tbuckley/cabot-search huggingface dataset:
Racial Differences in Glycemic Markers: A Cross-sectional Analysis of Community-Based Data
Authors: Elizabeth Selvin, Michael W. Steffes, Christie M. Ballantyne, Ron C. Hoogeveen, Josef Coresh, Frederick L. Brancati
Journal: Annals of Internal Medicine (2011)

Background: Although differences between black and white persons in hemoglobin A1c (HbA1c) values are well established, recent studies suggest that this might not reflect differences in glycemia. Objective: To investigate racial disparities in glycemic markers, including those that reflect biological processes independent of hemoglobin glycation and erythrocyte turnover. Design: Cross-sectional. Setting: Community-based. Participants: 1376 nondiabetic and 343 diabetic adults in a substudy of the Atherosclerosis Risk in Communities Study. Measurements: Hemoglobin A1c, fasting glucose, glycated albumin, fructosamine, and 1,5-anhydroglucitol levels. Results: Among persons with and without diabetes, black persons had significantly higher HbA1c, glycated albumin, and fructosamine levels than white persons before and after adjustment for covariates and fasting glucose concentration. Serum 1,5-anhydroglucitol levels, which are reduced in the setting of hyperglycemia-induced glycosuria, were lower in black persons than in white persons, although this difference was statistically significant only in nondiabetic adults. Limitation: The design was cross-sectional, a limited number of participants with a history of diabetes was included, and the study did not include integrated measures of circulating nonfasting glycemia. Conclusion: Differences between black and white persons in glycated albumin, fructosamine, and 1,5-anhydroglucitol levels parallel differences between these groups in HbA1c values. Racial differences in hemoglobin glycation and erythrocyte turnover cannot explain racial disparities in these serum markers. The possibility that black persons have systematically higher levels of nonfasting glycemia warrants further study. Primary Funding Source: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases.
Abstract LB-217: CK2 protein kinase promotes resistance to MAPK pathway inhibition
Authors: Bingying Zhou, Michelle Kassner, Holly Yin, Channing J. Der, Adrienne D. Cox
Journal: Cancer Research (2014)

Abstract Small molecule kinase inhibitors have opened potential new avenues for treating cancers dependent on the RAS-RAF-MEK-ERK MAPK pathway, yet identification of both de novo/innate/intrinsic and acquired resistance mechanisms will be critical for the successful application of these inhibitors in the clinic. We interrogated the kinome to identify resistance mechanisms towards the novel ERK1/2-selective inhibitor SCH772984. We first utilized a kinome-focused RNAi screen to identify genes that, when silenced, sensitized KRAS-dependent pancreatic cancer cells to SCH772984. In our drug dose-response screen of 711 kinases (QIAGEN library), we used 4 independent siRNA duplexes to knock down each gene, treated at 5 different drug doses, then evaluated viability with a standard CellTiter-Glo assay. Nineteen kinases enhanced sensitivity to SCH772984 (where at least 2 siRNAs for each target decreased IC50) at least 5-fold, indicating that they could drive ERK1/2 inhibitor resistance. Among these were 4 of the 9 protein kinases (Cot, Raf-1, PAK3 and PRKCH) identified in a cDNA expression screen for kinases that caused resistance of BRAF-mutant melanoma to the BRAF inhibitor vemurafenib. We therefore hypothesized that at least some of the kinases that scored positive in this screen might be conserved both across the MAPK pathway and across different cancer types. The tetrameric protein kinase CK2 (formerly casein kinase II) has crucial roles in cell survival, proliferation and differentiation, and its expression and/or activity is dysregulated in cancers including melanoma. In very recent studies, we have now determined that the alpha subunit of CK2 is sufficient to cause resistance to each of the three ERK MAPK pathway inhibitors currently approved for treatment of melanoma: vemurafenib (BRAFi), dabrafenib (BRAFi) and trametinib (MEKi). Co-inhibition of the MAPK pathway and CK2 (e.g., with CX-4945, currently in phase I trials) further enhanced sensitivity. Thus, this combination may offer an effective regimen to forestall or delay tumor relapse. We also observed that CK2alpha maintains ERK phosphorylation in the presence of MAPK inhibitors, and that it posttranslationally reduces abundance of the ERK phosphatase DUSP6/MKP-3, in a kinase-dependent manner. The relationship of these findings to CK2-mediated mechanisms of drug resistance will be discussed. Citation Format: Bingying Zhou, Michelle Kassner, Holly Yin, Channing J. Der, Adrienne D. Cox. CK2 protein kinase promotes resistance to MAPK pathway inhibition. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-217. doi:10.1158/1538-7445.AM2014-LB-217
Chronic Daily Headache
Authors: Robert D Gerwin
Journal: New England Journal of Medicine (2006)

