tbuckley/cabot-search huggingface dataset:
Characterization of a glomerular epithelial cell metalloproteinase as matrix metalloproteinase-9 with enhanced expression in a model of membranous nephropathy.
Authors: J I McMillan, J W Riordan, W G Couser, A S Pollock, D H Lovett
Journal: Journal of Clinical Investigation (1996)

The role of the glomerular visceral epithelial cell in the physiologic turnover and pathologic breakdown of the glomerular extracellular matrix has remained largely unexplored. In this study a 98-kD neutral proteinase secreted by cultured rat visceral glomerular epithelial cells was shown to be a calcium, zinc-dependent enzyme secreted in latent form. In addition, the protein was heavily glycosylated and demonstrated proteolytic activity against Type I gelatin, Type IV collagen gelatin, and fibronectin. The similarity in molecular mass and substrate specificities to the 92-kD human matrix metalloproteinase-9 (MMP-9, or gelatinase B) suggested the identity of this activity, which was confirmed by immunoprecipitation and Northern blot analysis. The differences in molecular mass (98 vs. 92 kD) were not due to species-specific differences in glycosylation patterns, since cultured rat peritoneal macrophages secreted MMP-9 as a 92-kD enzyme. Furthermore, transfection of the human MMP-9 cDNA into rat glomerular epithelial cells yielded the 98-kD product. Using a specific monoclonal anti-MMP-9 antibody and in situ reverse transcription (ISRT) analysis of MMP-9 mRNA, the expression of this enzyme was evaluated in vivo. Normal rat glomeruli expressed little immunohistochemical or ISRT staining for MMP-9, while in rats with passive Heymann nephritis there was a major increase in MMP-9 protein and mRNA staining within the visceral epithelial cells. The temporal patterns of MMP-9 expression correlated with the period of proteinuria associated with this model, suggesting that a causal relationship may exist between GEC MMP-9 expression and changes in glomerular capillary permeability.
Planimetry and Transthoracic Two-Dimensional Echocardiography in Noninvasive Assessment of Aortic Valve Area in Patients With Valvular Aortic Stenosis
Authors: Hiroyuki Okura, Kiyoshi Yoshida, Takeshi Hozumi, Takashi Akasaka, Junichi Yoshikawa
Journal: Journal of the American College of Cardiology (1997)
Scintilymphangiography with 99mTc-Antimony Sulfide Colloid in Hereditary Lymphedema (Nonne-Milroy Disease)
Authors: F I JACKSON, P BOWEN, B C LENTLE
Journal: Clinical Nuclear Medicine (1978)

A family of four patients suffering from Nonne-Milroy disease has been examined by pedal scintilymphangiography. Lower limb edema was present in three patients and was bilateral in two instances. Scintilymphangiographic abnormality was invariably present, ranging from almost total obstruction of lymphatic flow to lymphatic pooling. The inguinal, iliac and para-aortic nodes on the affected sides were also noted to be small and few in number. The examination is safe and simple and may be used to distinguish Nonne-Milroy edema from edema due to other causes.
The professor of “telepreventive medicine”
Authors: Gavin Yamey
Journal: BMJ (2004)

The Supercourse website collects hundreds of lectures on public health delivered by a global faculty of experts. Its founder, Ron LaPorte , tells Gavin Yamey about running a “university without walls” 

When an earthquake hit Iran on 26 December 2003, killing over a third of Bam's population of 90 000 people, Ron LaPorte, professor of epidemiology at the University of Pittsburgh, Pennsylvania, knew immediately what he had to do.

LaPorte runs the Supercourse, a freely available online library of about 1700 lectureson public health. Within three days, he and his colleagues had uploaded an authoritative lecture on the health consequences of earthquakes, written by Eric Noji, a world expert on responding to disasters.

Noji's lectures now sit alongside those on tornadoes, avian influenza, bovine spongiform encephalopathy, severe acute respiratory syndrome, and other public health crises. These lectures, says LaPorte, with his characteristic boyish enthusiasm, have “enormous potential to reduce fear and save lives.”

All the lectures are written by members of a networked global community of 13 000 scientists—including six Nobel prize winners—who are committed to what LaPorte calls “telepreventive medicine.”

