tbuckley/cabot-search huggingface dataset:
Capsaicin induced cough in cryptogenic fibrosing alveolitis
Authors: M J Doherty
Journal: Thorax (2000)

Cough is a common and troublesome symptom in cryptogenic fibrosing alveolitis (CFA) but the mechanisms responsible are not known. The cough threshold to inhaled capsaicin is increased in asthma and chronic obstructive pulmonary disease (COPD) where lung volumes are increased, but the relationship between cough response and symptom intensity has not been studied in CFA where lung volumes are reduced.Capsaicin challenge tests were performed on 15 subjects with proven CFA and 96 healthy controls. Symptoms, as assessed by daily diary card cough score and by visual analogue scale (VAS), were related to the capsaicin sensitivity (C5) and compared with lung volumes. Volume restriction was produced in a group of 12 normal healthy subjects by a plastic shell tightly strapped to the chest wall. Capsaicin challenge tests were performed in these subjects, both strapped and unstrapped, to determine whether volume restriction altered the cough reflex.The median C5 response in normal subjects was more than 500 microM compared with 15.6 microM in those with CFA (p<0.001). The C5 response of the CFA patients was not related to symptoms of cough (whether measured by diary card or by VAS), nor was it related to percentage predicted total lung capacity (TLC) or forced vital capacity (FVC). Volume restriction of normal subjects with chest strapping successfully restricted lung volumes to levels similar to that of the CFA patients but did not change the sensitivity to capsaicin.The cough reflex measured using capsaicin is markedly increased in patients with CFA. This increase is not the result of alterations in the deposition of inhaled particles of capsaicin brought about by volume restriction. It could be related to reduced lung compliance leading to sensitisation of rapidly adapting receptors, other mechanical changes, or to destruction of pulmonary C fibres secondary to interstitial inflammation. The capsaicin test may be a useful method of objectively monitoring cough propensity in CFA.
Arsenical Poisoning by Wall-Papers: I. Report on Evidence regarding the Injurious Effects on Health Arising from Arsenical Wall-Papers and Other Articles Containing Arsenic
Authors: T. L. Brunton
Journal: BMJ (1883)

The nature of the evidence is, first, that certain symptoms have occurred in persons exposed to the in- fi uence of certain conditions; secondly, that, on attempting to ana- lyse these conditions with the object of finding out the cause of injury, none could be discovered at all likely to produce the sym- ptoms, except arsenic; thirdly, that the symptoms coincided in many respects with those produced by arsenic when administered inter- nally; fourthly, that the symptoms disappeared when the arsenic was removed, although, as far as could be ascertained, the other conditions remained unaltered.The number of cases on which the report of the Committee of the Medical Society of London was based was a little over one hundred; and, besides these, numerous cases have been reported in medical journals.Considering the extensive use of arsenic in wall-papers and articles of clothing and furniture, the number of cases may appear very small, and quite insufficient to prove the necessity for any form of legislative inter- ference.This objection, we believe, however, to be invalid.It is exactly the same in kind as that which may be brought against interference with systems of drainage which contaminate drinking- water with typhoid excreta, or against the free distribution of milk supplied from dairies where typhoid or scarlet fever exists.
Mathematical Modeling of Herpes Simplex Virus Distribution in Solid Tumors: Implications for Cancer Gene Therapy
Authors: Wilson Mok, Triantafyllos Stylianopoulos, Yves Boucher, Rakesh K. Jain
Journal: Clinical Cancer Research (2009)

Although oncolytic viral vectors show promise for the treatment of various cancers, ineffective initial distribution and propagation throughout the tumor mass often limit the therapeutic response. A mathematical model is developed to describe the spread of herpes simplex virus from the initial injection site.The tumor is modeled as a sphere of radius R. The model incorporates reversible binding, interstitial diffusion, viral degradation, and internalization and physiologic parameters. Three species are considered as follows: free interstitial virus, virus bound to cell surfaces, and internalized virus.This analysis reveals that both rapid binding and internalization as well as hindered diffusion contain the virus to the initial injection volume, with negligible spread to the surrounding tissue. Unfortunately, increasing the dose to saturate receptors and promote diffusion throughout the tumor is not a viable option: the concentration necessary would likely compromise safety. However, targeted modifications to the virus that decrease the binding affinity have the potential to increase the number of infected cells by 1.5-fold or more. An increase in the effective diffusion coefficient can result in similar gains.This analysis suggests criteria by which the potential response of a tumor to oncolytic herpes simplex virus therapy can be assessed. Furthermore, it reveals the potential of modifications to the vector delivery method, physicochemical properties of the virus, and tumor extracellular matrix composition to enhance efficacy.
Recurrent pneumonia after cardiac surgery
Authors: N. Ho, P.R. Genta, T.Y. Takagaki
Journal: European Respiratory Journal (2002)

