Possible involvement of inositol phosphoglycan-P in human parturition

Preterm labour is a major cause of neonatal morbidity and mortality but the pathophysiology that underlies preterm labour is unknown. Inositolphosphoglycans (IPGs) comprise a ubiquitous family of putative carbohydrate second messengers and they have been linked to the pathogenesis of various conditions, including diabetes and pre-eclampsia. Studying IPG-P levels in normal and pre-eclamptic pregnancies, we noticed a constant rise of urinary IPG-P levels in all women at the time of delivery. A prospective pilot study of urinary IPG-P levels in 23 non-labouring and labouring women with uncomplicated pregnancies has, therefore, been performed. Levels of urinary IPG-P were significantly higher in labour than in the non-labouring group (P<0.0001). These higher levels have been found in both spontaneous and induced labour. The clinical significance of this observation with particular reference to the onset of labour itself is discussed.     

Emergency ultrasound for blunt abdominal trauma--meta-analysis update 2003

Emergency ultrasound has established itself as a key procedure of primary diagnostic work-up for blunt abdominal and multiple trauma. However, in a systematic review published in 2001 ultrasonography turned out to provide an unexpectedly low sensitivity. We conducted an update of this analysis to investigate if test characteristics will be maintained including recent studies. Prospective trials published between January 1957 and January 2003 were identified using the Medline/Oldmedline, Embase and Cochrane Controlled Trials Register databases. The searching strategy comprised a manual search as well as a search along the world-wide web. Qualitative rating was carried out by two investigators using criteria proposed by the Centre for Evidence-Based Medicine, Oxford. We investigated a composite endpoint (i. e., free fluid and/or organ laceration) as well as the single criteria organ injury and free intraabdominal fluid collections. After calculation of two-by-two-tables, Summary Receiver Operating Characteristics (SROC) and Q* values were determined together with their 95% confidence intervals. The Q* value was proposed as the point of intersection where sensitivity equals specificity. In addition, a random effects model was employed to compute common positive and negative likelihood ratios (LR). By assessing the title and/or abstract, 349 of 957 papers contained potentially valid information for the purpose of this review. A total of 67 studies were deemed eligible, nine of which had to be excluded from meta-analysis because of dual publication. This left 58 trials allocating 16,361 subjects for statistical analysis. Despite a trend towards improved study designs observed during the past decade, the included trials were of average methodological quality. Two-thirds of all investigations fulfilled two or less of the six possible quality criteria. The diagnostic reference standard was applied independently in only 40% of all protocols. With regard to the composite endpoint and the sonographic depiction of free fluid, the Q* value was estimated at 0.91, whereas Q* equaled 0.90 for the detection of organ injury. Q* values subsequently decreased with improving study quality and fell clearly below 0.80 in methodologically proper studies. Accounting for a negative LR of 0.23 (composite endpoint) and an assumed prevalence of 35% of intraabdominal injury, a post-test probability of 11% will remain in case of a negative sonogram. In pediatric trauma, ultrasound showed even worse test characteristics (negative LR = 0.43). Thus, in case of a 35% prevalence, the post-test probability has to estimated at 19%. Emergency ultrasound provides high specificity but insufficient sensitivity to reliably rule out intraabdominal injury.     

002 高血压及抗高血压药物与Ⅱ型糖尿病

本文采用前瞻性群体研究旨在确定降压药物的应用与继发Ⅱ型糖尿病的危险之间是否存在独立的相关性。 作者对12 550名(年龄45-64岁)无糖尿病的成年人进行全面健康评价(包括药物的使用及血压测定)。高血压判定标准为收缩压≥140mmH-g(1mmHg=0.1333 kPa)或舒张压≥90mmHg。确定高血压患者3 804例，根据使用降压药物的种类分为血管紧张素转化酶抑制剂(ACEI)162例，β阻滞剂543例，钙拮抗剂96例，噻嗪利尿剂458例，其它单一药物137例，多种药物(≥2种)934例，其余1 474例高血压患者未给予任何抗高血压药物治疗。随访3年及6年后，通过测定空腹血糖浓度[糖尿病判定标准为：空腹血糖≥126m/dl(≥7.0mmol/L)餐后血糖≥200m/dl(≥11.1mmol/L)]评价糖尿病新病例的发生率。     

Lacosamid (Vimpat®): Bericht eines Expertentreffens zu einem neuen Medikament zur Zusatzbehandlung fokaler Anfälle

