tbuckley/cabot-search huggingface dataset:
Cases of Jaundice due to Aneurysm of the Hepatic Artery and to Movable Kidney
Authors: W. H. White
Journal: BMJ (1892)

HEPATIC ARTERY. [ IMEDCl,BRJnURwAL .23 tnay, in an article on Colour Blindness in Denmark, pub- lished in Knapp's Archives of Ophthalrhology in 1881, says that he examined the eyes separately in,'217'cases, and' that the two were always alike.I do not recall any'later observations of this nature at the present moment.Fontenay mentions that Niemetscheck had reported four congenital monocular ecases, but stated that he himself regarded them as doubtful.My little patient belongs to a family in which the other members are quick sighted and endowed with acute hearing.They 'have not yet been tested for the presence of monocular colour defects.I 'Some years ago I drew attention2 to the importance of re--cognising the possibility of the colour perception not being alike in each eye.The following case was mentioned:-CASE ii.Dissimilar Defects in Colour Viswon in the Same Person.-Thepatient, a youth aged 21, bad, about twenty months before he was first seen, fallen from one of the large Liverpool docks and sustained serious in- juries-fracture of the fronital bone, of the inferior maxilla, of the riglht ifemur, and of the left wrist.He was stated also to have suffered from concussion of the brain, and quite recently had been the subject of " fits."At-the timie of his coming to me there was a large depression on the left side of the forehead.He mentioned vision as having become worse since the accident, but I have no note as to its condition when first seen.Later it is stated there was H. +5D. in each eye, and that corrected V. in the right was 2X, and in the left 20 Ophthalmoscopically there was nothing abnormal.The point of particular interest was the condition of his -colour vision.When about to test him he told me that he was less accurate with colours since his accident.He hesitated ratlher, and was slow in arranging Holm gren's wools, but he did so correctly, Each eye was then tested separately.With the right he sorted tlle wools as a red-blind :person would do, whilst with the left he did so more as a green-blind person but less distinctly so.Thus he appeared red blind with the right eye ana incompletely green blind with the left.Tested again with botl eyes open the correct sorting of the colours was repeated.It seenmed as ifthe faulty sense in one eye was counterbalanced by that which was good in the other.The tests were repeated several times, and left no doubt upon my mind as to their correctness.Unfortunately the patient disappeared shortly after, and I lhave not been able to trace him to see if liis condition has undergone clhange.
Randomized Controlled Trial of Reduced-Dose Bolus Fluorouracil Plus Leucovorin and Irinotecan or Infused Fluorouracil Plus Leucovorin and Oxaliplatin in Patients With Previously Untreated Metastatic Colorectal Cancer: A North American Intergroup Trial
Authors: Richard M. Goldberg, Daniel J. Sargent, Roscoe F. Morton, Charles S. Fuchs, Ramesh K. Ramanathan, Stephen K. Williamson, Brian P. Findlay, Henry C. Pitot, Steven Alberts
Journal: Journal of Clinical Oncology (2006)

Previously, we reported results of Intergroup N9741, which compared standard bolus fluorouracil (FU), leucovorin, plus irinotecan (IFL) with infused FU, leucovorin, plus oxaliplatin (FOLFOX4) and irinotecan plus oxaliplatin in patients with untreated metastatic colorectal cancer. High rates of grade > or = 3 toxicity on IFL (resulting in some deaths) led us to reduce the starting doses of both irinotecan and FU by 20% (rIFL). This article compares rIFL with FOLFOX4.The primary comparison was time to progression, with secondary end points of response rate (RR), overall survival, and toxicity.Three hundred five patients were randomly assigned. The North Central Cancer Treatment Group Data Safety Monitoring Committee interrupted enrollment at a planned interim analysis when outcomes crossed predetermined stopping boundaries. The results were significantly superior for FOLFOX4 compared with rIFL for time to progression (9.7 v 5.5 months, respectively; P < .0001), RR (48% v 32%, respectively; P = .006), and overall survival (19.0 v 16.3 months, respectively; P = .026). Toxicity profiles were not significantly different between regimens for nausea, vomiting, diarrhea, febrile neutropenia, dehydration, or 60-day all-cause mortality. Sensory neuropathy and neutropenia were significantly more common with FOLFOX4. Approximately 75% of patients in both arms received second-line therapy; 58% of rIFL patients received oxaliplatin-based second-line therapy, and 55% of FOLFOX4 patients received irinotecan-based regimens as second-line therapy.FOLFOX4 led to superior RR, time to progression, and overall survival compared with rIFL. The survival benefit for FOLFOX4 observed in the earlier stage of the study was preserved with equal use of either irinotecan or oxaliplatin as second-line therapy.
Prediction of Late Distant Recurrence After 5 Years of Endocrine Treatment: A Combined Analysis of Patients From the Austrian Breast and Colorectal Cancer Study Group 8 and Arimidex, Tamoxifen Alone or in Combination Randomized Trials Using the PAM50 Risk of Recurrence Score
Authors: Ivana Sestak, Jack Cuzick, Mitch Dowsett, Elena Lopez-Knowles, Martin Filipits, Peter Dubsky, John Wayne Cowens, Sean Ferree, Carl Schaper, Christian Fesl, Michael Gnant
Journal: Journal of Clinical Oncology (2014)