A 36-year-old woman with a long history of catamenial migraines had had a headache almost every day for a year. The background headache was mild, but it became severe and incapacitating at least twice a week, interfering with work and sleep. She took six to eight tablets containing a combination of aspirin, acetaminophen, and caffeine per day, with minimal relief. She did not have fever, weight loss, diplopia, or tinnitus. Her headaches were not exacerbated by a Valsalva maneuver or positional change. Her physical examination was normal. How should she be evaluated and treated?
A Long-Term Prevention Study with Oxprenolol in Coronary Heart Disease
Authors: S. H. Taylor, B. Silke, A. Ebbutt, G. C. Sutton, B. J. Prout, D. M. Burley
Journal: New England Journal of Medicine (1982)

We carried out a randomized double-blind controlled secondary-prevention trial of oxprenolol over seven years. Forty milligrams of oxprenolol or placebo was given twice daily to 1103 men 35 to 65 years old who had an acute myocardial infarction between 1 and 90 months previously. Overall, there was no difference in mortality or cardiac events between the placebo and oxprenolol groups. The major influence on prognosis was the time at which treatment was started after infarction. In 417 patients in whom treatment was started within four months of infarction oxprenolol increased the six-year cumulative survival rate from 77 to 95 per cent (P less than 0.001). In 274 patients with treatment starting between 5 and 12 months of infarction the survival rate was similar in the two groups, but in 412 patients entered between 1 and 7 1/2 years after their first infarction oxprenolol reduced the six-year survival rate from 92 to 79 per cent (P = 0.002). The increased mortality in this latter group mainly occurred late after withdrawal from active treatment. The value of low-dose oxprenolol in secondary prevention appears to be confined to patients treated relatively soon after myocardial infarction.
ROENTGENOLOGIC DIAGNOSIS OF CARCINOMA OF THE TAIL OF THE PANCREAS
Authors: THOMAS SCHOLZ
Journal: JAMA (1923)

The clinical picture in cases of carcinoma of the tail of the pancreas is so ill defined that a correct clinical diagnosis is made rarely, if ever. Any contribution tending to aid in the diagnosis of this type of cases, therefore, should be welcome.  The two cases of carcinoma of the tail of the pancreas here reported present interesting features clinically as well as roentgenologically. Both cases have been observed for a long period of time, and both came to operation. It will be seen that in the first case the roentgen-ray findings have been misinterpreted, while in the second case, as a result of our experience gained in the first case, the possibility of carcinoma of the tail of the pancreas was considered roentgenologically.  The roentgen-ray findings in both instances were so characteristic of gastric malignancy that a definite diagnosis of carcinoma of the stomach appeared justified. The clinical
Unbalanced Translocation t(5;17) Resulting In a TP53 Loss As Recurrent Aberration In Myelodysplastic Syndrome With Complex Karyotype
Authors: Gudrun Göhring, Beate Vajen, Philipp A Greif, Kathrin Thomay, Doris Steinemann, Sebastian Vosberg, Alexander Graf, Stefan Krebs, Helmut Blum, Stefan K. Bohlander, Brigitte Schlegelberger
Journal: Blood (2013)
Incidence and Type Distribution of Capsulated H. influenzae Strains
Authors: B. Dawson, K. Zinnemann
Journal: BMJ (1952)

DIABETES MELLITUS IN SURGICAL PATIENTS BRioushould be given in small doses (8 to 20 units) every four hours on the basis of urine examinations.It may be necessary to give such patients 20 g. of glucose by intravenous injection with the pre-operative dose of insulin, and fluid feeds containing 20 g. of carbohydrate every four hours for the first day after the operation.
Diseases of the Salivary Glands: Pathology— Diagnosis—Treatment—Facia Nerve Surgery
Authors: Fred Harbert
Journal: JAMA (1987)

