bluuebunny/crossref_metadata_2025_split huggingface dataset:
THE LIBERATION OF A SLOW‐REACTING SMOOTH MUSCLE‐STIMULATING SUBSTANCE IN ANAPHYLAXIS
Authors: Kellaway C. H. , Trethewie E. R. 
Published: December 2015

1. The response of the isolated jejunum of the sensitised guinea‐pig to the anaphylactic antigen resembles that produced by venoms and by S.R.S. in its latency, in the time required for relaxation, and in the after‐changes in excitability of the muscle.2. The contractions of the jejunum of the guinea‐pig to antigen, to histamine, and to the slow‐reacting muscle‐stimulant substance (S.R.S.) formed by venoms were compared under various conditions of decreased reactivity of the muscle. These were brought about by administration of S.R.S., lysocithin, histaminase (Torantil), CO2, the toxin of Cl. welchii type A, and by photodynamic action. In most cases the responses to histamine, S.R.S., and antigen were depressed to the same extent. After repeated treatment with S.R.S. the response to S.R.S. was greatly reduced or abolished, that to histamine was unimpaired, and the response to the antigen was only slightly affected. During recovery from lysocithin poisoning the response to the antigen was only slightly reduced, while those to S.R.S. and histamine were greatly reduced. After treatment with the toxin of Cl. welchii type A the response to S.R.S. was greatly reduced, whereas those to histamine and to the antigen were unimpaired. A similar dissociation was observed with the guinea‐pig's uterus after lysocithin.3. The inability of the jejunum of the guinea‐pig to respond to histamine when CO2 has been bubbled through the solution containing it does not result from the formation of a loose but inactive compound of histamine with CO2, but from an effect of CO2 on the muscle, causing a decrease in its reactivity to various stimuli.4. The intra‐arterial injection of antigen into the isolated perfused lung of the guinea‐pig causes the liberation of a slow‐reacting musclestimulant substance into the outflowing perfusate.5. Fresh saline extracts of sensitised lung show an increase in their S.R.S. content after incubation with antigen, but extracts of tissue desiccated after treatment with antigen and subsequently re‐extracted show no such increase.6. Fresh and desiccated extracts of sensitised jejunum incubated with antigen behave like lung extracts, but fresh saline extracts of sensitised uterus and liver similarly treated show no increase in activity.7. Desiccated as well as fresh extracts of intestine treated with cobra venom show a striking increase in their content of S.R.S.8. It is concluded that the anaphylactic contraction of smooth muscles is in part due to the liberation of histamine and probably in part also to S.R.S., which is liberated and not formed in the antigenantibody reaction.
THE DIFFERENCES BETWEEN BLOOD‐PRESSURE MEASUREMENTS OBTAINED SIMULTANEOUSLY ON THE TWO ARMS
Authors: Shock Nathan W. , Ogden Eric 
Published: December 2015

Seventy per cent. of a group of normal young adult males showed a significant difference between blood‐pressure measurements made simultaneously on the two arms. The distribution of the magnitude of these differences is presented.The same proportion of significant differences was found in 40 of the subjects when retested. The correlation between the magnitude of the differences for each individual in the two tests was low, indicating that the cause of the difference in blood‐pressure can rarely be a fixed structural characteristic of the individual.Since these differences are not easily reproducible by variation of standard physiological conditions, it is suggested that they may be of psychogenic origin.
THE PHARMACODYNAMICS OF THE DOMESTIC FOWL WITH RESPECT TO ERGONOVINE AND ERGOTAMINE
Authors: Vanderbrook M. J. , Vos Jun Bert J. 
Published: December 2015