We have previously shown that the PAM50-based risk of recurrence (ROR) score is significantly correlated with distant recurrence in both the translational research cohort within the Arimidex, Tamoxifen Alone or in Combination (ATAC) trial (TransATAC) and Austrian Breast and Colorectal Cancer Study Group 8 (ABCSG 8) randomized trials. Here, we focus on the ROR score for predicting distant recurrence after 5 years of follow-up in a combined analysis of these two randomized trials.
Association Between Type 2 Diabetes and Exposure to Persistent Organic Pollutants
Authors: Riikka Airaksinen, Panu Rantakokko, Johan G. Eriksson, Paul Blomstedt, Eero Kajantie, Hannu Kiviranta
Journal: Diabetes Care (2011)

The prevalence of type 2 diabetes is increasing alarmingly in both developed and developing countries. Recently, exposure to persistent organic pollutants (POPs) has been associated with the prevalence of type 2 diabetes. The purpose of this cross-sectional study is to examine the association between type 2 diabetes and POP exposure in the Helsinki Birth Cohort Study.The cohort consists of 8,760 people born in Helsinki during 1934-1944, before the global POP emission peak. In 2003, a clinical examination was performed, including blood sampling for laboratory analyses of serum lipids and POPs. Complete data from the examination were available for 1,988 participants. The concentrations of each POP were categorized into four groups on the basis of percentile intervals, and logistic regression was performed to examine diabetes prevalence across the POP categories, adjusting for sex, age, waist circumference, and mean arterial pressure and using the lowest category as the reference group.Among the participants with the highest exposure to oxychlordane, trans-nonachlor, 1,1-dichloro-2,2-bis-(p-chlorophenyl)-ethylene (p,p'-DDE, and polychlorinated biphenyl 153, the risk of type 2 diabetes was 1.64-2.24 times higher than that among individuals with the lowest exposure (P(lin) = 0.003-0.050, where P(lin) is the P value for linear trend across POP categories). In the stratified analysis, the associations between type 2 diabetes and oxychlordane and trans-nonachlor remained significant and were strongest among the overweight participants. Exposure to 2,2',4,4'-tetrabromodiphenyl ether (BDE 47) and 2,2',4,4',5,5'-hexabromodiphenyl ether (BDE 153) was not associated with type 2 diabetes.This study confirms the association between type 2 diabetes and adult-only exposure to organochlorine pesticides in a general urban population.
A METHOD TO OBJECTIVELY DEMONSTRATE THINKING DIFFICULTIES
Authors: Max F. Hausmann
Journal: American Journal of Psychiatry (1933)

A method is reported which purports to demonstrate objectively "thinking difficulties"; i. e., discrepancies between the general intellectual endowment and certain specific performances. It is hoped that this method can eventually be used to help to differentiate between "depressive" and schizophrenic reactions at an early stage. After describing the procedure, the results are presented in Table 1. Two typical case histories of the group showing a discrepancy are presented. It is pointed out that in combination with another psychobiological method a fair idea can be obtained of the depth involved in the disturbance.
<i>p18Ink4c</i> and <i>p53</i> Act as Tumor Suppressors in <i>Cyclin D1</i>–Driven Primitive Neuroectodermal Tumor
Authors: Raya Saab, Carlos Rodriguez-Galindo, Kelly Matmati, Jerold E. Rehg, Shannon H. Baumer, Joseph D. Khoury, Catherine Billups, Geoffrey Neale, Kathleen J. Helton, Stephen X. Skapek
Journal: Cancer Research (2009)

