tbuckley/cabot-search huggingface dataset:
Associations Between Cerebral Small-Vessel Disease and Alzheimer Disease Pathology as Measured by Cerebrospinal Fluid Biomarkers
Authors: Maartje I. Kester, Jeroen D. C. Goos, Charlotte E. Teunissen, Marije R. Benedictus, Femke H. Bouwman, Mike P. Wattjes, Frederik Barkhof, Philip Scheltens, Wiesje M. van der Flier
Journal: JAMA Neurology (2014)

It remains unclear if and how associations between cerebral small-vessel disease and Alzheimer disease (AD) pathology lead to cognitive decline and dementia.To determine associations between small-vessel disease and AD pathology.Cross-sectional study from January 2002 to December 2012 using the memory clinic-based Amsterdam Dementia Cohort. The study included 914 consecutive patients with available cerebrospinal fluid (CSF) and magnetic resonance imaging; 547 were patients diagnosed as having AD (54% female, mean [SD], 67 [8]; Mini-Mental State Examination score, mean [SD], 21 [5]), 30 were patients diagnosed as having vascular dementia (37% female, mean [SD], 76 [9]; Mini-Mental State Examination score, mean [SD], 24 [4]), and 337 were control participants with subjective memory complaints (42% female, mean [SD], 59 [59]; Mini-Mental State Examination score, mean [SD], 28 [2]). Linear regressions were performed with CSF biomarkers (log transformed) as dependent variables and magnetic resonance imaging measures (dichotomized) as independent, adjusted for sex, age, mediotemporal lobe atrophy, and diagnosis. An interaction term for diagnosis by magnetic resonance imaging measures was used for estimates per diagnostic group.We examined the associations of magnetic resonance imaging white matter hyperintensities (WMH), lacunes, microbleeds with CSF β-amyloid 42 (Aβ42), total tau, and tau phosphorylated at threonine 181 (P-tau181) as well as for a subset of apolipoprotein E (APOE) ε4 carriers and noncarriers.Microbleed presence was associated with lower CSF Aβ42 in AD and vascular dementia (standardized beta = -0.09, P = .003; standardized beta = -0.30, P = .01), and higher CSF tau in controls (standardized beta = 0.10, P = .03). There were no effects for P-tau181. The presence of WMH was associated with lower Aβ42 in control participants and patients with vascular dementia (standardized beta = -0.18, P = .002; standardized beta = -0.32, P = .02) but not in patients with AD. There were no effects for tau or P-tau181. The presence of lacunes was associated with higher Aβ42 in vascular dementia (standardized beta = 0.17, P = .07) and lower tau in AD (standardized beta = -0.07, P = .05) but there were no effects for Aβ42 or P-tau181. Stratification for apolipoprotein E genotype revealed that these effects were mostly attributable to ε4 carriers.Deposition of amyloid appears aggravated in patients with cerebral small-vessel disease, especially in apolipoprotein E ε4 carriers, providing evidence for pathophysiological synergy between these 3 biological factors.
The Wild Goose Chase and the Elephant's Relevance
Authors: Jerome P. Kassirer
Journal: JAMA (1986)

Interpretation and incorporation of new information into our clinical practices is a critical task, particularly as the torrent of published data accelerates. In this issue ofThe Journal, a new population-based study discloses that the frequency of serious outcomes in patients with asymptomatic microscopic hematuria is small and that it increases modestly with age.<sup>1</sup>Based on these data, Mohr et al conclude that complete urologic investigation of all patients with asymptomatic hematuria is not warranted, and they propose that the prevalence of serious disease, as signaled by the patient's age and the persistence of hematuria, might be a useful guide in choosing whether to test further. For more than 25 years, I have assiduously studied patients with microscopic hematuria as defined in this study. I search several urine sediments diligently for red blood cell casts and, not finding them, proceed to carry out an intravenous urogram. I ask the
Methods to identify increased risk of coronary disease in the general population: Authors' reply
Authors: S. Wilson
Journal: BMJ (2003)

Editor—Assmann et al have misunderstood the pragmatic question our study answered. In the United Kingdom treatment decisions for the primary prevention of cardiovascular disease are based on the Framingham 10 year coronary risk equation.1 Measuring the cholesterol of the entire population is not currently recommended.1 Given that the NHS has a finite budget we asked how general practitioners can target cholesterol measurement, and hence accurate risk assessment, to those people most likely to benefit from drug treatment to reduce their chance of a stroke or heart attack.

