bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronic but not inflammatory changes at the Achilles’ tendon differentiate patients with peripheral spondyloarthritis from other diagnoses – Results from a prospective clinical trial
Authors: Baraliakos Xenofon , Kiltz Uta , Appel Heiner , Dybowski Friedrich , Igelmann Manfred , Kalthoff Ludwig , Klink Claudia , Krause Dietmar , Saracbasi Ertan , Schmitz-Bortz Elmar , Rahmeh Feras , Braun Juergen
Published: December 2017

Background

Imaging has an essential role in the new spondyloarthritis (SpA) classification criteria for axial but not for peripheral manifestations. We evaluated the impact of imaging findings for identification and treatment decisions in patients with peripheral spondyloarthritis (pSpA) and controls (non-SpA).

Methods

Patients with pSpA (Assessment of SpA international Society criteria, n=30) and non-SpA (n=30), aged <45 years, with painful heels or knees, were recruited. Conventional radiography, grey-scale ultrasound including power Doppler (US/PDUS) and MRI of symptomatic areas were performed to assess inflammatory and structural changes. Mann-Whitney U test was used for group comparisons.

Results

In total, 105 painful entheses (71 heels, 34 knees) in 60 patients were examined. Differences between diagnoses were found for symptom duration (pSpA: 17.2±27.5 vs non-SpA: 4.4±4.3 months), human leucocyte antigen B27 prevalence (67% vs 13%) and gender distribution (53.3% vs 20% male, respectively), all P<0.05. Logistic regression analysis for baseline differences showed that chronic changes (erosions and calcification) in the heel were more frequent in pSpA versus non-SpA by US/PDUS (62.5% vs 28.6% patients and 59.5% vs 26.5% entheses, P<0.05). Inflammatory changes in heel or knee by US/PDUS and MRI could not differentiate between non-SpA and pSpA.

Conclusions

Differentiation between pSpA and non-SpA was only possible based on structural but not inflammatory changes in the heels and knees of symptomatic patients. US/PDUS was superior to MRI for this purpose. These findings imply that pSpA is associated with erosive changes at enthesitic sites, while inflammation and susceptibility are of minor influence for the development of erosions and calcification to pSpA.
Ixekizumab efficacy and safety with and without concomitant conventional disease-modifying antirheumatic drugs (cDMARDs) in biologic DMARD (bDMARD)-naïve patients with active psoriatic arthritis (PsA): results from SPIRIT-P1
Authors: Coates Laura C , Kishimoto Mitsumasa , Gottlieb Alice , Shuler Catherine L , Lin Chen-Yen , Lee Chin Hyok , Mease Philip J
Published: December 2017

Objective

To evaluate the efficacy and safety of ixekizumab alone or with concomitant conventional disease-modifying antirheumatic drugs (cDMARDs) versus placebo in patients with active psoriatic arthritis (PsA) as part of a SPIRIT-P1 subgroup analysis (NCT01695239).

Methods

Patients were stratified by cDMARD use (concomitant cDMARDs use (including methotrexate) or none (past or naïve use)) and randomly assigned to treatment groups (ixekizumab 80 mg every 4 weeks (IXEQ4W) or every 2 weeks (IXEQ2W) or placebo). Efficacy was evaluated versus placebo at week 24 by the American College of Rheumatology criteria (ACR20/50/70), modified total Sharp score and Health Assessment Questionnaire-Disability Index (HAQ-DI). Safety was assessed according to cDMARD status.

Results

Regardless of concomitant cDMARD usage, ACR20, ACR50 and ACR70 response rates were significantly higher versus placebo with IXEQ4W and IXEQ2W. The proportion of patients achieving HAQ-DI minimal clinically important difference was significantly higher versus placebo with IXEQ4W with concomitant cDMARD use and IXEQ2W, regardless of concomitant cDMARD use. Treatment-emergent adverse events (AE) were more frequent versus placebo for either ixekizumab-dosing regimen, regardless of concomitant cDMARD use. Serious AEs were not higher versus placebo, regardless of concomitant cDMARD use.

Conclusion

Ixekizumab treatment improved measures of disease activity and physical function in patients with active PsA relative to placebo, when used with or without concomitant cDMARD therapy.
Serum osteopontin: a biomarker of disease activity and predictor of relapsing course in patients with giant cell arteritis. Potential clinical usefulness in tocilizumab-treated patients
Authors: Prieto-González Sergio , Terrades-García Nekane , Corbera-Bellalta Marc , Planas-Rigol Ester , Miyabe Chie , Alba Marco A , Ponce Ariel , Tavera-Bahillo Itziar , Murgia Giuseppe , Espígol-Frigolé Georgina , Marco-Hernández Javier , Hernández-Rodríguez José , García-Martínez Ana , Unizony Sebastian H , Cid Maria C
Published: December 2017

Background

Osteopontin (OPN) is a glycoprotein involved in Th1 and Th17 differentiation, tissue inflammation and remodelling. We explored the role of serum OPN (sOPN) as a biomarker in patients with giant cell arteritis (GCA).

