tbuckley/cabot-search huggingface dataset:
Mucinous cystadenocarcinoma (mca) of the appendix: Role of adjuvant therapy
Authors: C. Aggarwal, J. Gibbs, G. Wilding, T. Mashtare, M. Javle
Journal: Journal of Clinical Oncology (2007)

15131 Introduction: MCA is the most common (non-carcinoid) appendiceal cancer. Adjuvant 5-fluorouracil (5-FU) based systemic chemotherapy (ASC) is often considered for MCA cases after surgery, extrapolating data from colon cancer. Patients (pts) with peritoneal disease are considered for regional perfusional therapy. However, the role of adjuvant therapy in this setting has not yet been established. Methods: Retrospective analysis of cases with the diagnosis of MCA. Pts treated with curative intent and subsequent adjuvant therapy [ASC or Intraperitoneal Hyperthermic Chemotherapy (IPHC)] were included. Pts who received surgery alone were compared to those who received surgery in combination with adjuvant therapy. Estimation of the survival distribution of each group was performed using the Kaplan-Meier method. Statistical assessment of observed differences in the survival distributions was per the log-rank test. Analyses were also performed adjusting for age and sex using the stratified log rank test. A 0.05 nominal significance level was used in all testing. Results: A total of 34 consecutive pts were treated between 8/1973 and 4/2005 for MCA. Pt characteristics were: 15 males (44%), median age 50 yrs (range 27–79), 33 (97%) Caucasian, 30 (88%) had peritoneal metastasis at diagnosis. All patients underwent surgical resection; 26 (76%) underwent &gt;1 of the following procedures. Surgeries were: right hemicolectomy (n=20, 58%), appendectomy (n=16, 47%), total abdominal hysterectomy (n=9, 26%), ileocolectomy (n=4, 11%) or debulking (n=12, 35%). Eight pts (23%) underwent IHPC with 5-FU (n=5), Mitomycin (n=2) or Yttrium 90 (n=1). Thirteen patients (38%) underwent ASC: 5-FU based (n=12) or Paclitaxel/ Carboplatin (n=1). Pts who underwent surgery alone had a median survival of 40 months. Pts who had surgery and also received ASC or IPHC had a median survival of 53 months. There was no statistical difference in the overall survival between the groups after adjusting for age, sex and stage differences (p=0.1). Conclusions: MCA is an aggressive tumor; optimally treated with radical surgery even at an advanced stage. Larger studies are required to determine the value of ASC or IPHC in this setting. No significant financial relationships to disclose.
Crystal-membrane interaction in kidney stone disease.
Authors: N Mandel
Journal: Journal of the American Society of Nephrology (1994)

Urolithiasis is a multifaceted process that initiates with the formation of microcrystals in the urine and terminates with the formation of mature renal calculi. The attachment of crystals by the urothelium is a major event in the successful formation of the mature stone. The papillary tip is the primary site for crystal attachment and stone maturation, and the attachment process appears to be mediated by specific molecular interactions between molecular structures on the surfaces of stone crystals and molecular arrays on the surfaces of cell membranes. Animal models have demonstrated the interaction between cells and crystals, and they have suggested a correlation between cellular damage and crystal interaction, especially when crystals bind to and then break free from the tubular epithelium. Cell culture studies on inner medullary late collecting duct (IMCD) cells have demonstrated that calcium oxalate monohydrate, hydroxyapatite, and uric acid crystals bind to IMCD cells in primary culture. The attachment of these crystals to IMCD cells was crystal structure dependent, saturable, and competitively inhibitable if more than one crystal type was present at the same time. The crystals preferentially attach to cells that have lost partial or complete intercellular junctional integrity. These crystal-attaching cells appear to have altered membrane composition and/or structure. Recent studies on red blood cells and IMCD cells that have been enriched with cholesterol and selected phospholipids suggest that crystal-membrane phospholipid interactions play a major role in crystal attachment.(ABSTRACT TRUNCATED AT 250 WORDS)
Human Non-Hodgkin's Lymphomas Overexpress a Wild-Type Form of p53 Which Is a Functional Transcriptional Activator of the Cyclin-Dependent Kinase Inhibitor p21
Authors: Roberta Maestro, Annunziata Gloghini, Claudio Doglioni, Sara Piccinin, Tamara Vukosavljevic, Daniela Gasparotto, Antonino Carbone, Mauro Boiocchi
Journal: Blood (1997)
Lesson of the Week: Crush syndrome following unconsciousness: need for urgent orthopaedic referral
Authors: A D Shaw, S U Sjolin, M M McQueen
Journal: BMJ (1994)

The acute compartment syndrome occurs when increased pressure within osteofascial compartments results in local muscle ischaemia. If left untreated it may lead to muscle necrosis and contractures. The systemic manifestations of this - the crush syndrome - are the results of haemodynamic and metabolic disburbances and acute renal failure.1 Failure to appreciate the importance of muscle necrosis as the underlying problem in the crush syndrome may have disastrous consequences.