We chose to combine the results of our analyses for men and women because, despite sex differences in risk, the optimum age cut-off point to maximise both sensitivity and specificity is similar for both sexes. Our strategy of screening everyone over the age of 50 identified 91% of men and 98% of women at 15% or more 10 year coronary risk.

Finally, Assmann et al are concerned about people under 50 being neglected because they are not offered a cholesterol test. Although a clinician may not measure cholesterol routinely, this does not imply that they ignore other important risk factors, such as smoking, obesity, and raised blood pressure.

Our study has shown that routine cholesterol measurement, and hence accurate risk assessment, in everyone aged 50 and over is a simple and efficient method of identifying people at high risk of coronary disease in the general population.
Pneumocystis carinii pneumonia as a complication of methotrexate treatment of asthma.
Authors: L M Kuitert, A C Harrison
Journal: Thorax (1991)

A 32 year old man with chronic severe asthma, requiring maintenance oral corticosteroids, was started on a weekly dose of methotrexate. Eleven weeks later he developed Pneumocystis carinii pneumonia. In the two years following treatment there has been no recurrence while oral corticosteroid treatment has been continued. Pneumocystis pneumonia should be considered in asthmatic patients taking methotrexate who present with fever, pulmonary infiltrates, and hypoxia.
Bacteriuria, Weighted Algorithmic Assessment Criteria, and the Consumer
Authors: RICHARD B. FREEMAN
Journal: Annals of Internal Medicine (1977)

Editorials1 May 1977Bacteriuria, Weighted Algorithmic Assessment Criteria, and the ConsumerRICHARD B. FREEMAN, M.D., F.A.C.P.RICHARD B. FREEMAN, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-86-5-647 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe traditional method of determining the outcome of treatment of urinary tract infections is to obtain follow-up urine cultures. In simple terms, negative cultures mean successful outcomes and positive cultures connote failure. A poor method of assessing outcome is to rely on the presence or absence of symptoms (1-5). The latter premise is epitomized by the term "asymptomatic bacteriuria," the title of scores of publications over the past two decades. In this issue, Rubenstein, Mates, and Sidel (p. 617) report the results of process and outcome of care of patients with urinary tract infections from a study conducted in two...References1. KASS E: Asymptomatic infections of the urinary tract. Trans Assoc Am Physicians 69:56-54, 1956 MedlineGoogle Scholar2. TURCKBROWDERLINDEMEYER MAR: Failure of prolonged treatment of chronic urinary-tract infections with antibiotics. N Engl J Med 267:999-1005, 1962 CrossrefMedlineGoogle Scholar3. MCCABEJACKSON WG: Treatment of pyelonephritis: bacterial drug and host factors in success or failure among 252 patients. N Engl J Med 272:1037-1044, 1965 CrossrefGoogle Scholar4. BRUMFITTREEVES WD: Recent developments in the treatment of urinary tract infection. J Infect Dis 120:61-81, 1969 CrossrefGoogle Scholar5. FREEMANSMITHRICHARDSON RWJ: Long-term therapy for chronic bacteriuria in men. U.S. Public Health Service Cooperative Study. Ann Intern Med 83:133-147, 1975 LinkGoogle Scholar6. : Fraud and Abuse Among Practitioners Participating in The Medicaid Programs. Washington, D.C., U.S. Government Printing Office, 1976 Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1977Volume 86, Issue 5Page: 647-648KeywordsPatientsUrine Issue Published: 1 May 1977 PDF DownloadLoading ...
Abstract 4464: C-erbB3 protein modifications are secondary to severe cell membrane alterations induced by Irvalec treatment in CHO cells
Authors: Tímea Váradi, José Manuel Molina Guijarro, György Vereb, Carlos M. Galmarini, János Szöllõsi, Peter Nagy
Journal: Cancer Research (2010)

