tbuckley/cabot-search huggingface dataset:
Mycophenolic acid in psoriasis
Authors: STANLEY SPATZ, ALICJA RUDNICKA, CHARLES J. McDONALD
Journal: British Journal of Dermatology (2006)

Mycophenolic acid (MPA) is a fermentation product of a penicillium mould which has shown anti-tumour activity in certain animal models. It blocks nucleic acid synthesis by interfering with the interconversions of inosine monophosphate (IMP), xanthine monophosphate (XMP) and guanine monophosphate (GMP) thereby inhibiting growth and/or replication of tumour cells. In vivo activity depends on the presence of a β-glucuronidase which is abundant in the cell wall of epithelial tissues. Encouraged by results obtained in earlier clinical trials, we have studied 28 patients with psoriasis, 21 in double-blind fashion. A comparison of disease severity in patients before and after receiving MPA versus patients receiving placebo clearly showed the superiority of drug over placebo. The mean severity score of patients receiving MPA as an initial course of therapy improved by 56% versus 9% in patients receiving placebo. Patients receiving MPA after an initial course of placebo therapy showed improvement in their mean severity score averaging 86%. Those patients receiving placebo after an initial course of MPA showed worsening of their mean severity score averaging 70%. Overall, about 75% of MPA treated patients have shown good to excellent responses, and toxicity appears low. Evidence suggests that MPA may be very useful in treating severe psoriasis.
Leukocyte Transfusions in Chronic Granulomatous Disease
Authors: E. Stephen Buescher, John I. Gallin
Journal: New England Journal of Medicine (1982)

CHRONIC granulomatous disease of childhood is an inherited disease in which phagocytes lack the ability to use molecular oxygen to generate microbicidal oxygen byproducts (hydrogen peroxide, hydroxyl radical, or Superoxide anion). Classically recognized by the inability of their blood leukocytes to reduce the yellow dye nitroblue tetrazolium to blue-purple formazan, patients with this disease have recurrent serious infections caused by both bacterial and fungal pathogens.In this article we report our experience with white-cell transfusions given to a patient with chronic granulomatous disease who had life-threatening mixed fungal and bacterial pneumonia. The transfused cells cleared rapidly (within three hours) from . . .
Origin and function of penicillinase: a problem in biochemical evolution.
Authors: M R Pollock
Journal: BMJ (1967)

The title of this lecture is intentionally provocative.It is well known that there are many varieties of the enzyme that can split the /3-lactam bond of penicillins and/or cephalosporins (Fig. 1)-the specific reaction referred to generally as "penicillinase."And their physiological role in the life history of the bacteria which produce them is still a matter of controversy.But the case I wish to argue will be one in favour both of recognizing the relation between the various "brands" of the enzyme, despite many striking chemical differences, and of considering the possibility of a common or similar evolutionary origin.
Prevalence of Microalbuminuria in Older-Onset Diabetes
Authors: Ronald Klein, Barbara E K Klein, Scot E Moss
Journal: Diabetes Care (1993)

OBJECTIVE To examine the prevalence of microalbuminuria and the relationships of microalbuminuria to blood pressure and other risk factors. RESEARCH DESIGN AND METHODS Individuals diagnosed with diabetes at ≥30 yr of age either taking insulin (n = 435) or not taking insulin (n = 363), who were participants in the population-based Wisconsin Epidemiologic Study of Diabetic Retinopathy, were examined during 1984-1986. Random urine samples were collected and an agglutination inhibition test was used to determine the presence of microalbuminuria, which is defined as ≥0.03 g/L but &amp;lt;0.3 g/L. RESULTS The frequency of microalbuminuria was 29.2% in those individuals taking insulin and 22.0% in those not taking insulin. Microalbuminuria was significantly associated with the male sex, older age, higher systolic blood pressure, higher GHb, use of insulin, higher recent alcohol consumption, and a history of cardiovascular disease. CONCLUSIONS These findings suggest a relationship between controllable risk factors, blood pressure and GHb, and microalbuminuria in older-onset diabetic individuals.
Leslie James Clark-Wilson
Authors: J. A. C. Wilson
Journal: BMJ (2011)