1. The practicability of the chicken as a laboratory animal is reaffirmed.2. The alkaloids ergonovine and ergotamine are about equally effective in their action upon the circulatory system of the chicken as judged by the magnitude of the blood‐pressure response, but the effects of ergonovine are more transitory.3. Much smaller doses of ergonovine are required to produce pressor responses in chickens than in cats or in other laboratory animals.4. In doses of about 10–20 mg. ergonovine and ergotamine are effective in inhibiting but not reversing the blood‐pressure response to epinephrine in the chicken.5. After moderate doses of ergonovine and ergotamine electrocardiograms show only a slowing of the heart. With excessive doses minor changes in the T‐wave are observed.6. In experiments on the perfused hearts of the fowl, cat, and rabbit small amounts of ergonovine and ergotamine give a striking reduction in the coronary flow. Ergotamine is some ten times more potent than ergonovine in this respect and also more persistent.7. The response of the oviduct to these alkaloids is irregular except in the case of the uterine portion, which is always stimulated by ergonovine. Epinephrine inhibits all segments.8. Studies on the isolated chicken intestine show a reduction in tone from ergonovine and ergotamine, the former being more effective. The response to both substances decreases from duodenum to colon.It is a pleasure to acknowledge the helpful guidance of Professor E. M. K. Geiling throughout this investigation. A portion of the expenses of this work has been met by a grant from the Biological Research Fund of the University of Chicago.
EFFECTS OF FREQUENT MILKING ON MILK SECRETION DURING LACTATION IN THE GOAT: RELATION TO FACTORS WHICH LIMIT THE RATE OF SECRETION
Authors: Blatchford D. R. , Peaker M. 
Published: December 2015

Goats were milked hourly with the aid of oxytocin at different stages of lactation. Udder volume and milk yield were also measured. The marked variation between goats in the time after parturition at which peak milk yield is attained and in the rate of decline after peak is illustrated. Hourly milking had a stimulatory effect on the rate of milk secretion in early lactation (before peak) and in declining lactation (after peak), in both cases at previous milk yields of 1·1–1·48 g/ml udder volume. d. There was no stimulatory effect of hourly milking on milk yield at or near peak lactation (yield before the experiment 〉 1·48 g/ml volume.d) or in late lactation (〈 1·1 g/ml.d).The responses of milk yield to hourly milking are discussed in relation to the factors which limit the rate of secretion. In particular, it is concluded that a stimulatory response indicates that before the experiment the rate of secretion could not have been limited directly by the arterial supply of one or more substrates for milk synthesis.It is stressed that the results were obtained under one dietary regime only.
Restoration of focal multiple innervation in rat muscles by transmission block during a critical stage of development
Authors: Brown M. C. , Holland R. L. , Hopkins W. G. 
Published: December 2015

1. The soleus, extensor digitorum longus and peroneus tertius muscles of the hind leg were paralysed by botulinum toxin injection in neonatal rats varying in age from 8 to 31 days. The soleus muscle was similarly paralysed in adult rats.2. Muscles were excised after different periods of block, neuromuscular transmission was assessed in vitro, and the nerve terminal size and amount of terminal sprouting and multiple innervation determined histologically using silver (Ag) and zinc iodide‐osmium (ZIO) tetroxide stains.3. Recovery from the block induced by botulinum toxin was more rapid in immature multiply‐innervated muscles than in muscles of older rats in which all multiple innervation had been eliminated.4. Terminals in muscles blocked during the first month after birth grew rapidly in size and developed a characteristic granulose morphology in the first few days following the block. This change did not occur in fully adult rat solei.5. Sprouts growing from the terminals were infrequent in muscles paralysed before day 16. Terminal sprouts were more frequent in muscles paralysed between 16 and 31 days of age, but were very infrequent in adult solei.6. In confirmation of Thompson, Kuffler & Jansen (1979) paralysis begun at 10 days was followed initially by a continued fall in multiple innervation detected electrophysiologically. After 2 days the percentage of muscle fibres with more than one input rose. The extra inputs did not come from terminal sprouts. They innervated the single synaptic site on each muscle fibre as they do during normal synaptogenesis.7. The amount of multiple innervation regained 5‐10 days after the start of paralysis became progressively less the later paralysis started and was approximately equal to the level existing at the time the block was begun. Thus paralysis starting on or after day 16 (when all excess inputs have normally withdrawn) caused no return of multiple innervation.8. The return of multiple inputs and the swelling of the nerve terminals are presumably responses of the motoneurone to growth stimuli from inactive muscle. It is not clear whether the return of multiple innervation in the 10‐15 day old rats is due to reactivation of inputs still in close contact with the end‐plate before withdrawal or to regrowth of partly retracted nerve branches.9. A parallel is drawn between the limited period when inactivity can reinstate multiple innervation, and the critical period in the developing visual cortex.
Impact of Anaerobiosis on Expression of the Iron-Responsive Fur and RyhB Regulons
Authors: Beauchene Nicole A. , Myers Kevin S. , Chung Dongjun , Park Dan M. , Weisnicht Allison M. , Keleş Sündüz , Kiley Patricia J. 
Published: December 2015