The lectures are presented in a slide format compatible with PowerPoint. They are aimed at “teaching the teachers” of public health, particularly in universities …
Drug-induced hypersensitivity syndrome associated with Epstein-Barr virus infection
Authors: V. Descamps, E. Mahe, N. Houhou, L. Abramowitz, F. Rozenberg, S. Ranger-Rogez, B. Crickx
Journal: British Journal of Dermatology (2003)

Summary Association of drug‐induced hypersensitivity syndrome with viral infection is debated. Human herpesvirus 6 (HHV‐6) reactivation has been the most frequently reported infection associated with this syndrome. However, a case of cytomegalovirus (CMV) infection was recently described associated with anticonvulsant‐induced hypersensitivity syndrome. We report a case of severe allopurinol‐induced hypersensitivity syndrome with pancreatitis associated with Epstein–Barr virus (EBV) infection. Active EBV infection was demonstrated in two consecutive serum samples by the presence of anti‐EBV early antigen (EA) IgM antibodies and an increase in anti‐EBV EA IgG antibodies, whereas no anti‐EBV nuclear antigen IgG antibodies were detected. EBV DNA was detected by polymerase chain reaction (PCR) in peripheral blood mononuclear cells. Reactivation of HHV‐6 was suggested only by the presence of anti‐HHV‐6 IgM antibodies, but HHV‐6 DNA was not detected by PCR in the serum. Other viral investigations showed previous infection (CMV, rubella, measles, parvovirus B19), immunization after vaccination (hepatitis B virus), or absence of previous infection (hepatitis C virus, human immunodeficiency virus). We suggest that EBV infection may participate in some cases, as do the other herpesviruses HHV‐6 or CMV, in the development of drug‐induced hypersensitivity syndrome.
Risk Stratification for Postoperative Cardiovascular Events via Noninvasive Assessment of Endothelial Function
Authors: Noyan Gokce, John F. Keaney, Liza M. Hunter, Michael T. Watkins, James O. Menzoian, Joseph A. Vita
Journal: Circulation (2002)

Background — Brachial artery endothelial function is impaired in individuals with atherosclerosis and coronary risk factors and improves with risk reduction therapy. However, the predictive value of brachial artery endothelial dysfunction for future cardiovascular events is unknown. Methods and Results — We preoperatively examined brachial artery vasodilation using ultrasound in 187 patients undergoing vascular surgery. Patients were prospectively followed for 30 days after surgery. Forty-five patients had a postoperative event, including cardiac death (3), myocardial infarction (12), unstable angina/ischemic ventricular fibrillation (2), stroke (3), or elevated troponin I, reflecting myocardial necrosis (25). Preoperative endothelium-dependent flow-mediated dilation was significantly lower in patients with an event (4.9±3.1%) than in those without an event (7.3±5%; P &lt;0.001), whereas endothelium-independent vasodilation to nitroglycerin was similar in both groups. In a Cox proportional-hazards model, the independent predictors of events were age ( P =0.001), renal insufficiency ( P =0.03), noncarotid surgery ( P =0.05), and lower brachial artery flow-mediated dilation ( P =0.007). If troponin I elevation was not considered an event, low flow-mediated dilation remained an independent predictor of risk (odds ratio 9.0, 95% CI 1.2 to 68; P =0.03). When a flow-mediated dilation cutpoint of 8.1% was used, endothelial function had a sensitivity of 95%, specificity of 37%, and negative predictive value of 98% for events. Conclusions — Impaired brachial artery endothelial function independently predicts postoperative cardiac events, which supports a role for endothelial dysfunction in the pathogenesis of cardiovascular disease. The strong negative predictive value of preserved endothelial function raises the possibility that assessment of brachial artery flow-mediated dilation will be useful in the management of patients undergoing vascular surgery.
PTU-006 Gastroenterology Trainees Express An Interest To Learn To Perform Ultrasound-assisted Liver Biopsies: Results Of A National Survey (uk)
Authors: GE Dolman, A Austin
Journal: Gut (2014)