Abstract The retinoblastoma (RB) tumor suppressor pathway is likely important in primitive neuroectodermal tumors (PNET) of the brain. In fact, 10% to 15% of children born with RB mutations develop brain PNETs, commonly in the pineal gland. Cyclin D1, which in association with cyclin-dependent kinase (Cdk) 4 and Cdk6 phosphorylates and inactivates the RB protein, is expressed in 40% of sporadic medulloblastoma, a PNET of the cerebellum. To understand tumorigenic events cooperating with RB pathway disruption in brain PNET, we generated a transgenic mouse where cyclin D1 was expressed in pineal cells. Cyclin D1 enhanced pinealocyte proliferation, causing pineal gland enlargement. However, proliferation ceased beyond 2 weeks of age with reversal of Cdk4-mediated Rb phosphorylation despite continued expression of the transgene, and the pineal cells showed heterochromatin foci suggestive of a senescent-like state. In the absence of the p53 tumor suppressor, cell proliferation continued, resulting in pineal PNET that limited mouse survival to ∼4 months. Interestingly, the Cdk inhibitor p18Ink4c was induced in the transgenic pineal glands independently of p53, and transgenic mice that lacked Ink4c developed invasive PNET, although at an older age than those lacking p53. Analogous to our mouse model, we found that children with heritable RB often had asymptomatic pineal gland enlargement that only rarely progressed to PNET. Our finding that the Cdk4 inhibitor p18Ink4c is a tumor suppressor in cyclin D1–driven PNET suggests that pharmacologic interventions to inhibit Cdk4 activity may be a useful chemoprevention or therapeutic strategy in cancer driven by primary RB pathway disruption. [Cancer Res 2009;69(2):440–8]
Insulin-Like Growth Factor-1 Exerts Ca <sup>2+</sup> -Dependent Positive Inotropic Effects in Failing Human Myocardium
Authors: Dirk von Lewinski, Kerstin Voß, Swen Hülsmann, Harald Kögler, Burkert Pieske
Journal: Circulation Research (2003)

Myocardial generation of insulin-like growth factor-1 (IGF-1) is altered in hypertrophy and heart failure, but there are no reports on acute functional effects of IGF-1 in human cardiac muscle. We examined inotropic responses and signal transduction mechanisms of IGF-1 in human myocardium. Experiments were performed in isolated trabeculae or cardiomyocytes from 46 end-stage failing hearts. The effect of IGF-1 (0.001 to 0.2 micromol/L) on isometric twitch force (37 degrees C, 1 Hz), intracellular Ca2+ transients (aequorin method), sarcoplasmic reticulum (SR) Ca2+ content (rapid cooling contractures), L-type Ca2+ current (whole-cell voltage clamp), and cAMP concentrations was assessed. In addition, the effects of blocking IGF-1 receptors, phosphoinositide 3-kinase (PI3-kinase), protein kinase C (PKC), or transsarcolemmal Ca2+ entry were tested. IGF-1 exerted concentration-dependent positive inotropic effects (twitch force increased to maximally 133+/-4% of baseline values at 0.1 micromol/L; P<0.05). The IGF-1 receptor antibody alphaIR3 or the PI3-kinase inhibitor wortmannin prevented the functional effects. The inotropic response was paralleled by increases in Ca2+ transients and SR Ca2+ content. IGF-1 (0.1 micromol/L) increased L-type Ca2+ current amplitude by 24+/-7% (P<0.05). Blockade of SR function did not affect the inotropic response to IGF-1. In contrast, L-type Ca2+ channel blockade with diltiazem partially prevented ( approximately 50%) the inotropic response to IGF-1. Inhibition of PKC (GF109203X), Na+-H+ exchange (HOE642), or reverse-mode Na+-Ca2+ exchange (KB-R7943) reduced the response to IGF-1 by approximately 60% to 70%. IGF-1 exerts Ca2+-dependent positive inotropic effects through activation of IGF-1 receptors and a PI3-kinase-dependent pathway in failing human myocardium. The increased [Ca2+]i with IGF-1 originates from both enhanced L-type Ca2+ currents and enhanced Na+-H+ exchange-dependent reverse-mode Na+-Ca2+ exchange. These nongenomic functional effects of IGF-1 may be of clinical relevance.
Primary Coronary Angioplasty vs Thrombolysis for the Management of Acute Myocardial Infarction in Elderly Patients
Authors: Alan K. Berger
Journal: JAMA (1999)

