tbuckley/cabot-search huggingface dataset:
The effect of inhaled mannitol on bronchial mucus clearance in cystic fibrosis patients: a pilot study
Authors: M. Robinson, E. Daviskas, S. Eberl, J. Baker, H-K Chan, S.d. Anderson, P.T.p. Bye
Journal: European Respiratory Journal (1999)

It has been postulated that hypertonic saline (HS) might impair the antimicrobial effects of defensins within the airways. Alternative non-ionic osmotic agents such as mannitol may thus be preferable to HS in promoting bronchial mucus clearance (BMC) in patients with cystic fibrosis (CF). This study reports the effect of inhalation of another osmotic agent, dry powder Mannitol (300 mg), compared with its control (empty capsules plus matched voluntary cough) and a 6% solution of HS on BMC in 12 patients with cystic fibrosis (CF). Mucus clearance was measured using a radioaerosol/gamma camera technique. Post-intervention clearance was measured for 60 min, followed by cough clearance for 30 min. Neither mannitol nor HS improved BMC during the actual intervention period compared with their respective controls. However during the post-intervention measurement there was a significant improvement in BMC for both the mannitol (8.7+/-3.3% versus 2.8+/-0.7%) and HS (10.0+/-2.3% versus 3.5+/-0.8%). There was also a significant improvement in cough clearance with the Mannitol (9.7+/-2.4%) compared with its control (2.5+/-0.8%). Despite premedication with a bronchodilator, a small fall in forced expiratory volume in one second (FEV1) was seen immediately after administration of both the mannitol (7.3+/-2.5%) and HS (5.8+/-1.2%). Values of FEV1 returned to baseline by the end of the study. Inhaled mannitol is a potential mucoactive agent in cystic fibrosis patients. Further studies are required to establish the optimal dose and the long-term effectiveness of mannitol.
Heat Stroke in Phenothiazine-Treated Patients: A Report of Three Fatalities
Authors: SAMUEL ZELMAN, RAMON GUILLAN
Journal: American Journal of Psychiatry (1970)

During a heat wave in July 1969, the authors encountered three fatal cases of heat stroke. All the patients had been treated with phenothiazines, which affect temperature regulation and suppress sweating, and two with anti-Parkinsonian agents, which also suppress sweating. The authors stress the need for lower phenothiazine dosages where possible, limited use of supplemental anticholinergic agents, and awareness of the susceptibility of phenothiazine-treated patients to the hazards of extreme temperatures.
Progestogen intolerance and compliance with hormone replacement therapy in menopausal women
Authors: N Panay
Journal: Human Reproduction Update (1997)

It is vital that we maximize compliance if patients are to receive the full benefits from hormone replacement therapy (HRT). One of the main factors for reduced compliance is that of progestogen intolerance. Progestogens have a variety of effects apart from the one for which their use was intended, that of secretory transformation of the endometrium. Endometrial effects vary between individuals and between different progestogens, leading to bleeding problems. Symptoms of fluid retention are produced by the sodium-retaining effect on the renin-aldosterone system. The nor-testosterone-derived progestogens can have adverse effects on skin, lipids, vasculature and insulin resistance. Negative mood effects are produced by most progestogens due to the effect on neurotransmitters via central nervous system progesterone receptors. Manipulation of the dosage and duration of progestogen, continuous administration of a low dose of progestogen and a reduction in the number of progestogenic episodes can be used to improve compliance. The progestogen and progesterone releasing coils and vaginal progesterone gel minimize systemic side effects and bleeding. Adverse effects can also be avoided by making use of the progesterone receptor-specific progestogens such as the pregnanes (e.g. cyproterone), nor-pregnanes (e.g. nomegestrol) and progesterone itself. Hysterectomy remains an option for the severely progestogen-intolerant woman. In the future, progestogen intolerance may not be an issue if selective oestrogen receptor modulators provide a complete alternative to HRT.
Regulation of Telomerase and Telomeres: Human Tumor Viruses Take Control
Authors: M. Bellon, C. Nicot
Journal: JNCI Journal of the National Cancer Institute (2008)