Methods

sOPN was measured by immunoassay in 76 treatment-naïve patients with GCA and 25 age-matched and sex-matched controls. In 36 patients, a second measurement was performed after 1 year of glucocorticoid treatment. Baseline clinical and laboratory findings, as well as relapses and glucocorticoid requirements during follow-up, were prospectively recorded. sOPN and C reactive protein (CRP) were measured in 32 additional patients in remission treated with glucocorticoids or tocilizumab (interleukin 6 (IL-6) receptor antagonist). In cultured temporal arteries exposed and unexposed to tocilizumab, OPN mRNA expression and protein production were measured by reverse transcription polymerase chain reaction (RT-PCR) and immunoassay, respectively.

Results

sOPN concentration (ng/mL; mean±SD) was significantly elevated in patients with active disease (116.75±65.61) compared with controls (41.10±22.65; p<0.001). A significant decline in sOPN was observed in paired samples as patients entered disease remission (active disease 102.45±57.72, remission 46.47±23.49; p<0.001). sOPN correlated with serum IL-6 (r=0.55; p<0.001). Baseline sOPN concentrations were significantly higher in relapsing versus non-relapsing patients (relapsers 129.08±74.24, non-relapsers 90.63±41.02; p=0.03). OPN mRNA expression and protein production in cultured arteries were not significantly modified by tocilizumab. In tocilizumab-treated patients, CRP became undetectable, whereas sOPN was similar in patients in tocilizumab-maintained (51.91±36.25) or glucocorticoid-maintained remission (50.65±23.59; p=0.49).

Conclusions

sOPN is a marker of disease activity and a predictor of relapse in GCA. Since OPN is not exclusively IL-6-dependent, sOPN might be a suitable disease activity biomarker in tocilizumab-treated patients.
Emergency department management of patients with rib fracture based on a clinical practice guideline
Authors: Hamilton Chase , Barnett Lauren , Trop Allison , Leininger Brian , Olson Adam , Brooks Aaron , Clark Daniel , Schroeppel Thomas
Published: December 2017

Background

Clinical practice guidelines (CPGs) have the ability to increase efficiency and standardize care. A CPG based on forced vital capacity (FVC) for rib fractures was developed as a tool for triage of these patients. The objectives of this study were to assess the efficacy and compliance of physicians with this rib fracture CPG.

Methods

Patients >18 that were discharged from an urban level 2 trauma center emergency department (ED) between the dates of January 1, 2014, to December 31, 2016, were eligible for the study. Demographics, mechanism, outcomes and FVC were abstracted by review of the electronic medical record. Compliance with the CPG was examined, and comparisons were made between patients successfully discharged and patients who returned.

Results

455 patients met were identified during the study period. 233 were eligible after exclusions. 64% of the cohort was male with median age of 53 years. Falls were the most common mechanism (59.6%). The median number of rib fractures was 2 and median FVC 2500 mL. 28 (12.0%) of the 233 returned to the ED after discharge. The groups were well matched with no significant differences. The most common reason for return was pain (95%). Adjusted analysis showed that increasing age (adjusted OR (AOR) 0.968) and FVC (AOR 0.999) were independent predictors. Adherence with the CPG was good for hemothorax/pneumothorax and bilateral fractures (96%), but lagged with the number of fractures (74%).

Conclusions

This study confirms that the rib fracture CPG is safe and an FVC of 1500 mL is a safe criterion for discharging patients with rib fractures. Interestingly, it appears that older age is protective. More work needs to be done on effective pain control to decrease return to ED visits using this CPG.

Level of evidence

IV.

Type of study

Therapeutic.
Thymic haemorrhage due to ingestion of human anticoagulant medication in a puppy
Authors: Vangrinsven Emilie , Girod Maud , Etienne Anne‐Laure , Gommeren Kris
Published: December 2017

A four‐month‐old male Shih‐Tzu was presented with lethargy, mild dyspnoea and acute thoracic pain. Thoracic radiography revealed the presence of a mediastinal mass at the level of the thymus and ultrasound confirmed a thymic haemorrhage. Coagulation times were beyond the detection limit of the machine. After preprandial and postprandial bile acids excluded hepatic insufficiency, an anticoagulant intoxication was strongly suspected. Disappearance of multiple doses of phenprocoumon in the house and rapid response to vitamin K administration as a treatment and blood transfusion confirmed authors' suspicion. The dog had clinically made a full recovery and was discharged after 36 hours. The following unique information has been provided: anticoagulant intoxication is commonly seen but the clinical presentation can be highly variable depending on the affected area. This report describes a rare thymic haemorrhage secondary to ingestion of human anticoagulant medication in a dog.
Motile Salmonella serotypes causing high mortality in poultry farms in three South‐Western States of Nigeria
Authors: Mshelbwala Fakilahyel Musa , Ibrahim Najume Doguwar‐Giginya , Saidu Shehu NaAllah , Azeez Aminullah Ajiyobiojo , Akinduti Paul Akinniyi , Kwanashie Clara Nna , Fakilahyel Kadiri Amina Kinta , Muhammed Maryam , Fagbamila Idowu Oluwabunmi , Luka Pam Dachung
Published: December 2017