Case historyA 38-yr-old male presented to the outpatient clinic complaining of recurrent episodes of pneumonia in the last 4 yrs.He had a past medical history of mitral and aortic valve disease due to rheumatic fever in childhood and was submitted to mitral comissurotomy through median sternotomy 5-yrs-ago.He had six episodes of productive cough with blood-streaked sputum, dyspnoea, fever, and wheezing in the last 4 yrs.Antibiotics were prescribed on all occasions.He had smoked for 30 pack-yrs.Spirometry revealed forced vital capacity (FVC) of 3.10 L (79%), forced expiratory volume in one second (FEV1) of 2.14 L (65%), FEV1/FVC of 0.69 (83%) with no response to bronchodilators.A chest radiograph and a computed tomography scan of the chest were performed (figs. 1 and 2).Bronchoscopic examination found extrinsic compression of the right lower-lobe bronchus, but no endobronchial lesions.He was submitted to right lower lobectomy through lateral thoracotomy.A partial atelectasis of the right lower lobe and a tumour were found.A right lower lobectomy was performed.The pathological examination is shown in fig. 3.
Latent HIV-1 infection in enriched populations of blood monocytes and T cells from seropositive patients.
Authors: M J McElrath, R M Steinman, Z A Cohn
Journal: Journal of Clinical Investigation (1991)

The extent of latent HIV-1 infection in blood T cells and monocytes of 23 seropositive individuals was examined using DNA amplification (PCR) of HIV-1 sequences. Amplified DNA was found in at least one cell type in all seropositives tested, including 13 asymptomatic, 5 ARC, and 5 AIDS patients. Amplification with two or more primer sets from the gag, env, LTR occurred in 21 (91%) patients' T cells and 17 (74%) patients' monocytes. However, amplification with the LTR primers in monocytes was uncommon. Among four patients tested, amplified DNA continued to be detected after a greater than one thousand-fold dilution (less than 500 cells) of both T cell and monocyte lysates. Repeat analysis after 7-9 mo in five seropositives yielded similar findings in T cells and monocytes, but some variation in the efficacy of amplification with individual primers occurred. There was no difference in those 10 patients who were taking AZT, compared to those who were untreated. Our results indicate that a fraction (less than 1%) of both T cells and monocytes in blood carry a latent infection in all stages of HIV-1 disease and can serve as reservoirs throughout AZT therapy.
Gammaglobulin treatment and anti-IgA antibodies in IgA-deficient patients.
Authors: J Koistinen, M Heikkila, J Leikola
Journal: BMJ (1978)

Antibodies to IgA may cause severe anaphylactic reactions during blood transfusions. Tests for anti-IgA antibodies were carried out on six patients with IgA deficiency (five of whom also had hypogammaglobulinaemia) who had received continuous gammaglobullin treatment for chronic or recurrent infections for three to eight years. Three patients had minute amounts of IgA, and three had none (less than 0.01 microgram/ml). Only one patient had anti-IgA. Her antibody titre did not change during treatment. No patient had any untoward effects of treatment, which relieved the symptoms of infection in every case. IgA determinations should be performed by more accurate methods than radial immunodiffusion when evaluating the risks of giving gammaglobulin to patients with hypogammaglobulinaemia and IgA deficiency. Probably the stimulus provided by intramuscular gammaglobulin in such patients is insufficient for the formation of anti-IgA antibody.
Targeted drug delivery for cancer therapy: the other side of antibodies
Authors: Michael A Firer, Gary Gellerman
Journal: Journal of Hematology & Oncology (2012)

