An integrated approach to distance learning with digital video in the French-speaking Virtual Medical University

The aim of the French-speaking Virtual Medical University project (UMVF) is to share common resources and specific tools in order to improve medical training. Digital video on IP is an attractive tool for higher education but there are a number of obstacles to widespread implementation. This paper describes the UMVF approach to integrating digital video technologies and services in educational projects.     

Safety and pharmacokinetics of paracetamol following intravenous administration of 5 g during the first 24 h with a 2-g starting dose

Intravenous (i.v.) paracetamol is used as 1-g infusions with a maximal daily dose of 4 g/day. However, a higher initial analgesic dose could be of interest in the immediate postoperative period when the pain is maximal. The purpose of the present study was to determine in healthy subjects the safety and the pharmacokinetics of i.v. paracetamol, starting with a 2-g dose, followed by 1-g doses every 6 h, leading to a total of 5 g the first 24 h. This was an open-label, single-sequence study. The paracetamol pharmacokinetic profile was assessed in 26 subjects after both the 2-g starting dose and the 1-g doses. Safety, especially hepatotoxicity, was evaluated up to 72 h after the initial 2-g dose. Following the first 15-min i.v. administration of paracetamol 2 g, plasma concentrations ranged from 67.9+/-21.8 mug/ml (peak plasma concentration (C(max)) at the end of infusion) to 6.2+/-2.3 mug/ml (trough plasma concentration (C(min)) measured just before the next infusion) without any C(max) in the toxic range for any subject. After the repeated 1-g infusions, the plasma concentrations were approximately 35% lower than that measured after 2 g, showing the absence of accumulation. No clinical adverse events related to the drug administration nor clinically relevant changes in laboratory parameters, including biochemical signs of hepatotoxicity, were reported. After i.v. administration of paracetamol 2-g starting dose and 5 g during the first 24 h, the pharmacokinetics of paracetamol remain unchanged, with concentrations far below the toxic threshold. Overall, these results demonstrate that the i.v. administration of a 2-g starting dose of paracetamol, followed by three i.v. administrations of 1 g during the first 24 h is safe in healthy subjects.     

自制冷热刀医疗设备靶向治疗肿瘤的性能实验

目的:考察新研制的真正集深低温冷冻治疗与高温热疗功能于一体的先进肿瘤治疗临床试验设备(冷热聚能刀,中国科学院理化技术研究所自主研制开发)的实际工作性能,为后期的临床实验提供初步而又有价值的参考依据。方法:将冷热刀探针(外径5mm)置于空气、明胶、猪肉以及活体兔子组织中实施局部靶向的快速冷冻(-196℃)及升温(88℃)试验,以检测探针外壁、针尖内部以及周边测温点的温度响应特性,并观察冰球的生长过程;同时,还基于红外热像仪及数码相机,对相应的冷冻及升温效果进行影像评估。结果:冷热刀工作时,探针刀头外壁总体上能在大约4min以内下降到极低温度(约-160℃),并维持稳定;而当冷热刀处于升温阶段时,刀头外壁温度可迅速上升,在大约2min左右即达到80℃,冰球紧贴刀杆部分随即熔化。结论:冷热刀临床试验设备具有优异的快速冷冻和高强度加热功能,可望在肿瘤的高效微创治疗上发挥关键作用。     

Changes in bone mineral density (BMD): a longitudinal study of osteoporosis patients in the real-world setting

Summary

In clinical practice, the frequency of patients achieving improved T-scores and the expected change in bone mineral density (BMD) according to osteoporosis drugs is unknown. We found that osteoporosis medications infrequently achieve improved femoral neck T-scores over 1.2 years. BMD increases were more often seen with IV bisphosphonates and denosumab.

Purpose

To determine the frequency of osteoporosis patients achieving improvement in T-scores and quantify the change in bone mineral density (BMD) over time according to osteoporosis medication use.

Methods

The study included all patients receiving clinical care at United Osteoporosis Centers, Gainesville, GA, 1995–2015, who had at least two measures of femoral neck BMD (N?=?1232). We evaluated successive pairs of BMD tests to describe the distribution of transitions between T-score categories. Generalized estimating equations were used to estimate %BMD change between successive pairs of BMD tests according to osteoporosis medication, adjusted for age, sex, height, weight, baseline BMD, previous fracture, and follow-up time.