<h3>Introduction</h3> Liver biopsy for the assessment of parenchymal liver disease is increasingly performed under direct ultrasound guidance by radiologists. As such, it is no longer a mandatory requirement for hepatology trainees in the UK to achieve competence in this procedure. <h3>Methods</h3> We aimed to determine whether trainees are receiving training to perform ultrasound-assisted liver biopsies; and whether they would be interested in doing so if not. Trainees anonymously responded to a 10 question, web based survey using a combination of pre-defined answers in drop down boxes and free text answers. <h3>Results</h3> Surveys were sent to approximately 800 trainees. 226 surveys were returned. Respondents represented all training grades (ST3-ST7). 75 respondents (33%) intend to pursue subspecialty accreditation in hepatology. 103 respondents (46%) have completed a period of training in a tertiary/transplant centre. 105 respondents (47%) have worked in a centre where physicians perform liver biopsies. 52 (23%) have been offered the opportunity to learn how to perform ultrasound assisted liver biopsy and 38 (17%) have been assessed and deemed competent in the procedure. Three respondents commented that they are trained in unguided liver biopsy; one trainee has used the Sonosite probe and one commented that he/she has performed liver biopsy after an appropriate site was marked by the radiologist 137 (61%) of trainees who responded to the survey would be interested in learning how to perform this procedure and a further 29 (13%) may be interested. 138 (61%) of respondents would be interested in attending a hands-on course to learn this procedure and 30 (13%) may be interested. Of the 75 respondents who intend to pursue subspecialty hepatology accreditation, 72 said they would be interested in learning how to perform ultrasound assisted liver biopsy. Trainees who participated in this survey reported that opportunities to learn this procedure were currently hit and miss. There were concerns about the practicality of maintaining competence during training and as a consultant and some respondents felt that it was safer for the procedure to be performed by radiologists. We cannot report the views of trainees who did not complete the survey and therefore our results may not be representative. However even if we make the assumption that all non-responders are not interested in learning this procedure, there is still an estimated 15–20% of trainees that would be interested (137/~ 800). <h3>Conclusion</h3> Trainees participating in this survey are interested in learning to perform ultrasound-assisted liver biopsies, but the infrastructure to offer this training is not currently well established. Discussion between trainees and training bodies should be considered to explore this issue further. <h3>Disclosure of Interest</h3> None Declared.
Children seen frequently out of hours in one general practice.
Authors: J M Morrison, H Gilmour, F Sullivan
Journal: BMJ (1991)

OBJECTIVE--To identify reasons why some children receive more out of hours visits than most. DESIGN--A one year prospective study to identify the study group. This was followed by a case-control study involving a record search and personal interviews. SETTING--One three doctor urban general practice in West Lothian with 4812 patients. SUBJECTS--40 children aged under 10 years identified as high users of the out of hours service (more than two visits a year) and 40 age and sex matched controls. MAIN OUTCOME MEASURES--Numbers of visits; social factors such as lone motherhood, low educational attainment; score for management response to clinical vignette. RESULTS--147/756 (19%) out of hours visits in the study year were to children aged under 10 years; 109 (74%) to 41 children (6%). Problems seen were mainly minor, and little active management was required. Family and social factors which were significantly more common for the cases than for the controls included a lone mother (15 v 4), low educational attainment by the mother (25 v 14), receipt of income support (22 v 7), and non-ownership of the home (45 v 22) or a car (19 v 9). Mothers of the cases were more likely to choose to contact a doctor when presented with vignettes describing common childhood illnesses (median score for 16 vignettes 16.5 for cases v 14.5 for controls, Wilcoxon signed rank test, p = 0.01). CONCLUSIONS--Children seen more frequently than expected out of hours came from more socially disadvantaged families and their mothers were more likely to seek medical advice about minor childhood illness. Maternal education, to promote confidence in managing minor illness, may reduce their use of the out of hours service.
Enhanced T cell responses against hepatitis C virus by ex vivo targeting of adenoviral particles to dendritic cells
Authors: Itziar Echeverria, Alexander Pereboev, Leyre Silva, Aintzane Zabaleta, José Ignacio Riezu-Boj, Marta Bes, María Cubero, Francisco Borras-Cuesta, Juan José Lasarte, Juan Ignacio Esteban, Jesús Prieto, Pablo Sarobe
Journal: Hepatology (2011)

