tbuckley/cabot-search huggingface dataset:
Cytokines in asthma
Authors: K F Chung, P J Barnes
Journal: Thorax (1999)

Cytokines are usually extracellular signalling proteins, usually less than 80 kD in size, and many are glycosylated. They are produced by many different cell types that are involved in cell-to-cell interactions acting through specific receptors on the surface of target cells. Cytokines usually have an effect on closely adjacent cells and therefore function in a predominantly paracrine fashion, although they may also act at a distance (endocrine) and may have effects on the cell of origin (autocrine). Cytokines may be regarded as a mechanism for cell-cell communication, and within this group may be included growth factors and cytokines with primarily chemoattractant properties (chemokines). They act on target cells to cause a wide array of cellular functions including activation, proliferation, chemotaxis, immunomodulation, release of other cytokines or mediators, growth and cell differentiation, and apoptosis. Cytokines were originally characterised (and named) according to some aspect of their functional activity that was initially discovered, but the cloning of the genes for these cytokines has now provided a better insight into their classification and grouping. It is apparent that there is a wide pleiotropy and element of redundancy in the cytokine family in that each cytokine has many overlapping functions, with each function potentially mediated by more than one cytokine.

The effect of an individual cytokine in the context of disease may not be easy to predict because it may be influenced by other cytokines released simultaneously from the same cell or from target cells following activation by the cytokine. The effects of cytokines are mediated by binding to cell surface high affinity receptors usually present in low numbers. The number of these receptors can be upregulated with cell activation, and there the effect of a cytokine may depend on the modulation of its receptors. Cytokines themselves may induce the expression of receptors which may …
'An innocent deception': placebo controls in the St Petersburg homeopathy trial, 1829-1830
Authors: M E Dean
Journal: Journal of the Royal Society of Medicine (2006)

Samuel Hahnemann (1755-1843), founder of the homeopathic school, began the systematic serial dilution and succussion of his medicines around 1814. 1 Since then the homeopathic materia medica has often been thought of as an elaborate collection of placebos, and it has long been known that placebo-controlled tests of homeopathy took place as early as the mid-1830s. 2A likely origin for this development in the history of clinical evaluation can be found in reports of two linked hospital-based trials of homeopathy that took place in Russia a few years earlier.The homeopath in both trials was a Dr Herrmann, who received a 1-year contract in February 1829 to test homeopathy with the Russian military. 3The first study took place at the Military Hospital in the market town of Tulzyn, in the province of Podolya, Ukraine. 4 At the end of 3 months, 164 patients had been admitted, 123 pronounced cured, 18 were convalescing, 18 still sick, and six had died.The homeopathic ward received many gravely ill patients, and the small number of deaths was shown at autopsy to be due to advanced gross pathologies.The results were interesting enough for the Russian government to order Herrmann to the Regional Military Hospital at St Petersburg to take part in a larger trial, supervised by a Dr Gigler.Patients were admitted to an experimental homeopathic ward, for treatment by Herrmann, and comparisons were made with the success rate in the allopathic wards, as happened in Tulzyn.The novelty was Gigler's inclusion of a 'no treatment' ward where patients were not subject to conventional drugging and bleeding, or homeopathic dosing.The untreated patients benefited from baths, tisanes, good nutrition and rest, but also: 'During this period, the patients were additionally subjects of an innocent deception.In order to deflect the suspicion that they were not being given any medicine, they were prescribed pills made of white breadcrumbs or cocoa, lactose powder or salep infusions, as happened in the homeopathic ward.' 3 (page 415)
Incidence of diagnosed polymyalgia rheumatica and temporal arteritis in the United Kingdom, 1990-2001
Authors: L Smeeth
Journal: Annals of the Rheumatic Diseases (2006)