OBJECTIVE--To determine the risk of suicide in patients attending an accident and emergency (A&amp;E) department with deliberate self harm. METHODS--Information was obtained on suicides and open verdicts from the coroner9s office and cross checked with computerised records in the A&amp;E department. RESULTS--There was a trend to suicide among younger socially isolated males and older females. CONCLUSIONS--There is a significant association between suicide and a previous attendance at A&amp;E with deliberate self harm. Appropriate assessment of these patients is an efficient way of managing self harm.
TCT-584 Nine Month Imaging and Twelve Month Clinical Results from the DESSOLVE II Randomized Trial of the MiStent® SES with Absorbable Polymer
Authors: William Wijns, Mathias Vrolix, Stefan Verheye, Danny Schoors, Ton Slagboom, Marcel Gosselink, Edouard Benit, Walter Desmet, Saquib Chowdhary, Alexandra Lansky, Hiram Bezerra, Peter Fitzgerald, David Kandzari, John Ormiston
Journal: Journal of the American College of Cardiology (2012)
Survey of general practitioners' treatment of the discharging ear
Authors: R C Bickerton, C Roberts, J T Little
Journal: BMJ (1988)

The prescribing habits of all (401) general practitioners in the North Staffordshire health district for the treatment of otorrhoea was ascertained by questionnaire; 301 (75%) responded. Of those, 198 (66%) would not give topical treatment when the tympanic membrane was perforated. Only 41 (14%) would give topical treatment in cases of discharging grommets. Although there is a theoretical risk of ototoxicity to aminoglycosides in topical preparations, this is the most effective medical treatment and is the standard teaching advocated in specialist textbooks and practised by otolaryngologists. The results of the survey suggest that there is undue concern about possible ototoxicity and a degree of confusion in the management of this common clinical condition.
Abstract A74: Tumor secreted Hsp90 initiates tumor growth and the epithelial to mesenchymal transition (EMT) in prostate cancer
Authors: Michael W. Hance, Krystal Nolan, Udhayakumar Gopal, Jessica E. Bohonowych, Agnieszka Jezierska-Drutel, Carola A. Neumann, Haibo Liu, Garraway P. Isla, Omar E. Franco, Simon W. Hayward, Jennifer S. Isaacs
Journal: Cancer Research (2013)

Abstract Prostate cancer (PCa) is the most frequently diagnosed malignancy and second most common cause of cancer related lethality in men. Disease mortality is due primarily to metastatic spread, highlighting the urgent need to identify factors involved in this progression. Increased secretion of heat shock protein 90 (Hsp90) has been reported in diverse cancer cells, and secreted, or extracellular Hsp90 (eHsp90) is also found in patient plasma. Although eHsp90 promotes cancer cell motility and invasion and facilitates tumor metastasis, the mechanistic basis for its activity has remained unknown. The goal of this study was to explore whether extracellular Hsp90 (eHsp90) may play a role in PCa progression. To explore this, 3 sets of lineage-related differentially metastatic cell pairs were utilized to evaluate eHsp90 expression and activity. We found that eHsp90 secretion correlated with PCa aggressiveness. To evaluate the functional role of eHsp90, we modulated its expression and activity. Upregulation of eHsp90 was accomplished by exposure of prostate epithelial cells to exogenous Hsp90 protein, or alternatively, cells were transduced with a lentivirus directing the secretion of Hsp90. Blockade of eHsp90 function was accomplished by exposure of cells to anti-Hsp90 antibodies or to a cell-impermeant specific inhibitor of Hsp90. We demonstrate that eHsp90 is a critical factor required for PCa cell motility and for initiation of the epithelial to mesenchymal transition (EMT) genetic program. Moreover, modest increases in eHsp90 were sufficient to induce tumor growth and localized invasion in a subrenal capsule xenograft model of PCa. Finally, eHsp90 was detected in human cancer specimens and its expression was correlated with upregulated expression of pro-invasive genes. Our findings offer insights into the mechanistic basis of eHsp90 in PCa, and further support a putative clinical role for eHsp90 as a potential driver of PCa progression. Citation Format: Michael W. Hance, Krystal Nolan, Udhayakumar Gopal, Jessica E. Bohonowych, Agnieszka Jezierska-Drutel, Carola A. Neumann, Haibo Liu, Garraway P. Isla, Omar E. Franco, Simon W. Hayward, Jennifer S. Isaacs. Tumor secreted Hsp90 initiates tumor growth and the epithelial to mesenchymal transition (EMT) in prostate cancer. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr A74.
Cyclosporine nephrotoxicity in type 1 diabetic patients. A 7-year follow-up study.
Authors: H H Parving, L Tarnow, F S Nielsen, P Rossing, T Mandrup-Poulsen, R Osterby, J Nerup
Journal: Diabetes Care (1999)