The crush syndrome was originally described during the London Blitz in civilians who had been buried beneath the debris of destroyed houses.2 Nowadays, victims are typically encountered in war zones, in mining disasters, after earthquakes, and in industrial or road traffic accidents.3 The syndrome may also develop after isolated compression of arms or legs by the victim's own body - for example, during unconsciousness after a drug overdose.1 Such patients often delay seeking medical attention or have other more apparent complications that need urgent attention. The local signs of muscle compression and necrosis may therefore initially be overlooked. We describe 11 such cases referred to our unit over 51 months.

During April 1989 to July 1993, 11 patients were admitted to this infirmary with the crush syndrome secondary to a drug overdose. They were all referred for orthopaedic assessment after a considerable delay - mean 35 hours (table). Nine patients were men. The mean age was 31 years (range 20-54 years). As all the patients had been unconscious for an unknown length of time before presentation, the delay from time of injury until medical attention was given could not always be assessed. Four patients were unconscious on admission. Ten patients had taken an overdose of sedatives or painkillers, and one patient had carbon monoxide poisoning. During the period of unconsciousness their torso had compressed one or more …
Managing cutaneous side effects associated with erlotinib in head and neck cancer (HNC) and non-small cell lung cancer (NSCLC) patients (pts)
Authors: K. J. Oishi, J. S. Garey, B. J. Burke, R. S. Herbst, E. S. Kim
Journal: Journal of Clinical Oncology (2006)

18538 Background: Erlotinib is an oral epidermal growth factor receptor (EGFR) targeted therapy. It is approved for therapy in NSCLC pts after failure of at least one prior chemotherapy regimen, and in combination with gemcitabine for pts with pancreatic cancer. It has also been studied in other tumors including HNC. Erlotinib has fewer side effects compared to standard chemotherapy. Cutaneous toxicities with erlotinib have been observed in approximately 70% of pts with most cases typically mild-to-moderate. The most common manifestations are an acneiform rash, pruritus, and dryness. As rash may be a marker of clinical benefit, continuing therapy through toxicities is important. Methods: We have described effective management of skin rash associated with erlotinib by using the proposed treatment algorithm in HNC pts enrolled in a phase II study in which they received erlotinib with chemotherapy. Pts were followed by physical exams and direct questionings about rash development and treatment response as they were treated based on the grade and characteristics (pruritic, macular, pustular, dryness, ulcerative) of rash. Results: Thus far, the HNC trial has enrolled 32 pts and 28 pts are evaluable for rash and treatment responses. 19 pts developed grade 1 rash, 8 pts grade 2, 1 pt grade 3, and none grade 4. Response to rash intervention (ie downgrading the rash) included 19/19 complete responses for grade 1, 6/8 partial responses for grade 2 (the non-responding patients were referred to dermatology and improved after several other treatments) and 1/1 partial response for grade 3 were noted. 4 pts experienced dose delay and/or dose modification. In addition, 33 NSCLC pts are also evaluable for toxicity. 25 pts developed grade 1 rash, 4 pts grade 2, 4 pts grade 3, and none grade 4. Response to rash intervention included 25/25 complete responses for grade 1, 4/4 complete/partial responses for grade 2 and 3. Four pts experienced dose delays and/or dose modifications. Conclusions: Successful management of rash associated with erlotinib can be achieved using the proposed treatment algorithm thus allowing pts to continue on treatment without delays or significant dosing changes. [Table: see text]
Next Generation Sequencing of Brca1/2 in High Grade Ovarian Tumors Expands Brca Defects Beyond Germline Mutations
Authors: M. Yates, K. Timms, M. Daniels, B. Batte, K. Ring, C. Neff, J. Potter, S. Chau, J. Chen, D. Williams, M. Perry, B. Morris, A. Gutin, Y. Amin, M. Munsell, K. Schmeler, J. Lanchbury, K. Lu
Journal: Annals of Oncology (2014)
Dysregulated Type I Interferon and Inflammatory Monocyte-Macrophage Responses Cause Lethal Pneumonia in SARS-CoV-Infected Mice
Authors: Rudragouda Channappanavar, Anthony R. Fehr, Rahul Vijay, Matthias Mack, Jincun Zhao, David K. Meyerholz, Stanley Perlman
Journal: Cell Host & Microbe (2016)
Association between Mitochondrial DNA Copy Number in Peripheral Blood and Incident CKD in the Atherosclerosis Risk in Communities Study
Authors: Adrienne Tin, Morgan E. Grams, Foram N. Ashar, John A. Lane, Avi Z. Rosenberg, Megan L. Grove, Eric Boerwinkle, Elizabeth Selvin, Josef Coresh, Nathan Pankratz, Dan E. Arking
Journal: Journal of the American Society of Nephrology (2016)

