tbuckley/cabot-search huggingface dataset:
Bethesda Guidelines: Relation to Microsatellite Instability and MLH1 Promoter Methylation in Patients with Colorectal Cancer
Authors: Jochen Raedle
Journal: Annals of Internal Medicine (2001)

Background: Microsatellite instability is a hallmark of mismatch repair deficiency in hereditary nonpolyposis colorectal cancer and results from mutations in the mismatch repair genes MLH1 or MSH2 or from gene inactivation associated with DNA methylation. The Bethesda guidelines were established to identify patients with colorectal cancer who should be tested for microsatellite instability. Objective: To assess the Bethesda guidelines for detection of microsatellite instability and to determine the role of MLH1 promoter methylation in colorectal cancer. Design: Prospective cohort study. Setting: Tertiary care referral center in Frankfurt, Germany. Patients: 125 consecutive patients with colorectal cancer. Measurements: Patients were assessed according to the Bethesda guidelines, and tumor specimens were analyzed for microsatellite instability. Patients with microsatellite instability were tested for MLH1 promoter methylation and MLH1 and MSH2 germline mutations. Results: Microsatellite instability was detected in 17 of 58 patients who fulfilled and 5 of 67 patients who did not fulfill criteria of the Bethesda guidelines. In 11 of 17 patients with microsatellite instability who fulfilled Bethesda guidelines, an MLH1 (n = 3), MSH2 (n = 7), or combined MLH1 and MSH2 (n = 1) mutation was found. Among the patients with microsatellite instability who did not fulfill Bethesda guidelines, no mutations were observed; MLH1 promoter methylation was observed in 6 of 11 patients with an MLH1 or MSH2 mutation and 5 of 11 patients without an MLH1 or MSH2 mutation. Conclusions: The Bethesda guidelines are useful for selecting patients for microsatellite instability testing. MLH1 and MSH2 testing should be recommended in all patients with colorectal cancer and microsatellite instability who fulfill at least one Bethesda criterion. MLH1 promoter methylation may accompany rather than initiate carcinogenesis in patients with colorectal cancer who have mismatch repair gene defects.
The Impact of Insulin-Dependent Diabetes on Ventilatory Control in the Mouse
Authors: VSEVOLOD Y. POLOTSKY, JESSICA A. WILSON, ABBY S. HAINES, MATTHEW T. SCHARF, SHAWN E. SOUTIERE, CLARKE G. TANKERSLEY, PHILIP L. SMITH, ALAN R. SCHWARTZ, CHRISTOPHER P. O'DONNELL
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Insulin-dependent diabetes mellitus (IDDM) can lead to ventilatory depression and decreased sensitivity to hypercapnia. We examined relationships between ventilation, plasma insulin, leptin, ketones, and blood glucose levels in two mouse models of IDDM: (1) streptozotocin-induced diabetes in C57BL/6J mice on a regular diet or with induced obesity from a high fat diet; and (2) spontaneous diabetes mellitus in NOD-Ltj mice. In both mouse models, IDDM resulted in depression of the hypercapnic ventilatory response (HCVR). This ventilatory depression was not associated with decreases in plasma insulin or leptin levels. There was, however, a strong association between the duration of hyperglycemia, the decline in HCVR, and increased glycosylation of the diaphragm. Hyperventilation was observed in only six of 14 C57BL/6J obese wild-type mice, despite a significant degree of diabetic ketoacidosis (DKA) in all 14 animals. In mice with DKA, there was a significant correlation between the increase in baseline minute ventilation (V˙ e) and hyperleptinemia (r = 0.77, p < 0.01). In leptin-deficient C57BL/6J-Lep ob mice, low levels of both V˙ e and ketones were observed. These results suggest that: (1) depression of the HCVR in IDDM is associated with hyperglycemia and glycosylation of the diaphragm; and (2) the hyperventilation of DKA is leptin dependent.
78O_PR The Role of Ap-1 in Endocrine-Resistant Breast Cancer
Authors: L. Malorni, M. Giuliano, I. Migliaccio, C. Creighton, M. Lupien, S. Hilsenbeck, X. Fu, M. Trivedi, C.K. Osborne, R. Schiff
Journal: Annals of Oncology (2012)
Prospective study of prenatal screening for Down's syndrome with free beta human chorionic gonadotrophin.
Authors: K Spencer, P Carpenter
Journal: BMJ (1993)