Abstract Irvalec® is a marine-derived antitumor agent that is currently undergoing phase II clinical trials. The compound induces a necrotic cell death associated with the appearance of membrane blebs and severe cell swelling reflecting a serious membrane damage caused by the drug. Indirect evidence has also suggested a possible role of ErbB proteins, in particular ErbB3, and lipid rafts in conferring sensitivity to Irvalec treatment. In order to assess the role of ErbB protein expression in the mechanism of action of Irvalec, and to measure the effect of drug treatment on the clustering properties of these proteins, we generated CHO cell lines stably transfected with ErbB2 (CHO-ErbB2) or with ErbB2 and ErbB3 (CHO-ErbB2-3). The IC50 values of the three cell lines for Irvalec did not differ significantly from each other. On the other hand treatment with Irvalec induced a significant increase in the binding of a conformational sensitive antibody to ErbB3 (ErbB3.105.5) without modifying the binding of other ErbB3 antibodies or antibodies against ErbB2. In addition, Irvalec treatment decreased the homoassociation of ErbB2 and ErbB3 measured by flow cytometric FRET. A431 cells transfected with GPI-anchored GFP or ErbB3-citrine showed significant Irvalec-induced patching of the GPI-anchor and ErbB3, whereas the distribution of ErbB1 and ErbB2 were not affected in cells transfected with ErbB1-GFP or ErbB2-mYFP. In conclusion, our data do not support a role for ErbB proteins in determining sensitivity to Irvalec, but show that these receptors are indirectly affected by exposing cells to the compound. These alterations should be ascribed to cell membrane modifications induced by Irvalec treatment Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4464.
Organisations challenge basis for recommending HPV vaccine for boys
Authors: J. Lenzer
Journal: BMJ (2011)

<h3>Background</h3> <i>GSTM1</i> encodes glutathione S-transferase <i>μ</i>-1 (GSTM1), which belongs to a superfamily of phase 2 antioxidant enzymes. The highly prevalent <i>GSTM1</i> deletion variant is associated with kidney disease progression in human cohorts: the African American Study of Kidney Disease and Hypertension and the Atherosclerosis Risk in Communities (ARIC) Study. <h3>Methods</h3> We generated a <i>Gstm1</i> knockout mouse line to study its role in a CKD model (involving subtotal nephrectomy) and a hypertension model (induced by angiotensin II). We examined the effect of intake of cruciferous vegetables and <i>GSTM1</i> genotypes on kidney disease in mice as well as in human ARIC study participants. We also examined the importance of superoxide in the mediating pathways and of hematopoietic <i>GSTM1</i> on renal inflammation. <h3>Results</h3> <i>Gstm1</i> knockout mice displayed increased oxidative stress, kidney injury, and inflammation in both models. The central mechanism for kidney injury is likely mediated by oxidative stress, because treatment with Tempol, an superoxide dismutase mimetic, rescued kidney injury in knockout mice without lowering BP. Bone marrow crosstransplantation revealed that <i>Gstm1</i> deletion in the parenchyma, and not in bone marrow–derived cells, drives renal inflammation. Furthermore, supplementation with cruciferous broccoli powder rich in the precursor to antioxidant-activating sulforaphane significantly ameliorated kidney injury in <i>Gstm1</i> knockout, but not wild-type mice. Similarly, among humans (ARIC study participants), high consumption of cruciferous vegetables was associated with fewer kidney failure events compared with low consumption, but this association was observed primarily in participants homozygous for the <i>GSTM1</i> deletion variant. <h3>Conclusions</h3> Our data support a role for the GSTM1 enzyme in the modulation of oxidative stress, inflammation, and protective metabolites in CKD.
QUANTITATIVE INVESTIGATIONS OF IDIOTYPIC ANTIBODIES
Authors: John E. Hopper, A. Bruce MacDonald, Alfred Nisonoff
Journal: The Journal of Experimental Medicine (1970)