This study was carried out to identify theSalmonellaserotypes causing high mortality in chickens in Lagos, Ogun and Oyo states, Nigeria. Chickens presented for postmortem examination during disease outbreaks that were characterised by high mortality (40 per cent to 80 per cent) in poultry farms in the study area were examined from January to December, 2013. Samples of the lungs, heart, liver, spleen, kidneys, proventriculus, intestine and caecum were collected from suspected cases of salmonellosis, for bacterial culture and identification.Salmonellaisolates were confirmed using PCR and serotyped using the Kauffman‐White scheme. Twenty‐six day‐old pullets were raised to two weeks and inoculated orally with 0.2 mL of 1×108 colony forming units ofSalmonellaZega identified in the present study to determine their pathogenicity, while another 26 served as control. TheSalmonellaserotypes wereSZega (n=13; 35.14 per cent),SalmonellaKentucky (n=9; 24.32 per cent),SalmonellaHerston (n=6; 16.22 per cent),SalmonellaNima (n=4; 10.81 per cent),SalmonellaTelelkebir (n=3; 8.11 per cent),SalmonellaColindale (n=1; 2.70 per cent) andSalmonellaTshiongwe (n=1; 2.70 per cent). Clinical signs in both natural and experimental infections were acute (70 per cent) and chronic (30 per cent), and included weakness, anorexia, yellowish diarrhoea, pasted vents, somnolescence and mortality, while gross lesions showed marked pulmonary congestion and oedema, necrotic foci in the myocardium; the liver, spleen and kidneys were markedly enlarged and had subcapsular multifocal necrosis. There were catarrhal proventriculitis and enteritis, and haemorrhagic typhlitis. While most of the serotypes identified in the present study have been isolated from poultry sources from commercial farms in Nigeria, to the best of the authors' knowledge, they have not been previously reported to cause high mortality in chickens in the study area.
Use of clinical vignette questionnaires to investigate the variation in management of keratoconjunctivitis sicca and acute glaucoma in dogs
Authors: White Constance N. , Downes Martin J. , Jones Gareth , Wigfall Corinne , Dean Rachel S. , Brennan Marnie L
Published: December 2017

There is little peer‐reviewed research assessing therapeutic effectiveness in canine eye disease. Current treatments used in first opinion and ophthalmology referral practices are also somewhat poorly documented. The aim of this study was to investigate the current management of canine keratoconjunctivitis sicca (KCS) and acute primary angle‐closure glaucoma (PACG) by veterinary surgeons. Questionnaires using clinical vignettes were administered to a cross section of general practitioners (‘GPs’) and veterinarians engaged in or training for postgraduate ophthalmology practice (‘PGs’). Similar treatment recommendations for KCS (topical cyclosporine, lubricant, antibiotic) were given by both groups of veterinarians with the single exception of increased topical antibiotic use by GPs. Treatment of acute glaucoma diverged between groups: PGs were much more likely to recommend topical prostaglandin analogues and a wider array of both topical and systemic treatments were recommended by both groups. Systemic ocular hypotensive agents were suggested infrequently. Our results suggest that treatments may vary substantially in ocular conditions, particularly in conditions for which neither guidelines nor high‐quality evidence exists. This study highlights the need for novel strategies to address evidence gaps in veterinary medicine, as well as for better evaluation and dissemination of current treatment experience.
Effects of carbohydrate mouth rinse and caffeine on high-intensity interval running in a fed state
Authors: Devenney Simon , Mangan Shane , Shortall Marcus , Collins Kieran
Published: December 2017

The current study aims to identify if mouth rinsing with a 6% carbohydrate mouth-rinse (CMR) solution and mouth rinsing and ingestion of caffeine (CMR+CAFF) can affect exercise performance during steady-state (SS) running and high-intensity intervals (HIIT) in comparison with a 0% control solution (PLA) when in a fed state. Eight recreationally trained males completed 3 trials (CMR, CMR+CAFF, and PLA) of 45 min SS running and an HIIT protocol (90% peak treadmill velocity) until fatigue in a double blinded, repeated-measures study. Participants ingested a capsule of either CAFF or PLA before and after SS. Participants received a 25-mL bolus of carbohydrate solution (CMR and CMR+CAFF trials) or taste-matched PLA (PLA trial) prior to HIIT protocol and after every second effort. Heart rate and lactate responses were recorded throughout the SS and HIIT protocol. CMR+CAFF was significantly different when compared with PLA (p = 0.001; Cohens d = 1.34) and CMR (p = 0.031; Cohens d = 0.87) in relation to distance covered before fatigue. Although there was no significant difference between CMR and PLA, there was a small benefit for CMR (p = 0.218; Cohens d = 0.46). Results indicate that CMR and ingestion of CAFF leads to improvements in performance during interval sessions while participants were in a fed state. These findings indicate that the regular use of CMR can decrease the risk of gastrointestinal distress reported by athletes, which can be applicable to athletes in a real-world setting.
A Discriminatively Learned CNN Embedding for Person Reidentification
Authors: Zheng Zhedong , Zheng Liang , Yang Yi
Published: December 2017

In this article, we revisit two popular convolutional neural networks in person re-identification (re-ID): verification and identification models. The two models have their respective advantages and limitations due to different loss functions. Here, we shed light on how to combine the two models to learn more discriminative pedestrian descriptors. Specifically, we propose a Siamese network that simultaneously computes the identification loss and verification loss. Given a pair of training images, the network predicts the identities of the two input images and whether they belong to the same identity. Our network learns a discriminative embedding and a similarity measurement at the same time, thus taking full usage of the re-ID annotations. Our method can be easily applied on different pretrained networks. Albeit simple, the learned embedding improves the state-of-the-art performance on two public person re-ID benchmarks. Further, we show that our architecture can also be applied to image retrieval. The code is available at https://github.com/layumi/2016_person_re-ID.
High-Mass Star and Massive Cluster Formation in the Milky Way
Authors: Motte Frédérique , Bontemps Sylvain , Louvet Fabien
Published: December 2017