Mitochondrial dysfunction in kidney cells has been implicated in the pathogenesis of CKD. Mitochondrial DNA (mtDNA) copy number is a surrogate measure of mitochondrial function, and higher mtDNA copy number in peripheral blood has been associated with lower risk of two important risk factors for CKD progression, diabetes and microalbuminuria. We evaluated whether mtDNA copy number in peripheral blood associates with incident CKD in a population-based cohort of middle-aged adults. We estimated mtDNA copy number using 25 high-quality mitochondrial single nucleotide polymorphisms from the Affymetrix 6.0 array. Among 9058 participants, those with higher mtDNA copy number had a lower rate of prevalent diabetes and lower C-reactive protein levels and white blood cell counts. Baseline eGFR did not differ significantly by mtDNA copy number. Over a median follow-up of 19.6 years, 1490 participants developed CKD. Higher mtDNA copy number associated with lower risk of incident CKD (highest versus lowest quartile: hazard ratio 0.65; 95% confidence interval, 0.56 to 0.75; P<0.001) after adjusting for age, sex, and race. After adjusting for additional risk factors of CKD, including prevalent diabetes, hypertension, C-reactive protein level, and white blood cell count, this association remained significant (highest versus lowest quartile: hazard ratio 0.75; 95% confidence interval, 0.64 to 0.87; P<0.001). In conclusion, higher mtDNA copy number associated with lower incidence of CKD independent of traditional risk factors and inflammation biomarker levels in this cohort. Further research on modifiable factors influencing mtDNA copy number may lead to improvement in the prevention and treatment of CKD.
Monthly pulses of vincristine and prednisone prevent bone marrow and testicular relapse in low-risk childhood acute lymphoblastic leukemia: a report of the CCG-161 study by the Childrens Cancer Study Group.
Authors: W A Bleyer, H N Sather, H J Nickerson, P F Coccia, J Z Finklestein, D R Miller, P S Littman, J N Lukens, S E Siegel, G D Hammond
Journal: Journal of Clinical Oncology (1991)

On study CCG-161 of the Childrens Cancer Study Group (CCSG), 631 children with acute lymphoblastic leukemia (ALL) at low risk for relapse were randomized to receive monthly pulses of vincristine-prednisone (VCR-PDN ) during maintenance therapy in addition to standard therapy with mercaptopurine (6MP) and methotrexate (MTX), and either cranial irradiation during consolidation or intrathecal (IT) MTX every 3 months during maintenance. All patients received six doses of IT MTX during induction and consolidation. With a minimum follow-up time of 4.25 years, 76.7% receiving VCR-PDN were in continuous complete remission at 5 years, in contrast to 63.9% receiving GMP-MTX alone (P = .002). The difference in relapse-free survival was due primarily to bone marrow relapse (P = .0008), and in boys also to testicular relapse (P = .003). Among the nonirradiated patients, the 5-year disease-free survival (DFS) was 79.4% for patients randomized to the VCR-PDN pulses, in contrast to 61.2% for the patients randomized to receive 6MP-MTX alone (P = .0002). Among the irradiated patients, the DFS was not significantly different. Of the four combinations of maintenance and CNS therapy studied, the highest DFS was achieved with VCR-PDN pulses and maintenance IT MTX.
Nesiritide in patients hospitalized for acute heart failure: does timing matter? Implication for future acute heart failure trials
Authors: Yee Weng Wong, Robert J. Mentz, G.Michael Felker, Justin Ezekowitz, Karen Pieper, Gretchen Heizer, Vic Hasselblad, Marco Metra, Christopher M. O'Connor, Paul W. Armstrong, Randall C. Starling, Adrian F. Hernandez
Journal: European Journal of Heart Failure (2016)
Effect of Pregnancy and Nursing on the Growth of Metastases From &lt;italic&gt;N&lt;/italic&gt;-Nitroso-&lt;italic&gt;N&lt;/italic&gt;-methylurea-lnduced Mammary Carcinomas
Authors: P M Gullino, F H Grantham, D M Hill, H M Pettigrew
Journal: JNCI Journal of the National Cancer Institute (1985)

