Genetic mapping of a major susceptibility locus for juvenile myoclonic epilepsy on chromosome 15q

The epilepsies are a group of disorders characterised by recurrent seizures caused by episodes of abnormal neuronal hyperexcitability involving the brain. Up to 60 million people are affected worldwide and genetic factors may contribute to the aetiology in up to 40% of patients. The most common human genetic epilepsies display a complex pattern of inheritance. These are categorised as idiopathic in the absence of detectable structural or metabolic abnormalities. Juvenile myoclonic epilepsy (JME) is a distinctive and common variety of familial idiopathic generalised epilepsy (IGE) with a prevalence of 0.5- 1.0 per 1000 and a ratio of sibling risk to population prevalence (lambda(s)) of 42. The molecular genetic basis of these familial idiopathic epilepsies is entirely unknown, but a mutation in the gene CHRNA4, encoding the alpha4 subunit of the neuronal nicotinic acetylcholine receptor (nAChR), was recently identified in a rare Mendelian variety of idiopathic epilepsy. Chromosomal regions harbouring genes for nAChR subunits were therefore tested for linkage to the JME trait in 34 pedigrees. Significant evidence for linkage with heterogeneity was found to polymorphic loci encompassing the region in which the gene encoding the alpha7 subunit of nAChR (CHRNA7) maps on chromosome 15q14 (HLOD = 4.4 at alpha = 0.65; Z(all) = 2.94, P = 0.0005). This major locus contributes to genetic susceptibility to JME in a majority of the families studied.      

Insulin-dependent diabetes mellitus (IDDM) is associated with CTLA4 polymorphisms in multiple ethnic groups

Linkage disequilibrium (association) analysis was used to evaluate a candidate region near the CTLA4/CD28 genes using a multi-ethnic collection of families with one or more children affected by IDDM. In the data set unique to this study (Spanish, French, Mexican-American, Chinese and Korean), the transmission/disequilibrium test (TDT) revealed a highly significant deviation for transmission of alleles at the (AT)n microsatellite marker in the 3' untranslated region (P = 0.002) and the A/G polymorphism in the first exon (P = 0.00002) of the CTLA4 gene. The overall evidence for transmission deviation of the CTLA4 A/G alleles is also highly significant (P = 0.00005) in the combined data set (669 multiplex and 357 simplex families) from this study and a previous report on families from USA, Italy, UK, Spain and Sardinia. Significant heterogeneity was observed in these data sets. The British, Sardinian and Chinese data sets did not show any deviation for the A/G polymorphism, while the Caucasian-American data set showed a weak transmission deviation. Strong deviation for transmission was seen in the three Mediterranean-European populations (Italian, Spanish and French) (P = 10(-5)), the Mexican-American population (P = 0.002) and the Korean population (P = 0.03). These results suggest that a true IDDM susceptibility locus (designated IDDM12) is located near CTLA4.      

Clinical, brain electric earth map, endothelin and transcranial ultrasonic Doppler findings after hyperbaric oxygen treatment for severe brain injury

Objective　To analyze the effect and mechanism of hyperbaric oxygen (HBO) treatment for severe brain injury (SBI). Methods　Fifty-five patients were divided into a treatment group of 35 patients and a control group of 20 patients. We observed the alterations of clinical, brain electric earth map (BEAM), endothelin (ET) and transcranial ultrasonic Doppler (TCD) findings before and after HBO treatment as well as outcome. Results　In the treatment group, Glasgow coma scale, BEAM and outcome improved after HBO treatment; compared with that of the control group, it showed a significant difference. After one course of treatment, treatment group ET was reduced from 91.24±12.18?ng/L to 68.88±14.37?ng/L (P<0.01); in control group, ET was reduced from 90.78±15.71?ng/L to 83.12±12.22?ng/L, with a statistically significant difference (P<0.05). TCD records of MCA mean velocity (Vm) was reduced from 64.2±4.8?cm/s to 51.6±4.2?cm/s (P<0.01), and a decrease in MCA systolic velocity (Vs) and pulse index (PI) values was statistically significant (P<0.01). Conclusion　HBO treatment can improve the clinical, BEAM and outcome of severely brain injured patients, by decreasing acute stage ET and improving the blood velocity of MCA and decreasing cerebral vascular resistance. HBO treatment can reduce cerebral vascular spasms, cerebral ischemia and hypoxia. One of the important mechanisms of HBO treatment for severe brain injury is the lowering of intracranial pressure.     

Factors influencing the use of a Web-based application for supporting the self-care of patients with type 2 diabetes: a longitudinal study

Background

The take-up of eHealth applications in general is still rather low and user attrition is often high. Only limited information is available about the use of eHealth technologies among specific patient groups.