This review examines the state-of-the-art knowledge of high-mass star and massive cluster formation, gained from ambitious observational surveys, which acknowledges the multiscale characteristics of these processes. After a brief overview of theoretical models and main open issues, we present observational searches for the evolutionary phases of high-mass star formation, first among high-luminosity sources and more recently among young massive protostars and the elusive high-mass prestellar cores. We then introduce the most likely evolutionary scenario for high-mass star formation, which emphasizes the link of high-mass star formation to massive cloud and cluster formation. Finally, we introduce the first attempts to search for variations of the star-formation activity and cluster formation in molecular cloud complexes in the most extreme star-forming sites and across the Milky Way. The combination of Galactic plane surveys and high–angular resolution images with submillimeter facilities such as Atacama Large Millimeter Array (ALMA) are prerequisites to make significant progress in the forthcoming decade.
Invariant Kalman Filtering
Authors: Barrau Axel , Bonnabel Silvère
Published: December 2017

The Kalman filter—or, more precisely, the extended Kalman filter (EKF)—is a fundamental engineering tool that is pervasively used in control and robotics and for various estimation tasks in autonomous systems. The recently developed field of invariant extended Kalman filtering uses the geometric structure of the state space and the dynamics to improve the EKF, notably in terms of mathematical guarantees. The methodology essentially applies in the fields of localization, navigation, and simultaneous localization and mapping (SLAM). Although it was created only recently, its remarkable robustness properties have already motivated a real industrial implementation in the aerospace field. This review aims to provide an accessible introduction to the methodology of invariant Kalman filtering and to allow readers to gain insight into the relevance of the method as well as its important differences with the conventional EKF. This should be of interest to readers intrigued by the practical application of mathematical theories and those interested in finding robust, simple-to-implement filters for localization, navigation, and SLAM, notably for autonomous vehicle guidance.
Hands-on laboratory experience in teaching-learning physiology.
Authors: Randall W C , Burkholder T
Published: December 2017

Reactivation of several model 5 (vacuum tube) Grass polygraphs for active hands-on laboratory experiments by small student groups, in contrast to demonstrations and pretaped illustrations of physiological principles, resulted in remarkable rejuvenation of interest and excitement for learning in premed and introductory science classes at Taylor University. Accurate and perceptive observations were performed on the students themselves, each recording his own electrocardiogram, for example, as well as direct recordings from the pithed frog, the turtle heart, the anesthetized rabbit, and noninvasive recordings from students subjects during exercise. In the latter experiment, sweat recruitment patterns were recorded initially on the lower extremities, followed by successive appearances on thigh and abdomen and with final occurrence on the upper extremities and face. To our knowledge, this is the first report of such recruitment patterns during exercise. Results of actual student participation, with organized group discussions, convince us that laboratory teaching remains the premiere mechanism for teaching and learning organ-system physiology.
Echocardiography for teaching cardiac physiology in practical student courses.
Authors: Brunner M , Moeslinger T , Spieckermann P G
Published: December 2017

We have introduced echocardiography into the physiology courses for medical students to improve their understanding of cardiac physiology. Echocardiography allows a visualization of the events of the cardiac cycle and facilitates the correlation of anatomic structures with their physiological functions. The students record views on the human heart in the long and short axis, they follow wall and value motions, and they interpret the obtained data in correlation with electrocardiography and phonocardiography. Echocardiography offers the opportunity to measure the interval of isovolumetric contraction and isovolumetric relaxation and permits the calculation of parameters assigned to left ventricular contractility. An evaluation showed that medical students consider echocardiography to be the most significant and interesting part of the physiology courses. In conclusion, echocardiography has been shown to be a valuable tool for teaching cardiac physiology.
Introducing high school students to neurophysiology.
Authors: Schmidt B , Stavraky T
Published: December 2017

University-based scientists are increasingly meeting the challenge to communicate with the public to improve general science literacy, explain their research to a lay audience, and recruit science students. At the University of Western Ontario, graduate student volunteers of Let's Talk Science have launched a project that introduces senior high school students to research presentations given by undergraduate physiology students. The project has given the undergraduate students an opportunity to present their work to an interested audience other than their peers or faculty, while it provides the high school students with positive role models and a greater awareness of postsecondary science. This project was judged a success by all participants, because many of the high school students became interested in physiology and claimed to be more confident in their ability to participate in science, and it also appeared to improve the presentation and communication skills of the undergraduates. This innovative and cost-efficient project is an effective way to demonstrate the excitement of physiology to potential future scientists while showing undergraduate students that public communication of science is not only important but can also be fun.
Venipuncture in the medical physiology laboratory.
Authors: Martin B J , Watkins J B , Ramsey J
Published: December 2017