Pregnancy increased the survival times of inbred BUF/N rats bearing occult metastasis of a mammary carcinoma at the time of conception. Nursing following delivery nullified the effect of pregnancy. The similarity of the controlled experimental data with the limited clinical observations is noted. An experimental model of rat mammary carcinoma has been described that possesses a highly metastasizing capacity and can be utilized to study the behavior of clinically silent metastasis.
John Joseph Hamblin
Authors: M Hamblin
Journal: BMJ (2015)

After qualifying with double honours, John Hamblin (“JJ”) completed his junior posts at the Royal London and Poplar hospitals. National service beckoned thereafter. He was initially awarded a six month commission and subsequently accepted a post in Nigeria, working for the medical corps within the UN peacekeeping force deployed for the Congo war.

After his spell in west Africa he returned to the Royal London Hospital and worked on the hospital’s medical unit the for the next five years. This period of his postgraduate training culminated in his appointment as consultant physician at Southend Hospital in 1967, at the unusually tender age of 32.

John subsequently forged a successful and rewarding career. He rapidly established himself …
Abstract 3590: Resistance mechanisms to ALK inhibitors
Authors: Ryohei Katayama, Noriko Yanagitani, Sumie Koike, Takuya Sakashita, Satoru Kitazono, Makoto Nishio, Yasushi Okuno, Jeffrey A. Engelman, Alice T. Shaw, Naoya Fujita
Journal: Cancer Research (2015)

Abstract Purpose: ALK-rearranged non-small cell lung cancer (NSCLC) was first reported in 2007. Approximately 3-5% of NSCLCs harbor an ALK gene rearrangement. The first-generation ALK tyrosine kinase inhibitor (TKI) crizotinib is a standard therapy for patients with advanced ALK-rearranged NSCLC. Several next-generation ALK-TKIs have entered the clinic and have shown promising antitumor activity in crizotinib-resistant patients. As patients still relapse even on these next-generation ALK-TKIs, we examined mechanisms of resistance to one next-generation ALK-TKI - alectinib - and potential strategies to overcome this resistance. Experimental Procedure: We established a cell line model of alectinib resistance, and analyzed resistant tumor specimens from patients who had relapsed on alectinib. Cell lines were also established under an IRB-approved protocol when there was sufficient fresh tumor tissue. We established Ba/F3 cells expressing EML4-ALK and performed ENU mutagenesis to compare potential crizotinib or alectinib-resistance mutations. In addition, we developed Ba/F3 models harboring ALK resistance mutations and evaluated the potency of multiple next-generation ALK-TKIs including 3rd generation ALK inhibitor in these models and in vivo. To elucidate structure-activity-relationships of ALK resistance mutations, we performed computational thermodynamic simulation with MP-CAFEE. Results: We identified multiple resistance mutations, including ALK I1171N, I1171S, and V1180L, from the ENU mutagenesis screen and the cell line model. In addition we found secondary mutations at the I1171 residue from the Japanese patients who developed resistance to alectinib or crizotinib. Both ALK mutations (V1180L and I1171 mutations) conferred resistance to alectinib as well as to crizotinib, but were sensitive to ceritinib and other next-generation ALK-TKIs. Based on thermodynamics simulation, each resistance mutation is predicted to lead to distinct structural alterations that decrease the binding affinity of ALK-TKIs for ALK. Conclusions: We have identified multiple alectinib-resistance mutations from the cell line model, patient derived cell lines, and tumor tissues, and ENU mutagenesis. ALK secondary mutations arising after alectinib exposure are sensitive to other next generation ALK-TKIs. These findings suggest a potential role for sequential therapy with multiple next-generation ALK-TKIs in patients with advanced, ALK-rearranged cancers. Citation Format: Ryohei Katayama, Noriko Yanagitani, Sumie Koike, Takuya Sakashita, Satoru Kitazono, Makoto Nishio, Yasushi Okuno, Jeffrey A. Engelman, Alice T. Shaw, Naoya Fujita. Resistance mechanisms to ALK inhibitors. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3590. doi:10.1158/1538-7445.AM2015-3590
Abstract P174: Kidney Function and Progression of Coronary Artery Calcification in Community-Dwelling Older Adults: The Rancho Bernardo Study
Authors: Simerjot K Jassal, Gail A Laughlin, Kevin M Cummins, Michel Chonchol, Gerard Smits, Caroline K Kramer, Elizabeth Barrett-Connor
Journal: Circulation (2012)