Idiotypic antibodies were investigated quantitatively by a method of indirect precipitation, which utilizes labeled F(ab')(2) fragments of specifically purified antibenzoate antibody from the donor, anti-antibody, and an antiglobulin reagent. The contribution of allotypic and hidden determinants to these reactions was excluded. Greater fractions of an idiotypic antibody population are precipitated by this method, as compared to direct precipitation, and in two instances large proportions of idiotypic antibodies were detected in populations which failed to form precipitates by double diffusion in agar gel. The greater sensitivity of the indirect method was attributed to its capacity to detect molecules bearing a small number of antigenic determinants. Extensive studies of cross-reactions, carried out by an inhibition technique, failed to reveal any strong reactions of anti-idiotypic antibodies with heterologous antibenzoate antibody preparations, heterologous sera, or IgG, although a few weak cross-reactions were noted. One definite cross-reaction was observed by a direct binding measurement with heterologous antiserum. Antisera prepared in more than one recipient against a single donor preparation reacted with identical or overlapping subpopulations of the donor molecules. Instances in which two recipient antisera reacted with different proportions of the molecules of a single donor provided evidence for the existence of more than one idiotypic antibody population in the antibenzoate antibody of an individual rabbit.
Physiology of Human Conception
Authors: John Rock
Journal: New England Journal of Medicine (1949)

ALTHOUGH simple parthenogenesis is not at all uncommon in invertebrates — for instance, in ants and bees — it does not, as far as is known, occur in human beings, who must produce eggs and sperm and then effect their conjugation. The following discussion concerns itself only with the somatic aspects of this complicated process since the beguiling psychologic motivation and mechanisms lie in a mixture of too much fancy with too little fact.Among various vertebrate species the sequential evolvement of the primordial oocyte, within its epithelial capsule, to the mature ovum, in the rupturing follicle, is impressively similar, . . .
A quantitative approach to epidermal wound healing: the effect of dexamethasone on regenerating epithelium
Authors: H. DEVITT, M.A. CLARK, R. MARKS, W. PICTON
Journal: British Journal of Dermatology (1978)

The effect of dexamethasone on the regeneration of new epithelium over the base of an excised suction blister has been studied over a period of 9 days. It was found that dexamethasone did not significantly affect the migration of epidermis over the blister base but it did significantly reduce the number of cells in DNA synthesis and post wounding acanthosis of wound edge and regenerating epithelium.
Borrelia burgdorferi in the Central Nervous System
Authors: Michael S. Donnenberg
Journal: JAMA (1992)

To the Editor.  —In their study of CNS invasion byB burgdorferi, Luft et al1have taken great care to minimize the risk of contamination of CSF samples in the laboratory, pointing out the extreme sensitivity of the PCR they used to detectB burgdorferiDNA. However, they fail to address the issue of sample contamination during collection. A lumbar puncture is an invasive diagnostic intervention that frequently results in sample contamination with blood. Clinically, we are familiar with the observation that erythrocytes present in the first tube of CSF are often absent in the fourth tube, suggesting dilution of contaminating blood. Contamination of CSF samples with even a minute volume of blood containing target DNA could lead to the erroneous conclusion that the CSF was the source of the sequences amplified. Although we are given the values of CSF fluid protein, glucose, and leukocyte counts in Table 1,
Giannini, Semmelweiss, and Handwashing
Authors: FRANCO R. CLARA
Journal: Annals of Internal Medicine (1977)

Comments and Correction1 February 1977Giannini, Semmelweiss, and HandwashingFRANCO R. CLARA, M.D.FRANCO R. CLARA, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-86-2-241_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: I wish to offer a comment stimulated by the recent letter in your journal on Semmelweiss and handwashing (Ann Intern Med 85:398, 1976).Ignaz Philipp Semmelweiss (1818-1865) had a precursor who anticipated his idea that handwashing could have prevented transmissible disease. This was Guiseppe Alessandro Giannini (1774-1818), who succeeded in arresting the extension of an epidemic of typhus exanthematicus by introducing in 1807 isolation, disinfection, and hand-washing with diluted acetic acid after every contact with the patient at the Ospedale Maggiore, Milano (Italy).Giannini, out of his experiences with the jennerian vaccine (1799-1800), came to the conclusion...References1. GIANNINI G: Delia natura delle febbri e dei metodi di curarle. Milano 1805-1809 Google Scholar2. CLARA F: Guiseppe Giannini (1774-1818): Le traite "Delia natura delle febbri e dei metodi di curarle." Zurich, 1974 Google Scholar3. CLARA F: Guiseppe Giannini, precurseur de la chimiotherapie des maladies infectieuse. Medecine et Hygiene 33:1869-1873, 1975 Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Ospedale Civico CH-6900 Lugano Switzerland PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByTHE HISTORY OF HAND INFECTIONSEffect of an Automated Sink on Handwashing Practices and Attitudes in High-Risk UnitsSemmelweis 1 February 1977Volume 86, Issue 2Page: 241-241KeywordsDisinfectionTyphusVaccines Issue Published: 1 February 1977 PDF DownloadLoading ...
Cardiologists are putting in stents needlessly, doctors say
Authors: S. Bhaumik
Journal: BMJ (2013)