Medical physiology laboratories, traditionally devoted to animal experimentation, face unprecedented difficulties linked to cost, staffing, instrumentation, and the use of animals. At the same time, laboratory experiences with living creatures play a unique role in medical education. In this article we describe the use of venipuncture and subsequent blood analysis, with medical students serving as both subjects and experimenters, in a sequence of first-year physiology laboratories. These experiments are safe, robust, inexpensive, and time efficient, and they teach the principles of cardiovascular, respiratory, renal, nutritional, and gastrointestinal physiology. In addition, they enhance medical education in several other important dimensions. First, they teach safe venous blood collection and handling, a training appropriate for students at this level. Second, by serving each week as subjects as well as experimenters, students experience aspects of both sides of the doctor-patient relationship. Third, the laboratories can be used to teach fundamentals of research design and analysis. Finally, because blood analysis is central to medicine, and because the student's own blood data are discussed, students are enthusiastic and cooperative, and the clinical relevance of the data is clear.
Using round table labs to complement didactic lectures and experimental labs.
Authors: Nekvasil N P
Published: December 2017

In an effort to teach the volume of material needed by physiology students as well as to enhance the student's understanding of physiological mechanisms, a combination of teaching methods is being used at the undergraduate level. Didactic lectures are used to convey the mass of information needed, experimental labs are used to aid the student in visualizing concepts, and situational labs [called round table labs (RTLs) here] are used to provide an opportunity for the student to learn, in a risk-free setting, how to answer application questions. The RTLs utilize discussion, writing, verbal communication, and analytic thinking. The major emphasis of the RTLs is on the integrative nature of physiology. Use of the RTLs bridges, the gap among the facts learned in the didactic lecture, the hands-on learning of the experimental lab, and the need to be able to apply what is being learned. Using this combination facilitates student learning such that the student reaches a level of proficiency with the subject beyond that which can be attained with the more traditional lecture-exam format.
Exploring the context of biomedical research through a problem-based course for undergraduate students.
Authors: Rangachari P K
Published: December 2017

Students in an interdisciplinary program explored the manufacture of biomedical knowledge in a problem-based course. Because the class size was two to three times larger than the normal tutorial group, suitable modifications were made (formation of floating groups around defined learning tasks, formal presentations, written reports, and evaluations by students and tutor). A variety of problems and/or cases drawn from research papers, newspapers, biographies, or web pages permitted students to appreciate the complex interactions between ideals, individuals, institutions, and investments that comprise modern biomedical research.
Manuscript peer review: a helpful checklist for students and novice referees.
Authors: Seals D R , Tanaka H
Published: December 2017

The ability to contribute consistent, fundamentally sound critiques is an essential element of the scientific peer review process and an important professional skill for investigators. Despite its importance, many students and junior scientists do not have an adequate working knowledge of how to effectively critique research manuscripts. Part of the problem, in our view, is that novice referees often lack a comprehensive understanding of the basic issues that should be considered in evaluating scientific articles. Specifically, they tend to overemphasize certain limitations (usually methodological), while missing other key points related to the scientific method that should be weighed much more heavily. In our journal club and graduate courses we have been using a "checklist" to help graduate students and postdoctoral fellows critically analyze original research papers. In this article we present these guidelines in the hope that they will serve as a helpful resource for students and other novice reviewers when critiquing scientific manuscripts.
Please pass the cauliflower: a recipe for introducing undergraduate students to brain structure and function.
Authors: Masters J , Christensen M
Published: December 2017

Neurophysiology/pathophysiology content is a frequent source of anxiety for undergraduate students and their instructors. This learning module supplements traditional lecture and overhead presentations to offer a novel, nonthreatening, and entertaining introduction to neuropathology. The module is based on a ridiculous analogy between the human brain and the cauliflower. This module has been used with both underclassmen and more advanced health science undergraduate students and has produced enthusiastic student responses while deescalating both student and instructor anxiety.
SMALL GROUP TEACHING: CLINICAL CORRELATION WITH A HUMAN PATIENT SIMULATOR
Authors: Euliano Tammy Y.
Published: December 2017

The popularity of the problem-based learning paradigm has stimulated new interest in small group, interactive teaching techniques. Medical educators of physiology have long recognized the value of such methods, using animal-based laboratories to demonstrate difficult physiological principles. Due to ethical and other concerns, a replacement of this teaching tool has been sought. Here, the author describes the use of a full-scale human patient simulator for such a workshop. The simulator is a life-size mannequin with physical findings (palpable pulses, breath/heart sounds, blinking eyes, etc.) and sophisticated mechanical and software models of the cardiovascular and pulmonary systems. It can be connected to standard physiological monitors to reproduce a realistic clinical environment. In groups of 10, first-year medical students explore Starling’s law of the heart, the physiology of the Valsalva maneuver, and the function of the baroreceptor in a clinically realistic context using the simulator. With the use of a novel pre-/postworkshop assessment instrument that included student confidence in their answers, student confidence improved for all questions and survey items following the simulator session ( P < 0.0001). The students give these laboratory exercises uniformly superior evaluations with >85% of the students rating the workshop “very good” or “excellent.”
HEMODYNAMICS FOR MEDICAL STUDENTS
Authors: Badeer Henry S.
Published: December 2017

The flow of blood through the cardiovascular system depends on basic principles of liquid flow in tubes elucidated by Bernoulli and Poiseuille. The elementary equations are described involving pressures related to velocity, acceleration/deceleration, gravity, and viscous resistance to flow (Bernoulli-Poiseuille equation). The roles of vascular diameter and number of branches are emphasized. In the closed vascular system, the importance of gravity is deemphasized, and the occurrence of turbulence in large vessels is pointed out.
CARDIOVASCULAR PRESSURE-FLOW RELATIONSHIPS: WHAT SHOULD BE TAUGHT?
Authors: Carroll Robert G.
Published: December 2017