Abstract: Injection of dendritic cells (DCs) presenting viral proteins constitutes a promising approach to stimulate T cell immunity against hepatitis C virus (HCV). Here we describe a strategy to enhance antigen loading and immunostimulatory functions of DCs useful in the preparation of therapeutic vaccines. Incubation of murine DCs with CFm40L, an adapter molecule containing the coxsackie-adenovirus receptor fused to the ecto-domain of murine CD40L-induced DC maturation, produced high amounts of interleukin-12 and up-regulation of molecules associated with T helper 1 responses. Accordingly, targeting of an adenovirus encoding HCV NS3 protein (AdNS3) to DCs with CFm40L strongly enhanced NS3 presentation in vitro , activating interferon-γ–producing T cells. Moreover, immunization of mice with these DCs promoted strong CD4 and CD8 T cell responses against HCV NS3. CFh40L, a similar adapter molecule containing human CD40L, enhanced transduction and maturation of human monocyte-derived DCs. Comparison of DCs transduced with AdNS3 and CFh40L from patients with chronic HCV infection and healthy donors revealed similar maturation levels. More importantly, DCs from the patients induced NS3-specific responses when transduced with AdNS3 and CFh40L but not with AdNS3 alone. Conclusion: DCs transduced with AdNS3 and the adapter molecule CFm/h40L exhibit enhanced immunostimulatory functions, induce robust anti-HCV NS3 immunity in animals, and can induce antiviral immune responses in subjects with chronic HCV infection. This strategy may serve as therapeutic vaccination for patients with chronic hepatitis C. (HEPATOLOGY 2011;)
Abstract 451: HIF-1 alpha silencing in MDA-MB-231 human breast cancer cells alters choline phospholipid metabolism
Authors: Tariq Shah, Balaji Krishnamachary, Flonne Wildes, Zaver M. Bhujwalla
Journal: Cancer Research (2010)

Abstract Hypoxia-inducible factor-1 (HIF-1) over-expression has been associated with an increased patient mortality rate in many cancer types including breast cancer. Suppression of HIF-1 gene expression has been shown to inhibit tumor growth. Here we have studied the effect of HIF-1 silencing on the metabolism of MDA-MB-231 cells using a magnetic resonance (MR)- compatible cell perfusion assay. Previous studies have identified choline kinase (Chk), the enzyme that converts choline to phosphocholine (PC), and the resulting increase of PC and total choline (tCho) as markers of an aggressive phenotype. We found that HIF-1 silencing resulted in significantly reduced Chk expression together with reduced tCho and PC, compared to parental cells. The sequence for shRNA against HIF-1α was cloned into a lentivirus vector with a green fluorescent protein (GFP) reporter construct (pRRL-pGK-GFP). Viral supernatant preparation and transduction of MDA-MB-231 breast cancer cells was performed following standard protocol. Transduced cells were validated for HIF-1α knock-down by western blots and by quantitative real-time polymerase chain reaction (q RT-PCR). Cell perfusion studies were performed using an MR-compatible perfusion assay to determine intracellular levels of metabolites using 1H and 31P MR spectroscopy (MRS). Experiments were performed in triplicates. The Mann Whitney-U test was used to determine statistical significance (p &amp;lt;0.05). HIF-1α protein expression increased following treatment with 200μM of the hypoxia mimetic CoCl2 in parental MDA-MB-231 cells but not in cells transduced with HIF-1α shRNA. Reduced expression of Chk in HIF-1α silenced cells was observed following CoCl2 treatment, while its expression was induced in parental cells. Quantitative data from 1H and 31P MRS showed significantly reduced levels of tCho (p &amp;lt;0.05) and PC (p &amp;lt; 0.01) in HIF-1α silenced cells compared to parental MDA-MB-231 cells, confirming that silencing of HIF-1α reduced levels of choline containing metabolites by reducing Chk expression. We previously observed that Chk is up regulated under hypoxia and have established a HIF-1 binding site on the Chk promoter. The reduction of choline metabolites in HIF-1α silenced cells further confirms the role of HIF-1α in the regulation of Chk. The reduction of Chk, total choline and PC levels in HIF-1α silenced cells are also typical of a less aggressive metabolic phenotype. 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 451.
Theories with Regard to Secondary Growths in Carcinoma of the Breast
Authors: M. Thorne
Journal: BMJ (1912)

SECONDARY GROWTHS IN MAMMARY CARCINOMA.[I T 1M I745 the smaller, group with severe symptoms the lesions are "latent " onlybecause deep-seated.Even if no gravity should be manifestkd in: the! symptoms, the possiblility of grave lesions demands for safetv a dorsal perc-ussion, as this almost invariably yields at least some minor indica- 'tions not otherwise to be got."Central" or "anterior" esions may not be latent to an abdominal examination when they are extensive.In that event their manifest
Physician, cherish thyself. The hazards of self-prescribing
Authors: G. E. Vaillant
Journal: JAMA (1992)