In this work, pathological and clinical entities are described under numerous headings, with emphasis on the former. The majority of the more than 600 illustrations are black-and-white histological sections. Modification of treatment based on histological variations in specific disease entities is stressed. Statements in the text are immediately and profusely documented by names and dates in addition to standard references between sections. Some readers may find this diverting. Descriptions are succinct and often colorful; eg, the facial nerve is "meat in a parotid sandwich," or "in a groove formed by the gland doubling on itself." Basic function is fully described and related to pathological changes. Saliva, secreted in acini, has ingredients and concentrations similar to those of blood serum, including infectious agents such as hepatitis B virus without disease of the gland. This may be because IgA, secreted by plasma cells in the parotid, is 100 times higher than in
Congenital Communication of a Coronary Artery with a Cardiac Chamber or the Pulmonary Trunk ("Coronary Artery Fistula")
Authors: HENRY N. NEUFELD, RICHARD G. LESTER, PAUL ADAMS, RAY C. ANDERSON, C. WALTON LILLEHEI, JESSE E. EDWARDS
Journal: Circulation (1961)

Anatomic, clinical, hemodynamic, and roentgenographic findings in six patients with congenital communication of a coronary artery with a cardiac chamber or the pulmonary trunk are presented. The literature is reviewed. A coronary artery may communicate anomalously, with any of the cardiac chambers, more commonly with those on the right side. In the six cases presented, the right coronary artery communicated with the right atrium in one case and with the right ventricle in another. The left coronary artery communicated with the right atrium and right ventricle in one case each, and with the pulmonary trunk in two cases. The most striking feature observed clinically was a continuous murmur. If a continous murmur is localized in an area atypical for patent ductus arteriosus, the diagnosis should be suspected. Conventional roentgenographic and electrocardiographic studies yielded no specific diagnostic features. The results of cardiac catheterization may reveal a left-to-right shunt, but they are diagnostically useful only when correlated with clinical findings. The only precise method of demonstrating the abnormality is by means of selective aortography performed by injecting medium into the very origin of the aorta. Cure is possible by surgical interruption of the fistulous tract.
DISSENT ON QUESTION OF THE MONTH
Authors: NORMAN O. ROTHERMICH
Journal: Annals of Internal Medicine (1969)

Letters and Comments1 June 1969DISSENT ON QUESTION OF THE MONTHNORMAN O. ROTHERMICH, M.D., F.A.C.P.NORMAN O. ROTHERMICH, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-70-6-1280_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editor: I take exception to the "Question of the Month" (Rheumatology), No. 92 which appeared in the December issue of the ANNALS.The patient is a 40-year-old white man undergoing severe stress (myocardial infarction), who after 3 days develops a bursitis followed in 2 days by evidence of synovitis. I am sure most rheumatologists, given such a sequence of events, would first think of gout. The hemarthrosis that is reported to be the correct answer must be an extremely rare complication of anticoagulant therapy and should be considered quite low in the order of probabilities for correct diagnosis.... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: The Columbus Medical Center Columbus Ohio 43215 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 June 1969Volume 70, Issue 6Page: 1280-1280KeywordsAnticoagulant therapyGoutHemarthrosisMyocardial infarctionRheumatology ePublished: 1 December 2008 Issue Published: 1 June 1969 PDF downloadLoading ...
New Method for Coronary Arteriography
Authors: Aydin M. Bilgutay
Journal: JAMA (1962)

Coronary arteriography under acetylcholine asystole is a valuable diagnostic procedure provided reliable means are available for restoring the heartbeat. In the procedure herein described, a catheter is selectively positioned in the ascending aorta, opposite the origins of the coronary arteries, as usual. In addition, a conductive catheter is inserted into the right ventricle via a peripheral vein and connected to a pacemaker. The heart is arrested with acetylcholine, the film for the arteriogram is exposed, and the heart is then immediately restarted at the desired moment by turning on the pace-maker. Clinical application has shown that this procedure is feasible.
Comparison of a hydrocolloid dressing and paraffin gauze in the treatment of venous ulcers
Authors: S.E. HANDFIELD-JONES, C.E.H. GRATTAN, ROSEMARY A. SIMPSON, C.T.C. KENNEDY
Journal: British Journal of Dermatology (1988)

