tbuckley/cabot-search huggingface dataset:
Nitrite in Human Saliva. Its Possible Relationship to Nitrosamine Formation23
Authors: S.R. Tannenbaum, A.J. Sinskey, M. Weisman, W. Bishop
Journal: JNCI Journal of the National Cancer Institute (1974)

Nitrite was consistently found in human saliva at levels of usually 6-10 ppm. The nitrite level did not seem to be strongly influenced by the composition of a meal, and in some individuals a narrow range of nitrite concentration was maintained for a long time. In agreement with earlier work, parotid ductal saliva was found to be free of nitrite, and a major route of nitrite formation was via microbial reduction of nitrate naturally present in saliva. Exploration of various parameters related to the reduction of nitrate to nitrite did not demonstrate a clear correlation between measurements on individuals and their level of salivary nitrite. The microorganisms responsible for nitrite formation were identified and quantified, and the relationships between nitrate consumption and nitrite formation explored. These complex relationships suggested that the tree nitrite in saliva represents the "spillover" of that formed in microbial cells.
PTU-195 Robotic colorectal surgery: a single centre experience of first 100 consecutive cases
Authors: J Ahmed, H Abbass, S Stefan, K Flashman, J Khan, A Parvaiz
Journal: Gut (2015)

<h3>Introduction</h3> Robotic surgery has gained momentum in various surgical disciplines. The provision of a stable platform with excellent 3D view and improved access which enhances surgical capabilities for precise dissection in a narrow surgical field has made it an attractive option for colorectal surgeons. The aim of this study was to present the clinical outcomes of first 100 robotic colorectal procedures performed in a single centre between May 2013 and January 2015. <h3>Method</h3> Prospectively collected data related to 100 consecutive patients who underwent robotic colorectal surgery was analysed for surgical and oncological outcomes. <h3>Results</h3> There were 68 male patients (68%) with a median age of 68 years (range 24–92). 15% of patients had neoadjuvant chemoradiotherapy. 23% patients had BMI &gt;30. Rectal resections were performed in 95 patients (85 for cancer and 10 for colitis). Other procedures included right hemicolelctomy (1%), Hartmanns procedure (2%) and left hemicolectomy (2%). Median operating time was 240 min (range- 128–456). whilst median blood loss was 10 mls (range 0–200). There was no conversion to open or laparoscopy and no intra-operative complications. Median length of stay was 7 days (range- 3–48). 30 days mortality was nil whilst readmission rate was 8%. 2 patients had anastomotic leak and 2 had small bowel obstruction, requiring reoperation (4%). 42 patients had tumour stage T3 or 4. R0 resection was achieved in 95% cases and median of lymph node harvest was 16 (range 6–43). <h3>Conclusion</h3> Robotic colorectal surgery is safe and feasible. This approach shows promising clinical and oncological outcomes and may become an integral part of colorectal surgery in future. <h3>Disclosure of interest</h3> None Declared.
Reduction of Immune Complexes and Immunoglobulins Induced by D-Penicillamine in Primary Biliary Cirrhosis
Authors: Owen Epstein, Deborah De Villiers, Stefan Jain, Barry J. Potter, Howard C. Thomas, Sheila Sherlock
Journal: New England Journal of Medicine (1979)

Penicillamine has an effect on immune complexes and immunoglobulins both in vivo and in vitro. We therefore studied the effect of penicillamine on immune complexes and immunoglobulins in primary biliary cirrhosis. Twenty-eight patients were randomly allocated into a treatment group receiving 600 to 900 mg of penicillamine, or a control group, and followed for a maximum of 24 months. After 12 and 24 months, serum immune complexes had fallen significantly in treated patients as compared to controls (P less than 0.05, P less than 0.01). Treatment reduced IgA, IgG and IgM concentrations, with IgM being significantly different from controls at six, 12 and 24 months (P less than 0.01). Over 24 months, serum aspartate transaminase levels fell in treated patients but rose in controls (P less than 0.01). Bilirubin concentrations increased at a slower rate in treated patients. Penicillamine may favorably influence the course of primary biliary cirrhosis by its immunologic action in addition to its copper-chelating action.
Lithium Carbonate Attenuation of Chemotherapy-Induced Neutropenia
Authors: Richard S. Stein, Colleen Beaman, Mohammed Y. Ali, Richard Hansen, David D. Jenkins, Hani G. Jumean
Journal: New England Journal of Medicine (1977)