To evaluate kidney function 7 years after the end of treatment with cyclosporine A (CsA) (initial dosage of 9.3 tapered off to 7.0 mg.kg-1.day-1) in young patients (mean age 20 years) with newly diagnosed type 1 diabetes participating in a randomized, double-blind, placebo-controlled CsA trial.In this study, 21 patients received CsA for 12.5 +/- 4.0 months (mean +/- SD) and 19 patients received placebo for 14.4 +/- 3.8 months. The two groups were similar with regard to mean arterial blood pressure (BP), urinary albumin excretion rate (UAER), serum creatinine, and estimated glomerular filtration rate (GFR [Cockcroft and Gault]) at initiation of CsA treatment (baseline). HbA1c (mean +/- SEM) during 7 years of follow-up was also the same: 8.7 +/- 0.4 vs. 8.3 +/- 0.4% in the CsA and placebo groups, respectively.During the 7 years after cessation of study medication, two CsA group patients and one control patient were lost to follow-up. One placebo-treated patient developed IgA nephropathy (biopsy proven) and was excluded. Four CsA-treated patients developed persistently elevated UAER > 30 mg/24 h (n = 3 with microalbuminuria), whereas all the 17 placebo-treated patients had normal UAER (< 30 mg/24 h) after 7 years of follow-up. At the end of follow-up, the CsA group had a more pronounced rise in UAER: 2.5-fold (95% CI 1.4-4.5) higher than baseline value vs. 1.1-fold (0.7-1.7) in the placebo-treated group (P < 0.05). Estimated GFR (ml.min-1.1.73 m-2) declined from baseline to end of follow-up (1994) by 6.3 +/- 6.0 in the former CsA group, whereas it rose by 7.4 +/- 5.0 in the placebo group (P = 0.05). In 1994, 24-h blood pressure was nearly the same: 131/77 +/- 4/2 vs. 127/75 +/- 2/2 mmHg (NS) in the CsA and placebo groups, respectively. Five randomly selected CsA-treated patients had a kidney biopsy performed shortly after the CsA treatment was stopped. Interstitial fibrosis/tubular atrophy and/or arteriolopathy were present in two subjects who both subsequently developed persistent microalbuminuria.The results of our 7-year follow-up study suggested that short-lasting CsA treatment in young, newly diagnosed type 1 diabetic patients accelerated the rate of progression in UAER and tended to induce a loss in kidney function. Longer term follow-up is mandatory to clarify whether CsA-treated patients are at increased risk of developing clinical nephropathy.
Vitamin E In Porphyria
Authors: Pertti Mustajoki
Journal: JAMA (1972)

<h3>To the Editor.—</h3> Vitamin E has recently been shown to influence porphyrin metabolism.<sup>1,2</sup>Nair and his co-workers<sup>3</sup>have treated four patients with symptoms of porphyria with vitamin E. They found improvement in the clinical condition of the patients and decrease of urinary porphyrins and porphyrin precursors. This matter has also recently been treated in an EDITORIAL inThe Journal.<sup>4</sup> This led us to study the effect of vitamin E on the porphyrin excretion in five porphyric patients. They were all women, aged 24 to 32 years, and from different families. During the experiment, one had mild symptoms pointing at porphyria. In four patients, the biochemical findings were typical for acute, intermittent porphyria, and in one patient for variegate porphyria. Four patients were given dl-alfa-tocopherol (Evitol forte, Orion Pharmaceutical Co, Finland) 100 to 200 mg/day, and one was given d-alfa-tocopherol (IDO-E, Pharmacia, Sweden) 400 mg/day. During a four-week
Three trocar laparoscopic Roux-en-y gastric bypass: A novel technique en route to the single-incision laparoscopic approach
Authors: Alan A. Saber, Mohamed H. Elgamal, Tarek H. El-Ghazaly, Alain R. Elian, Aditya V. Dewoolkar, Abir Hassan Akl
Journal: International Journal of Surgery (2009)
Active and passive smoking and development of glucose intolerance among young adults in a prospective cohort: CARDIA study
Authors: Thomas K Houston, Sharina D Person, Mark J Pletcher, Kiang Liu, Carlos Iribarren, Catarina I Kiefe
Journal: BMJ (2006)