In-patients with venous leg ulcers showed increased healing rates with a hydrocolloid dressing (Granuflex), as compared with a traditional paraffin gauze dressing (Jelonet), in a randomized sequential crossover trial, although the difference was not statistically significant. Bacteriological studies showed that the hydrocolloid dressing favoured growth of both aerobes and anaerobes in significantly greater numbers compared with paraffin gauze. Heavy bacterial colonization had no effect on the healing rates of the ulcers. Granuflex is said to produce an anaerobic environment--survival of Pseudomonas aeruginosa, a strict aerobe, under Granuflex dressings, makes this seem unlikely.
Treatment of Acute Lymphoblastic Leukemia -- 30 Years' Experience at St. Jude Children's Research Hospital
Authors: Gaston K. Rivera, Donald Pinkel, Joseph V. Simone, Michael L. Hancock, William M. Crist
Journal: New England Journal of Medicine (1993)

Therapy for childhood lymphoblastic leukemia has evolved during the past three decades, but key questions about what are the least toxic, most effective forms of treatment remain unanswered because of the lack of comprehensive follow-up information.To assess long-term outcome in the series of clinical trials conducted at St. Jude Hospital, we compared the results of treatment typical of four eras: exploratory combination chemotherapy (era 1, 1962 to 1966; 91 patients), regimens for the control of meningeal leukemia (era 2, 1967 to 1979; 825 patients), limited intensification of therapy (era 3, 1979 to 1983; 428 patients), and extended intensification of therapy (era 4, 1984 to 1988; 358 patients). ("Intensification" refers to strategies of systemic chemotherapy that are more aggressive than conventional ones.) The major end points were survival and event-free survival; we also calculated the relative risk of treatment failure and the rate of relapse or death after treatment ended (post-treatment failure rate).The probability of event-free survival improved significantly in each successive era (P < 0.001 by the log-rank test), reaching 71 percent in era 4. There was a decrease of approximately 50 percent in the risk of treatment failure from one era to the next in each subgroup of patients defined according to different combinations of the leukocyte count, race, age, and sex. Leukemia appeared to be eradicated in patients who remained in complete remission for three years or more after treatment in era 4. The incidence of death due to nonleukemic causes remained 4 to 6 percent despite the trend toward more intensive treatment. An estimated 765 patients (45 percent) are long-term survivors; most of them (80 percent) have no health problems related to leukemia or its treatment.The development and successful application of preventive therapy for meningeal leukemia, followed by the intensification of systemic chemotherapy, has progressively improved the rate of cure of childhood lymphoblastic leukemia, with relatively few adverse sequelae.
The Thoc1 Ribonucleoprotein and Prostate Cancer Progression
Authors: M. Chinnam, Y. Wang, X. Zhang, D. L. Gold, T. Khoury, A. Y. Nikitin, B. A. Foster, Y. Li, W. Bshara, C. D. Morrison, R. D. Payne Ondracek, J. L. Mohler, D. W. Goodrich
Journal: JNCI Journal of the National Cancer Institute (2014)

The majority of newly diagnosed prostate cancers will remain indolent, but distinguishing between aggressive and indolent disease is imprecise. This has led to the important clinical problem of overtreatment. THOC1 encodes a nuclear ribonucleoprotein whose expression is higher in some cancers than in normal tissue. The hypothesis that THOC1 may be a functionally relevant biomarker that can improve the identification of aggressive prostate cancer has not been tested. THOC1 protein immunostaining was evaluated in a retrospective collection of more than 700 human prostate cancer specimens and the results associated with clinical variables and outcome. Thoc1 was conditionally deleted in an autochthonous mouse model (n = 22 or 23 per genotype) to test whether it is required for prostate cancer progression. All statistical tests were two-sided. THOC1 protein immunostaining increases with higher Gleason score and more advanced Tumor/Node/Metastasis stage. Time to biochemical recurrence is statistically significantly shorter for cancers with high THOC1 protein (log-rank P = .002, and it remains statistically significantly associated with biochemical recurrence after adjusting for Gleason score, clinical stage, and prostate-specific antigen levels (hazard ratio = 1.61, 95% confidence interval = 1.03 to 2.51, P = .04). Thoc1 deletion prevents prostate cancer progression in mice, but has little effect on normal tissue. Prostate cancer cells deprived of Thoc1 show gene expression defects that compromise cell growth. Thoc1 is required to support the unique gene expression requirements of aggressive prostate cancer in mice. In humans, high THOC1 protein immunostaining associates with prostate cancer aggressiveness and recurrence. Thus, THOC1 protein is a functionally relevant molecular marker that may improve the identification of aggressive prostate cancers, potentially reducing overtreatment.
n-Butyrate induces plasminogen activator inhibitor type 1 messenger RNA in cultured Hep G2 cells
Authors: T Smith
Journal: Hepatology (1996)