Lacosamide (LCM, R-2-acetamido-N-benzyl-3-methoxypropionamide) belongs to the group of functionalized amino acids. In experimental animal models, LCM proved to be an effective drug against partial seizures and additionally showed a potential effect on the mechanisms of epileptogenesis. LCM selectively enhances slow inactivation of voltage-gated sodium channels without affecting fast inactivation, which is known for other antiepileptic drugs like carbamazepine, phenytoine or lamotrigine. Furthermore, LCM binds to collapsin-response mediator protein 2 (CRMP-2). The resulting effect is still unknown. Lacosamide is rapidly and completely absorbed. Its absorption does not interfere with food uptake. Beside oral application (tablet, syrup), LCM is available as an intravenous formulation as well. An elimination half-life of 13 hours allows for twice-daily dosing. Due to renal excretion, it is necessary to adapt the dosage in elderly or other patients with severe renal impairment. LCM neither induces nor inhibits cytochrome P-450 isoenzymes. No clinically relevant interactions with other antiepileptic drugs have been observed, which is an important clinical advantage compared to strong enzyme-inducing drugs like carbamazepine, phenobarbitale, phenytoine but also to drugs with lesser induction potentials like oxcarbazepine and lamotrigine. Add-on treatment with LCM 200-600 mg/d in randomized, placebo-controlled clinical trials in patients with focal epilepsies was superior to placebo. LCM can be titrated within 1-3 weeks to the labelled dosage range of 200-400 mg/d. Beside the side effects of the central nervous system typical for antiepileptic drugs, the tolerability of LCM was good. Psychiatric side effects occurred in 4% of the patients; changes of body weight were not detected. A dose-dependent prolongation of the PR interval of 14.3 ms under LCM 400 mg/d (placebo 11.2 ms) was detected but no correlation with clinical symptoms could be found. This needs further clinical follow-up In summary, efficacy, titration schedule, favorable pharmacokinetic profile and low psychiatric side effect profile speak in favour of lacosamide.     

Bodyweight gain under pregabalin therapy in epilepsy: mitigation by counseling patients?

OBJECTIVE: To evaluate bodyweight gain during pregabalin therapy for epilepsy and the utility of a short counseling program to prevent this side effect. METHODS: Randomized controlled trial on the effects of extended versus standard patient counseling on the risk of bodyweight gain with 3- and 6-month follow-up including a consecutive sample of adult outpatients with epilepsy eligible for pregabalin add-on treatment (N=98). RESULTS: The seizure response rate was about 30%, the seizure freedom rate was 5% at the 6-month follow-up (intent-to-treat sample, N=98). The median bodyweight gain for the according-to-protocol sample (N=62) was 4.0 kg with no effect of extended counseling. Bodyweight gain was correlated with number of anticonvulsant drugs (r=.32, p<.05). CONCLUSIONS: Pregabalin treatment is associated with a high risk for bodyweight gain which in part depends on total anticonvulsant drug load. This side effect cannot be prevented by extended patient counseling within a standard clinical setting.     

Human primary auditory cortex: cytoarchitectonic subdivisions and mapping into a spatial reference system

The transverse temporal gyrus of Heschl contains the human auditory cortex. Several schematic maps of the cytoarchitectonic correlate of this functional entity are available, but they present partly conflicting data (number and position of borders of the primary auditory areas) and they do not enable reliable comparisons with functional imaging data in a common spatial reference system. In order to provide a 3-D data set of the precise position and extent of the human primary auditory cortex, its putative subdivisions, and its topographical intersubject variability, we performed a quantitative cytoarchitectonic analysis of 10 brains using a recently established technique for observer-independent definition of areal borders. Three areas, Te1.1, Te1.0, and Te1.2, with a well-developed layer IV, which represent the primary auditory cortex (Brodmann area 41), can be identified along the mediolateral axis of the Heschl gyrus. The cell density was significantly higher in Te1.1 compared to Te1.2 in the left but not in the right hemisphere. The cytoarchitectonically defined areal borders of the primary auditory cortex do not consistently match macroanatomic landmarks like gyral and sulcal borders. The three primary auditory areas of each postmortem brain were mapped to a spatial reference system which is based on a brain registered by in vivo magnetic resonance imaging. The integration of a sample of postmortem brains in a spatial reference system allows one to estimate the spatial variability of each cytoarchitectonically defined region with respect to this reference system. In future, the transfer of in vivo structural and functional data into the same spatial reference system will enable accurate comparisons of cytoarchitectonic maps of the primary auditory cortex with activation centers as established with functional imaging procedures.