Results

Mean (±SD) age was 68 (±10) years, and 90% of patients were women. Mean baseline T-score was ??2.04 (±?0.85). In total, 1232 patients had 4918 pairs of successive BMD tests, with a mean 1.2 years (±?0.9) between assessments. Frequency of transition to an improved T-score category was 41% when prior T-score ≤???3.5, and 15% when prior T-score ??1.99 to ??1.50. Most individuals (69%) remained in the same T-score category. BMD increased 0.54% (95% CI 0.23–0.85%) with IV bisphosphonates and 1.23% (95% CI 0.56–1.90%) with denosumab, whereas no significant change was seen with oral bisphosphonates, teriparatide, or raloxifene.

Conclusions

Osteoporosis patients are unlikely to improve femoral neck T-scores over 1.2 years. Additional studies are needed to determine the optimal time to repeat BMD testing while receiving osteoporosis treatment and to determine whether fracture risk is reduced in patients who achieve target T-scores.

     

Oestrogen upregulates the sarcoplasmic reticulum Ca2+ ATPase pump in coronary arteries

The presence of circulating plasma 17β‐oestradiol (E2) is beneficial in women against abnormal vascular tone development, such as coronary arterial vasospasms. Several vascular diseases have demonstrated that increased expression of the sarcoplasmic reticulum Ca²⁺‐ATPase pump (SERCA2b) serves to limit the excessive accumulation of intracellular Ca²⁺. Therefore, the hypothesis of the present study was that E2 would increase SERCA2b expression in the coronary vasculature. Coronary arteries were dissected from hearts obtained from mature female pigs. Artery segments were cultured for 24 h in E2 (1 pmol/L or 1 nmol/L) and homogenized for western blot analysis. At 1 nmol/L, E2 induced an approximate 50% increase in immunoreactivity for SERCA2b. In addition, E2 increased the protein expression of the known SERCA regulatory proteins, protein kinase A (PKA) and protein kinase G (PKG). The E2‐induced increase in SERCA2b was attenuated when the culture medium was supplemented with the oestrogen receptor (ER) α/β antagonist ICI 182,780 and the PKG antagonist KT5823 (10 μmol/L, 24 h for both). The PKA antagonist (KT5720; 10 μmol/L, 24 h) had no effect on SERCA2b expression. Removal of the endothelium (using a wooden toothpick) from artery segments prior to culture decreased the E2‐mediated increase in SERCA2b and PKG expression by 45% and 47%, respectively. Overall, the findings suggest that one of the potential cardiovascular benefits of E2 in women is upregulation of SERCA2b, via activation of the classic ERα and ERβ pathway.     

Effect of eccentric versus concentric exercise training on mitochondrial function

Introduction: The effect of eccentric (ECC) versus concentric (CON) training on metabolic properties in skeletal muscle is understood poorly. We determined the responses in oxidative capacity and mitochondrial H₂O₂ production after eccentric (ECC) versus concentric (CON) training performed at similar mechanical power. Methods: Forty‐eight rats performed 5‐ or 20‐day eccentric (ECC) or concentric (CON) training programs. Mitochondrial respiration, H₂O₂ production, citrate synthase activity (CS), and skeletal muscle damage were assessed in gastrocnemius (GAS), soleus (SOL) and vastus intermedius (VI) muscles. Results: Maximal mitochondrial respiration improved only after 20 days of concentric (CON) training in GAS and SOL. H₂O₂ production increased specifically after 20 days of eccentric ECC training in VI. Skeletal muscle damage occurred transiently in VI after 5 days of ECC training. Conclusions: Twenty days of ECC versus CON training performed at similar mechanical power output do not increase skeletal muscle oxidative capacities, but it elevates mitochondrial H₂O₂ production in VI, presumably linked to transient muscle damage. Muscle Nerve 50 : 803–811, 2014     

Anatomic basis for use of a distal pedicle leg flap

Summary The cutaneous blood-supply of the limbs is ensured by three types of arteries: the large septo-cutaneous arteries, the slender musculocutaneous arteries, and the rare satellites of the cutaneous nerves. The skin cover of the outer aspect of the leg is particularly well vascularized thanks to its special situation, centered on the intermuscular septa bounding the outer compartment of the leg. Neuromuscular arteries are rare at this site, but there are numerous septo-cutaneous arteries at intervals along the septa. This anatomic study is based on 20 dissections and a radiologic survey and provides findings confirming the reliability of a distally based lateral leg flap. This pedicle arises from the fibular artery behind and the anterior tibial artery in front. It is situated, on average, 10.8 cm from the lateral malleolus, thus allowing coverage of peripheral losses of substances at the malleoli and heel.

