Study of the pituitary-thyroid functions at high altitude in man.

The alterations in serum levels of T3, T4, TSH and TBG, TSH response to 100 mug iv TRH, and urinary excretion of T3 and T4 were studied in 8 healthy men at sea level (SL), on days 1, 2, 4, 8 and 16 after arrival by air at high altitude (3,700 m, HA), and during days 5 to 7 after their return to SL. No significant alterations in serum levels of TSH and TBG or TSH response to TRH were observed during exposure to HA or on return to SL. There was, however, an acute elevation in both serum total T3 and T4. Serum total T3 from a mean basal+/-SE value of 128+/-13 ng/dl increased to 320+/-18 on day 1 and remained significantly elevated at 225+/-48 up to day 8 after arrival at high altitude. Similarly serum total T4 increased from basal level of 9+/-0.92 mug/dl to 15.2+/-1.2 and remained elevated till day 16 and it was 11+/-1.19 mug/dl during days 5 to 7 after return to SL. The urinary excretion of both T3 and T4 was decreased. These changes perhaps were the result of complex physiologic adjustments on acute exposure to high altitude, like shrinkage of the T3 and T4 distribution pools, altered binding capacities of thyroid hormones binding proteins, and a reduction in clearance of thyroid hormones from the plasma compartment; and were probably not suggestive of an enhanced thyroid activity. Their actual significance in high altitude adaptation in man is not clearly understood.     

Use of pH-impedance testing to evaluate patients with suspected extraesophageal manifestations of gastroesophageal reflux disease

GOALS: To report the use of pH-impedance testing in evaluating patients with suspected gastroesophageal reflux disease (GERD) with atypical symptoms. BACKGROUND: Although the role of acid reflux in causing atypical GERD symptoms is generally accepted, the role, if any, of nonacid reflux is controversial, largely because until recently it has not been possible to detect nonacid reflux. The advent of intraluminal combined pH impedance testing (MII-pH), to detect nonacid reflux has heightened interest in its possible contribution to atypical symptoms. STUDY: Fifty consecutive patients referred for MII-pH testing to evaluate the cause of atypical symptoms presumed due to GERD were evaluated. The symptoms were either refractory to acid inhibition therapy or so atypical that further work up was desired by the referring physician. Patients underwent MII-pH testing to determine whether reflux was present, and, if so, if it was due to acid, nonacid, or gas. RESULTS: Only 16%, 22%, and 2% patients were found to have symptoms due to acid reflux, nonacid reflux, or both, respectively. Ten percent of these patients had gas reflux. MII-pH testing was useful in redirecting the management of patients who did not have reflux as the cause of their symptoms. CONCLUSIONS: MII-pH testing is useful in determining whether gastroesophageal reflux is present in patients with atypical symptoms that have not responded to proton pump inhibitor therapy. It also distinguishes between reflux due to acid, nonacid, and gas, with consequences for management.     

Chaos and stability of the solar system

Over the last two decades, there has come about a recognition that chaotic dynamics is pervasive in the solar system. We now understand that the orbits of small members of the solar system-asteroids, comets, and interplanetary dust-are chaotic and undergo large changes on geological time scales. Are the major planets' orbits also chaotic? The answer is not straightforward, and the subtleties have prompted new questions.     

The natural history of a genetic subtype of arrhythmogenic right ventricular cardiomyopathy caused by a p.S358L mutation in TMEM43

To determine the phenotype and natural history of a founder genetic subtype of autosomal dominant arrhythmogenic right ventricular cardiomyopathy (ARVC) caused by a p.S358L mutation in TMEM43. The age of onset of cardiac symptoms, clinical events and test abnormalities were studied in 412 subjects (258 affected and 154 unaffected), all of which occurred in affected males significantly earlier and more often than unaffected males. Affected males were hospitalized four times more often than affected females (p ≤ 0.0001) and died younger (p ≤ 0.001). The temporal sequence from symptoms onset to death was prolonged in affected females by 1–2 decades. The most prevalent electrocardiogram (ECG) manifestation was poor R wave progression (PRWP), with affected males twice as likely to develop PRWP as affected females (p ≤ 0.05). Left ventricular enlargement (LVE) occurred in 43% of affected subjects, with 11% fulfilling criteria for dilated cardiomyopathy. Ventricular ectopy on Holter monitor was common and occurred early: the most diagnostically useful clinical test. No symptom or test could rule out diagnosis. This ARVC subtype is a sex‐influenced lethal arrhythmogenic cardiomyopathy, with a unique ECG finding, LV dilatation, heart failure and early death, where molecular pre‐symptomatic diagnosis has the greatest clinical utility.     

Lessons learnt from an obstetric and neonatal emergency simulation program in India

BackgroundCombined obstetric and neonatal emergency simulation based training is gaining popularity in healthcare settings. Methods: In this qualitative study, through semi-structured one to one interviews, we evaluated participant attitudes, perceptions of retention of learning, and application to clinical practice one year after a simulation workshop. Audio recordings of interviews were transcribed, collated and subjected to thematic analysis. Results: Five major themes were identified through the thematic analysis: comparing simulation to clinical practice; learning and working in teams; thinking retention and sustainability; relating relevance of simulation based education to roles; and managing leadership. Conclusions: Participants’ acknowledgement of training being relevant to their routine practice, and keenness to learn management of complicated births highlighted the sustained impact of obstetric and neonatal emergency simulation training.     

