Sebastian Lunemann, Gloria Martrus, Angelique Hölzemer, Anais Chapel, Maja Ziegler, Christian Körner, Wilfredo Garcia Beltran, Mary Carrington, Heiner Wedemeyer, Marcus Altfeld
Journal: Journal of Hepatology (2016)
A Molecular Approach to the Stratification of Cardiovascular Risk in Families with Marfan's Syndrome
Authors: Lygia Pereira, Orna Levran, Francesco Ramirez, Jennifer R. Lynch, Bryan Sykes, Reed E. Pyeritz, Harry C. Dietz
Journal: New England Journal of Medicine (1994)

The fibrillin gene encodes a protein in the extracellular matrix, and this protein is widely distributed in elastic tissues. The fibrillin gene is the site of mutations causing Marfan's syndrome. This disorder shows a high degree of clinical variability both between and within families. Each family appears to have a unique mutation in the fibrillin gene, which precludes the routine use of mutation screening for presymptomatic diagnosis of the disorder. The goal of this study was to develop a widely applicable method of molecular diagnosis.
FRI0301 Assessment of the Effect of 12 Months Administration of Denosumab in Patients with Rheumatic Diseases – Bone Mineral Density Increase in Lumbar Spine is Negatively Correlated with Baseline Oral Prednisolone Dose and Predicted by Decreasing Rate of Serum Undercarboxylated Osteocalcin at 6 Months
Authors: K. Ebina, J. Hashimoto, M. Hirao, K. Hagihara, T. Noguchi, H. Yoshikawa
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Receptor activator of nuclear factor kappa-B ligand (RANKL) is a key inducer of osteoclast differentiation and activation, which plays a crucial role in osteoporosis and bone erosion of rheumatic diseases. Denosumab (DSM) is an anti-RANKL antibody approved for the treatment of postmenopausal osteoporosis, while its effect in rheumatic diseases (especially in glucocorticoid-induced osteoporosis) still remains unknown. <h3>Objectives</h3> The aim of this study is to clarify the effect of 12 months administration of DSM on patients with rheumatic diseases (RD). <h3>Methods</h3> DSM was introduced in 145 RD patients (127 female, 61.5 years old, 95 RA, 28 SLE, 4 dermatomyositis, 4 sarcoidosis, 14 other diseases, 77.2% taking prednisolone (PSL) with average dose 4.3mg/day, 21.4% taking biologics, lumbar spine (LS) T-score -1.7, femoral neck (FN) T-score -2.2, total hip (TH) T-score -1.9, prior vertebral fracture 1.0, prior treatment; bisphosphonate 63.4%, teriparatide 18.6%, none 16.6%) and followed up for 12 months by monitoring bone mineral density (BMD) and bone turnover markers. <h3>Results</h3> BMD increase from baseline to 6→12 months was as follows. LS; 3.0→5.4%, TH; 1.6→2.6%, FN; 2.0→3.1%. Baseline dose of oral PSL showed negative correlation with baseline value of bone turnover markers [Type I collagen N-terminal propeptide (P1NP) (r=-0.31, p=0.0004), Isoform 5b of tartrate-resistant acid phosphatase (TRACP-5b) (r=-0.32, p=0.0003), undercarboxylated osteocalcin (ucOC) (r=-0.42, p=0.000004)] and BMD increase of LS at 6 months (r=-0.27, p=0.002) and 12 months (r=-0.29, p=0.04), and also with TH at 12 months (r=-0.39, p=0.01). BMD increase of LS at 12 months (%) was positively correlated with baseline value of bone turnover markers [P1NP (r=0.51, p=0.001), TRACP-5b (r=0.50, p=0.001), ucOC (r=0.54, p=0.001)] and their decreasing rate at 6 months [TRACP-5b (r=0.37, p=0.02), ucOC (r=0.53, p=0.003)]. Multivariate logistic regression analysis with a forward stepwise procedure revealed that significant indicator of LS BMD change at 12 months was decreasing rate of ucOC at 6 months (β=0.50, 95%CI=-0.13 to -0.03, p=0.005). <h3>Conclusions</h3> Our findings indicate that BMD increasing effects of 12 months DSM administration in patients with RD is significantly correlated with baseline bone metabolism turnover which is suppressed by baseline oral PSL dose-dependently. In addition, BMD increase of LS at 12 months is strongly predicted by decreasing rate of ucOC at 6 months. <h3>Disclosure of Interest</h3> None declared
AB0960 Grip Strength in Joint Hipermobility Sydnrome: Table 1.
Authors: P. Yazgan, T. Duymaz
Journal: Annals of the Rheumatic Diseases (2015)

Background Muscle strength can be defined as the ability of a muscle or muscle group to exert force against a resistance. Manuel gripping strength has been referred to as being a good indicator of total muscle strength but this is an indispensable physiologic variable fort he performance of day to day tasks, maintenance of functional independence and autonomy. Objectives Joint hypermobility is a common and heritable connective tissue disorder that mainly characterized by joint hypermobility joint instability and fatique laxity of ligaments may affect muscle power. The objective of this study using Jamar hand held dynamometer was to assess muscle strength in young people with bening joint hypermobility syndrome (BJH). Methods We studied 38 female participants, evaluated in a multidisiplinary outpatient clinic dedicated to BJH. Subjects were selected on the basis of clinically confirmed diagnosis of BJH, diagnosis was established on Beighton criteria. A group composed by 36 healthy female adults was included as control group. Manuel muscle test was used for checking strength of hip flexor muscles, hip abductor muscles and knee extansor muscles. Grip strength was assessed by Jamar hand halded dynamometer. Results There were no difference gender age and BMI between patients and control groups ([Table 1][1]). Mean hand grip values were similar 25.72±7.82 kg right hand, 24.11±9.03 kg left hand in BJH group 32.9±11.5 kg right hand, 31.19±10.9 kg left hand in control group. The mean grip strength of both hands was significant lower in hypermobile group than control group (24.2±6.03, 32.9±11.5 p=0.0001 right hand, 22.6±7.7, 31.03±10.9, p=0.05 left hand). There were no difference global lower extremitymuscle powers in both groups p>0.05. View this table: Table 1. Clinical and demografic features Conclusions Ligament laxity can be important muscle weakness in hypermobility. References 1. Scheper M, Vries J, Beelen A, Vos R, Nollet F, Engelbert R. Generalized Joint Hypermobility, Muscle Strength and Physical Function in Healthy Adolescents and Young Adults. Curr Rheumatol Rev. 2015 Jan 19. 2. Wolf JM, Cameron KL, Owens BD. Impact of joint laxity and hypermobility on the musculoskeletal system.J Am Acad Orthop Surg. 2011 Aug;19(8):463-71. Disclosure of Interest None declared [1]: #T1