ABSTRACTIron, a major protein cofactor, is essential for most organisms. Despite the well-known effects of O2on the oxidation state and solubility of iron, the impact of O2on cellular iron homeostasis is not well understood. Here we report that inEscherichia coliK-12, the lack of O2dramatically changes expression of genes controlled by the global regulators of iron homeostasis, the transcription factor Fur and the small RNA RyhB. Using chromatin immunoprecipitation sequencing (ChIP-seq), we found anaerobic conditions promote Fur binding to more locations across the genome. However, by expression profiling, we discovered that the major effect of anaerobiosis was to increase the magnitude of Fur regulation, leading to increased expression of iron storage proteins and decreased expression of most iron uptake pathways and several Mn-binding proteins. This change in the pattern of gene expression also correlated with an unanticipated decrease in Mn in anaerobic cells. Changes in the genes posttranscriptionally regulated by RyhB under aerobic and anaerobic conditions could be attributed to O2-dependent changes in transcription of the target genes: aerobic RyhB targets were enriched in iron-containing proteins associated with aerobic energy metabolism, whereas anaerobic RyhB targets were enriched in iron-containing anaerobic respiratory functions. Overall, these studies showed that anaerobiosis has a larger impact on iron homeostasis than previously anticipated, both by expanding the number of direct Fur target genes and the magnitude of their regulation and by altering the expression of genes predicted to be posttranscriptionally regulated by the small RNA RyhB under iron-limiting conditions.IMPORTANCEMicrobes and host cells engage in an “arms race” for iron, an essential nutrient that is often scarce in the environment. Studies of iron homeostasis have been key to understanding the control of iron acquisition and the downstream pathways that enable microbes to compete for this valuable resource. Here we report that O2availability affects the gene expression programs of twoEscherichia colimaster regulators that function in iron homeostasis: the transcription factor Fur and the small RNA regulator RyhB. Fur appeared to be more active under anaerobic conditions, suggesting a change in the set point for iron homeostasis. RyhB preferentially targeted iron-containing proteins of respiration-linked pathways, which are differentially expressed under aerobic and anaerobic conditions. Such findings may be relevant to the success of bacteria within their hosts since zones of reduced O2may actually reduce bacterial iron demands, making it easier to win the arms race for iron.
Clinical characteristics, management and 1-year outcomes of patients with acute coronary syndrome in Iran: the Iranian Project for Assessment of Coronary Events 2 (IPACE2)
Authors: Kassaian Seyed Ebrahim , Masoudkabir Farzad , Sezavar Hashem , Mohammadi Mohammad , Pourmoghaddas Ali , Kojouri Javad , Ghaffari Samad , Sanaati Hamidreza , Alaeddini Farshid , Pourmirza Bahin , Mir Elham 
Published: December 2015