Despite evidence from randomized trials that, compared with early thrombolysis, primary percutaneous transluminal coronary angioplasty (PTCA) after acute myocardial infarction (AMI) reduces mortality in middle-aged adults, whether elderly patients with AMI are more likely to benefit from PTCA or early thrombolysis is not known.To determine survival after primary PTCA vs thrombolysis in elderly patients.The Cooperative Cardiovascular Project, a retrospective cohort study using data from medical charts and administrative files.Acute care hospitals in the United States.A total of 20683 Medicare beneficiaries, who arrived within 12 hours of the onset of symptoms, were admitted between January 1994 and February 1996 with a principal discharge diagnosis of AMI, and were eligible for reperfusion therapy.Thirty-day and 1-year survival.A total of 80356 eligible patients had an AMI at hospital arrival and met the inclusion criteria, of whom 23.2% received thrombolysis and 2.5% underwent primary PTCA within 6 hours of hospital arrival. Patients undergoing primary PTCA had lower 30-day (8.7% vs 11.9%, P=.001) and 1-year mortality (14.4% vs 17.6%, P=.001). After adjusting for baseline cardiac risk factors and admission and hospital characteristics, primary PTCA was associated with improved 30-day (hazard ratio [HR] of death, 0.74; 95% confidence interval [CI], 0.63-0.88) and 1-year (HR, 0.88; 95% CI, 0.73-0.94) survival. The benefits of primary coronary angioplasty persisted when stratified by hospitals' AMI volume and the presence of on-site angiography. In patients classified as ideal for reperfusion therapy, the mortality benefit of primary PTCA was not significant at 1-year follow-up (HR, 0.92; 95% CI, 0.78-1.08).In elderly patients who present with AMI, primary PTCA is associated with modestly lower short- and long-term mortality rates. In the subgroup of patients who were classified as ideal for reperfusion therapy, the observed benefit of primary PTCA was no longer significant.
A biomarker panel for acute graft-versus-host disease
Authors: Sophie Paczesny, Oleg I. Krijanovski, Thomas M. Braun, Sung W. Choi, Shawn G. Clouthier, Rork Kuick, David E. Misek, Kenneth R. Cooke, Carrie L. Kitko, Angela Weyand, Daniel Bickley, Dawn Jones, Joel Whitfield, Pavan Reddy, John E. Levine, Samir M. Hanash, James L. M. Ferrara
Journal: Blood (2008)
Human Aromatase: Gene Resequencing and Functional Genomics
Authors: Cynthia X. Ma, Araba A. Adjei, Oreste E. Salavaggione, Josefa Coronel, Linda Pelleymounter, Liewei Wang, Bruce W. Eckloff, Daniel Schaid, Eric D. Wieben, Alex A. Adjei, Richard M. Weinshilboum
Journal: Cancer Research (2005)

Abstract Aromatase [cytochrome P450 19 (CYP19)] is a critical enzyme for estrogen biosynthesis, and aromatase inhibitors are of increasing importance in the treatment of breast cancer. We set out to identify and characterize genetic polymorphisms in the aromatase gene, CYP19, as a step toward pharmacogenomic studies of aromatase inhibitors. Specifically, we “resequenced” all coding exons, all upstream untranslated exons plus their presumed core promoter regions, all exon-intron splice junctions, and a portion of the 3′-untranslated region of CYP19 using 240 DNA samples from four ethnic groups. Eighty-eight polymorphisms were identified, resulting in 44 haplotypes. Functional genomic studies were done with the four nonsynonymous coding single nucleotide polymorphisms (cSNP) that we observed, two of which were novel. Those cSNPs altered the following amino acids: Trp39Arg, Thr201Met, Arg264Cys, and Met364Thr. The Cys264, Thr364, and double variant Arg39Cys264 allozymes showed significant decreases in levels of activity and immunoreactive protein when compared with the wild-type (WT) enzyme after transient expression in COS-1 cells. A slight decrease in protein level was also observed for the Arg39 allozyme, whereas Met201 displayed no significant changes in either activity or protein level when compared with the WT enzyme. There was also a 4-fold increase in apparent Km value for Thr364 with androstenedione as substrate. Of the recombinant allozymes, only the double mutant (Arg39Cys264) displayed a significant change from the WT enzyme in inhibitor constant for the aromatase inhibitors exemestane and letrozole. These observations indicate that genetic variation in CYP19 might contribute to variation in the pathophysiology of estrogen-dependent disease.
The General Fertility Rate in Women With Psychotic Disorders
Authors: Louise Michele Howard, Channi Kumar, Morven Leese, Graham Thornicroft
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: This study determined the general fertility rate and age-specific fertility rates for women with psychotic disorders. METHOD: This historical matched-cohort study of patient records from a primary care database (the General Practice Research Database) was carried out for women of childbearing age (15–44 years) with psychotic disorders. RESULTS: The women with psychotic disorders (N=7,936) had a lower overall general fertility rate than the normal comparison subjects (N=23,023), although fertility was only significantly lower in the women aged 25 and above. This lower fertility rate was less marked in women with affective psychoses. There was no evidence that treatment with neuroleptics influenced the fertility rate in women with nonaffective psychoses. CONCLUSIONS: This study found markedly lower fertility rates in women with psychotic disorders than in matched normal comparison subjects, particularly in women with nonaffective disorders. Knowledge of fertility rates in women with psychotic disorders is fundamental for clinicians and researchers, since it has implications for family planning services, prevention of obstetric complications, child-care support, and hypotheses about the etiology of these disorders.
Neuropathy of Impaired Glucose Tolerance and Its Measurement
Authors: Andrew J.M. Boulton, Rayaz A. Malik
Journal: Diabetes Care (2009)