Therapeutic monoclonal antibody (TMA) based therapies for cancer have advanced significantly over the past two decades both in their molecular sophistication and clinical efficacy. Initial development efforts focused mainly on humanizing the antibody protein to overcome problems of immunogenicity and on expanding of the target antigen repertoire. In parallel to naked TMAs, antibody-drug conjugates (ADCs) have been developed for targeted delivery of potent anti-cancer drugs with the aim of bypassing the morbidity common to conventional chemotherapy. This paper first presents a review of TMAs and ADCs approved for clinical use by the FDA and those in development, focusing on hematological malignancies. Despite advances in these areas, both TMAs and ADCs still carry limitations and we highlight the more important ones including cancer cell specificity, conjugation chemistry, tumor penetration, product heterogeneity and manufacturing issues. In view of the recognized importance of targeted drug delivery strategies for cancer therapy, we discuss the advantages of alternative drug carriers and where these should be applied, focusing on peptide-drug conjugates (PDCs), particularly those discovered through combinatorial peptide libraries. By defining the advantages and disadvantages of naked TMAs, ADCs and PDCs it should be possible to develop a more rational approach to the application of targeted drug delivery strategies in different situations and ultimately, to a broader basket of more effective therapies for cancer patients.
Fifty-Year Trend in Incidence Rates of Bronchogenic Carcinoma by Cell Type in Olmsted County, Minnesota
Authors: C. M. Beard, M. B. Jedd, L. B. Woolner, R. L. Richardson, E. J. Bergstralh, L. J. Melton
Journal: JNCI Journal of the National Cancer Institute (1988)

An earlier report suggested that incidence rates of primary bronchogenic carcinoma had leveled off for men in Olmsted County, MN. Extension of that study to cover 50 years in this midwestern community now shows that lung cancer incidence continues to increase in both sexes, with rates in women approaching those found in men 20 years ago. This increase was seen for all cell types of bronchogenic carcinoma. Because one pathologist reevaluated tissues, changing histologic classifications were not responsible for secular trends; nor were the results influenced by referral bias inasmuch as the study was population based. [J Natl Cancer Inst 1988;80:1404–1407]
CXCR3 Chemokine Receptor-Ligand Interactions in the Lymph Node Optimize CD4+ T Helper 1 Cell Differentiation
Authors: Joanna R. Groom, Jillian Richmond, Thomas T. Murooka, Elizabeth W. Sorensen, Jung Hwan Sung, Katherine Bankert, Ulrich H. von Andrian, James J. Moon, Thorsten R. Mempel, Andrew D. Luster
Journal: Immunity (2012)
Detecting Positive and Purifying Selection at Synonymous Sites in Yeast and Worm
Authors: T. Zhou, W. Gu, C. O. Wilke
Journal: Molecular Biology and Evolution (2010)

We present a new computational method to identify positive and purifying selection at synonymous sites in yeast and worm. We define synonymous substitutions that change codons from preferred to unpreferred or vice versa as nonconservative synonymous substitutions and all other substitutions as conservative. Using a maximum-likelihood framework, we then test whether conservative and nonconservative synonymous substitutions occur at equal rates. Our approach replaces the standard rate of synonymous substitutions per synonymous site, dS, with two new rates, the conservative synonymous substitution rate (dSC) and the nonconservative synonymous substitution rate (dSN). Based on the ratio dSN/dSC, we find that 0.05% of all yeast genes and none of worm genes show evidence of positive selection at synonymous sites (dSN/dSC > 1). On the other hand, 9.44% of all yeast genes and 5.12% of all worm genes show evidence of significant purifying selection on synonymous sites (dSN/dSC < 1). We also find that dSN correlates strongly with gene expression level, whereas the correlation between expression level and dSC is very weak. Thus, dSN captures most of the signal of selection for translational accuracy and speed, whereas dSC is not strongly influenced by this selection pressure. We suggest that the ratio dN/dSC may be more appropriate than the ratio dN/dS to identify positive or purifying selection on amino acids.
Positive Selection of Cd4+ T Cells Is Induced in Vivo by Agonist and Inhibited by Antagonist Peptides
Authors: Piotr Kraj, Rafal Pacholczyk, Hanna Ignatowicz, Pawel Kisielow, Peter Jensen, Leszek Ignatowicz
Journal: The Journal of Experimental Medicine (2001)