OBJECTIVE--To assess the value and impact of a screening programme for Down9s syndrome that uses the two maternal serum markers: alpha fetoprotein and free beta human chorionic gonadotrophin. DESIGN--All women booked into clinics were screened. Further tests were offered to women with a risk of one in 300 or greater of having an affected baby. Follow up of outcome of all pregnancies. SETTING--Biochemical screening laboratory serving two health districts. SUBJECTS--8179 women of all ages with singleton pregnancies screened between 15 and 22 weeks9 gestation from 1 April 1991 to 31 March 1992. MAIN OUTCOME MEASURES--Detection rate of Down9s syndrome, false positive rate, uptake of screening, uptake of amniocentesis in women identified as at increased risk, prevalence of Down9s syndrome at birth. RESULTS--Overall 89% (8317/9345) of women underwent screening. The rate of detection of Down9s syndrome was 69% (11/16; 95% confidence interval 41 to 89%) with a 5.2% false positive rate (426/179; 4.7 to 5.7%). In women under 30 the detection rate was 50% (four out of eight; 32 to 86%) Uptake of amniocentesis was 89% (389/437), resulting in a reduction of prevalence of Down9s syndrome at birth from 1.1 per 1000 in previous years (66/59,696) to 0.4 per 1000 during the screening year (4/9345). Additionally, several other abnormalities were identified. CONCLUSION--The benefit of a high detection rate with this approach and the additional anomalies identified should encourage others to introduce screening programmes for Down9s syndrome that use free beta human chorionic gonadotrophin and alpha fetoprotein.
Rearrangement of the bcl-6 Gene as a Prognostic Marker in Diffuse Large-Cell Lymphoma
Authors: Kenneth Offit, Francesco Lo Coco, Diane C. Louie, Nasser Z. Parsa, Denis Leung, Carol Portlock, Bihui H. Ye, Florigio Lista, Daniel A. Filippa, Ayala Rosenbaum, Marc Ladanyi, Suresh Jhanwar, Riccardo Dalla-Favera, R.S.K. Chaganti
Journal: New England Journal of Medicine (1994)

About 40 percent of non-Hodgkin's lymphomas are diffuse lymphomas with a large-cell component (DLLC). Current therapy can induce a long-term remission in half the patients with DLLC, but more intensive treatment has the potential to improve outcome, particularly in patients at high risk for treatment failure. Clinical and cytogenetic markers can identify subgroups at high or low risk. Rearrangement of a novel candidate proto-oncogene, bcl-6, is a possible prognostic indicator in DLLC.
Mucocutaneous Reactions to Antineoplastic Agents
Authors: R. M. Adrian, A. F. Hood, A. T. Skarin
Journal: CA A Cancer Journal for Clinicians (1980)

Mucocutaneous reaction patterns in patients receiving cancer therapy are not only variable, but in many instances identical patterns are produced by different pathologic mechanisms. For example, patients with leukemia or lymphoma may present with nodular skin lesions that may represent malignant infiltration, septic emboli, vasculitis, or a drug eruption. The most banal skin eruption may signal an impending or ongoing catastrophe. If one is able to make some clinical evaluation regarding the likelihood of a drug being responsible for the mucocutaneous eruption, it may help avoid further clinical or laboratory investigation and patient discomfort. Unfortunately, only a few antineoplastic agents have "characteristic" skin manifestations. If, however, these are kept in mind they may be helpful in the diffential diagnosis of mucocutaneous eruptions occurring in patients treated with cancer chemotherapeutic agents.
Hepatic Hemangioma With Normal Angiograms
Authors: William D. Davis
Journal: JAMA (1990)

Three cases of symptomatic cavernous hemangioma of the liver are reported. All three patients have normal angiograms. A review of the literature shows that the diagnosis of hemangioma may be made noninvasively with a high degree of accuracy. Technetium Tc 99m-labeled red blood cell scanning is very specific, while dynamic computed tomography may be more sensitive for small lesions. A combination of the two modalities makes the diagnosis in greater than 90% of cases. Magnetic resonance imaging is also sensitive and specific. Angiography, as shown in these cases, may not only be questionably indicated, but may be misleading. The treatment for symptomatic lesions is resection, and secondary alternatives are discussed.
ANTIBODY-MEDIATED SUPPRESSION OF THE IMMUNE RESPONSE IN VITRO
Authors: Erwin Diener, Marc Feldmann
Journal: The Journal of Experimental Medicine (1970)