The administration of lithium to psychotic patients is associated with leukocytosis.1 2 3 Although the mechanism of this leukocytosis is not established, preliminary studies have suggested that the drug increases granulocyte production.4 5 6 Clinical evaluation of lithium-induced granulocytosis has been limited.7 8 9 In this study we evaluated the ability of lithium to affect the neutropenia associated with cancer chemotherapy.MethodsTwenty patients receiving combination chemotherapy regimens not including corticosteroids entered the study. Patients on low salt diets or diuretics were excluded. The majority of patients had either breast or lung cancer.The experimental design employed each patient as his own control. Cycles on lithium . . .
PTH-113 Clinical Response to Induction Anti-Tnf Therapy has no Effect on Haemoglobin Levels in Patients with IBD
Authors: T C Shepherd, P Balendran, J Goodhand, E Cronin, K Greveson, E Wood, L Marelli, C Murray
Journal: Gut (2013)

<h3>Introduction</h3> Iron deficiency anaemia (IDA), as a consequence of intestinal bleeding and inflammation, is arguably the most common complication of inflammatory bowel disease (IBD). In controlled trials, oral iron is reportedly as effective as IV iron; however, few studies have included patients with active disease where inflammation through the release of hepcidin may limit the efficacy of oral or dietary iron. <h3>Methods</h3> To further study the relationship between inflammation and anaemia, we hypothesised that haemoglobin (Hb) levels would rise more in anaemic patients that responded, than in patients who did not respond, to induction anti-TNF therapy. Using electronic case note review, we assessed the prevalence, severity, type and mean change in Hb (ΔHb) of 174 [97 Male] consecutive patients undergoing induction therapy with an anti-TNF agent [Infliximab 139: Adalimumab 35]. Anaemia was defined according to age-sex adjusted WHO criteria. Primary response was assessed at 14 weeks and defined as, at least two of; the absence of symptoms, having withdrawn from steroids, and/or a normal serum C-reactive protein. Non-response was defined as one or none of the above. <h3>Results</h3> 89% [156/174] patients had Crohn’s disease: the mean [SD] age, age at diagnosis, and disease duration were 34 [17], 24[13], 10 [10] years respectively. Overall 49% [85/174] patients were anaemic at initiation of ant-TNF treatment with a mean [SD] haemoglobin of 10.9 [1.3] g/dl. Only 48% [41/85] had haematinics checked within 3 months of commencing an anti-TNF: 63% [26/41], 31% [13/41] had anaemia of chronic disease and 5% [2/41] were folate deficient. Overall, 37% [31/85] of the anaemic patients were prescribed iron therapy. Considering all anaemic patients, there were no differences in the baseline Hb in patients who responded (11.1 [1.2] g/dl) compared with those who did not respond (10.6 [1.6] g/dl, p = 0.11) to anti-TNF therapy. Regardless of concurrent iron therapy, there was no difference in the mean [SD] change in Hb (ΔHb) between patients that responded to anti-TNF therapy (0.51 [1.2] g/dl) and those who did not (0.47 [1.4] g/dl, p = 0.85). <h3>Conclusion</h3> Iron deficiency anaemia is common but frequently undertreated in IBD patients receiving anti-TNF therapy. Induction anti-TNF therapy, with or without oral iron therapy, has no effect on haemoglobin levels. In patients with IDA receiving anti-TNF therapies, gastroenterologists should consider IV iron therapy. <h3>Disclosure of Interest</h3> None Declared.
OP0050 Erosion Detection on the Si-Joints - A Comparison between X-Ray, Low Dose CT and MRI Including High Resolution Sequences
Authors: T. Diekhoff, J. Greese, M. Krohn, A. Huppertz, B. Hamm, K.-G. Hermann
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> The value of magnetic resonance imaging (MRI) in the detection of erosions on the sacroiliac joints (SI-joints) is controversial. Structural changes on the other hand are getting more and more into scientific focus. <h3>Objectives</h3> The aim of this study is a comparison between x-ray, low dose computed tomography (CT) and MRI. The presented data are preliminary results from the sacroiliac joint magnetic resonance imaging and computed tomography (SIMACT) study. <h3>Methods</h3> We investigated prospectively 30 patients with lower back pain and the suspicion of axSpA expressed by an experienced rheumatologist. All patients underwent a low dose CT (Somatom Definition Flash, Siemens, Germany) and an MRI (3.0T Magnetom Skyra, Siemens, Germany) of the SI-joints. Imaging data were compared with X-ray of the pelvis. The MRI protocol contained these sequences: T1-weighted spine echo (T1-SE), short tau inversion recovery (STIR), T1-weighted 3D volumetric interpolated breath hold examination (VIBE) high resolution sequence, all in paracoronal orientation. The grade of the disease was scored in X-ray according to the modified New York criteria and the erosions were counted by quadrant by a blinded reader. The final diagnosis made by the rheumatologist was also used for comparison. <h3>Results</h3> CT and T1-SE showed no significant differences in detecting erosions. 3D-VIBE found significantly more erosions in patients with axSpA compared to CT and T1-SE. (n=22; CT 178 erosions, T1 163, VIBE 421; average CT 5.9, T1 5.4, VIBE 14.0; p&lt;0.001). In other diagnosis (osteoarthritis N=4, triangular hyperostosis N=3, others N=1) there were no significant differences among imaging modalities. The erosion count in 3D-VIBE correlated with the grade of sacroiliitis in X-ray (r=0.123, p=0.007). <h3>Conclusions</h3> High-resolution 3D MR sequences like 3D-VIBE are more suitable in detecting erosions on the SI-joints than conventional MRI (T1-SE) and even low dose CT. They are therefore a reasonable supplement to any MRI protocol and may improve the ability of MRI for diagnosis both in early and advanced SpA. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2145
Prevention of Skin Cancer in Xeroderma Pigmentosum with the Use of Oral Isotretinoin
Authors: Kenneth H. Kraemer, John J. DiGiovanna, Alan N. Moshell, Robert E. Tarone, Gary L. Peck
Journal: New England Journal of Medicine (1988)