<b>Objective:</b> To investigate time trends, geographical variation, and seasonality in the incidence of diagnosis of polymyalgia rheumatica (PMR) and temporal arteritis (TA) in the United Kingdom. <b>Methods:</b> Analysis of computerised medical records from UK general practices. Participants were registered with a practice contributing to the General Practice Research Database during the period 1990–2001. The main outcome measures were rates of diagnosis by year, age, sex, geographical region, and calendar month. <b>Results:</b> 15 013 people had a first diagnosis of PMR and 3928 a first diagnosis of TA during 17 830 028 person-years of observation. The age adjusted incidence rate of PMR was 8.4/10 000 person-years (95% CI 8.3 to 8.6), rising from 6.9/10 000 person-years in 1990 to 9.3/10 000 in 2001. The age adjusted incidence rate of TA was 2.2/10 000 person-years (95% CI 2.1 to 2.3) with no increase observed. Both PMR and TA were more common in the south than in the north of the UK, and both were more commonly diagnosed in the summer months. <b>Conclusions:</b> The explanation for the findings is unclear. Variations in diagnostic practice and accuracy are likely to have contributed in part to the patterns seen. However, the findings are also likely to reflect, at least in part, variations in the incidence of disease. The striking geographical pattern may be partly attributable to a risk factor which is more prevalent in the south and east of the United Kingdom.
Gene Survival and Death on the Human Y Chromosome
Authors: Melissa A. Wilson Sayres, Kateryna D. Makova
Journal: Molecular Biology and Evolution (2012)

Y chromosomes have long been dismissed as "graveyards of genes," but there is still much to be learned from the genetic relics of genes that were once functional on the human Y. We identified human X-linked genes whose gametologs have been pseudogenized or completely lost from the Y chromosome and inferred which evolutionary forces may be acting to retain genes on the Y. Although gene loss appears to be largely correlated with the suppression of recombination, we observe that X-linked genes with functional Y homologs evolve under stronger purifying selection and are expressed at higher levels than X-linked genes with nonfunctional Y homologs. Additionally, we support and expand upon the hypothesis that X inactivation is primarily driven by gene loss on the Y. Using linear discriminant analysis, we show that X-inactivation status can successfully classify 90% of X-linked genes into those with functional or nonfunctional Y homologs.
Changing Epidemiology of Small-Cell Lung Cancer in the United States Over the Last 30 Years: Analysis of the Surveillance, Epidemiologic, and End Results Database
Authors: Ramaswamy Govindan, Nathan Page, Daniel Morgensztern, William Read, Ryan Tierney, Anna Vlahiotis, Edward L. Spitznagel, Jay Piccirillo
Journal: Journal of Clinical Oncology (2006)

Purpose Small-cell lung cancer (SCLC) is a histologic subtype of lung cancer with a distinct biology and clinical course. It has been observed that the incidence of SCLC has been decreasing over the last several years. Methods We used the Surveillance, Epidemiologic, and End Results (SEER) database to determine the incidence of SCLC over the last 30 years. In addition, we sought to determine sex- and stage-based differences in the incidence and survival of SCLC among a proportion of reported cases of lung cancer over the last 30 years (1973 to 2002). Joinpoint analyses were applied to test the trends in annual percentage change for statistical significance. Results The proportion of SCLC (among all lung cancer histologic types) decreased from 17.26% in 1986 to 12.95% in 2002. Of all patients with SCLC, the proportion of women with SCLC increased from 28% in 1973% to 50% in 2002. A modest but statistically significant improvement in 2- and 5-year survival was noted among both limited-stage SCLC and extensive-stage SCLC cohorts during the study period. Conclusion Our analysis indicates that the incidence of SCLC is decreasing in the United States, and only modest improvements have been seen in survival over the last 30 years. Possible explanations for the decreasing incidence include the decrease in the percentage of smokers and the change to low-tar filter cigarettes. Despite trends toward modest improvement in survival, the outcome remains very poor.
Boxing and medicine.: Ed R C Cantu. (Pp 207; pound28.50.) Leeds: Human Kinetics Europe Ltd, 1995. ISBN 0-87322-797-2.
Authors: Ian Mcgibbon
Journal: British Journal of Sports Medicine (2000)

I enjoyed reading this book. A book consisting solely of accounts of boxing related injuries would probably have been a chore to read and reinforced my prejudices about a pastime in which participants have to punch their opponents to score points. However, this is a well balanced book that sets out the medical aspects of boxing in a logical fashion.