Human tumor viruses are responsible for one-fifth of all cancers worldwide. These viruses have evolved multiple strategies to evade immune defenses and to persist in the host by establishing a latent infection. Proliferation is necessary for pretumor cells to accumulate genetic alterations and to acquire a transformed phenotype. However, each cell division is associated with a progressive shortening of the telomeres, which can suppress tumor development by initiating senescence and irreversible cell cycle arrest. Therefore, the ability of virus-infected cells to circumvent the senescence program is essential for the long-term survival and proliferation of infected cells and the likelihood of transformation. We review the multiple strategies used by human DNA and RNA tumor viruses to subvert telomerase functions during cellular transformation and carcinogenesis. Epstein-Barr virus, Kaposi sarcoma-associated herpesvirus, human papillomavirus, hepatitis B virus, hepatitis C virus, and human T-cell leukemia virus-1 each can increase transcription of the telomerase reverse transcriptase. Several viruses appear to mediate cis-activation or enhance epigenetic activation of telomerase transcription. Epstein-Barr virus and human papillomavirus have each developed posttranscriptional mechanisms to regulate the telomerase protein. Finally, some tumor virus proteins can also negatively regulate telomerase transcription or activity. It is likely that, as future studies further expose the strategies used by viruses to deregulate telomerase activity and control of telomere length, novel mechanisms will emerge and underscore the importance of increased telomerase activity in sustaining virus-infected cells and its potential in therapeutic targeting.
THE CIRCUITRY OF V1 AND V2: Integration of Color, Form, and Motion
Authors: Lawrence C. Sincich, Jonathan C. Horton
Journal: Annual Review of Neuroscience (2005)

Primary and secondary visual cortex (V1 and V2) form the foundation of the cortical visual system. V1 transforms information received from the lateral geniculate nucleus (LGN) and distributes it to separate domains in V2 for transmission to higher visual areas. During the past 20 years, schemes for the functional organization of V1 and V2 have been based on a tripartite framework developed by Livingstone & Hubel (1988) . Since then, new anatomical data have accumulated concerning V1's input, its internal circuitry, and its output to V2. These new data, along with physiological and imaging studies, now make it likely that the visual attributes of color, form, and motion are not neatly segregated by V1 into different stripe compartments in V2. Instead, there are just two main streams, originating from cytochrome oxidase patches and interpatches, that project to V2. Each stream is composed of a mixture of magno, parvo, and konio geniculate signals. Further studies are required to elucidate how the patches and interpatches differ in the output they convey to extrastriate cortex.
Usefulness of Serum Carboxy-Terminal Propeptide of Procollagen Type I in Assessment of the Cardioreparative Ability of Antihypertensive Treatment in Hypertensive Patients
Authors: Begoña López, Ramón Querejeta, Nerea Varo, Arantxa González, Mariano Larman, José L. Martínez Ubago, Javier Díez
Journal: Circulation (2001)

We investigated whether serum concentration of carboxy-terminal propeptide of procollagen type I (PIP), a marker of collagen type I synthesis, can be used to assess the ability of antihypertensive treatment to regress myocardial fibrosis in hypertensive patients.The study was performed in 37 patients with essential hypertension and hypertensive heart disease. After randomization, 21 patients were assigned to losartan and 16 patients to amlodipine treatment. At baseline and after 12 months, right septal endomyocardial biopsies were performed to quantify collagen volume fraction (CVF) on picrosirius red-stained sections with an automated image-analysis system. Serum PIP was measured by specific radioimmunoassay. Nineteen patients in the losartan group and 11 in the amlodipine group finished the study. Time-course changes in blood pressure during treatment were similar in the 2 groups of patients. In losartan-treated patients, CVF decreased from 5.65+/-2.03% to 3.96+/-1.46% (P<0.01) and PIP from 127+/-30 to 99+/-26 microgram/L (P<0.01). Neither CVF or PIP changed significantly in amlodipine-treated patients. CVF was directly correlated with PIP (r=0.44, P<0.001) in all hypertensives before and after treatment.These findings suggest that the ability of antihypertensive treatment to regress fibrosis in hypertensives with biopsy-proven myocardial fibrosis is independent of its antihypertensive efficacy. Our data also suggest that blockade of the angiotensin II type 1 receptor is associated with inhibition of collagen type I synthesis and regression of myocardial fibrosis in hypertensives. Thus, determination of serum PIP may be useful to assess the cardioreparative properties of antihypertensive treatment in hypertensives.
Gender differences in the long QT syndrome: effects of β-adrenoceptor blockade
Authors: C Conrath
Journal: Cardiovascular Research (2002)

