Familial defective apolipoprotein B-100: a common cause of primary hypercholesterolemia

Summary Familial defective apolipoprotein B-100 (FDB) is a recently identified dominantly inherited genetic disorder characterized by a decreased binding of low density lipoprotein (LDL) to the LDL receptor due to defective apo B-100. FD B is caused by a G to A mutation at nucleotide 10 708 in exon 26 of the apo B gene creating a substitution of glutamine for arginine in the codon for amino acid 3500. The arginine₍₃₅₀₀₎ glutamine mutation has been observed in several populations in North America and Europe with a similar frequency of approximately 1/500 to 1/700. Haplotype analysis has demonstrated that the arginine₍₃₅₀₀₎ glutamine mutation occurs on the same chromosomal background. The fact that all individuals with FDB are of Caucasian extraction implies that the mutation has its origin in this population. The arginine₍₃₅₀₀₎ glutamine mutation has a profound impact of varying strength on the plasma LDL cholesterol level, leading to heterogeneous clinical expression comparable to classic familial hypercholesterolemia (FH) caused by a defective LDL receptor: tendon xanthoma, premature atherosclerosis and arcus lipoides. The present data suggest that the combination of these clinical features is no longer appropriate for the diagnosis of LDL-receptor-defective FH, but may be a common feature of a defective LDL receptor pathway originating either from defective LDL receptors or from malfunctioning ligand apo B-100.Abbreviations apo B-100 apolipoprotein B-100 - CAD coronary artery diseae - FDB familial defective apolipoprotein B100 - FH familial hypercholesterolemia - HDL high density lipoprotein - HL hyperlipidemia - LDL low density lipoprotein - PAD peripheral artery disease - PCR polymerase chain reaction - VLDL very low density lipoprotein     

Association of DNA-haplotypes in the human LDL-receptor gene with normal serum cholesterol levels

For the low density lipoprotein receptor (LDLR), many mutations have been characterized which identify this gene as one with an important role in lipid metabolism in patients with familial hypercholesterolemia (FH). Genetic heterogeneity at this locus raises the possibility that the LDLR may also contribute to variation in cholesterol levels in the normocholesterolemic population. We have determined genotypes at the LDLR locus using restriction fragment length polymorphisms (RFLPs) detected with the enzymes StuI, ApalI, PvuII and NcoI in 324 normocholesterolemic individuals from Germany. A significant association (p less than 0.01) was detected between the cutting site for the PvuII RFLP and lower cholesterol levels, and variation associated with this polymorphism explains 3% of the sample variance in cholesterol levels. In family studies we have determined four-RFLP haplotypes of 148 independent LDLR genes and have observed 9 haplotypes in the population. Three of these haplotypes containing the cutting site for PvuII are associated with a reduction in plasma LDL-cholesterol levels. Phylogenetic analysis indicates that these three haplotypes are related by evolutionary history, and this suggests that a single functionally important sequence change in the LDLR explains our observations. Our data confirm other reports and strongly suggest that the LDLR locus may be one of those genes involved in determining serum cholesterol levels in the normal population.     

A randomised control trial of the effectiveness of personalised letters sent subsequent to school dental inspections in increasing registration in unregistered children

Background

The Child Perceptions Questionnaires (CPQ_8–10 and CPQ_11–14) are indicators of child oral health-related quality of life. The aim of this study was to assess the validity and reliability of the self-applied CPQ_8–10 and CPQ_11–14 in Brazilian children, after translations and cultural adaptations in the Brazilian Portuguese language.

Methods

Schoolchildren were recruited from general populations for pre-testing (n = 80), validity (n = 210), and test-retest reliability (n = 50) studies. They were also examined for dental caries, gingivitis, fluorosis, and malocclusion.

Results

Children with greater dental caries experience in primary dentition had higher impacts on CPQ domains. Girls had higher scores for CPQ_8–10 domains than boys. Mean CPQ_11–14 scores were highest for 11-year-old children and lowest for 14-year-old children. Construct validity was supported by significant associations between the CPQ_8–10 and CPQ_11–14 scores and the global rating of oral health (r = 0.38, r = 0.43) and overall well-being (r = 0.39, r = 0.60), respectively. The Cronbach's alpha was 0.95 for both questionnaires. The test-retest reliabilities of the overall CPQ_8–10 and CPQ_11–14 scores were both excellent (ICC = 0.96, ICC = 0.92).

Conclusion

The Brazilian Portuguese version of CPQ_8–10 and CPQ_11–14 was valuable and reliable for use in the Brazilian child population, although discriminant validity was sporadic due to the fact that impacts are mediated by others factors, such personal, social, and environmental variables.     

患者的权利

许多人都知道,有一个患者权利法案,但大多数患者不知道他们的权利。许多人只是按照医生告诉他们的去做。一些人甚至不问为什么。许多人不问为什么是因为他们不想耽误医生或护士的时间,或者可能缺少医疗知识,一些人甚至不知道要问些什么问题。护士们应该确信患者和家属知道他们的权利。美国医院协办(AHA)1973年首次起草了患者的权利法案,1992年做了修订。AHA起草这个文件的目的是为了支持那些提供最佳医护的医院和保健护理部门,但在过去只是把权利写进了文件中。这个文件也保护患者的权益。AHA建议所有的患者和保健护理部门都要知道这些…     

Incidence of injuries in high school softball and baseball players

Context:

Participation in high school sports has grown 16.1% over the last decade, but few studies have compared the overall injury risks in girls'' softball and boys'' baseball.