Objective

The aim of this study was to explore the factors that influence the initial and long-term use of a Web-based application (DiabetesCoach) for supporting the self-care of patients with type 2 diabetes.

Methods

A mixed-methods research design was used for a process analysis of the actual usage of the Web application over a 2-year period and to identify user profiles. Research instruments included log files, interviews, usability tests, and a survey.

Results

The DiabetesCoach was predominantly used for interactive features like online monitoring, personal data, and patient–nurse email contact. It was the continuous, personal feedback that particularly appealed to the patients; they felt more closely monitored by their nurse and encouraged to play a more active role in self-managing their disease. Despite the positive outcomes, usage of the Web application was hindered by low enrollment and nonusage attrition. The main barrier to enrollment had to do with a lack of access to the Internet (146/226, 65%). Although 68% (34/50) of the enrollees were continuous users, of whom 32% (16/50) could be defined as hardcore users (highly active), the remaining 32% (16/50) did not continue using the Web application for the full duration of the study period. Barriers to long-term use were primarily due to poor user-friendliness of the Web application (the absence of “push” factors or reminders) and selection of the “wrong” users; the well-regulated patients were not the ones who could benefit the most from system use because of a ceiling effect. Patients with a greater need for care seemed to be more engaged in long-term use; highly active users were significantly more often medication users than low/inactive users (P = .005) and had a longer diabetes duration (P = .03).

Conclusion

Innovations in health care will diffuse more rapidly when technology is employed that is simple to use and has applicable components for interactivity. This would foresee the patients’ need for continuous and personalized feedback, in particular for patients with a greater need for care. From this study several factors appear to influence increased use of eHealth technologies: (1) avoiding selective enrollment, (2) making use of participatory design methods, and (3) developing push factors for persistence. Further research should focus on the causal relationship between using the system’s features and actual usage, as such a view would provide important evidence on how specific technology features can engage and captivate users.     

A European approach to categorizing medicines for fitness to drive: outcomes of the DRUID project

AIMS

To illustrate (i) the criteria and the development of the DRUID categorization system, (ii) the number of medicines that have currently been categorized, (iii) the added value of the DRUID categorization system and (iv) the next steps in the implementation of the DRUID system.

METHODS

The development of the DRUID categorization system was based on several criteria. The following steps were considered: (i) conditions of use of the medicine, (ii) pharmacodynamic and pharmacokinetic data, (iii) pharmacovigilance data, including prevalence of undesirable effects, (iv) experimental and epidemiological data, (v) additional data derived from the patient information leaflet, existing categorization systems and (vi) final categorization. DRUID proposed four tiered categories for medicines and driving.

RESULTS

In total, 3054 medicines were reviewed and over 1541 medicines were categorized (the rest were no longer on the EU market). Nearly half of the 1541 medicines were categorized 0 (no or negligible influence on fitness to drive), about 26% were placed in category I (minor influence on fitness to drive) and 17% were categorized as II or III (moderate or severe influence on fitness to drive).

CONCLUSIONS

The current DRUID categorization system established and defined standardized and harmonized criteria to categorize commonly used medications, based on their influence on fitness to drive. Further efforts are needed to implement the DRUID categorization system at a European level and further activities should be undertaken in order to reinforce the awareness of health care professionals and patients on the effects of medicines on fitness to drive.     

Continuous mannose infusion in carbohydrate-deficient glycoprotein syndrome type I

The effects on isoelectrofocusing patterns of serum glycoproteins were studied in a patient with CDG syndrome type I and phosphomannomutase deficiency during 3 weeks of continuous intravenous mannose infusion. Doses of 5. 7 g/kg/day led to stable serum mannose levels up to 2. 0 mmol/1 and were well tolerated without signs of liver or renal toxicity. While most of the pathological glycoprotein patterns, including α₁-antitrypsin, typical for CDG syndrome type I remained unchanged, mannose infusion led to a unique change of the isoelectrofocusing pattern of serum sialotransferrins with appearance of two extra bands after 3 weeks of treatment.     

短链脂肪酸在溃疡性结肠炎病因及治疗中的作用

溃疡性结肠炎(ulcerative colitis,UC)的病因仍不是十分清楚.关于该疾病的假说主要集中在粘膜损伤的启动及持续机制上.病因学假说有短链脂肪酸(short chain fally acid,SCFA)的代谢障碍[1],细菌的化学趋向性多肽导致表皮屏障功能的丧失[2]、细菌内毒素[3]、细菌产生的硫化物[1]及免疫网络的失调和肠腔粘膜免疫活性的增强[4]等.有许多证据支持上述假说,但也有一些不尽完善之处.现就SCFA在UC病因及治疗上的研究成果作一综述.