Cardiologists in India have been accused of cashing in on the rapidly increasing incidence of coronary heart disease there by recommending stenting and other invasive coronary procedures to patients who may not need them.

A report by Global Industry Analysts says that the worldwide market in coronary stents is predicted to reach $1.8bn (Rs96bn; £1.1bn; €1.3bn) by 2017.1 With the death rate from coronary heart disease rapidly falling in developed nations, much of the burgeoning market for stents is due to increasing demand from India, which has one of the world’s highest rates of death from coronary heart disease.2

Concern is growing in India that cardiologists are carrying out …
The Fixed Eruption
Authors: Vincent J. Derbes
Journal: JAMA (1964)

Un médecin vous guérit de la colic; deux médecins vous guérissent de la médecine (One physician cures you of the colic; two physicians cure you of the medicine). Although disseminated skin eruptions caused ^by drugs are regrettably common, those that appear only in one or a very few places, the socalled fixed eruptions, occur relatively infrequently. If the medicament responsible for the latter type is repeated at sufficiently long intervals, the eruption will heal either completely or partially, but will reappear in the same place with each renewed exposure to the offending drug or other agent. Thus the term "fixed" has an anatomic and not a temporal meaning. Brocq,<sup>1</sup>who wrote the classic article on the subject, is generally credited with defining thiscondition, although Archer<sup>2</sup>described such eruptions earlier. A number of agents capable of causing fixed eruptions are listed in the table. <h3>Characteristics</h3> The lesion, which
Splenic Trauma, Splenosis, and Death From Sepsis
Authors: David D. Oakes
Journal: JAMA (1982)

<h3>To the Editor.—</h3> The CLINICAL NOTE "Fulminant Meningococcemia After Splenectomy" by Holmes et al (1981; 246:1119) raises two important issues that deserve further emphasis. First is the danger of overwhelming sepsis in normal adolescents and adults after splenectomy for trauma. Second is the ineffectiveness of intraperitoneal splenic implants (splenosis) in preventing death from fulminant septicemia in asplenic persons. Overwhelming postsplenectomy infection is an unusual but highly distinctive syndrome in which patients who lack splenic function frequently progress from good health to death in less than 24 hours.<sup>1</sup>Although the initial symptoms may be mild and nonspecific (headache, fever, malaise, vomiting), the illness rapidly advances and produces convulsions, coma, cardiovascular collapse, and often death. The clinical course resembles the Waterhouse-Friderichsen syndrome, and bilateral adrenal hemorrhages are commonly found at autopsy. Uniquely characteristic of overwhelming postsplenectomy infection is a massive bacteremia. Organisms may be visible in routine smears of unspun peripheral
Bilateral Stereotaxic Lesions in the Management of Parkinsonism and the Dyskinesias
Authors: F. J. Gillingham, S. Kalyanaraman, A. A. Donaldson
Journal: BMJ (1964)

Since the establishment of stereotaxic surgery as a therapeutic procedure of value in the management of Parkinsonism and the dyskinesias, most centres specializing in this operation have carried it out bilaterally in some of their patients. However, bilateral stereotaxic surgery has been associated with a certain amount of hazard, somewhat greater than in the case of unilateral operations. There has been a general reluctance to subject these patients to operation on both hemispheres, and the criteria for selection for surgery have been more strictly applied before the second procedure.