Impaired glucose tolerance (IGT) was originally shown in the prospective Whitehall Study (1) to carry an increased risk of large-vessel disease only. Whether or not IGT may also confer an increased risk for microvascular complications is not clear. Although microalbuminuria has been shown to be increased in those with IGT compared with control subjects (2), the incidence of retinopathy (IGT 6.7% vs. NGT 5.8%) (3) and moderate neuropathy (IGT 5.7% vs. NGT 2.8%) (4) have been found to be similar.

Nevertheless, it has been proposed that IGT may cause neuropathy (5). However, little is new in clinical medicine; over 40 years ago Ellenberg (see ref. 5) suggested that neuropathy may indeed occur in pre-diabetes, although it is interesting that the interpretation was that factors other than hyperglycemia may cause the neuropathy. The recent resurgence of interest in IGT neuropathy is based on four separate studies of patients with idiopathic small-fiber neuropathy, where the prevalence of IGT was found to be 34–35.6%, three times the prevalence in age-matched control subjects (5). We believe the interpretation of these studies has significant limitations because the populations studied were selected for the presence of idiopathic small-fiber neuropathy, rather than IGT. Furthermore, as pointed out by Dyck et al. (6) in a critical review, the association between IGT and neuropathy remains to be confirmed in an ongoing prospective study. Added to this the relationship between the metabolic syndrome, and its component constituents, to IGT neuropathy has come under scrutiny. …
Ethnic Differences in Out-of-Hospital Fatal Pulmonary Embolism
Authors: Yingying Tang, Barbara Sampson, Stephanie Pack, Krunal Shah, Sung Yon Um, Dawei Wang, Tao Wang, Mechthild Prinz
Journal: Circulation (2011)

In-hospital pulmonary embolism (PE) has been extensively studied in large populations; however, out-of-hospital fatal PE studies are rare. Here, we systematically evaluated a large number of decedents who suffered fatal PE outside of hospitals and were subsequently investigated by the New York City Office of Chief Medical Examiner.A total of 578 consecutive out-of-hospital fatal PE cases were analyzed. All underwent autopsy, toxicology, microbiology, and genetic testing. Incidence rates and baseline characteristics were analyzed. Race-adjusted incidence rates of out-of-hospital fatal PE (per 100 000 people per year) were as follows: blacks, 3.73 (95% confidence interval, 3.31 to 4.11); whites, 1.15 (95% confidence interval, 0.96 to 1.33); and Hispanics, 0.93 (95% confidence interval, 0.72 to 1.10). Overall, obesity (body mass index ≥30 kg/m(2)) was 2.5- to 3-fold higher in fatal PE cases than in the New York City population as a whole. Carrier frequencies for prothrombin G20210A in fatal PE were 2- to 10-fold higher than reported frequencies in ethnically matched controls. Cumulative distribution curves showed that compared with whites, blacks and Hispanics died at significantly younger ages (P<0.001). Univariate and multiple linear regression analyses showed that in addition to nonwhite ethnicity, heterozygous carriers for factor V Leiden (P=0.001) and obesity (P=0.002) are significantly associated with younger age at death.There are unique epidemiological differences in out-of-hospital fatal PE between ethnic groups in New York City.