Immunological tolerance to H antigens of Salmonella adelaide may be induced in vitro by the exposure of mouse spleen cells for 6 hr to an immunogenic dose of polymerized flagellin in the presence of low concentrations of specific antibody. Such antibody-mediated tolerance requires an optimal antigen: antibody ratio for its induction. A shift in this ratio in favor of the antibody concentration results in failure of tolerance induction and leads to immune suppression commonly known as antibody-mediated feedback inhibition which is not analogous to immunological tolerance. Fragment A of flagellin fails to induce immunological tolerance in vitro. Tolerance to polymerized flagellin may however be induced in vitro, provided the spleen cells are exposed to fragment A in the presence of specific antibody for 6 hr. The results are discussed in the light of current theories of the mechanism of tolerance induction.
Hydroxyurea in Chronic Myelogenous Leukemia.
Authors: B. J. Kennedy
Journal: Annals of Internal Medicine (1969)

s1 May 1969Hydroxyurea in Chronic Myelogenous Leukemia.B. J. Kennedy, M.D., F.A.C.P.B. J. Kennedy, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-70-5-1084_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptHydroxyurea has antitumor activity in animals and man. It produces bone marrow suppression and megaloblastosis which are reversible after discontinuing treatment. Measurement of nucleic acid synthesis in mouse ascites tumor revealed a differential inhibition of deoxyribonucleic acid (DNA) synthesis in the presence of permissive ribonucleic acid synthesis. Almost 90% inhibition of DNA synthesis was seen at the higher concentrations of hydroxyurea. It is probable that hydroxyurea has more than one site of action to account for its effects.The treatment of chronic myelogenous leukemia with hydroxyurea during the past 5 years in 20 patients demonstrates the beneficial effect of this... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Minneapolis, Minnesota PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byTherapeutic options in chronic myeloid leukaemiaTreatment of chronic myeloid leukaemiaChronic Myeloid Leukemia — A Brief History 1 May 1969Volume 70, Issue 5Page: 1084-1085KeywordsAscitesAttentionBone marrowChronic myelogenous leukemiaDNA synthesisNucleic acidsRNA Issue Published: 1 May 1969 PDF downloadLoading ...
An Alternatively Spliced Variant of CXCR3 Mediates the Inhibition of Endothelial Cell Growth Induced by IP-10, Mig, and I-TAC, and Acts as Functional Receptor for Platelet Factor 4
Authors: Laura Lasagni, Michela Francalanci, Francesco Annunziato, Elena Lazzeri, Stefano Giannini, Lorenzo Cosmi, Costanza Sagrinati, Benedetta Mazzinghi, Claudio Orlando, Enrico Maggi, Fabio Marra, Sergio Romagnani, Mario Serio, Paola Romagnani
Journal: The Journal of Experimental Medicine (2003)

The chemokines CXCL9/Mig, CXCL10/IP-10, and CXCL11/I-TAC regulate lymphocyte chemotaxis, mediate vascular pericyte proliferation, and act as angiostatic agents, thus inhibiting tumor growth. These multiple activities are apparently mediated by a unique G protein–coupled receptor, termed CXCR3. The chemokine CXCL4/PF4 shares several activities with CXCL9, CXCL10, and CXCL11, including a powerful angiostatic effect, but its specific receptor is still unknown. Here, we describe a distinct, previously unrecognized receptor named CXCR3-B, derived from an alternative splicing of the CXCR3 gene that mediates the angiostatic activity of CXCR3 ligands and also acts as functional receptor for CXCL4. Human microvascular endothelial cell line-1 (HMEC-1), transfected with either the known CXCR3 (renamed CXCR3-A) or CXCR3-B, bound CXCL9, CXCL10, and CXCL11, whereas CXCL4 showed high affinity only for CXCR3-B. Overexpression of CXCR3-A induced an increase of survival, whereas overexpression of CXCR3-B dramatically reduced DNA synthesis and up-regulated apoptotic HMEC-1 death through activation of distinct signal transduction pathways. Remarkably, primary cultures of human microvascular endothelial cells, whose growth is inhibited by CXCL9, CXCL10, CXCL11, and CXCL4, expressed CXCR3-B, but not CXCR3-A. Finally, monoclonal antibodies raised to selectively recognize CXCR3-B reacted with endothelial cells from neoplastic tissues, providing evidence that CXCR3-B is also expressed in vivo and may account for the angiostatic effects of CXC chemokines.
Simplified Electrophysiologically Directed Catheter Ablation of Recurrent Common Atrial Flutter
Authors: Dipen C. Shah, Michel Haïssaguerre, Pierre Jaïs, Bruno Fischer, Atsushi Takahashi, Meleze Hocini, Jacques Clementy
Journal: Circulation (1997)