Gender differences have been reported in patients with the congenital long QT syndrome (LQTS). We analyzed whether electrocardiographic differences existed in females, males, girls and boys in response to beta-adrenoceptor blockade.12-lead ECGs before and during beta-adrenoceptor blockade were collected in 87 genotyped LQTS patients (48 women, 14 men, 12 girls and 13 boys). Up to three QTc intervals were determined in each lead of the ECG. V4 was used for QT/QTc analysis. Difference between longest and shortest QT interval was taken as a measure for dispersion of QT intervals.(1) Adult males had the greatest shortening of the QTc interval upon treatment with beta-adrenoceptor blockade. During treatment, adult males with LQTS(1) (mutation in the KCNQ1 gene, affecting I(Ks) current) were found to have shorter QTc intervals than adult females; this difference did not exist in LQTS(2) patients (mutation in the HERG gene, affecting I(Kr) current). (2) Female LQTS(2) patients had a 50% larger dispersion than female LQTS(1) patients both before and during treatment. (3) Adult male LQTS(1) patients constitute the only patient group with a marked decrease in QTc intervals and dispersion associated with a 100% efficacy of treatment in response to beta-adrenoceptor blockade.These findings indicate that, in addition to underlying differences in repolarization between men and women, cardiac electrophysiological responses to beta-adrenoceptor blockade can be modulated by gender-related factors.
The Effect of Ganglionic Blockade on the Pressor Response to Angiotensin in Systemic Hypertension
Authors: J. Hamer, E. Jackson
Journal: Cardiovascular Research (1969)

The pressor effects of angiotensin infusion in nine hypertensive subjects were augmented by ganglionic blockade. The findings suggest an abnormality of capacitance vessel tone in patients with hypertension.
Retinal microvasculature in acute lacunar stroke: a cross-sectional study
Authors: Richard I Lindley, Jie Jin Wang, Meng-Cheong Wong, Paul Mitchell, Gerald Liew, Peter Hand, Joanna Wardlaw, Deidre A De Silva, Michelle Baker, Elena Rochtchina, Christopher Chen, Graeme J Hankey, Hui-Meng Chang, Victor SC Fung, Lavier Gomes, Tien Y Wong
Journal: The Lancet Neurology (2009)
Factor H and Atypical Hemolytic Uremic Syndrome
Authors: Mihály Józsi, Stefan Heinen, Andrea Hartmann, Clemens W. Ostrowicz, Steffi Hälbich, Heiko Richter, Anja Kunert, Christoph Licht, Rebecca E. Saunders, Stephen J. Perkins, Peter F. Zipfel, Christine Skerka
Journal: Journal of the American Society of Nephrology (2005)

Atypical hemolytic uremic syndrome is a disease that is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. Mutations in the complement regulator factor H are associated with the inherited form of the disease, and >60% of the mutations are located within the C terminus of factor H. The C-terminus of factor H, represented by short consensus repeat 19 (SCR19) and SCR20, harbors multiple functions; consequently, this study aimed to examine the functional effects of clinically reported mutations in these SCR. Mutant factor H proteins (W1157R, W1183L, V1197A, R1210C, R1215G, and P1226S) were recombinantly expressed and functionally characterized. All six mutant proteins showed severely reduced heparin, C3b, C3d, and endothelial cell binding. By peptide spot analyses, four linear regions that are involved in heparin, C3b, and C3d binding were localized in SCR19 and SCR20. A three-dimensional homology model of the two domains suggests that these four regions form a common binding site across both domains. In addition, this structural model identifies two types of residues: Type A residues are positioned on the SCR surface and are represented by mutants W1157R, W1183L, R1210C, and R1215G; and type B residues are buried within the SCR structure and affect mutations V1197A and P1226S. Mutations of both types of residue result in the same functional defects, namely the reduced binding of factor H to surface-attached C3b molecules and reduced complement regulatory activity at the cell surfaces. The buried type B mutations seem to affect ligand interaction of factor H more severely than the surface-exposed mutations.
Erythrocyte sedimentation rate and C reactive protein in the assessment of polymyalgia rheumatica/giant cell arteritis on presentation and during follow up.
Authors: V Kyle, T E Cawston, B L Hazleman
Journal: Annals of the Rheumatic Diseases (1989)

