tbuckley/cabot-search huggingface dataset:
Glucose Derangements in Very Young Children With Cystic Fibrosis and Pancreatic Insufficiency
Authors: Enza Mozzillo, Valeria Raia, Valentina Fattorusso, Mariateresa Falco, Angela Sepe, Fabiola De Gregorio, Rosa Nugnes, Giuliana Valerio, Adriana Franzese
Journal: Diabetes Care (2012)

Cystic fibrosis–related diabetes (CFRD) is considered the most common comorbidity in patients affected by cystic fibrosis (CF), with a prevalence increasing with age (1). Recently, more attention has been turned to other less severe glucose metabolism derangements (GMD), since prediabetes may be related to increased morbidity (1), and early treatment may improve the clinical course in patients with CF (2). According to recent guidelines released by the Cystic Fibrosis Foundation, the American Diabetes Association, and the Pediatric Endocrine Society, the oral glucose tolerance test (OGTT) is recommended yearly in patients with CF over 10 years of age (3). Some authors recommend annual OGTT after the age of 6 years in CF patients with pancreatic insufficiency (4).

In …
Book Review Cutaneous Medicine and Surgery: An integrated program in dermatology Edited by Kenneth A. Arndt, June K. Robinson, Philip E. Leboit, and Bruce U. Wintroub. 1899 pp. in two volumes, illustrated. Philadelphia, W.B. Saunders, 1996. $250. 0-7216-4852-5
Authors: Mark V. Dahl
Journal: New England Journal of Medicine (1996)
P1-06-24: Nuclear Localization of Stat5a Predicts Response to Antiestrogen Therapy and Prognosis of Clinical Breast Cancer Outcome.
Authors: AR Peck, AK Witkiewicz, C Liu, AC Klimowicz, GA Stringer, E Pequignot, B Freydin, N Yang, TH Tran, AL Rosenberg, JA Hooke, AJ Kovatich, CD Shriver, DL Rimm, AM Magliocco, T Hyslop, H Rui
Journal: Cancer Research (2011)

Abstract Nuclear-localized and tyrosine-phosphorylated Stat5 has been reported as a favorable prognostic marker and predictor of response to antiestrogen therapy in breast cancer. Phospho-Stat5 antibodies do not distinguish between phosphorylated Stat5a and the closely related Stat5b, but Stat5a is considered more critical for normal mammary development than Stat5b. The purpose of this study was to determine whether levels of nuclear-localized Stat5a protein (Nuc-Stat5a) were prognostic of clinical outcome or predictive of antiestrogen response. Stat5a was detected by traditional diaminobenzidine-chromogen immunohistochemistry (IHC) and pathologist scoring or by quantitative immunofluorescence in five archival cohorts of breast cancer. Levels of nuclear-localized Stat5a (Nuc-Stat5a) were evaluated by pathologist scoring of whole tissue sections detected by IHC or automated quantitative analysis (AQUA) of immunofluorescently-labeled tissue microarrays. Levels of Nuc-Stat5a were reduced in invasive breast cancer tissues and lymph node metastases compared to normal tissue and ductal carcinoma in situ when quantified by AQUA (Material I; n=180). Tissues from patients not treated with adjuvant therapy or treated with antiestrogen monotherapy were analyzed according to Nuc-Stat5a status for breast cancer-specific survival (CSS) and time to recurrence (TTR) using univariate and multivariate statistical models, adjusting for clinical features including tumor grade, size, lymph node and ER, PR and Her2 status. In two prognostic cohorts of node-negative breast cancer patients, low expression of Nuc-Stat5a, detected by standard IHC (Material II; n=223) or quantitative analysis (Material III; n=198), was prognostic of poor breast cancer outcome as measured by univariate and multivariate CSS (Material II/III) and TTR (Material II). CSS and TTR analysis of two independent materials of tumors from patients treated with antiestrogen monotherapy and analyzed by standard IHC (Material IV; n=73) or quantitative immunofluorescence (Material V; n=97) indicated that patients whose tumors expressed low levels of Nuc-Stat5a were at a greater than 4-fold risk of antiestrogen therapy failure when adjusted for hormone receptor status and clinical features (multivariate CSS: Material IV HR=4.3 (1.2,15.6), p=0.03; Material V HR=5.0 (1.87,13.06), p=0.001). In conclusion, loss of Nuc-Stat5a is a promising independent marker of poor breast cancer prognosis in node-negative, non-adjuvant treated breast cancer patients. Additionally, Nuc-Stat5a may be a useful clinical tool to predict tumor response to antiestrogen therapy. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-06-24.
Compound Cytotoxicity Profiling Using Quantitative High-Throughput Screening
Authors: Menghang Xia, Ruili Huang, Kristine L. Witt, Noel Southall, Jennifer Fostel, Ming-Hsuang Cho, Ajit Jadhav, Cynthia S. Smith, James Inglese, Christopher J. Portier, Raymond R. Tice, Christopher P. Austin
Journal: Environmental Health Perspectives (2007)