The differences between amateur and professional boxing are explained, and there are chapters that address …
Role of Human Papillomavirus Genotype in Prognosis of Early-Stage Cervical Cancer Undergoing Primary Surgery
Authors: Chyong-Huey Lai, Chee-Jen Chang, Huei-Jean Huang, Swei Hsueh, Angel Chao, Jung-Erh Yang, Cheng-Tao Lin, Shang-Lang Huang, Ji-Hong Hong, Hung-Hsueh Chou, Tzu-I Wu, Kuan-Gen Huang, Chun-Chieh Wang, Ting-Chang Chang
Journal: Journal of Clinical Oncology (2007)

Purpose Our aim was to evaluate the prognostic significance of human papillomavirus (HPV) genotype in early-stage cervical carcinoma primarily treated with surgery in a large tertiary referral medical center. Patients and Methods Consecutive patients who underwent primary surgery for invasive cervical carcinoma of International Federation of Gynecology and Obstetrics (FIGO) stage I to IIA between 1993 and 2000 were retrospectively reviewed. Polymerase chain reaction (PCR) using a general primer set followed by reverse-blot detection of 38 types of HPV DNA in a single reaction was performed for genotyping. E6 type-specific PCR was performed to validate multiple types. Results A total of 1,067 eligible patients were analyzed. HPV DNA sequences were detected in 95.1% of the specimens, among which 9.6% contained multiple types. HPV 16 was detected in 63.8% of the samples, and HPV 18 was detected in 16.5% of the samples. The median follow-up time of surviving patients was 77 months. By multivariate analysis, FIGO stage, lymph node metastasis, depth of cervical stromal invasion, grade of differentiation, and HPV 18 positivity were significantly related to cancer relapse. FIGO stage II, deep stromal invasion, parametrial extension, HPV 18 positivity, and age older than 45 years were significant predictors for death. Using the seven selected variables from either recurrence-free or overall survival analysis, death-predicting (P &lt; .0001) and relapse-predicting (P &lt; .0001) models classifying three risk groups (low, intermediate, and high risk) were constructed and endorsed by internal validation. Conclusion The independent prognostic value of HPV genotype is confirmed in this study. The prognostic models could be useful in counseling patients and stratifying patients in future clinical trials.
Mitochondrial fission mediates high glucose-induced cell death through elevated production of reactive oxygen species
Authors: Tianzheng Yu, Shey-Shing Sheu, James L. Robotham, Yisang Yoon
Journal: Cardiovascular Research (2008)

One of the main causes of cardiovascular complications in diabetes is the hyperglycaemia-induced cell injury, and mitochondrial fission has been implicated in the apoptotic process. We investigated the role of mitochondrial fission in high glucose-induced cardiovascular cell injury. We used several types of cultured mouse, rat, and bovine cells from the cardiovascular system, and evaluated mitochondrial morphology, reactive oxygen species (ROS) levels, and apoptotic parameters in sustained high glucose incubation. Adenoviral infection was used for the inhibition of the fission protein DLP1. We found that mitochondria were short and fragmented in cells incubated in sustained high glucose conditions. Under the same conditions, cellular ROS levels were high and cell death was increased. We demonstrated that the increased level of ROS causes mitochondrial permeability transition (MPT), phosphatidylserine exposure, cytochrome c release, and caspase activation in prolonged high glucose conditions. Importantly, maintaining tubular mitochondria by inhibiting mitochondrial fission in sustained high glucose conditions normalized cellular ROS levels and prevented the MPT and subsequent cell death. These results demonstrate that mitochondrial fragmentation is an upstream factor for ROS overproduction and cell death in prolonged high glucose conditions. These findings indicate that the fission-mediated fragmentation of mitochondrial tubules is causally associated with enhanced production of mitochondrial ROS and cardiovascular cell injury in hyperglycaemic conditions.
Characterization of Hereditary Nonpolyposis Colorectal Cancer Families From a Population-Based Series of Cases
Authors: D. J. Peel
Journal: JNCI Journal of the National Cancer Institute (2000)