To confirm reports that skin cancer can be prevented with retinoids, we conducted a three-year controlled prospective study of oral isotretinoin (also called 13-cis retinoic acid) in five patients with xeroderma pigmentosum who had a history of multiple cutaneous basal-cell or squamous-cell carcinomas. Patients were treated with isotretinoin at a dosage of 2 mg per kilogram of body weight per day for two years and then followed for an additional year, without the drug. Before, during, and after treatment, biopsies of all suspicious lesions were performed, and skin cancers were surgically removed. The patients had a total of 121 tumors (mean, 24; range, 8 to 43) in the two-year interval before treatment. During two years of treatment with isotretinoin, there were 25 tumors (mean, 5; range, 3 to 9), with an average reduction in skin cancers of 63 percent (P = 0.019). After the drug was discontinued, the tumor frequency increased a mean of 8.5-fold (range, 2- to 19-fold) over the frequency during treatment (P = 0.007). Although all patients experienced mucocutaneous toxic effects, and triglyceride, liver-function, or skeletal abnormalities developed in some, high-dose oral isotretinoin was effective in the chemoprophylaxis of skin cancers in patients with xeroderma pigmentosum. (N Engl J Med 1988; 318:1633–7.)
Malignant Tumors Occurring after Treatment of Aplastic Anemia
Authors: Gerard Socie, Michel Henry-Amar, Andrea Bacigalupo, Jill Hows, Andre Tichelli, Per Ljungman, Shaun R. McCann, Norbert Frickhofen, Elizabeth Van't Veer-Korthof, Eliane Gluckman
Journal: New England Journal of Medicine (1993)

Recent studies have shown that long-term survivors of acquired aplastic anemia may be at high risk for malignant diseases. We assessed the risk of cancer after aplastic anemia was treated with immunosuppression or bone marrow transplantation and sought to identify risk factors according to treatment. The study population consisted of 860 patients treated by immunosuppression and 748 patients who had received bone marrow transplants for the treatment of severe aplastic anemia. The risk of cancer was analyzed overall and according to treatment relative to the risk in the general population. In calculating relative risk, we excluded patients with myelodysplastic syndromes or acute leukemias arising less than 6 months after treatment, and solid cancers arising less than 12 months after treatment, because of a possible association with aplastic anemia itself rather than with the treatment received.
SPECT Brain Imaging in Chronic Lyme Disease
Authors: Sam T. Donta, Richard B. Noto, John A. Vento
Journal: Clinical Nuclear Medicine (2012)