LC-MS/MS测定人血浆中对乙酰氨基酚及其人体药动学和生物等效性研究

目的 建立一种快速、灵敏的高效液相色谱-串联质谱（HPLC-MS/MS）方法以测定人血浆中对乙酰氨基酚浓度,并应用于两种对乙酰氨基酚制剂的人体药代动力学和生物等效性研究。方法 以替硝唑为内标,200μL血浆样品经5倍于其体积的乙酸乙酯液液萃取,再经Waters XBridge? C18柱等度洗脱分离后导入串联质谱,以正离子多反应监测模式进行定量分析,对乙酰氨基酚和内标的选择性反应离子对分别是m/z 152→110和248→121。方法经验证后应用于19名健康受试者单剂量空腹口服两种对乙酰氨基酚制剂500mg后药代动力学和生物等效性的研究。结果 血浆中对乙酰氨基酚在0.1～8.0 μg·mL-1范围内线性良好（r2 > 0.99）,最低检测限为 0.1 μg·mL-1,提取回收率为91.0%～98.7%,日内和日间准确度分别为98.8%～111.3% （精密度：CV ? 9.03%）和94.9%～102.6% （精密度：CV ? 10.68%）。生物等效性试验中,受试制剂与参比制剂的主要药代动力学参数Cmax、AUC0-t和AUC0-∞ 几何均值比的90%置信区间分别为83.50%～105.79%,94.25%～101.54%和93.24%～101.02%,均落在生物等效可接受标准80.00%～125.00%范围内。结论 所建立测定人血浆中对乙酰氨基酚浓度的HPLC-MS/MS法具有快速灵敏、回收率高、选择性好的特点,适用于对乙酰氨基酚片人体药代动力学和生物等效性研究。受试制剂与参比制剂在人体内吸收速度和程度相似,两种制剂生物等效。     

Cast index in predicting outcome of proximal pediatric forearm fractures

Background:Many pediatric forearm fractures can be treated in plaster following closed reduction. The cast index (CI, a ratio of anteroposterior to lateral internal diameters of the cast at the fracture site) is a simple, reliable marker of quality of molding and a CI of >0.8 correlates with increased risk of redisplacement. Previously, CI has been applied to all forearm fractures. We hypothesize that an acceptable CI is more difficult to achieve and does not predict outcome in fractures of the proximal forearm.Results:The mean CI was 0.77. Remanipulation was required in five cases (6%), all distal half fractures – mean CI 0.79. CI was higher in proximal half forearm fractures (0.83 vs. 0.76, P = 0.006), nonetheless these fractures did not re-displace more than distal fractures.Conclusion:Cast index is useful in predicting redisplacement of manipulated distal forearm fractures. We found that in proximal half forearm fractures it is difficult to achieve a CI of <0.8, but increased CI does not predict loss of position in these fractures. We therefore discourage the use of CI in proximal half forearm fractures.     

What are Journals for?

‘The secret is comprised in three words – work, finish, publish.’Michael FaradayThere are many reasons doctors want to publish their work. For most at an early stage in their career, this may be to add a line to their curriculum vitae and advance their careers but for academics, publishing is an expectation. Many will believe they have something important to say, and wish to provoke debate and discussion; others wish to share knowledge and experiences, which in medicine can lead to a satisfying change in clinical practice. All serve to register one’s idea and educate others. However, for some, the reason is as basic as money. As we celebrate the 350th anniversary of the first academic publication, perhaps we have come full circle when it comes to why people publish?Publishing is a flourishing business. There were approximately 28,100 active scholarly peer-reviewed journals in mid-2012, collectively publishing about 1.8–1.9 million articles per year. The number of articles published each year and the number of journals have both grown steadily for more than two centuries, by about 3% and 3.5% per year respectively.¹ Journals have a responsibility to refine and define information and act as a scientific filter. Many of us will receive daily invitations in our email inbox from eclectic and new journals that are likely to take anything – is the filter now too porous? But this industry is like any other commercial activity and the supply still far outstrips the demand. Perhaps the internet revolution has merely fuelled our hunger to publish more?The launch of this exciting and innovative series about publishing coincides with the 350th celebration of the publication of the first academic journal. In the age of social media, the first question is ‘What are journals for?’, which Simon Rallison sets out to answer. Simon is Director of Publications at the Physiological Society, and was previously a journal publisher with Earthscan, Springer and Blackwell.Writing is hard work and, through this series, I hope the reader will get some useful insight into this service industry for academia.Jyoti ShahCommissioning EditorIn an age of the internet and social media, why are we still using (admittedly with refinements and improvements) a form of publication dating from 1665? What exactly is a journal in the 21st century and what role does it have to perform? Surprisingly, the academic journal has not evolved since it was invented 350 years ago.¹ The first issue of the Philosophical Transactions of the Royal Society was published in 1665, the brainchild of Henry Oldenburg and Robert Hooke. Since then, journals have digitised and now offer greater opportunity for research communication – but are authors taking advantage of what journals can offer? The academic and research community is generally very conservative about what it reads and how it views journals. There are, however, also frequent misunderstandings about the operation of journals.