The propensity of compounds to produce adverse health effects in humans is generally evaluated using animal-based test methods. Such methods can be relatively expensive, low-throughput, and associated with pain suffered by the treated animals. In addition, differences in species biology may confound extrapolation to human health effects.The National Toxicology Program and the National Institutes of Health Chemical Genomics Center are collaborating to identify a battery of cell-based screens to prioritize compounds for further toxicologic evaluation.A collection of 1,408 compounds previously tested in one or more traditional toxicologic assays were profiled for cytotoxicity using quantitative high-throughput screening (qHTS) in 13 human and rodent cell types derived from six common targets of xenobiotic toxicity (liver, blood, kidney, nerve, lung, skin). Selected cytotoxicants were further tested to define response kinetics.qHTS of these compounds produced robust and reproducible results, which allowed cross-compound, cross-cell type, and cross-species comparisons. Some compounds were cytotoxic to all cell types at similar concentrations, whereas others exhibited species- or cell type-specific cytotoxicity. Closely related cell types and analogous cell types in human and rodent frequently showed different patterns of cytotoxicity. Some compounds inducing similar levels of cytotoxicity showed distinct time dependence in kinetic studies, consistent with known mechanisms of toxicity.The generation of high-quality cytotoxicity data on this large library of known compounds using qHTS demonstrates the potential of this methodology to profile a much broader array of assays and compounds, which, in aggregate, may be valuable for prioritizing compounds for further toxicologic evaluation, identifying compounds with particular mechanisms of action, and potentially predicting in vivo biological response.
Miscellaneous: A son is killed
Authors: M Colebrook
Journal: BMJ (1983)

understandably petrified young man with new confidence (see previous page).Close at hand on his desk were a stethoscope with new diaphragm attachment, a sphygmomanometer, and a micro- scope.The consultation-the constant central episode of medical practice-included a whole new technology undreamt of a century earlier.The relation and balance of power between physician and patient were subtly altered, but we have yet to learn much about the history of this change.The social history of the consultation, and the influence, for example, of white coats, diagnostic equipment, and laboratory data on the attitudes of-doctors and the expectations of patients, are fascinating and a scarcely explored territory in the history of medical practice.
THE IN VITRO INACTIVATION OF PITRESSIN BY NORMAL AND CIRRHOTIC HUMAN LIVER 1
Authors: George E. Miller, Charles E. Townsend, Mary Claire Jones
Journal: Journal of Clinical Investigation (1954)

A generally acceptable explanation of the mecha- nism responsible for the formation of ascites and peripheral edema in the patient with hepatic cir- rhosis has yet to be formulated.Reduction in se- rum oncotic pressure, portal hypertension, and distortion of sodium metabolism have each had their champions and their detractors.A prominent current controversy concerns the role of antidiu- retic hormone in the pathogenesis of this fluid retention.It has been demonstrated that hepatic tissue is capable of inactivating antidiuretic hormone both in vitro and in vivo (1, 2).The available evidence suggests that this is accomplished by the activity of an enzyme system whose maximal effectiveness is limited to a narrow range of temperature and pH (1-3).The presence of an antidiuretic material in the urine and serum of patients with fluid retention and cirrhosis (4-6) has suggested to several work- ers that an impairment of the hepatic inactivation of antidiuretic hormone may play an important role in producing the accumulation of ascites and peripheral edema in this disease.The frequent observation of oliguria and the reported delay in onset of diuresis following a water load (7-9) in such patients has been interpreted as additional evi- dence to support this point of view.Recently, all of these observations have been challenged.When the dog, rather than the rat was used for assay, Van Dyke, Ames, and Plough (10) were unable to confirm the presence of significant antidiuretic activity in the urine of cirrhotic pa- tients.Other workers (11, 12) have been un- able to demonstrate any delay in diuresis following a water load, any increased sensitivity to, or
The Revival of Didactic Instruction.
Authors: Frank Jones.
Journal: JAMA (1904)