To assess whether active and passive smokers are more likely than non-smokers to develop clinically relevant glucose intolerance or diabetes.Coronary artery risk development in young adults (CARDIA) is a prospective cohort study begun in 1985-6 with 15 years of follow-up.Participants recruited from Birmingham, Alabama; Chicago, Illinois; Minneapolis, Minnesota; and Oakland, California, USA.Black and white men and women aged 18-30 years with no glucose intolerance at baseline, including 1386 current smokers, 621 previous smokers, 1452 never smokers with reported exposure to secondhand smoke (validated by serum cotinine concentrations 1-15 ng/ml), and 1113 never smokers with no exposure to secondhand smoke.Time to development of glucose intolerance (glucose > or = 100 mg/dl or taking antidiabetic drugs) during 15 years of follow-up.Median age at baseline was 25, 55% of participants were women, and 50% were African-American. During follow-up, 16.7% of participants developed glucose intolerance. A graded association existed between smoking exposure and the development of glucose intolerance. The 15 year incidence of glucose intolerance was highest among smokers (21.8%), followed by never smokers with passive smoke exposure (17.2%), and then previous smokers (14.4%); it was lowest for never smokers with no passive smoke exposure (11.5%). Current smokers (hazard ratio 1.65, 95% confidence interval 1.27 to 2.13) and never smokers with passive smoke exposure (1.35, 1.06 to 1.71) remained at higher risk than never smokers without passive smoke exposure after adjustment for multiple baseline sociodemographic, biological, and behavioural factors, but risk in previous smokers was similar to that in never smokers without passive smoke exposure.These findings support a role of both active and passive smoking in the development of glucose intolerance in young adulthood.
Should Children Decide Whether They Are Enrolled in Nonbeneficial Research?
Authors: David Wendler, Seema Shah
Journal: The American Journal of Bioethics (2003)

The U.S. federal regulations require investigators conducting nonbeneficial research to obtain the assent of children who are capable of providing it. Unfortunately, there has been no analysis of which children are capable of assent or even what abilities ground the capacity to give assent. Why should investigators be required to obtain the positive agreement of some children, but not others, before enrolling them in research that does not offer a compensating potential for direct benefit? We argue that the scope of children's research decision making should be based on the principles of respect for autonomy and nonmaleficence. These principles imply that the threshold for assent should be fixed at 14 years of age, and a dissent requirement should be adopted for all children in the context of nonbeneficial research.
Surgical Treatment of Chronic Frontal Sinusitis
Authors: W. Howarth
Journal: BMJ (1947)

JBUTISH from disintegration and families enabled once again to take their place as self-directing and self-respecting members of the community.Co-ordination of existing work and the co- operation of all agencies concerned with the problem are essential.The aim of F.S.U. is to provide a service at the disposal of other departments and bodies to be used by them on particular cases needing specialized treatment.The committee plan first to take responsibility for the exist- ing work in Liverpool and Manchester, and then to establish a new unit in London as soon as personnel becomes available.The keynote of successful work in this field must be friend- ship, and the work will call for personal self-sacrifice of a high order.The work of the committee will continue for some time to be experimental.The problem family tails to utilize or benefit from such faci ities for its betterWnt as exist at present.Rehousing, family -allowances, and a national medical service are not enough.This is a task in which voluntary effort and personal service in the home must play a preponderant part, and it is a task in which personal service alone can be successful.Among the objects we have in view is a comprehensive investi- gation into the nature, extent, and causes of this form of social subnormality.A two years' period will, we think, be sufficient to establish the facts, and we ask for a sum of £15,000, which is sufficient to support the existing centres during that time and to establish one new centre in London.
Epithelial cell proliferation in childhood enteropathies.
Authors: T C Savidge, A N Shmakov, J A Walker-Smith, A D Phillips
Journal: Gut (1996)