Background Despite verification of bidirectional conduction block after radiofrequency (RF) catheter ablation in the inferior vena cava (IVC)–tricuspid annulus (TA) isthmus, recurrence of common atrial flutter is relatively common. Although complete linear reablation is usually performed, we evaluated a simplified electrophysiological strategy selectively targeting recovered conducting isthmus tissue. Methods and Results Twenty-one patients (18 men and 3 women, age, 54±10 years) with a recurrence of typical atrial flutter 6±7 months after an apparently successful catheter ablation in the IVC-TA isthmus prospectively underwent electrophysiologically targeted reablation during flutter. Sites with narrow electrograms or fractionated electrograms interposed between adjacent sites with double potentials considered to represent gaps were ablated without movement of the catheter. Mapping showed that 18 of 21 patients had a single gap. Successful ablation required a single application in 14 patients and, in the group as a whole, a median of one application (mean, 2±2; range, 1 to 11) with resultant bidirectional block in 13 of 16. A single narrow electrogram (duration, 48±6 ms; amplitude, 0.1±0.05 mV) was noted at the successful site in 11, whereas a fractionated electrogram (97±32 ms, 0.05±0.04 mV, P &lt;.05) was noted in 9. There were four additional recurrences during a follow-up at 7±5 months; three were similarly ablated with a median of one pulse. Conclusions Transmural ablation lesions in the isthmus can be recognized during flutter by double potentials separated by an isoelectric interval. Postablation recurrent flutter is usually due to a single discrete recovered gap; this is represented by a single or a fractionated potential spanning the isoelectric interval of adjacent double potentials, which can be selectively targeted to minimize repeat ablation.
Rising Cost of Medical Care
Authors: Max Bader
Journal: JAMA (1977)

<h3>To the Editor. —</h3> In his commentary "A Prescription for the Rising Cost of Medical Care" (237:2383, 1977), Vernon Mark, MD, suggests the abandonment of Medicaid in favor of a municipal, county, and state hospital system, which he feels could provide the services needed by the medically indigent more cheaply, without sacrifice in quality of services, and with less fraud. He implied that the problem of the old government hospital system related to physical facilities, not to inadequate medical care. I do not agree. Seattle-King County has had a better county hospital than most in the country. Hospital care provided there in the past and currently has technically been good, often excellent. Today it still sees many Medicaid patients as part of the medical care mainstream (as it should be). The patient has freedom of choice to the extent that the private sector is willing to participate in Medicaid. During the
DRUG ERUPTION FROM PALUDRINE (PROGUANIL) HYDROCHLORIDE: REPORT OF A CASE
Authors: L. J. A. LOEWENTHAL
Journal: British Journal of Dermatology (1952)

Journal Article DRUG ERUPTION FROM PALUDRINE (PROGUANIL) HYDROCHLORIDE: REPORT OF A CASE Get access L. J. A. LOEWENTHAL, M.D., M.R.C.P., D.T.M. & H. L. J. A. LOEWENTHAL, M.D., M.R.C.P., D.T.M. & H. Johannesburg, South Africa Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 64, Issue 3, 1 March 1952, Pages 106–107, https://doi.org/10.1111/j.1365-2133.1952.tb16171.x Published: 01 March 1952
Inactivated Poliomyelitis Vaccination
Authors: E. Russell Alexander
Journal: JAMA (1984)

It is difficult to look back at an important scientific contribution and to assess the full significance of the work. It must be evaluated in relation to the time in which it was written. What were its roots? What was the notable contribution of this work? Furthermore, where did it lead us? Only with that precious gift of knowing what really happened can we now look back and assess the broader significance of the contribution. Thus, we can examine the important article, "Considerations in the Preparation and Use of Poliomyelitis Vaccine," by Jonas Salk, published inThe Journalin August 1955.<sup>1</sup> <h3>First Polio Vaccine</h3> In that year, there was an urgent problem, and this article represented one important response. Salk had been the first to take advantage of the basic contribution of Enders et al<sup>2</sup>in the propagation of poliovirus in non-neural tissue cultures and produced a formalininactivated
Abstract 4246: Enhanced anti-vascular and anti-tumor effects upon combination therapy with aflibercept (VEGF Trap) and other anti-angiogenic drugs
Authors: Alexander P. Adler, Pranitha Vangala, Carla Castanaro, Christopher Daly, Gavin Thurston, Alexandra Eichten
Journal: Cancer Research (2011)