Cardiovascular physiology reflects the interrelations of flow, pressure, and resistance. Undergraduate students are often confused by the complexity of the system. This symposium presents a sequential presentation of the underlying concepts, building on analogies, past experience, and conceptual models to allow students to develop a physiologically appropriate understanding of cardiovascular physiology.
Models of venous admixture
Authors: Bigeleisen Paul E.
Published: December 2017

Medical students, residents, and allied health professionals often have difficulty quantitating ventilation-perfusion mismatch in ill patients. This manuscript quantitates ventilation-perfusion mismatch using the underlying physiological concepts and equations that describe mismatch. In addition, clinical problems with diagrams and worked-out solutions are supplied to help students master these equations as well as their practical limitations.
Thyroid hormone control of Na+-K+-ATPase and K+-dependent phosphatase in rat heart
Authors: Philipson K. D. , Edelman I. S.
Published: December 2017

To assess the possible role of the Na+ pump in mediating physiological responses to thyroid hormone in the rat myocardium, we examined the effects of L-3,5,3'-triiodothyronine (T3) on the activities of the closely associated enzymes, Na+-K+-dependent adenosine triphosphatase (Na-K-ATPase) and K+-dependent p-nitrophenyl phosphatase (K-dep-pNPPase). In hypothyroid rats, administration of T3 (50 microng/100 g body wt) resulted in significant increases (greater than 50%) in Na-K-ATPase and K-dep-pNPPase activities in both crude homogenates and microsomal fractions of the rat ventricle. Significant effects on Na-K-ATPase activity were also attained with low doses (1 microng/100 g body wt) of T3. A method was developed for assaying K-dep-pNPPase activity in cardiac slices. With this technique, enhancement in K-dep-pNPPase activity of 89.2% was found in ventricle slices after treatment of hypothyroid rats with T3 (50 microng/100 g body wt), implying that augmentation of the capacity of the Na+ pump is achieved in vivo. The potent analogue, L-3,5-diiodo-3' isopropyl thyronine (isopropyl T2) had the same effects on cardiac growth and Na-K-ATPase as T3, in hypothyroid rats. In contrast, the relatively inactive isomer, L-3,3',5'-triiodothyronine (reverse T3) had no significant effect on the heart weight-to-body weight ratio or on ventricular Na-K-ATPase activity.
Membrane permeability of isolated lung cells to nonelectrolytes
Authors: Garrick R. A. , Redwood W. R.
Published: December 2017

Mixtures of viable endothelial and epithelial cells were separated by enzymatic digestion from rabbit lung and recovered by centrifugation. The cells were mixed with an extracellular marker and packed by centrifugation into small-diameter polyethylene tubing and pulsed with tritiated water and 14C-labeled alcohols. Calculation of diffusion coefficients for the packed cell column (D), intracellular material (D2), and extracellular fluid (D1) was based on a local steady-state one-dimensional diffusional model. Permeability coefficients were: tritiated water, 288 X 10(-5) cm s-1; methanol, 385 X 10(-5) cm s-1; ethanol, 214 X 10(-5) cm s-1; propanol, 277 X 10(-5) cm s-1; and hexanol, 1255 X 10(-5) cm s-1. The permeability coefficients of these aliphatic alcohols show a minimum at ethanol with hexanol having the highest value of all substances tested. The results support the concept of parallel aqueous and lipid pathways for small solutes in the plasma membrane. Study of the permeability properties of isolated lung cells can provide information on the cellular pathway in the transcapillary transport of water and solutes in the lung.
Blockade of myocardial slow inward current at low pH
Authors: Vogel S. , Sperelakis N.
Published: December 2017

The effect of low pH on the slow cationic inward current was studied in isolated perfused embryonic chick ventricles (16-21 days old). In order to study the slow current, the fast Na+ current was inactivated by partial depolarization to about -40 mV by elevation of K+ (25 mM). Subsequent exposure of the tissue to catecholamines or methylxanthines allowed slowly rising overshooting electrical responses (the "slow response") with with accompanying contractions to be elicited by electrical stimulation. These slow responses are insensitive to tetrodotoxin and are Na+- and Ca2+-dependent. It was found that the isoproterenol- and caffeine-induced slow responses were abolished at about pH 6.1; 50% inhibition occurred at about pH 6.5. The rate of rise of the normal action potential, which is dependent on a fast Na+ current, was only slightly affected at these same pH levels; however, electromechanical uncoupling occurred, as expected from inhibition of the slow current. Therefore, the slow current was blocked at an acid pH that did not block the fast Na+ current.
Possible role of gap junctions in activation of myometrium during parturition
Authors: Garfield R. E. , Sims S. M. , Kannan M. S. , Daniel E. E.
Published: December 2017

Gap junctions between smooth muscle cells of the myometrium of pregnant rats were found only immediately prior to, during and immediately after parturition by quantitative thin-section and freeze-fracture microscopy. Ovariectomy of 16- to 17-days-pregnant rats resulted in premature termination of pregnancy and the appearance of gap junctions. Methods that prolonged normal pregnancy in rats or maintained pregnancy in ovariectomized animals (progesterone treatment) prevented the appearance of gap junctions. Gap junctions formed in tissues incubated for 24--96 h in vitro without any hormonal influence. We propose that gap junctions are essential for normal labor and delivery for synchronous contraction of the muscle of the uterus. We present a model for control of parturition that may apply to other animals including humans. The model proposes: 1) the possible roles progesterone, prostaglandins, or estrogens may play in initiating gap-junction formation; 2) that the formation of gap junctions is a necessary step in activation of the myometrium leading to labor; and 3) that agents used to stimulate or inhibit labor may do so by affecting gap junctions.
Sensitivity of excitable and inexcitable membranes to alpha-dihydrograyanotoxin II
Authors: Starkus J. G. , Narahashi T.
Published: December 2017