Objective:

To examine the incidence of injury in high school softball and baseball players.

Design:

Cohort study.

Setting:

Greenville, South Carolina, high schools.

Patients or Other Participants:

Softball and baseball players (n = 247) from 11 high schools.

Main Outcome Measure(s):

Injury rates, locations, types; initial or subsequent injury; practice or game setting; positions played; seasonal trends.

Results:

The overall incidence injury rate was 4.5/1000 athlete-exposures (AEs), with more injuries overall in softball players (5.6/1000 AEs) than in baseball players (4.0/1000 AEs). Baseball players had a higher initial injury rate (75.9/1000 AEs) than softball players (66.4/1000 AEs): rate ratio (RR) = 0.88, 95% confidence interval (CI) = 0.4, 1.7. The initial injury rate was higher than the subsequent injury rate for the overall sample (P < .0001) and for softball (P < .0001) and baseball (P < .001) players. For both sports, the injury rate during games (4.6/1000 AEs) was similar to that during practices (4.1/1000 AEs), RR = 1.22, 95% CI = 0.7, 2.2. Softball players were more likely to be injured in a game than were baseball players (RR = 1.92, 95% CI = 0.8, 4.3). Most injuries (77%) were mild (3.5/1000 AEs). The upper extremity accounted for the highest proportion of injuries (63.3%). The incidence of injury for pitchers was 37.3% and for position players was 15.3%. The rate of injury was highest during the first month of the season (7.96/1000 AEs).

Conclusions:

The incidence of injury was low for both softball and baseball. Most injuries were minor and affected the upper extremity. The injury rates were highest in the first month of the season, so prevention strategies should be focused on minimizing injuries and monitoring players early in the season.     

Model to predict mortality in critically ill adults with acute kidney injury

Summary

Background and objectives

Acute kidney injury (AKI) requiring dialysis is associated with high mortality. Most prognostic tools used to describe case complexity and to project patient outcome lack predictive accuracy when applied in patients with AKI. In this study, we developed an AKI-specific predictive model for 60-day mortality and compared the model to the performance of two generic (Sequential Organ Failure Assessment [SOFA] and Acute Physiology and Chronic Health Evaluation II [APACHE II]) scores, and a disease specific (Cleveland Clinic [CCF]) score.

Design, setting, participants, & measurements

Data from 1122 subjects enrolled in the Veterans Affairs/National Institutes of Health Acute Renal Failure Trial Network study; a multicenter randomized trial of intensive versus less intensive renal support in critically ill patients with AKI conducted between November 2003 and July 2007 at 27 VA- and university-affiliated centers.

Results

The 60-day mortality was 53%. Twenty-one independent predictors of 60-day mortality were identified. The logistic regression model exhibited good discrimination, with an area under the receiver operating characteristic (ROC) curve of 0.85 (0.83 to 0.88), and a derived integer risk score yielded a value of 0.80 (0.77 to 0.83). Existing scoring systems, including APACHE II, SOFA, and CCF, when applied to our cohort, showed relatively poor discrimination, reflected by areas under the ROC curve of 0.68 (0.64 to 0.71), 0.69 (0.66 to 0.73), and 0.65 (0.62 to 0.69), respectively.

Conclusions

Our new risk model outperformed existing generic and disease-specific scoring systems in predicting 60-day mortality in critically ill patients with AKI. The current model requires external validation before it can be applied to other patient populations.     

Patients with medically unexplained symptoms and their significant others: Illness attributions and behaviors as predictors of patient functioning over time

Objective

Previous research suggests that medically unexplained symptoms (MUS) are maintained in an interpersonal context. The current study examined MUS concurrently and prospectively by measuring specific interpersonal predictors of symptom severity and health care use.

Methods

A total of 127 patients with MUS and their significant others were recruited through primary care offices and assessed with self-report questionnaires and structured interviews about illness attributions, illness behavior and responses, relationship quality, symptom severity, and health care use at baseline and 6-month follow-up.

Results

Illness attributions and interpersonal illness behaviors of patients with MUS were cross-sectionally associated with illness attributions and responses of the patients' significant others. Relationship quality was related to specific illness behaviors and responses. Symptom severity at baseline was predicted by patients' somatic illness attributions. Symptom severity at 6-month follow-up was predicted by somatic illness attributions of patients and withdrawal of patients' significant others at baseline, but these predictors became insignificant when correcting for baseline symptomatology. Health care use at baseline was predicted by a greater amount of coping behavior and higher anxiety scores of patients, and health care use at 6-month follow-up was predicted by more attention-seeking behaviors and health care use of patients at baseline.

Conclusion

The results document the interpersonal influences on the maintenance of MUS. The perspective of significant others should be considered for enhancement of psychological approaches to the treatment of patients with MUS.