Lyme disease is an infectious disease that frequently involves the central nervous system, leading to cognitive and/or mood dysfunction. The basis for these symptoms remains to be defined but may be the result of a vasculitis or metabolic abnormality secondary to the infection. SPECT scans of the brain might provide an objective measure of abnormalities present in patients with otherwise difficult to objectify clinical findings. The objective of this study was to determine the frequency, location, and severity of abnormalities in SPECT scans of the brain of patients with chronic Lyme disease.A total of 183 individuals who met the clinical definition of chronic Lyme disease underwent SPECT scanning of the brain using Tc and standard nuclear imagine techniques. Abnormalities of perfusion to affected areas of the brain were defined as mild, moderate, or severe.Of all patients, 75% demonstrated abnormalities in perfusion to various areas of the brain, most notably the frontal, temporal, and parietal lobes. Patients considered to be seropositive and those considered seronegative had similar rates, types, and severity of perfusion defects. Abnormalities of MRI of the brain were seen in 14% of patients. Treatment with antibiotics, especially those with intracellular-penetrating activity, resulted in resolution or improvement of abnormalities in 70% of patients over a 1- to 2-year period.Brain SPECT scans are abnormal in most patients with chronic Lyme disease, and these scans can be used to provide objective evidence in support of the clinical diagnosis. The use of certain antibiotic regimens seems to provide improvement in both clinical status and SPECT scans.
Scintigraphy of an Avulsion Injury of the Rectus Femoris Muscle
Authors: PAUL ANNETT, WARWICK BRUCE, KIRSTEN SWEETLAND, HANS VAN DER WALL
Journal: Clinical Nuclear Medicine (2001)

ANNETT, PAUL M.B.B.S., F.A.C.S.P.; BRUCE, WARWICK M.B.B.S., F.R.A.C.S., F.A.Ortho.; SWEETLAND, KIRSTEN B.app.Sc. (N.M.T.); VAN DER WALL, HANS M.B.B.S., Ph.D., F.R.A.C.P. Author Information
Abstract LB-212: Mcl-1 and FBW7 control a dominant survival pathway underlying HDAC and Bcl-2 inhibitor synergy in squamous cell carcinoma.
Authors: Lei He, Kristine Torres-Lockhart, Nicole Forster, Saranya Ramakrishnan, Patricia Greninger, Mathew J. Garnett, Ultan McDermott, S. Michael Rothenberg, Cyril Benes, Leif Ellisen
Journal: Cancer Research (2013)

Abstract Effective targeted therapeutics for squamous cell carcinoma (SCC) are lacking. Here we uncover Mcl-1 as a dominant and tissue-specific survival factor in SCC, providing a roadmap for a new therapeutic approach. Treatment with the HDAC inhibitor vorinostat regulates Bcl-2 family member expression to disable the Mcl-1 axis and thereby induce apoptosis in SCC cells. Although Mcl-1 dominance renders SCC cells resistant to the BH3 mimetic ABT-737, vorinostat primes them for sensitivity to ABT-737 by shuttling Bim from Mcl-1 to Bcl-2/Bcl-xl, resulting in dramatic synergy for this combination and sustained tumor regression in vivo. Moreover, somatic FBW7 mutation in SCC is associated with stabilized Mcl-1 and high Bim levels, resulting in a poor response to standard chemotherapy but a robust response to HDAC inhibitors and enhanced synergy with combination vorinostat/ABT-737. Collectively, our findings provide a biochemical rationale and predictive markers for the application of this therapeutic combination in SCC. Citation Format: Lei He, Kristine Torres-Lockhart, Nicole Forster, Saranya Ramakrishnan, Patricia Greninger, Mathew J. Garnett, Ultan McDermott, S. Michael Rothenberg, Cyril Benes, Leif Ellisen. Mcl-1 and FBW7 control a dominant survival pathway underlying HDAC and Bcl-2 inhibitor synergy in squamous cell carcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-212. doi:10.1158/1538-7445.AM2013-LB-212
Abstract 2560: MicroRNA target site polymorphisms and colorectal cancer risk in the Ashkenazi Jewish population.
Authors: Stephanie L. Stenzel, Jeremy Gollub, Michael Shapero, Andrea Finn, Gad Rennert, Stephen B. Gruber
Journal: Cancer Research (2013)