ObjectivesTo assess contemporary data on characteristics, management and 1-year postdischarge outcomes in Iranian patients hospitalised with acute coronary syndrome (ACS).Setting11 tertiary care hospitals in 5 major cities in the Islamic Republic of Iran.ParticipantsPatients aged ≥20 and ≤80 years discharged alive with confirmed diagnosis of ACS including ST-segment elevation myocardial infarction (STEMI), non-STEMI (NSTEMI) and high-risk unstable angina (HR-UA).Primary and secondary outcome measuresPatients were followed up regarding the use of medications and the end points of the study at 1 month and 1 year after discharge. The primary end point of the study was 1-year postdischarge major adverse cardiac and cerebrovascular events (MACCEs), defined as mortality (cardiac and non-cardiac), ACS and cerebrovascular attack (stroke and/or transient ischaemic attack). The secondary end points were hospital admission because of congestive heart failure, revascularisation by coronary artery bypass grafting surgery or percutaneous coronary intervention (PCI), and major and minor bleeds.ResultsA total of 1799 patients (25.7% STEMI and 74.3% HR-UA/NSTEMI) discharged alive with confirmed diagnosis of ACS were included in the final analysis. During hospitalisation, the majority of the patients received aspirin (98.6%), clopidogrel (91.8%), anticoagulants (93.4%), statins (94.3%) and β-blockers (89.3%). Reperfusion therapy was performed in 62.6% of patients with STEMI (46.3% thrombolytic therapy and 17.3% primary PCI). The mean door-to-balloon and door-to-needle times were 82.9 and 45.6 min, respectively. In our study, 64.7% and 79.5% of the patients in HR-UA/NSTEMI and STEMI groups, respectively, underwent coronary angiography. During the 12 months after discharge, MACCEs occurred in 15.0% of all patients.ConclusionsOur study showed that the composition of Iranian patients with ACS regarding the type of ACS is similar to that in developed European countries and is unlike that in developing countries of the Middle East and Africa. We found that our patients with ACS are treated with high levels of adherence to guideline-recommended in-hospital medications.
Effect of smoking on physical and cognitive capability in later life: a multicohort study using observational and genetic approaches
Authors: North Teri-Louise , Palmer Tom M , Lewis Sarah J , Cooper Rachel , Power Chris , Pattie Alison , Starr John M , Deary Ian J , Martin Richard M , Aihie Sayer Avan , Kumari Meena , Cooper Cyrus , Kivimaki Mika , Kuh Diana , Ben-Shlomo Yoav , Day Ian N M 
Published: December 2015

ObjectivesThe observed associations between smoking and functional measures at older ages are vulnerable to bias and confounding. Mendelian randomisation (MR) uses genotype as an instrumental variable to estimate unconfounded causal associations. We conducted a meta-analysis of the observational associations and implemented an MR approach using the smoking-related single nucleotide polymorphism rs16969968 to explore their causal nature.Setting9 British cohorts belonging to the HALCyon collaboration.ParticipantsIndividual participant data on N=26 692 individuals of European ancestry (N from earliest phase analysed per study) of mean ages 50–79 years were available for inclusion in observational meta-analyses of the primary outcomes.Primary outcomesPhysical capability, cognitive capability and cognitive decline. The smoking exposures were cigarettes per day, current versus ex-smoker, current versus never smoker and ever versus never smoker.ResultsIn observational analyses current and ever smoking were generally associated with poorer physical and cognitive capability. For example, current smokers had a general fluid cognition score which was 0.17 z-score units (95% CI −0.221 to −0.124) lower than ex-smokers in cross-sectional analyses. Current smokers had a walk speed which was 0.25 z-score units lower than never smokers (95% CI −0.338 to −0.170). An MR instrumental variable approach for current versus ex-smoker and number of cigarettes smoked per day produced CIs which neither confirmed nor refuted the observational estimates. The number of genetic associations stratified by smoking status were consistent with type I error.ConclusionsOur observational analysis supports the hypothesis that smoking is detrimental to physical and cognitive capability. Further studies are needed for a suitably powered MR approach.
Unintentional, non-fatal drowning of children: US trends and racial/ethnic disparities
Authors: Felton Heather , Myers John , Liu Gil , Davis Deborah Winders 
Published: December 2015

ObjectiveThe current study aimed to better understand trends and risk factors associated with non-fatal drowning of infants and children in the USA using two large, national databases.MethodsA secondary data analysis was conducted using the National Inpatient Sample and the Nationwide Emergency Department Sample databases. The analytic sample (n=19 403) included children <21 years of age who had a diagnosis code for near-drowning/non-fatal drowning. Descriptive, χ2and analysis of variance techniques were applied, and incidence rates were calculated per 100 000 population.ResultsNon-fatal drowning incidence has remained relatively stable from 2006 to 2011. In general, the highest rates of non-fatal drowning occurred in swimming pools and in children from racial/ethnic minorities. However, when compared with non-Hispanic Caucasian children, children from racial/ethnic minorities were more likely to drown in natural waterways than in swimming pools. Despite the overall lower rate of non-fatal drowning among non-Hispanic Caucasian children, the highest rate of all non-fatal drowning was for non-Hispanic Caucasian children aged 0–4 years in swimming pools. Children who were admitted to inpatient facilities were younger, male and came from families with lower incomes.ConclusionsData from two large US national databases show lack of progress in preventing and reducing non-fatal drowning admissions from 2006 to 2011. Discrepancies are seen in the location of drowning events and demographic characteristics. New policies and interventions are needed, and tailoring approaches by age and race/ethnicity may improve their effectiveness.
Perceptions of generic medication in the general population, doctors and pharmacists: a systematic review
Authors: Colgan Sarah , Faasse Kate , Martin Leslie R , Stephens Melika H , Grey Andrew , Petrie Keith J 
Published: December 2015