Memphis, Tenn., July 25, 1904. <h3>To the Editor:</h3> —The didactic lecture hall, the recitation room, the clinical amphitheater, the hospital wards and the laboratories should all be utilized to the fullest extent in teaching modern medicine. I regret to note the sentiment prevailing in some of our great schools against didactic work. No student can read unless he first learns his alphabet. Nor can he solve a problem in mathematics unless he knows his figures. He can not parse a sentence in English or solve a problem until he has been thoroughly grounded in the rules governing each case. The didactic lecture is the alphabet, the unit one, the rules in teaching medicine. Let the didactic professor preach typhoid fever in the most forcible manner, then let the clinical professor teach typhoid fever in the hospital wards. I am a hearty champion of didactic work along with clinical. Medical schools
Androgen Therapy in Hereditary Angioneurotic Edema
Authors: Fred S. Rosen, K. Frank Austen
Journal: New England Journal of Medicine (1976)

Under normal conditions, an alpha globulin designated as C1̄ inhibitor (C1̄-INH) inhibits the activated first component of complement (C1̄). In hereditary angioneurotic edema, which is transmitted as classic Mendelian autosomal dominant, the serum of affected persons either contains a nonfunctional alpha globulin or lacks the inhibitor altogether. This deficiency was identified independently by Landerman et al.,1 who found the plasma of a patient unable to inhibit kallikrein generation of bradykinin, and by Donaldson and Evans,2 who reported on the inability of another patient's plasma to inhibit C1̄. Both observations were shown to be correct when Kagan and Becker3 demonstrated that . . .
Depressed immune function in patients with cirrhosis before emergence of hepatocellular carcinoma
Authors: Toshiji Saibara, Takashi Maeda, Masako Miyazaki, Saburo Onishi, Yasutake Ymamot
Journal: Hepatology (1993)

Hegpatocellular carcinomas 1 cm in diameter with high or low echogenicity can be detected on ultrasonography and confirmed on fine-needle biopsy, but it is still very difficult to detect small hepatocellular carcinomas with isoechogenicity. In this study, we assessed lymphokine-activated killer cell activity and interferon-γ production prospectively every 1 to 3 mo for 23 ± 4 mo (mean ± 1 S.D.) in 227 patients with cirrhosis. Transient depression of lymphokine-activated killer activity was detected in 43 patients (defective lymphokine-activated killer group), and hepatocellular carcinoma was detected in 24 cases before the end of the 18-mo follow-up. Twenty-one (87.5%) of the 24 hepatocellular carcinoma patients were included in the defective lymphokine-activated killer group. Defective lymphokine-activated killer activity was detected more than 6 mo before detection of a space occupying lesion in the liver or elevation of α-fetoprotein level above 400 ng/ml. Serum α-fetoprotein level was elevated above 400 ng/ml in only five cases in which hepatocellular carcinoma was detected as a space-occupying lesion. Our results indicate that sequential assessment of lymphokine-activated killer activity may be a predictor of hepatocellular carcinoma and that the depression of immune function in cirrhotic patients is a serious risk factor for hepatocellular carcinoma emergence. (HEPATOLOGY 1993;18:315–319).
Relation of Supraventricular Paroxysmal Tachycardia to Heart Disease and the Basal Metabolism Rate
Authors: R. W. KISSANE, RICHARD BROOKS, THOMAS E. CLARK
Journal: Circulation (1950)

The records of 9,950 private patients were reviewed to determine the incidence of supraventricular paroxysmal tachycardia. The relationship of the tachycardia to the various types of heart disease was determined. The incidence of tachycardia in normal persons and in patients with hyperthyroidism or hypothyroidism was also studied.
Manometric Evaluation of Sphincter of Oddi after Endoscopic Sphincterotomy, and in Patients with Previous Surgical Sphincterotomy
Authors: J. Ponce, T. Sala, V. Pertejo, R. Pina, J. Berenguer
Journal: Endoscopy (1983)