Abstract MicroRNAs (miRNAs) act as key post-transcriptional regulators of gene expression via binding to the 3’ untranslated regions (UTRs) of mRNAs. Single nucleotide polymorphisms (SNPs) found in the miRNA sequence and/or corresponding binding sites can affect the fidelity of this interaction, and evidence from candidate miRNA studies suggests that such SNPs may increase or decrease risk of tumor development. This study was designed to expand the search for miRNA-related polymorphisms important in cancer etiology across the genome and to investigate the association between thousands of genetic variants in miRNA target sites and colorectal cancer (CRC) risk using a novel genotyping platform, the Axiom® miRNA Target Site Genotyping Array (237,858 markers). The final study sample after quality control filtering included 605 cases and 615 controls from the Molecular Epidemiology of Colorectal Cancer (MECC) study, a population-based case-control study of incident CRC cases in a geographically-defined area of northern Israel. The marginal association between each marker with minor allele frequency &amp;gt;=1% and CRC risk was examined assuming a log-additive genetic model using logistic regression adjusted for sex, age, and the first two principal components (PC) to capture fine-scale population structure. There were 11 markers with p-values less than 3E-4, and the most statistically significant association involved rs12130051 (chr1:19545053; 3’-UTR of KIAA0090) with an OR of 2.24 (1.52,3.31) and p=4.48E-5. In addition, rs1051690 (chr5:142605172; 3’-UTR of ARHGAP26), was statistically significantly associated with decreased CRC risk (OR (95% CI): 0.71 (0.59, 0.85); p = 2.03E-4). Further, this study provided evidence for replication of a previously published locus, rs1051690 in the 3’UTR region of the insulin receptor gene, INSR (OR (95% CI): 1.27 (0.96,1.67); p = 0.09). A fixed-effects meta-analysis of sample-size weighted p-values from a recent publication in Carcinogenesis describing the INSR variant (Landi et al., 2012) and from the current MECC study yielded a combined p-value of 0.01. To our knowledge, this is the first study to examine the association between genetic variation in miRNA target sites and cancer risk using a genome-wide approach. Work is ongoing to replicate findings from this study and to characterize the functional impact of prioritized polymorphisms. Citation Format: Stephanie L. Stenzel, Jeremy Gollub, Michael Shapero, Andrea Finn, Gad Rennert, Stephen B. Gruber. MicroRNA target site polymorphisms and colorectal cancer risk in the Ashkenazi Jewish population. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2560. doi:10.1158/1538-7445.AM2013-2560
Abstract C11: Investigation of a novel molecular descriptor for the lead optimization of 4-aminoquinazolines as vascular endothelial growth factor receptor-2 inhibitors
Authors: Joel K. Kawakami, Yannica Martinez, Brandi Sasaki, Melissa Harris, Wendy E. Kurata, Alan F. Lau
Journal: Cancer Research (2011)

Abstract We investigated the use of infrared vibrational frequency of ligands as a potential novel molecular descriptor in three different molecular target and chemical series. The vibrational energy of a ligand was approximated from the sum of infrared (IR) absorptions of each functional group within a molecule and normalized by its molecular weight (MDIR). Calculations were performed on a set of 4-aminoquinazolines with similar docking scores for the VEGFR2/KDR receptor. 4-Aminoquinazolines with MDIR values ranging 192–196 provided compounds with KDR inhibitory activity. The correlation of KDR inhibitory activity was similarly observed in a separate chemical series, the pyrazolo[1,5-a]pyrimidines. Initial exploration of this molecular descriptor supports a tool for rapid lead optimization in the 4-aminoquinazoline chemical series and a potential method for scaffold hopping in pursuit of new inhibitors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr C11.
Focal Splenic FDG Uptake in a Patient With Kala-Azar (Visceral Leishmaniasis)
Authors: Jordi Fuertes, Josep-Roland Garcia-Bennett, Simona Iftimie, Mònica Danús, José Angel Abreu
Journal: Clinical Nuclear Medicine (2014)

We present a woman with a history of Gaucher disease and secondary portal hypertension. She went to hospital for treatment of resistant fever without apparent cause. A conventional study of fever of unknown origin did not show any pathology. For this reason, she was referred to our department for a PET/CT, which did not demonstrate a cause for the fever. Two months after, she was admitted again in hospital for fever recurrence. A new PET/CT showed FDG avid hypodense splenic lesions, suspicious for infection. Splenectomy was performed and histopathologic analysis demonstrated intracellular organisms compatible with Leishmania.