The erythrocyte sedimentation rate (ESR) and C reactive protein (CRP) were measured in 74 patients with polymyalgia rheumatica (PMR)/giant cell arteritis (GCA) on presentation, in the first month of treatment, and at long term follow up (up to 177 weeks). Before treatment the ESR was raised (greater than 30 mm/h) in all cases and the CRP was raised (greater than 6 mg/l) in 49/55 cases. The ESR was a better indicator of clinical disease activity except in patients who felt completely well at week 1. 'False positive' increases of ESR or CRP were rare. During relapses ESR was normal in 37/77 (48%) of cases and CRP in 41/73 (56%). It is suggested that ESR is the most useful laboratory parameter in assessing PMR/GCA.
Influence of heat and humidity on the airway obstruction induced by exercise in asthma.
Authors: R H Strauss, E R McFadden, R H Ingram, E C Deal, J J Jaeger
Journal: Journal of Clinical Investigation (1978)

We examined the degree of airway obstruction that developed in eight asthmatics who exercised while breathing air under four conditions: (a) ambient room temperature and water content; (b) body temperature and ambient water content; (c) ambient room temperature fully saturated; and (d) body temperature fully saturated. These test conditions were performed in random order. Multiple aspects of pulmonary mechanics were measured before and 5 min after exercise. When air at ambient conditions was inhaled, the expected airway obstruction developed after exercise, and all variables changes significantly from their pre-challenge values. Heating the air to body temperature did not influence this response. Increasing the humidity at ambient temperatures significantly blunted the response, and by inhaling body temperature, fully saturated air completely prevented it from occurring. Thus, the water content of inspired air is an important variable in the development of exercise induced asthma.
Resection rates and postoperative mortality in 7,899 patients with lung cancer
Authors: RA Damhuis, PR Schutte
Journal: European Respiratory Journal (1996)

Postoperative death used to be an important complication of resections for lung cancer, especially in elderly patients. To support decision making in a general situation, contemporary results and prognostic factors were evaluated. The computer records of 7899 lung cancer patients, diagnosed from 1984 until 1992 in hospitals connected to the Rotterdam Cancer Registry, were analysed to evaluate resection rates and 30 day postoperative mortality. Resections were carried out in 20% of all patients. In patients 70 yrs of age and older, the resection rate was 14%, and in younger patients 26%. The postoperative mortality was 3.1%; 3.6% for males and 0.4% for females. According to multivariate analysis, age and extent of surgery were the major determinants of operative risk. For patients aged 0-59, 60-69 and &gt; or = 70, postoperative mortality rates were 1.4, 3.5 and 4.0%, respectively. The operative risk was 5.7% after pneumonectomy, 4.4% after bilobectomy, and 1.4% after lesser resections. Pneumonectomies were performed less often in elderly patients: 27% of operations in patients &gt; or = 70 yrs versus 37% of operations in younger patients. Age appears to be related to treatment choice and postoperative mortality in patients with lung cancer. However, even in patients over 70 yrs of age, resections can be performed at acceptable risk, implying that chronological age should not automatically determine treatment decisions.
Lasting Controversy on Ranibizumab and Bevacizumab
Authors: Lihui Zou, Huiying Lai, Qi Zhou, Fei Xiao
Journal: Theranostics (2011)

Vascular endothelial growth factor (VEGF), an important angiogenic factor that is able to stimulate the proliferation and migration of endothelial cells, is the best-studied hallmark of angiogenesis. Neovascularization is a major cause of age-related macular degeneration (AMD) which is a leading cause of blindness in the elderly population. Specific molecular inhibitors of VEGF have been proved to be useful in the treatment of AMD. Ranibizumab and Bevacizumab are structurally similar to anti-VEGF drugs in the treatment of AMD. Many studies have indicated that Ranibizumab and Bevacizumab are of roughly equal short-term efficacy and safety, Bevacizumab is an attractive alternative to Ranibizumab due to its lower cost. However, only Ranibizumab has received Food and Drug Administration (FDA) approval for the treatment of macular degeneration. More multicenter clinical trials are required to compare the relative efficacy and safety of these two drugs and some progress has been achieved. This review discusses the clinical effectiveness, safety, cost and other practical implications of Ranibizumab and Bevacizumab.
Quality of life in psoriasis and chronic hand eczema: the discrepancy in the definition of severity in NICE guidelines and its implications
Authors: M.K.A. Basra, M.M.U. Chowdhury, E.V. Smith, N. Freemantle, V. Piguet
Journal: British Journal of Dermatology (2011)