Background: Despite growing evidence for the separate and joint contributions of declining estimated glomerular filtration rate (eGFR) and presence of albuminuria to cardiovascular death, longitudinal studies of the association of these risk factors with coronary artery calcification, a marker of subclinical cardiovascular disease (CVD), are contradictory. Methods: We evaluated 421 community-dwelling men and women (mean age 67 years) without known heart disease who had eGFR estimated by the Modification of Diet in Renal Disease equation and albuminuria assessed by urine albumin/creatinine ratio (ACR) between 1997-99. Coronary artery calcium (CAC) was measured by electron beam computed tomography between 2001-02; 338 participants returned for a repeat scan between 2005-06, a mean of 4.5 (0.5) years later. CAC progression was defined as a difference between the follow-up square-root transformed CAC volume score and the baseline square-root transformed score &gt; 2.5 mm 3 . Results: At baseline, mean eGFR was 78 mL/min/1.73m 2 , median ACR was 10 mg/g. Median total Agatston CAC score was 77 at the baseline scan and 112 at follow-up; 45% (191 of 421) of participants had CAC&gt;100 at baseline and 46% (157 of 338) showed CAC progression. Logistic regression analyses showed no separate or joint association between eGFR or ACR with baseline CAC or with CAC progression. Table 1 shows the odds ratio (95% CI) for CAC progression for each 1 SD decrease in eGFR or increase in ACR. Conclusions: In a cohort of community-dwelling older adults, we found no longitudinal association between eGFR or ACR with CAC progression. This information may enhance our understanding of CAC progression across the spectrum of kidney function in community-dwelling adults without prevalent CVD or kidney disease. 4 Year CAC Progression per 1 SD Decrease in eGFR or Increase in ACR 1997-99 Estimated Glomerular Filtration Rate Urine Albumin/Creatinine Ratio (n=338) (n=292) Covariates Odds Ratio (95% CI) p value Odds Ratio (95% CI) p value Model 1 1.07 (0.86, 1.33) 0.54 0.99 (0.78, 1.26) 0.93 Model 2 1.04 (0.84, 1.30) 0.69 0.97 (0.77, 1.24) 0.82 Model 3 1.06 (0.85, 1.33) 0.57 1.06 (0.82, 1.37) 0.67 Model 4 1.07 (0.85, 1.33) 0.57 1.05 (0.81, 1.36) 0.69 Model 5 1.05 (0.82, 1.36) 0.68 1.06 (0.82, 1.38) 0.66 Model 6 1.10 (0.83, 1.43) 0.53 0.99 (0.75, 1.30) 0.94 Model 1: Unadj; Model 2: Age, time lapse adj; Model 3: Age, time lapse, sex adj; Model 4: Age, timelapse, sex, BMI adj; Model 5: Age, time lapse, sex, BMI and (eGFR or ACR) adj; Model 6: Age, time lapse, sex, BMI, SBP, FPG, HDL and (eGFR or ACR) adj
Molecular Size of Carcinoembryonic Antigen in the Plasma of Patients With Malignant Disease2
Authors: Q. Pietsch, D. M. Goldenberg
Journal: JNCI Journal of the National Cancer Institute (1974)

Plasma from patients with various malignancies was chromatographed by gel filtration, and the molecular size of carcinoembryonic antigen (CEA) was determined. As measured by the Hansen Z-gel radioimmunoassay, the circulating antigen was heterogenous in molecular size. The CEA in the plasma of patients with cancers of the colon, ovary, cervix, and bronchus had a molecular size of ≈370,000 daltons, whereas CEA in the plasma of rectal-tumor patients was 200,000 daltons.