The incidence of hereditary nonpolyposis colon cancer (HNPCC) in the general population is not well defined because of the lack of large population-based studies. We characterized the incidence of HNPCC in a large, population-based cohort of colorectal cancer probands and analyzed the location of colorectal tumors.Of the participating 1134 probands from three counties in Southern California, 907 had a negative family history of colorectal cancer and 227 had a positive family history of colorectal cancer. In addition, 11 referral case subjects with HNPCC were used to study mutation frequencies in two mismatch repair genes (MSH2 and MLH1) and microsatellite instability. All statistical tests were two-sided.Among the probands diagnosed in Orange County during 1994 (population-based sample, all ages), five were consistent with the Amsterdam criteria for HNPCC (0.9%; 95% confidence interval [CI] = 0. 3%-2.1%). Among probands diagnosed at less than 65 years of age-from the wider three-county area and a longer time span-16 (2.1%; 95% CI = 1.2%-3.4%) had a clinical history consistent with the Amsterdam criteria for HNPCC. Five (approximately 45%) of 11 of the referral HNPCC case subjects had a mutation in MSH2 or MLH1 and also showed microsatellite instability. The family members of case subjects with mutations tended to show an earlier age at diagnosis of HNPCC and more multiple primary cancers than those of case subjects without detectable mutations. Many of the known characteristics of HNPCC, including the presence of ureteral and endometrial cancers, were seen in both sets of families. The previously reported proximal location of colorectal tumors in HNPCC kindreds was not seen in the population-based dataset but was similar to the location reported in the referral cases.On the basis of our data, we believe that the prevalence of HNPCC in the general population is likely to be closer to 1% than to 5%. Furthermore, our study suggests that some previously reported characteristics of HNPCC, such as the proximal location of tumors in the syndrome, may not always hold true in a population-based sample.
Comparison of peanut agglutinin and S100 stains in the paraffin tissue diagnosis of Langerhans cell histiocytosis
Authors: JANET McLELLAND, A. C. CHU
Journal: British Journal of Dermatology (1988)

We compared peanut agglutinin and S100 stains on paraffin embedded material from a variety of sites involved in Langerhans cell histiocytosis (LCH), The two techniques were comparable in terms of ease of performance, time taken and cost. Peanut agglutinin produced dense cell surface and paranuclear staining of the characteristic LCH cells seen in lesions, which was easier to distinguish than the more diffuse cytoplasmic staining produced by the S100 technique. This characteristic staining pattern is more specific than that for the S100 protein which is present in a variety of different cells, including some malignant histiocytes. We recommend that peanut agglutinin be used as a routine diagnostic test for all samples suspected of being LCH.
An unusual presentation of immersion foot
Authors: D M Macgregor
Journal: British Journal of Sports Medicine (2004)

We report a case of “green foot” in a child with a plaster cast applied for a fractured metatarsal who subsequently re-presented with circulatory compromise. The foot was green and smelly and profuse Pseudomonas aeruginosa was cultured. The infection cleared with simple exposure to air. Perhaps this diagnosis should be considered in patients presenting with circulatory compromise in a cast as severe infection can result in amputation.
Method for Study of Contraction of Isolated Heart Muscle Under Various Physical Conditions
Authors: JOHN R. BLINKS
Journal: Circulation Research (1961)

Since the actions of physical and chemical influences upon myocardial contractility are not necessarily independent, study of interactions between the two may give clues to the mechanisms of action of both. A method is described for study of the interrelations of temperature, the interval between contractions, distending pressure, volume, amplitude of contraction against constant pressure, and pressure generated by contraction at constant volume in isolated thin-walled cardiac chambers. Unusual features are the use of gas as a distending medium and a volume recorder which measures the conductance of the fluid displaced by the chamber. As illustrations of use of the method, observations on some fundamental properties of rabbit atria are presented. Hysteresis and slow yielding to stress are prominent. The passive pressure-volume relationship is not affected by contractions against constant pressure, but is changed slightly by contractions at constant volume. The Starling curve of the isolated rabbit atrium always has a descending limb at high atrial volumes. However, the distending pressures required to produce a prominent descending limb are so high that their application causes irreversible changes in the muscle.
JAKS AND STATS: Biological Implications
Authors: Warren J. Leonard, John J. O'Shea
Journal: Annual Review of Immunology (1998)