n-Butyrate, a short-chain aliphatic carboxylic acid with pleiotropic actions, is present at high concentrations in the portal circulation and thus may play an important role in the regulation of specific gene expression in the mammalian liver. We report here that n-butyrate can increase substantially the level of plasminogen activator inhibitor type 1 (PAI-1) messenger RNA (mRNA) in Hep G2 cells, up to eightfold above control cultures. Maximal effects occurred at a concentration of 3 mmol/L n-butyrate and with a treatment period of 8 to 12 hours. Increases in PAI-1 mRNA were accompanied by modest increases (twofold) in the encoded protein as assessed by specific enzyme-linked immunosorbent assay and by [35S]methionine incorporation into immunoprecipitable PAI-1 in the culture medium. Nuclear run-on studies showed that the rate of transcription of the PAI-1 gene did not appear altered by treatment with 3 mmol/L n-butyrate for 6 hours. The increases in steady-state PAI-1 mRNA caused by exposure to n-butyrate can be blocked by cycloheximide. Enhanced stability of mature PAI-1 transcript could not be demonstrated in Hep G2 cells treated with the carboxylic acid. We have reported previously that n-butyrate can reduce the level of beta-galactoside alpha 2,6-sialyltransferase expression in Hep G2 cells. That effect was attenuated with inhibitors of protein and RNA synthesis and was mediated at the post-transcriptional level. Thus, n-butyrate can influence the expression of multiple genes in this hepatoblastoma cell through its actions on events that appear to be posttranscriptional. These observations may be relevant to the normal physiology of the mammalian liver because of the high concentrations of n-butyrate and related compounds to which the organ is ordinarily exposed.
New Method for Nonfluoroscopic Endocardial Mapping in Humans
Authors: Joep L. R. M. Smeets, Shlomo A. Ben-Haim, Luz-Maria Rodriguez, Carl Timmermans, Hein J. J. Wellens
Journal: Circulation (1998)

Accurate mapping of the site of origin and activation sequence of a cardiac arrhythmia is essential for a successful catheter ablation procedure. To achieve this, precise and reproducible catheter manipulation is mandatory. The aim of this study was (1) to assess the accuracy of a new nonfluoroscopic mapping system in humans and (2) to report the first result of endocardial activation mapping with this system during sinus rhythm and several types of supraventricular and ventricular tachycardias.Fifteen patients were studied. Accuracy measurements were performed in 5 of them (patients 5, 6, 7, 8, and 14). The distances between two subsequent catheter positions in the inferior caval vein as determined by the nonfluoroscopic mapping system were compared with measurements made with calipers by four independent investigators using identification marks on the catheter shaft. The difference between these two methods was 0.95+/-0.8 mm. In 15 patients, activation of the right atrium and/or the right or left ventricle was recorded during sinus rhythm. Three-dimensional activation maps were constructed in patients with atrial and ventricular tachycardias and Wolff-Parkinson-White syndrome.With this new nonfluoroscopic mapping technique, accurate positioning of the catheter tip is possible. A three-dimensional activation map can be reconstructed during sinus rhythm and during supraventricular and ventricular tachycardias of different compartments of the heart.
Digoxin levels should be kept to a minimum in men with heart failure
Authors: S. Gottlieb
Journal: BMJ (2003)

The heart drug digoxin seems to increase survival in men with heart failure but only when the blood level of the drug is kept to a minimum. With higher levels, the drug provides no benefit and may even be harmful ( JAMA 2003;289:871-8).

The new findings are based on a post hoc analysis of data from the Digitalis Investigation Group (DIG) trial, conducted from August 1991 to December 1995 and published in 1997. The DIG trial seemed to show that digoxin did not increase survival but did help to keep patients out of hospital …