Pressures in the sphincter of Oddi and common bile duct were determined in eight patients with previous surgical sphincterotomy, and in 14 patients before and after endoscopic sphincterotomy. Motor activity in the sphincter of Oddi was seen during manometric examination in 6 out of 8 patients of the surgical group. These six patients had common bile duct stones after cholecystectomy. Endoscopic sphincterotomy equalized the choledochoduodenal gradient and reduced the sphincter pressure in all the patients except three. In two of them further extension of the length of the sphincterotomy permitted removal of the stones and substantial reduction of the motor activity of the sphincter of Oddi.
Time in Therapeutic Range (TTR) Value of Patients who use Warfarin and Factors which Influence TTR
Authors: Lale Dinç Asarcıklı, Taner Şen, Esra Gücük İpek, Habibe Kafes, Muhammet Cebeci, Murat Gül, Selçuk Kanat, Ahmet Temizhan
Journal: Journal of the American College of Cardiology (2013)
Neutrophil chemoattractants generated in two phases during reperfusion of ischemic myocardium in the rabbit. Evidence for a role for C5a and interleukin-8.
Authors: C L Ivey, F M Williams, P D Collins, P J Jose, T J Williams
Journal: Journal of Clinical Investigation (1995)

The neutrophil chemoattractants generated in a model of myocardial infarction in the anesthetized rabbit were investigated. Coronary artery occlusion was followed by reperfusion for periods from 5 min to 4.5 h. Extracts of myocardial tissue in normal and post-ischemic zones were tested for C5a and interleukin-8 (IL-8) using specific radioimmunoassays. In the post-ischemic zone, immunoreactive C5a was detected within 5 min and rose progressively to reach a plateau at 3-4.5 h. In contrast, immunoreactive IL-8 concentrations rose after a delay and were highest at the last time point tested, 4.5 h. Myeloperoxidase activity levels, an index of neutrophil accumulation, rose progressively as the concentrations of chemoattractants increased. Using cation exchange and reversed phase HPLC, immunoreactive C5a and IL-8 co-eluted with authentic standards. Fractions taken at the C5a and IL-8 peaks from reversed phase HPLC exhibited neutrophil aggregating activity which was neutralized by the respective antibody used in the radioimmunoassays. Depletion of circulating neutrophils virtually abolished immunoreactive IL-8 in the post-ischemic myocardial tissue. These observations suggest a sequential release of chemoattractants: the first, C5a is generated in interstitial fluid, followed by IL-8 generated by infiltrating neutrophils. Thus, over the time period studied, IL-8 generation would be expected to be indirectly dependent on C5a production.
Royal College of Physician's wishful lead in stroke
Authors: N. Dudley
Journal: BMJ (2010)

Many of Heath’s comments ring true for stroke, in which the benefits of treatment are exaggerated and wishful thinking often trumps the published evidence.1 A good example is the Royal College of Physicians’ press release that accompanied its 2010 stroke audit report.2

The statement, “There has also been a five-fold improvement in the number of stroke patients receiving thrombolysis over last year’s figures”2 is clearly wrong. …
Alcohol misuse, public health, and public policy
Authors: Soumen Sengupta, Lesley Hoyle
Journal: BMJ (2005)

<h3>Abstract</h3> The study investigated the effect of unintentional learning of semantically unrelated word pairs on event-related brain potentials. Two experiments were conducted, in whose acquisition phase participants listened to five pairs of semantically unrelated words, each pair being repeated twenty times. In the test phase of Experiment 1, these “old” pairs were presented mixed with “new” pairs containing other words. In the test phase of Experiment 2, a third condition was added in which the first word in a pair was one of the words presented during acquisition but the second word was new. In both experiments, the second word in new word pairs elicited an N400 and a late (550-1000 ms) frontal positivity. The amplitude of the N400 to new second words in Experiment 2 was significantly larger when the first word in the pair was an old (previously learnt) word, as compared with the condition in which both first and second words were new. The results indicate that, in addition to a repetition effect, unintentional learning of word pairs results in building new associations between previously unrelated words.
Elevations in T-helper-2-initiating cytokines (interleukin-33, interleukin-25 and thymic stromal lymphopoietin) in lesional skin from chronic spontaneous (‘idiopathic’) urticaria
Authors: A.B. Kay, P. Clark, M. Maurer, S. Ying
Journal: British Journal of Dermatology (2014)