Cytokines and interferons are molecules that play central roles in the regulation of a wide array of cellular functions in the lympho-hematopoietic system. These factors stimulate proliferation, differentiation, and survival signals, as well as specialized functions in host resistance to pathogens. Although cytokines are known to activate multiple signaling pathways that together mediate these important functions, one of these pathways, the Jak-STAT pathway, is the focus of this chapter. This pathway is triggered by both cytokines and interferons, and it very rapidly allows the transduction of an extracellular signal into the nucleus. The pathway uses a novel mechanism in which cytosolic latent transcription factors, known as signal transducers and activators of transcription (STATs), are tyrosine phosphorylated by Janus family tyrosine kinases (Jaks), allowing STAT protein dimerization and nuclear translocation. STATs then can modulate the expression of target genes. The basic biology of this system, including the range of known Jaks and STATs, is discussed, as are the defects in animals and humans lacking some of these signaling molecules.
Prone position in acute respiratory distress syndrome
Authors: P. Pelosi, L. Brazzi, L. Gattinoni
Journal: European Respiratory Journal (2002)

In the last few years prone positioning has been used increasingly in the treatment of patients with acute respiratory distress syndrome (ARDS) and this manoeuvre is now considered a simple and safe method to improve oxygenation. However, the physiological mechanisms causing respiratory function improvement as well as the real clinical benefit are not yet fully understood. The aim of this review is to discuss the physiological and clinical effects of prone positioning in patients with ARDS. The main physiological aims of prone positioning are: 1) to improve oxygenation; 2) to improve respiratory mechanics; 3) to homogenise the pleural pressure gradient, the alveolar inflation and the ventilation distribution; 4) to increase lung volume and reduce the amount of atelectatic regions; 5) to facilitate the drainage of secretions; and 6) to reduce ventilator-associated lung injury. According to the available data, the authors conclude that: 1) oxygenation improves in approximately 70-80% of patients with early acute respiratory distress syndrome; 2) the beneficial effects of oxygenation reduce after 1 week of mechanical ventilation; 3) the aetiology of acute respiratory distress syndrome may markedly affect the response to prone positioning; 4) extreme care is necessary when the manoeuvre is performed; 5) pressure sores are frequent and related to the number of pronations; 6) the supports used to prone and during positioning are different and nonstandardised among centres; and 7) intensive care unit and hospital stay and mortality still remain high despite prone positioning.
The Center for Epidemiologic Studies Depression Scale: its use in a community sample
Authors: Robert E. Roberts, Sally W. Vernon
Journal: American Journal of Psychiatry (1983)

The authors gave the Center for Epidemiologic Studies Depression (CES-D) Scale, a self-report depression symptom scale, to 528 subjects drawn from a larger longitudinal community survey. Interviewers also assessed respondents using the Schedule for Affective Disorders and Schizophrenia (SADS), a structured clinical interview; on the basis of the SADS the subjects were then given diagnoses according to the Research Diagnostic Criteria. The results corroborated earlier findings of a modest relationship between self-reported symptoms of depression and the diagnosis of depression. The authors conclude that the CES-D Scale may be useful as an initial or first-stage screening test.
A comparison of the energy expenditure between weight supported and unsupported exercise in obesity
Authors: Rachael Evans, Thomas Dolmage, Priscila Robles, Dina Brooks, Roger Goldstein
Journal: European Respiratory Journal (2012)

Background 

Weight loss is better achieved by a combination of diet and exercise. We hypothesised that obese individuals may be able to endure cycling (weight supported) for longer than walking (weight unsupported). We therefore investigated whether weight supported or unsupported exercise was associated with greater energy expenditure in obese individuals.

Methods 

Individuals were recruited from a sleep clinic with a BMI > 30 kg/m2 and treated obstructive sleep apnoea. Patients with pulmonary or cardiac disease were excluded. On separate days in a randomised order, participants performed an incremental cardiopulmonary exercise test on a cycle ergometer (CE) and a treadmill (TM) with expired gas analysis to determine the peak oxygen uptake (VO2pk). Two endurance tests were performed on each modality matched at 80% and 60% of the highest VO2 pk determined by the incremental tests. The total energy expenditure during each endurance test was calculated from the total oxygen uptake.

Results 

12 participants completed all six tests: 7 male, mean [SD] age 57 [14] y, BMI 34.5 [7.1] kg/m2. The peak VO2 on the TM vs CE was 2275 [522] vs 1791 [390] ml/min, respectively. Table one shows the duration (tlimit) and energy expenditure at 80 and 60% VO2 pk on the TM and CE.

View this table:

Table 1





Conclusion 

In obese individuals, treadmill walking (weight unsupported) at a matched metabolic intensity led to significantly higher total energy expenditure than cycling.