The nature of peptides that positively select T cells in the thymus remains poorly defined. Here we report an in vivo model to study the mechanisms of positive selection of CD4+ T cells. We have restored positive selection of TCR transgenic CD4+ thymocytes, arrested at the CD4+CD8+ stage, due to the lack of the endogenously selecting peptide(s), in mice deficient for H2-M and invariant chain. A single injection of soluble agonist peptide(s) initiated positive selection of CD4+ transgenic T cells that lasted for up to 14 days. Positively selected CD4+ T cells repopulated peripheral lymphoid organs and could respond to the antigenic peptide. Furthermore, coinjection of the antagonist peptide significantly inhibited agonist-driven positive selection. Hence, contrary to the prevailing view, positive selection of CD4+ thymocytes can be induced in vivo by agonist peptides and may be a result of accumulation of signals from TCR engaged by different peptides bound to major histocompatibility complex class II molecules. We have also identified a candidate natural agonist peptide that induces positive selection of CD4+ TCR transgenic thymocytes.
The safety of homeopathic products * Author's reply
Authors: P. Fisher, F. Dantas, H. Rampes, B. J Kirby
Journal: Journal of the Royal Society of Medicine (2002)

It is regrettable that Professor Kirby's editorial (May 2002 JRSM1) did not mention a review of this topic conducted and published by us2. This was a formal systematic review using prospectively defined inclusion and exclusion criteria and data extraction procedures. It comprised a review of English-language publications and enquiries with manufacturers and regulatory agencies.

Table 1 shows a sample of the data: in therapeutic clinical trials (as opposed to healthy-volunteer homeopathic pathogenetic trials) the incidence of reported adverse effects (AEs) is higher in the verum group than in the placebo group (mean incidence 9.4/6.1).



Table 1

Adverse effects (AEs) of homeopathy reported in therapeutic clinical trials





The conclusions were based on these data and reports of apparent AEs from homeopathic pathogenetic trials (provings) and case reports. The main conclusions were:



Homeopathic medicines may provoke AEs, but these are generally mild and transient


There is under-reporting


There are cases of ‘mistaken identity’, where herbal and other medicines were described as homeopathic


The main risks associated with homeopathy are indirect, relating to the prescriber rather than the medicine.






Although strictly speaking outside the remit of the editorial, the last point is particularly important. Not only is it the main risk of homeopathy, but it is a topical issue. Medical practice in the UK is currently essentially unregulated; anybody, irrespective of training or registration, can describe themselves as a homeopath. This is the main preventable source of risk. In their evidence to the House of Lords Select Committee on Complementary and Alternative Medicine3, bodies representing non medically qualified acupuncturists and herbalists stated that their professions wished to become statutorily regulated, the Select Committee's report endorsed this view, and the process towards statutory regulation of these professions is now underway.

The non-medical homeopaths, however, indicated that they did not currently wish statutory regulation, despite the view of the Faculty of Homeopathy (doctors and other health professionals practising homeopathy) that homeopathy should be practised only by statutorily registered professionals, and that a new profession should be created if necessary.
Effect of lignocaine, sodium cromoglycate, and ipratropium bromide in exercise-induced asthma
Authors: W. Tullett, K. Patel, K. Berkin, J. Kerr
Journal: Thorax (1982)