The mechanism of wealing in chronic spontaneous urticaria (CSU) is largely unknown. We previously demonstrated increased expression of T-helper 2 [interleukin (IL)-4 and IL-5] cytokines in skin biopsies from CSU. This suggested that Th2-initiating cytokines [IL-33, IL-25 and thymic stromal lymphopoietin (TSLP)], released through innate immune mechanisms, may play a role in pathogenesis.To identify Th2-initiating cytokines in lesional and nonlesional skin from patients with CSU and to compare the results with a control group.Paired biopsies (one from a 4-8 h spontaneous weal and one from uninvolved skin) were taken from eight patients with CSU and nine control subjects, and studied by immunohistochemistry and confocal microscopy.There were increases in IL-4(+) and IL-5(+) cells in lesional skin vs. controls (P = 0·03 and P < 0·001, respectively) and marked elevations in the numbers of IL-33(+), IL-25(+) and TSLP(+) cells in the dermis of lesional skin vs. both nonlesional skin (P = 0·002, P = 0·01 and P = 0·04, respectively) and controls (P = 0·001, P < 0·001 and P = 0·005, respectively). There was also a correlation between the numbers of IL-33(+) and IL-25(+) cells (r = 0·808, P = 0·015). IL-33 localized to CD31(+) endothelial cells, CD90(+) fibroblasts, CD68(+) macrophages and tryptase(+) mast cells, whereas IL-25 was expressed by epithelial cells, mast cells and major basic protein-positive eosinophils. IL-33 and IL-25 were constitutively expressed in the epidermis of both controls and patients with CSU.Increased expression of Th2-initiating cytokines in lesional skin in CSU suggests that innate pathways might play a role in the mechanism of wealing. As Th2-initiating cytokines play a role in mast cell activation, inflammation and vascular leakage in CSU, these findings may also have therapeutic implications.
RESULTS OF VARIOUS OPERATIONS FOR PROLAPSE OF THE UTERUS
Authors: VIRGIL S. COUNSELLER
Journal: JAMA (1930)

Of the various operations for prolapse of the uterus, those most used probably are the Watkins-Wertheim, the Mayo vaginal hysterectomy, the Kocher fixation, the modified Gilliam, and various other types of intra-peritoneal shortening of the round ligaments combined with vaginal plastic operations. The technic of each has undergone various modifications and is described in detail in the literature. The value of any one of these procedures as a corrective operation is determined largely by the results obtained from its use, by the ability of the surgeon to execute the technic correctly and by its application to the properly selected case.  Masson 1 has stated that the choice of operation depends on several factors. Chiefly these are: the age of the patient, her marital state, the risk of an abdominal or vaginal operation, and the degree of prolapse with its accompanying symptoms. The practice of using an operation as a routine
Optimum imaging for small suspected hepatocellular carcinoma
Authors: M. Sherman
Journal: Gut (2010)

Hepatocellular carcinoma (HCC) has progressed within the last 10–15 years from being a cancer that was almost universally fatal to one that is potentially curable in the majority of cases. However, for this to happen it is essential that the HCC is found early. Patients at risk for HCC have to undergo regular surveillance with ultrasound. Lesions detected during surveillance have to be aggressively investigated and aggressively treated. If HCC can be diagnosed when the lesion is  90%.1 2 Treated patients remain at risk for the development of a second primary, but the treated HCC can be completely cured.

Ultrasound surveillance identifies many small lesions in the liver that may or may not be HCC. These include dysplastic nodules, cirrhotic nodules and haemangioma. Making the distinction between HCC and haemangioma is usually not difficult, but distinguishing between cirrhotic nodules, dysplastic nodules and HCC can be difficult. The tools available include contrast-enhanced radiological imaging, or biopsy. It is possible to diagnose HCC without biopsy. Indeed, if the typical radiological features are present, the diagnostic accuracy is almost 100%. The highly characteristic features are that in the arterial phase of a dynamic contrast-enhanced study the HCC shows hypervascularity—that is, it gives a brighter signal that the surrounding liver. In the portal venous phase of the study and in the delayed phase ∼3 min …
Measurement of bone density in osteoporosis
Authors: E M Tayler
Journal: BMJ (1995)

The molecular structures of 19-nor-11-deoxycorticosterone (III) and 21-hydroxypregna-4,11-diene-3,20-dione (IV) were determined by X-ray crystallographic analysis and the factors affecting the binding affinities for the mineralocorticoid receptor were examined with six aldosterone derivatives (I-VI) containing these two compounds. The most important factor was found to be the steric one; affinity increased with increasing flatness of the structure. The electronic factor may be a minor influence although a good relationship was found between the affinity and the 13C-NMR chemical shift of the C(5) atom. The factor playing no role in the binding is the hydrophobic one.