A variety of excitable and inexcitable preparations have been examined for their sensitivity to the depolarizing action of alpha-dihydrograyanotoxin II. alpha-Dihydrograyanotoxin II was effective in producing membrane depolarization in giant axons from the crayfish (Procambarus clarki) and sartorius muscle fibers from the frog (Rana pipiens) and the salamander (Taricha torosa). The toxin-induced depolarization was reversed by lowering the external sodium concentration. High concentrations of tetrodotoxin and saxitoxin were also effective in reversing the depolarization in the various grayanotoxin-sensitive preparations studied except in the salamander sartorius muscle, in which sodium-dependent action potentials were highly resistant to tetrodotoxin and saxitoxin. In contrast, alpha-dihydrograyanotoxin II was ineffective in changing the resting membrane potential in the muscle fibers of the crayfish (Procambarus clarki and Orconectes virilis) and in the salivary gland giant cells from Drosophila virilis. Of the preparations that were examined, only the membranes that produce a sodium-dependent action potential are sensitive to the depolarizing action of alpha-dihydrograyanotoxin II.
Maintenance of ion concentration gradients in the cold in aorta from rat and ground squirrel
Authors: Kamm K. E. , Zatzman M. L. , Jones A. W. , South F. E.
Published: December 2017

Cell water and ionic content were measured in aortic smooth muscle from rats and ground squirrels during 48 h of incubation in oxygenated Krebs solution held at low temperatures. Cells from the ground squirrel, a hibernator, maintained sodium and potassium contents near normal levels during incubation at 7 degrees C. In sharp contrast, cells from the rat lost potassium and gained sodium with half times of 14 and 11 h, respectively. The [K] in cell water for the rat decreased 138 mM while [Na] in cell water increased about 148 mM. Cells from the hibernator tended to lose 10 mM K and gain 13 mM Na. Vascular smooth muscle of both the rat and squirrel was able to maintain K content at 17 degrees C. Tissue content of the divalent cations Ca and Mg did not change in vessels from either animal. The present findings suggest that aortic smooth muscle cells from a hibernator have adapted in such a way as to maintain ionic gradients upon prolonged exposure to low temperatures.
Effect of stretch on conduction velocity and cable properties of cardiac Purkinje fibers
Authors: Dominguez G. , Fozzard H. A.
Published: December 2017

Cardiac Purkinje fibers were studied before and after stretch to 30% and 50% in excess of their slack length, and membrane properties and conduction velocity were measured in relation to the stretch. Conduction velocity increased by 26% with 50% stretch. The resting potentials averaged -77 mV and did not change with stretch. In addition, the action potential height, maximal upstroke velocity, duration, and time constant of the foot did not change. These results suggested that the increase in conduction velocity was not due to a change in membrane excitability. Two geometric models of stretch, called unfolding and uncoiling, were considered. Cable analyses were performed to distinguish between these models. The effects were mixed, with about 2/3 of the length change resulting from unfolding and 1/3 from uncoiling. These results support the concept of redundancy of the surface membrane by folding. The changes are likely to be of importance in activation of the heart by the His-Purkinje system, especially in cardiac dilatation due to disease.
Dissociation of avian salt gland: separation procedures and characterization of dissociated cells
Authors: Hootman S. R. , Ernst S. A.
Published: December 2017

A procedure for dissociation of the nasal salt glands of the domestic duck, Anas platyrhynchos, into suspensions of individual cells has been developed. This technique employs enzymatic digestion with collagenase, hyaluronidase, and chymotrypsin; divalent cation chelation with EDTA; and gentle mechanical dispersion. Average cellular yields of 39 and 26% based on DNA recovered were obtained from the glands of freshwater- and saline-adapted ducks, respectively. Epithelial secretory cells comprised 60-80% of the cell suspensions with the remainder of the populations consisting of endothelial cells, fibroblasts, and blood cells. The dissociated cells were viable as judged by trypan blue exclusion (80-100%, maintenance of ultrastructural integrity, and retention of responsiveness to secretagogues and metabolic inhibitors. Methacholine chloride (0.5 mM) stimulated oxygen consumption by suspensions of both freshwater- and saline-adapted cells, whereas ouabain (0.05 mM) abolished the methacholine-stimulated respiratory response. These cell suspensions provide a promising system for the in vitro study of secretory mechanisms in the avian salt gland.
Intestinal electrophysiology and transmural ion transport in freshwater prawns
Authors: Ahearn G. A.
Published: December 2017