---

Bases anatomiques de l'utilisation d'un lambeau jambier à pédicule distal

Résumé La vascularisation cutanée des membres est assurée par trois types d'artères: les artères septocutanées qui sont volumineuses; les artères musculo-cutanées qui sont grêles et les artères superficielles, satellites du nerf à destinée cutanée, qui sont rares. Le revêtement cutané de la face latérale de la jambe est particulièrement bien vascularisé, grâce à sa situation privilégiée, centré sur les septa intermusculaires limitant la loge externe de la jambe. Les artères neuromusculaires sont rares à ce niveau. Par contre, on retrouve de nombreuses artères septo-cutanées volumineuses étagées le long des septa. Nous avons entrepris un travail anatomique reposant sur 20 dissections et sur une étude radiologique. Nos résultats nous permettent d'établir ces données et confirment la fiabilité d'un lambeau jambier latéral à pédicule distal. Ce pédicule naît de l'artère fibulaire en arrière et de l'artère tibiale antérieure en avant. Il est situé à 10,8 cm en moyenne de la malléole latérale permettant ainsi de couvrir les pertes de substance périphériques malléolaires et talonnières.

     

<Emphasis Type="Italic">MTNR1B</Emphasis> rs10830963 is associated with fasting plasma glucose,HbA<Subscript>1C</Subscript>and impaired beta-cell function in Chinese Hans from Shanghai

Background  

Genome-wide association studies (GWAS) in White Europeans have shown that genetic variation rs10830963 in melatonin receptor 1B gene (MTNR1B) is associated with fasting glucose and type 2 diabetes, which has also been replicated in several Asian populations. As a variant in the gene involved in the regulation of circadian rhythms, the effect of the variant on sleep status remains unknown. This study aimed to investigate the effects of MTNR1B rs10830963 on fasting glucose, type 2 diabetes and sleep status in Chinese Hans.     

5-HT2A and 5-HT2C receptor polymorphisms and psychopathology in late onset Alzheimer's disease

The psychopathology of Alzheimer's disease (AD) is varied and includes both behavioural and psychological symptoms. Behavioural and psychological symptoms are common and contribute to the difficulties experienced by carers. However, the mechanism whereby these symptoms occur in some individuals with AD is not understood. We hypothesized that common genetic polymorphisms in neurotransmitter systems are risk factors for these symptoms in the course of AD. A total of 211 subjects from a population-based prospective study of psychopathology within late-onset AD were genotyped for the 5-HT2A receptor polymorphism 102- T/C and the 5-HT2C receptor polymorphism Cys23Ser. Associations were found between the presence of the C102 allele and the presence of visual (Fisher's exact test, one-tailed, P = 0.003) and auditory hallucinations (Fisher's exact test, one-tailed, P = 0.004) and between the presence of the Ser23 allele and visual hallucinations (chi2 = 7.5, df = 1, P = 0.006) (P = 0.03, 0.04 and 0.06, respectively, after Bonferroni correction). In addition, there was an association between the Cys23Ser polymorphism and hyperphagia (chi2 = 6.7, df = 2, P = 0.03) (P = 0.3 after Bonferroni correction). We conclude that common 5- HT2A and 5-HT2C genetic polymorphisms previously showing only weak associations with psychotic illness are associated with psychotic symptoms in AD but are clinically silent until the onset of the neurodegenerative process.      

The expression of the urinary forms of human luteinizing hormone beta fragment in various populations as assessed by a specific immunoradiometric assay

Human gonadotrophins undergo metabolic transformations which result in the presence of several smaller, structurally and immunologically related forms of gonadotrophins in the urine. For luteinizing hormone (LH), a beta core fragment (LHbeta cf) has been isolated from the pituitary and characterized. The corresponding urinary fragment is inferred from mass spectral and immunochemical analysis of chromatographically separated urinary forms. Physicochemical characteristics, primarily mass spectral and chromatographic, indicate that the pituitary and urinary forms of LHbeta cf have a different structure, probably in the carbohydrate moieties. This communication characterizes the expression of LHbeta cf in the urine of both reproductive and post-reproductive age women and in men, employing assays highly specific for the pituitary form of the fragment. It was found that LHbeta cf is the predominant LH associated molecular form in the urine during peri-ovulatory period, peaking 1-3 days later than intact LH and reaching a concentration of approximately 600 fmol/mg creatinine, 7-fold higher than either LH or LH free beta subunit. Corresponding concentrations of human chorionic gonadotrophin (HCG) beta cf were <1% that of LHbeta cf. LHbeta cf cross-reaction with some LH or LHbeta monoclonal antibodies may well interfere with the accurate estimation of the day of the LH surge when urinary tests are utilized.