Funding sources: Manuscript development was supported by unconditional funding from Basilea Pharmaceutical International Ltd., Basel, Switzerland. Conflicts of interest: M.K.A.B. and E.V.S. none declared; M.M.U.C. has received educational grants and consultancy fees from Basilea; N.F. has received funding for research and consulting from Pfizer, Basilea and MSD; V.P. has received educational grants and/or consulting fees from Pfizer, GSK, Abbott, Basilea, MSD/Schering and Janssen. Madam, Psoriasis and chronic hand eczema (CHE) are skin conditions that have a profound detrimental effect on the quality of life (QoL) of those affected. Apart from the physical symptoms, the impact of psoriasis on QoL seems to be dominated by the disfigurement caused, which is manifested in terms of psychological distress. In contrast, CHE seems to have a more direct impact on an individual’s ability to work and their productivity, with difficulty in pursuing normal daily activities, frequent sick leave and even job loss in some instances.1, 2 This implies that these aspects should be given proper emphasis when measuring the overall severity and impact of these skin conditions from the patients’ perspective.
Challenges to Autism Research
Authors: D. S. Shirley
Journal: Journal of the Royal Society of Medicine (2005)

Like many parents of a child with autism, the disorder has come to dominate my life. For 35 years I was involved with the daily experiences of caring, then with support services, schools and various strategic initiatives in the autism sector. But, perhaps inevitably, I am nowadays focused on research into causes. I do this via NAAR [the National Alliance for Autism Research] and its global affiliates. I try to work always with respect: respect for people with autism who, like my late son, are without speech, epileptic and with profound learning disabilities; also respect for those high performing individuals at the other end of the spectrum who denounce the search for causes.
A gender-related defect in lipid metabolism and glucose homeostasis in peroxisome proliferator- activated receptor alpha- deficient mice.
Authors: F Djouadi, C J Weinheimer, J E Saffitz, C Pitchford, J Bastin, F J Gonzalez, D P Kelly
Journal: Journal of Clinical Investigation (1998)

The peroxisome proliferator-activated receptor alpha (PPARalpha) is a nuclear receptor implicated in the control of cellular lipid utilization. To test the hypothesis that PPARalpha is activated as a component of the cellular lipid homeostatic response, the expression of PPARalpha target genes was characterized in response to a perturbation in cellular lipid oxidative flux caused by pharmacologic inhibition of mitochondrial fatty acid import. Inhibition of fatty acid oxidative flux caused a feedback induction of PPARalpha target genes encoding fatty acid oxidation enzymes in liver and heart. In mice lacking PPARalpha (PPARalpha-/-), inhibition of cellular fatty acid flux caused massive hepatic and cardiac lipid accumulation, hypoglycemia, and death in 100% of male, but only 25% of female PPARalpha-/- mice. The metabolic phenotype of male PPARalpha-/- mice was rescued by a 2-wk pretreatment with beta-estradiol. These results demonstrate a pivotal role for PPARalpha in lipid and glucose homeostasis in vivo and implicate estrogen signaling pathways in the regulation of cardiac and hepatic lipid metabolism.
The effect of statin usage on airway inflammatiory cells and markers, and clinical indices in asthmatic patients
Authors: Sehnaz Olgun Tandogdu, Berrin Bagci Ceyhan, Aygun Ikinci, Rengin Ahiskali
Journal: European Respiratory Journal (2011)

Introduction: Asthma has been characterized with airway inflammation. Statins have immunomodulatory properties in addition to lowering cholesterol. However their effects in asthmatic patients have not been evaluated yet.  Aim: To define the effect of statins on inflammatory markers, cells and clinical indices in asthmatics.  Method: 51 patients with asthma were included in the study. Pulmonary function tests (PFT), metacholine bronchoprovocation test, peripheral blood smear, blood total IgE value, IgE specific sub-groups were evaluated during the initial evaluation. After taking asthma questionnaires, ACQ and AQLQ, induced sputum samples were collected. Cells were counted in the induced sputum and the supernatant was evaluated for IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, TNF-alfa and VEGF levels with ELISA in all patients at the baseline. 25 asthmatic patients with LDL >130mg/dl were treated with Rosuvastatin at the following 8 weeks, then all patients were re-evaluated with the same studies.  Results: 8 week treatment with Rosuvastatin resulted in improvement of MEF (L/s) (p  Conclusion: We conclude that statins suppress inflammatory and allergic markers and improve PFT in asthmatic patients. This may be an opportunity to develop a new treatment for asthmatic patients.