Eight patients with exercise-induced asthma participated in a single-blind trial comparing the protective effects of inhaled lignocaine (estimated dose 48 mg), sodium cromoglycate (estimated dose 12 mg), and ipratropium bromide (estimated dose 120 μg). Saline was used as control. Effects were assessed from the mean maximal percentage fall in forced expiratory volume in one second (FEV<sub>1</sub>) and maximal mid-expiratory flow rates (MMFR) after they had run on a treadmill for eight minutes. There was no significant change in baseline FEV<sub>1</sub> or MMFR before each agent was given. Saline, lignocaine, and sodium cromoglycate did not alter the mean baseline FEV<sub>1</sub> or MMFR significantly. Ipratropium caused bronchodilatation with an increase of 16·3% in the mean FEV<sub>1</sub> (p&lt;0·001) and of 43·4% in the mean MMFR (p&lt;0·05). After exercise the maximal percentage falls in FEV<sub>1</sub> (means and SEM) after saline, lignocaine, sodium cromoglycate, and ipratropium bromide were 38·1% (5·0), 34·5% (6·1), 11·3% (3·7), and 19·3% (7·4) respectively. Similarly, the mean maximal falls in MMFR after saline, lignocaine, sodium cromoglycate, and ipratropium bromide were 54·4% (5·2), 52·9% (7·7), 23·6% (6·6), and 32·1% (10·5) respectively. The inhibitory effects of sodium cromoglycate and ipratropium bromide were significant whereas lignocaine failed to produce an effect. These results suggest that mediator release is an important factor in exercise-induced asthma and that in some patients the effects of the mediators may be on the postsynaptic muscarinic receptors. Local anaesthesia of sensory vagal receptors, on the other hand, does not prevent exercise asthma and these receptors do not appear to have any important role in exercise-induced bronchoconstriction.
IgE class immune complexes in Felty's syndrome: characterisation of antibody activities in isolated complexes.
Authors: K Merétey, A Falus, U Böhm, H Permin, A Wiik
Journal: Annals of the Rheumatic Diseases (1984)

By means of a double polyethylene glycol (PEG) precipitation and PRIST technique IgE was detected in 3% PEG precipitates and in the immune complex enriched fractions purified by solid-phase Clq adsorption from sera of 11 of 20 patients with Felty's syndrome. No correlation was found between the occurrence of complexed IgE and total protein content of the immune complex enriched material. IgE rheumatoid factor and anti-IgE antibody activity were detected in some of the immune complex fractions. Serum levels of complement C3, C4, and factor B were low in IgE immune complex positive cases. Only 4 of 20 patients with articular rheumatoid arthritis had IgE-containing immune complexes.
Kidney Allograft and Patient Survival in Type I Diabetic Recipients of Cadaveric Kidney Alone Versus Simultaneous Pancreas/Kidney Transplants
Authors: Suphamai Bunnapradist, Yong W. Cho, J. Michael Cecka, Alan Wilkinson, Gabriel M. Danovitch
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Simultaneous pancreas-kidney transplant (SPK) is now a common treatment for insulin-dependent diabetic patients with end-stage renal disease. Renal graft survival rates after SPK have been less well studied. This study compared the kidney survival results for 3642 SPK and 2374 cadaveric renal transplants (CRT) in type I diabetic patients at 112 US transplant centers reported to UNOS during 1994 through 1997. The analysis included follow-up information through September 2000. The kidney graft survival rates were significantly lower among recipients of CRT compared with SPK recipients (<i>P</i> &lt; 0.001). Patients who received SPK were younger, less often sensitized, transplanted after shorter periods on dialysis, and less often black. The donors of SPK organs were younger, more often died from head trauma, were less often female, and more often black. SPK renal grafts were transplanted with a shorter cold ischemia time to more poorly HLA-matched recipients. After adjustment of these and other factors, whether a patient was recipient of CRT or SPK was not associated with increased risk of kidney graft failure or patient death. SPK recipients experienced half the rate of delayed kidney function (11% <i>versus</i> 23%) but nearly double the rate of rejections during the initial hospitalization (15% <i>versus</i> 9%) compared with CRT recipients. SPK was associated with better renal allograft survival compared with CRT, despite a higher rate of renal allograft rejection. This observation was explained by favorable donor and recipient factors in the SPK group. After controlling for these factors, SPK provided no protective or detrimental effect on short-term renal allograft or patient survival. E-mail: bunnapradist@cshs.org
Gap junctional uncoupling plays a trigger role in the antiarrhythmic effect of ischaemic preconditioning
Authors: R PAPP, M GONCZI, M KOVACS, G SEPRENYI, A VEGH
Journal: Cardiovascular Research (2007)

Objective: The aim of this study was to determine whether uncoupling of gap junctions (GJ) prior to ischaemia would modify the antiarrhythmic effect of ischaemic preconditioning (PC) in a canine model of ischaemia/reperfusion.