BACKGROUND/AIM: The aim of this study was to investigate epithelial cell turnover in childhood enteropathy to establish whether common disease related mechanisms operate. Levels of epithelial cell proliferation were measured in children with food intolerance (cows9 milk protein intolerance and coeliac disease), and after infection with Giardia lamblia, Cryptosporidium, and enteropathogenic Escherichia coli. METHODS: Comparative measures of epithelial cell proliferation were performed by recording mitotic activity and MIB-1 immunoreactivity in proximal small intestinal biopsy specimens. RESULTS/CONCLUSIONS: A hyperplastic crypt response was evident in all of the disease states examined and was particularly pronounced in coeliac disease and in infection with enteropathogenic E coli, where mitotic and MIB-1 labelling indices were significantly raised above control values. In contrast with coeliac disease, increased crypt cell production rates in enteropathogenic E coli infection were also due to an expansion of the crypt proliferation compartment, without a comparable increase in crypt cell numbers. Crypt hyperplasia is therefore a common tissue response to mucosal damage in food allergy and infection, although disease specific mechanisms are evident.
The pancreatic stellate cell: a star on the rise in pancreatic diseases
Authors: M. Bishr Omary, Aurelia Lugea, Anson W. Lowe, Stephen J. Pandol
Journal: Journal of Clinical Investigation (2007)

Pancreatic stellate cells (PaSCs) are myofibroblast-like cells found in the areas of the pancreas that have exocrine function. PaSCs are regulated by autocrine and paracrine stimuli and share many features with their hepatic counterparts, studies of which have helped further our understanding of PaSC biology. Activation of PaSCs induces them to proliferate, to migrate to sites of tissue damage, to contract and possibly phagocytose, and to synthesize ECM components to promote tissue repair. Sustained activation of PaSCs has an increasingly appreciated role in the fibrosis that is associated with chronic pancreatitis and with pancreatic cancer. Therefore, understanding the biology of PaSCs offers potential therapeutic targets for the treatment and prevention of these diseases.
Retinal Axon Growth at the Optic Chiasm: To Cross or Not to Cross
Authors: Timothy J. Petros, Alexandra Rebsam, Carol A. Mason
Journal: Annual Review of Neuroscience (2008)

At the optic chiasm, retinal ganglion cell axons from each eye converge and segregate into crossed and uncrossed projections, a pattern critical for binocular vision. Here, we review recent findings on optic chiasm development, highlighting the specific transcription factors and guidance cues that implement retinal axon divergence into crossed and uncrossed pathways. Although mechanisms underlying the formation of the uncrossed projection have been identified, the means by which retinal axons are guided across the midline are still unclear. In addition to directives provided by transcription factors and receptors in the retina, gene expression in the ventral diencephalon influences chiasm formation. Throughout this review, we compare guidance mechanisms at the optic chiasm with those in other midline models and highlight unanswered questions both for retinal axon growth and axon guidance in general.
Chlamydia pneumoniae-specific circulating immune complexes in patients with chronic coronary heart disease.
Authors: E Linnanmäki, M Leinonen, K Mattila, M S Nieminen, V Valtonen, P Saikku
Journal: Circulation (1993)

BACKGROUND An association of chronic Chlamydia pneumoniae infection to coronary heart disease has been suggested recently. In a recent study, we demonstrated circulating immune complexes containing chlamydial genus-specific lipopolysaccharide in patients with coronary heart disease. The objective of the present study was to investigate whether C. pneumoniae species-specific immune complexes are present in chronic coronary heart disease. METHODS AND RESULTS The presence of Chlamydia-specific circulating immune complexes was studied in 46 patients with chronic coronary heart disease and in control subjects. Chlamydial lipopolysaccharide-containing immune complexes were detected with the antigen-specific capture method, and they were present in 41% of patients and 15% of control subjects (p &lt; 0.01). The presence of C. pneumoniae antibodies in circulating immune complexes was studied by testing the specificity of antibodies derived from isolated and dissociated immune complexes by microimmunofluorescence testing and immunoblotting. The C. pneumoniae indexes based on the relative amount of immune complex-derived antibodies and free antibodies were significantly higher among patients compared with control subjects (median, 1/8 versus 1/16; p &lt; 0.001). Immune complex bound antibodies showed specificity for 98-kd and 42-kd proteins of C. pneumoniae. CONCLUSIONS The results suggest that the majority of the patients with chronic coronary heart disease have a chronic C. pneumoniae infection in which chlamydial components have an easy access to circulation to form immune complexes with preexisting antibodies. These findings give further evidence for the association of chronic C. pneumoniae infection with coronary heart disease.