ObjectiveTo investigate negative perceptions about generic medicines and evaluate the proportions of lay people, doctors and pharmacists who hold these perceptions.DesignA systematic review of observational studies.Data sourcesMEDLINE, EMBASE, PsycInfo and Scopus.Eligibility criteriaQuantitative data from cross-sectional and prospective studies published in English after 1980, using self-report measures to evaluate perceptions about generic medicines, presented as percentages of the total sample assessed.ResultsAfter screening 2737 articles, 52 articles were included in the final analysis. A high proportion of doctors, pharmacists and lay people had negative perceptions of generics. Lay people were significantly more likely to view generics as less effective than branded medication (35.6%, 95% CI 34.8% to 36.4%) compared to doctors (28.7%, 27.5% to 29.9%) and pharmacists (23.6%, 21.2% to 26.2%), p<0.0001. Pharmacists (33.4%, 31.0% to 35.9%) were significantly more likely to believe generics were of inferior quality compared to branded medication than were doctors (28.0%, 26.3% to 29.9%), p=0.0006, and lay people (25.1%, 24.2% to 26.0%), p<0.0001. Doctors believed generics caused more side effects than branded medication (24.4%, 22.2% to 26.9%), compared to pharmacists (17.6%, 15.3% to 20.1%) and lay people (18.8%, 17.8% to 19.8%), p<0.0001. Doctors (28.5%, 26.9% to 30.2%) and pharmacists (25.4%, 21.4% to 29.9%) had significantly more safety concerns about generics than did lay people (18.0%, 17.0% to 19.0%), p≤0.0002. A greater proportion of lay people felt negatively about generic substitution (34.0%, 33.2% to 34.9%), compared to doctors (24.1%, 22.0% to 26.4%) and pharmacists (11.0%, 9.6% to 12.7%), p<0.0001. Rates of negative perceptions of generics do not appear to have changed substantially over time in the general population or among physician groups, p≥0.431, but such negative beliefs show a decreasing trend in pharmacists over the study period, p=0.034.ConclusionsA significant proportion of doctors, pharmacists and lay people hold negative perceptions of generic medicines. It is likely these attitudes present barriers to the wider use of generics.
Qualitative investigation of patients’ experience of a glaucoma virtual clinic in a specialist ophthalmic hospital in London, UK
Authors: Kotecha Aachal , Bonstein Karen , Cable Richard , Cammack Jocelyn , Clipston Jane , Foster Paul 
Published: December 2015

ObjectivesTo explore how patients felt about delivery of care in a novel technician-delivered virtual clinic compared with delivery of care in a doctor-delivered model.DesignA qualitative investigation using one-to-one interviews before and after patients’ appointments at either the standard outpatient glaucoma clinic or the new technician-delivered virtual glaucoma clinic (Glaucoma Screening and Stable Monitoring Service, GSMS).SettingA glaucoma clinic based in a tertiary ophthalmic specialist hospital in London.Participants43 patients (38 Caucasian, 5 African/Afro-Caribbean) were interviewed prior to their glaucoma appointment; 38 patients were interviewed between 4 and 6 weeks after their appointment. Consecutive patients were identified from patient reception lists and telephoned prior to their appointment inviting them to participate.ResultsTrust in the patient–provider relationship emerged as a key theme in patients’ acceptance of not being seen in a traditional doctor-delivered service. Patients who were well informed regarding their glaucoma status and low risk of progression to sight loss were more accepting of the GSMS. Patients valued the reassurance received through effective communication with their healthcare practitioner at the time of their appointment.ConclusionsThis study suggests that patients are accepting of moving to a model of service delivery whereby the doctor is removed from the consultation as long as they are informed about the status of their condition and reassured by the interaction with staff they meet. This study highlights the importance of patient engagement when introducing new models of service delivery.