The report by Hughes et al<sup>1</sup>on the prevalence of substance use among US physicians helps to rescue our knowledge of the matter both from fantasy and from parochialism. The authors sent questionnaires to a random sample of 9600 US physicians and they made an effort to analyze their results in terms of gender, age, region of the country, and the type of drug use. To obtain similar stratified results from the population as a whole, the authors took advantage of comparable data from the National Institute on Drug Abuse's National Household Survey of Drug Abuse. The study represents a methodological advance over prior efforts to assess doctors' misuse of mood-altering agents, and the findings allow us to estimate trends of drug use and drug abuse among different physician cohorts. See also p 2333. Surprisingly, the fact that Hughes et al obtained only a 59% questionnaire completion rate may
Acquired factor XI inhibitors in congenitally deficient patients
Authors: S. F. Schnall, T. P. Duffy, L. P. Clyne
Journal: American Journal of Hematology (1987)

Abstract Four factor XI (F XI)‐deficient patients are described, all of whom formed circulating anticoagulants against F X1. In the three most severely affected patients (F XI 0%–6% activity), the anticoagulant appeared to have been stimulated by plasma infusion. However, in the milder case (25% F XI activity), no infusion had been documented. The findings in these cases emphasize the diversity of F XI inhibitors in congenitally deficient patients. Awareness of the potential development of these inhibitors will be helpful in both daily management and perioperative care of such patients.
Intramuscular Injections within 30 Days of Immunization with Oral Poliovirus Vaccine — A Risk Factor for Vaccine-Associated Paralytic Poliomyelitis
Authors: Peter M. Strebel, Nicolae Ion-Nedelcu, Andrew L. Baughman, Roland W. Sutter, Stephen L. Cochi
Journal: New England Journal of Medicine (1995)

In Romania the rate of vaccine-associated paralytic poliomyelitis is for unexplained reasons 5 to 17 times higher than in other countries. Long ago it was noted that intramuscular injections administered during the incubation period of wild-type poliovirus infection increased the risk of paralytic disease (a phenomenon known as "provocation" poliomyelitis). We conducted a case-control study to explore the association between intramuscular injections and vaccine-associated poliomyelitis in Romania.The patients were 31 young children in whom vaccine-associated paralytic poliomyelitis developed from 1988 through 1992. Eighteen were vaccine recipients, and 13 had acquired the disease by contact with vaccine recipients. Each of these children was matched with up to five controls according to health center, age, and in the case of vaccine recipients, history of receipt of the live attenuated oral poliovirus vaccine. Data were abstracted from medical records that documented the injections administered in the 30 days before the onset of paralysis.Of the 31 children with vaccine-associated disease, 27 (87 percent) had received one or more intramuscular injections within 30 days before the onset of paralysis, as compared with 77 of the 151 controls (51 percent) (matched odds ratio, 31.2; 95 percent confidence interval, 4.0 to 244.2). Nearly all the intramuscular injections were of antibiotics, and the association was strongest for the patients who received 10 or more injections (matched odds ratio for > or = 10 injections as compared with no injections, 182.1; 95 percent confidence interval, 15.2 to 2186.4). The risk of paralytic disease was strongly associated with injections given after the oral polio virus vaccine, but not with injections given before or at the same time as the vaccine (matched odds ratio, 56.7; 95 percent confidence interval, 8.9 to infinity). The attributable risk in the population for intramuscular injections given in the 30 days before the onset of paralysis was 86 percent (95 percent confidence interval, 66 to 95 percent); that is, we estimate that 86 percent of the cases of vaccine-associated paralytic poliomyelitis in this population might have been prevented by the elimination of intramuscular injections within 30 days after exposure to oral poliovirus vaccine.Provocation paralysis, previously described only for wild-type poliovirus infection, may rarely occur in a child who receives multiple intramuscular injections shortly after exposure to oral poliovirus vaccine, either as a vaccine recipient or through contact with a recent recipient. This phenomenon may explain the high rate of vaccine-associated paralytic poliomyelitis in Romania, where the use of intramuscular injections of antibiotics in infants with febrile illness is common.