Abstract Experimental and clinical development of anti-angiogenic drugs to date has mostly focused on the VEGF pathway, although other signaling pathways, including Dll4-Notch and Angiopoietin-Tie, are now also being explored. Targeting one pathway, however, might not result in maximum anti-vascular and anti-tumor effects. In this study, we compared the rapid effects on tumor perfusion of single agent blockade of VEGF, Dll4 or Ang2 to the effects of combined therapy (VEGF blockade plus either Dll4 or Ang2 blockade), and compared long-term tumor growth responses to these early effects on tumor perfusion. Using aflibercept (VEGF Trap) alone and in combination with a blocking Dll4 antibody or a blocking Ang2 antibody, we compared various tumors with a wide range of long-term growth responses to each agent: C6 rat glioma tumors, HT1080 human fibrosarcoma and Colo205 human colon carcinoma tumors, all grown subcutaneously in SCID/CB17 mice. Tumor vascular perfusion was assessed using contrast-enhanced micro-ultrasound at 24 and 72 hr after treatment. We found that aflibercept treatment rapidly decreased vascular perfusion in C6 (59% after 24 hr) and Colo205 (32%) tumors, whereas there was no decrease observed in HT1080 tumors. These changes in perfusion correlated with long-term tumor growth inhibition upon aflibercept treatment. Dll4 blockade resulted in decreased vascular perfusion in C6 (30% after 24 hr), Colo205 (77%), and HT1080 (54%) tumors, which again correlated with long-term growth inhibition of the different tumors. Treatment with an anti-Ang2 antibody produced a slight decrease in perfusion of Colo205 tumors (13% after 24 hr), associated with a decrease in tumor growth. However, combination treatments with aflibercept plus either anti-Dll4 or anti-Ang2 antibodies were more potent in all tumor types compared to single agent treatments at reducing tumor perfusion as well as inhibiting long-term tumor growth. Taken together, these data show that changes in tumor perfusion correlate with long-term tumor responses to combination treatment of aflibercept plus either anti-Dll4 or anti-Ang2 antibody suggesting that decreases in tumor perfusion could be an early biomarker predictive of response to anti-angiogenic therapies. Measuring the increased effectiveness of combination therapy in patients treated with different anti-angiogenic drugs may facilitate the improvement of current treatment regimens. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4246. doi:10.1158/1538-7445.AM2011-4246
Lack of specialist diabetes teams in hospitals is "absolutely disgraceful," says NHS clinical lead
Authors: I. Torjesen
Journal: BMJ (2012)

The long term health and quality of life of patients with diabetes is being put at risk by the poor standard of care they receive in primary and secondary care, two reports have warned this week.

State of the Nation 2012: England , published by the charity Diabetes UK on Monday 14 May,1 found that less than half of patients are receiving the basic standard regular care that they need: nine simple regular checks recommended by the national service framework for diabetes and the National Institute for Health and Clinical Excellence (NICE). Then on Thursday 17 May the national diabetes inpatient audit (NaDIA) showed that a third of patients with diabetes who are admitted to hospital in England and Wales are being put at risk of dangerously high or low …
Low Accuracy of Color Doppler Ultrasound in the Detection of Proximal Leg Vein Thrombosis in Asymptomatic High-Risk Patients
Authors: Bruce L. Davidson, C. Gregory Elliott, Anthonie W. A. Lensing
Journal: Annals of Internal Medicine (1992)

Objective: To evaluate the ability of color Doppler ultrasound to detect proximal deep venous thrombosis (DVT) in asymptomatic high-risk patients who subsequently underwent contrast venography. Design: Prospective cohort study using blinded observers, with contrast venography as the comparison standard. Setting: Seven medical centers (university and community hospitals) participating in a clinical trial of low-molecular-weight heparin for prevention of DVT. Patients: A total of 385 consecutive patients undergoing elective unilateral hip or knee replacement. Measurements: Ten days after surgery or before hospital discharge (whichever occurred first), patients had bilateral color Doppler ultrasound examinations of the proximal veins of the lower extremities. Subsequently, a contrast venogram of the operated leg was obtained. Results: Color Doppler ultrasound studies and venograms were both evaluable in 319 of the 385 patients. Deep venous thrombosis was identified by contrast venography in 80 patients (prevalence, 25%; 95% Cl, 20% to 30%) and involved the proximal veins in 21 patients (prevalence, 7%; Cl, 4% to 10%). For proximal DVT, color Doppler ultrasound showed poor sensitivity (38%; Cl, 18% to 62%), moderately good specificity (92%; Cl, 89% to 95%), and a poor positive predictive value for this population (26%). Conclusion: Color Doppler ultrasound examinations are insensitive to proximal DVT in asymptomatic high-risk patients and should not be substituted for venography for identifying proximal DVT in such patients.