A steady-state transmural potential difference of 1.63 +/- 0.26 mV (mean +/- SE, lumen negative) is recorded across the isolated, perfused intestine of the freshwater prawn, Macrobrachium rosenbergii, when saline approximating hemolymph in composition is present on both surfaces of the preparation. The magnitude of this potential is a hyperbolic function of bilateral K concentration. It is abolished by metabolic poinsons (NaN3 and iodoacetate) or ouabain and appears to result largely from the combined net transmural fluxes of Na, Cl, and K. Net fluxes of Na (1,49 +/- 0;30 mu mol . cm-2 . h-1) and Cl (0.72 +/- 0.22) are absorptive, whereas that of K (0.47 +/- 0.11) IS SECRETORY. Bilateral absence of Na abolishes net K secretion, whereas bilateral addition of ouabain (0.5 mM) eliminates net Na absorption. One-third of net K secretion appears to be transcellular and coupled to the net cellular transfer of Na in the opposite direction. The remaining component of K secretion can be attributed to paracellular cation flow responsive to transmural PD, Transmural diffusion potentials generated in the presence and absence of metabolic poisons provide the following passive permeability properties of the tissue: PK:PNa:PCl = 5.1:1.1:0.5. The symmetrical nature of these diffusion potentials implies the occurrence of a single rate-limiting barrier to ion flow with the above characteristics--probably the cell junction (septate desmosome) and paracellular channel. A model for transepithelial ion transport is presented where transmural potential difference is largely a result of an apparent 9 Na/1 K basolateral cationic exchange.
Cytoplasmic regulation of tight-junction permeability: effect of plant cytokinins
Authors: Bentzel C. J. , Hainau B. , Ho S. , Hui S. W. , Edelman A. , Anagnostopoulos T. , Benedetti E. L.
Published: December 2017

The significance of the "leaky" tight junction might be understood better if cells of the epithelial monolayer possessed mechanisms to regulate molecular flow through the junction. To test this possibility, Necturus gallbladder, a representative leaky epithelium, was studied before, during, and after mucosal exposure to plant cytokinins and two other microfilament-active drugs, cytochalasin B and phalloidin. Concomitant with morphological changes in microfilaments, cytokinins induced rapid reversible increases in transepithelial resistance and potential difference (PD) and decreases in NaCl dilution potentials, with no change in the ratio of relative cell membrane resistances. Cytochalasin B (0.2-1.2 microM) and phalloidin (0.6-12.7 microM) caused similar changes in transepithelial resistance and PD. When the intramembranous structure of tight junctions was studied by freeze fracture, peak cytokinin-induced increments in transepithelial resistance were associated with more disorder in the strand meshwork resulting in a small increase in tight junction depth, but there was no evidence of de novo strand assembly. These studies suggest that permeability of the tight junction of Necturus gallbladder is subject to rapid reversible modulation, possibly under cytoskeletal control.
Mechanics and energetics of lengthening of active airway smooth muscle
Authors: Hanks B. S. , Stephens N. L.
Published: December 2017

For smooth muscle in general there appears only one report dealing with force-velocity (FV) relationships of active muscle subjected to forcible elongation by application of loads (P) greater than its maximum isometric tetanic tension (Po); for airway smooth muscle (ASM) there is none. Since ASM may be subjected to increasing stretch during inspiration, the relationship is important and was therefore studied with canine tracheal smooth muscle (TSM) as a model. FV data for P less than Po could be fitted by Hill's hyperbolic equation. For P greater than Po, lengthening velocity was greater than predicted by the equation. However at equivalent velocities, the muscle during elongation could support a load three times greater than during shortening; in this it resembled skeletal muscle. From this it may be speculated that distension of the airway during inspiration would not be associated with mechanical instability. With reference to energy requirements of the elongating TSM it was shown, as has been for skeletal muscle, that the net rate of energy liberation (assessed by measuring tissue levels of adenosine triphosphate and creatine phosphate) in an elongating active muscle is less than that of a muscle contracting isometrically.
Contraction of guinea pig ileal smooth muscle by acetyl glyceryl ether phosphorylcholine
Authors: Findlay S. R. , Lichtenstein L. M. , Hanahan D. J. , Pinckard R. N.
Published: December 2017

Acetyl glyceryl ether phosphorylcholine (AGEPC) is a chemical that has the biological activity of what was formerly termed platelet-activating factor. We report here that synthetic AGEPC induces the contraction of guinea pig ileal smooth muscle. Antagonists of histamine, acetylcholine, and slow-reacting substances (SRS) do not block AGEPC-induced contraction. These responses were long lasting, resistant to washing, and displayed complete agonist specific desensitization. Histamine- and SRS-induced contractions were unaffected by AGEPC. These studies show that AGEPC has the potential to produce a component of anaphylactically induced smooth muscle contraction.
Effects of serine on protein synthesis and insulin receptors
Authors: Galbraith R. A. , Buse M. G.
Published: December 2017

Erythroblastic leukemic cells incubated in media containing essential amino acids, glutamine, and serine subsequently bound approximately 30% more [125I]insulin than those incubated without serine. The effect was due to an increase in receptor number, without change in affinity. Other nonessential amino acids had no effect. Increased insulin binding was observed with serine concentrations of 5.5 microM and maximum effects were seen at 22 microM. Serine-induced increases in insulin binding were detectable after 15 min of incubation and were abolished by the addition of cycloheximide (1 micrograms/ml) but not by actinomycin D (1 microgram/ml). Incorporation of [3H]leucine into protein was increased fourfold within 1 h by incubation with serine. The effect was detectable with 5.5 microM serine but, in contrast to insulin binding, reached a maximum at 88 microM serine. This differential dose responsiveness may represent selective posttranscriptional control of receptor synthesis, processing, insertion into the membrane, or recycling.