Use of a smartphone platform for temporomandibular joint arthroscopy.

Temporomandibular joint (TMJ) arthroscopy, a diagnostic and therapeutic procedure involving the introduction of a small-calibre optical scope into the joint compartments for the treatment of internal derangement, has been gaining prominence and is now being recommended as the first therapeutic option due to the good results obtained and minimal invasiveness. However, the technical difficulty, high cost, need for specific instruments, and video tower system remain limiting factors for the implementation of TMJ arthroscopy by practicing professionals. The objective of this study was to examine the possibility of using a smartphone optical adaptation platform in TMJ arthroscopy. Ten qualified examiners with different levels of expertise in TMJ arthroscopy located four points of interest in the upper TMJ compartment of a validated realistic simulator and assessed the resolution of the images obtained and ergonomics of the smartphone platform for each point of interest, assigning a score of 0-2 (0 = poor, 1 = intermediate, and 2 = good performance in comparison to the video tower). For image quality, 77.5% of scores were 'good', while 22.5% were 'intermediate'. For ergonomics, 62.5% of scores were 'good' and 37.5% were 'intermediate'. In conclusion, the platform appears to be safe for TMJ arthroscopy in humans.

Gaps in using bronchodilators, inhaled corticosteroids and influenza vaccine among 23 high- and low-income sites.

BACKGROUND: Increasing access to essential respiratory medicines and influenza vaccination has been a priority for over three decades. Their use remains low in low- and middle-income countries (LMICs), where little is known about factors influencing use, or about the use of influenza vaccination for preventing respiratory exacerbations. METHODS: We estimated rates of regular use of bronchodilators, inhaled corticosteroids and influenza vaccine, and predictors for use among 19 000 adults in 23 high-income countries (HICs) and LMIC sites. RESULTS: Bronchodilators, inhaled corticosteroids and influenza vaccine were used significantly more in HICs than in LMICs, after adjusting for similar clinical needs. Although they are used more commonly by people with symptomatic or severe respiratory disease, the gap between HICs and LMICs is not explained by the prevalence of chronic obstructive pulmonary disease or doctor-diagnosed asthma. Site-specific factors are likely to influence use differently. The gross national income per capita for the country is a strong predictor for use of these treatments, suggesting that economics influence under-treatment. CONCLUSION: We still need a better understanding of determinants for the low use of essential respiratory medicines and influenza vaccine in low-income settings. Identifying and addressing these more systematically could improve the access and use of effective treatments.

A mosaic activating mutation in AKT1 associated with the Proteus syndrome.

BACKGROUND: The Proteus syndrome is characterized by the overgrowth of skin, connective tissue, brain, and other tissues. It has been hypothesized that the syndrome is caused by somatic mosaicism for a mutation that is lethal in the nonmosaic state. METHODS: We performed exome sequencing of DNA from biopsy samples obtained from patients with the Proteus syndrome and compared the resultant DNA sequences with those of unaffected tissues obtained from the same patients. We confirmed and extended an observed association, using a custom restriction-enzyme assay to analyze the DNA in 158 samples from 29 patients with the Proteus syndrome. We then assayed activation of the AKT protein in affected tissues, using phosphorylation-specific antibodies on Western blots. RESULTS: Of 29 patients with the Proteus syndrome, 26 had a somatic activating mutation (c.49G→A, p.Glu17Lys) in the oncogene AKT1, encoding the AKT1 kinase, an enzyme known to mediate processes such as cell proliferation and apoptosis. Tissues and cell lines from patients with the Proteus syndrome harbored admixtures of mutant alleles that ranged from 1% to approximately 50%. Mutant cell lines showed greater AKT phosphorylation than did control cell lines. A pair of single-cell clones that were established from the same starting culture and differed with respect to their mutation status had different levels of AKT phosphorylation. CONCLUSIONS: The Proteus syndrome is caused by a somatic activating mutation in AKT1, proving the hypothesis of somatic mosaicism and implicating activation of the PI3K-AKT pathway in the characteristic clinical findings of overgrowth and tumor susceptibility in this disorder. (Funded by the Intramural Research Program of the National Human Genome Research Institute.).

A genome-wide association study suggests that a locus within the ataxin 2 binding protein 1 gene is associated with hand osteoarthritis: the Treat-OA consortium.

To identify the susceptibility gene in hand osteoarthritis (OA) the authors used a two-stage approach genome-wide association study using two discovery samples (the TwinsUK cohort and the Rotterdam discovery subset; a total of 1804 subjects) and four replication samples (the Chingford Study, the Chuvasha Skeletal Aging Study, the Rotterdam replication subset and the Genetics, Arthrosis, and Progression (GARP) Study; a total of 3266 people). Five single-nucleotide polymorphisms (SNPs) had a likelihood of association with hand OA in the discovery stage and one of them (rs716508), was successfully confirmed in the replication stage (meta-analysis p = 1.81x10(-5)). The C allele conferred a reduced risk of 33% to 41% using a case-control definition. The SNP is located in intron 1 of the A2BP1 gene. This study also found that the same allele of the SNP significantly reduced bone density at both the hip and spine (p<0.01), suggesting the potential mechanism of the gene in hand OA might be via effects on subchondral bone. The authors' findings provide a potential new insight into genetic mechanisms in the development of hand OA.

Genetic and environmental determinants on bone loss in postmenopausal Caucasian women: a 14-year longitudinal twin study.

SUMMARY: This longitudinal twin study documented that genetic factors explain 44-56% of the between-individual variance in bone loss at femoral neck, lumbar spine, and forearm in postmenopausal Caucasian women, providing a rationale for identifying the specific genes involved. INTRODUCTION: Although there is a significant genetic effect on peak BMD, until recently, no substantive studies on heritability of bone loss in human were available. The aim of the study was to estimate the heritability of the bone loss at multiple sites in postmenopausal Caucasian women. METHODS: Postmenopausal female monozygotic (MZ) and dizygotic (DZ) twins aged 40 or above at baseline were selected from the TwinsUK registry and followed up for an average of 8 years (range 5-14 years). All twins were noncurrent hormone replacement therapy users and not on any osteoporosis treatment. They had dual-energy X-ray absorptiometry (DXA) scans of their hip, lumbar spine, and forearm several times (range 2-9) during the follow-up period. Individual bone losses at femoral neck, lumbar spine, and forearm were estimated by linear regression modeling. Structural equation modeling was utilized to estimate the heritability of the bone loss. RESULTS: A total of 712 postmenopausal Caucasian female twins (152 MZ and 204 DZ pairs) were included. MZ twins were older and had slightly lower BMD at all sites than DZ twins. DZ twins had slightly higher bone loss at lumbar spine, but similar at femoral neck and forearm compared to MZ twins. Intraclass correlation coefficients (ICC) for the bone loss at all sites were significantly higher in MZ than DZ twin pairs (p = 0.0045, 0.0003, and 0.0007 for femoral neck, lumbar spine, and forearm, respectively), indicating a significant genetic influence on bone loss at these sites. After adjustment for age at baseline and weight change during the follow-up, the heritability estimate was 47% (95% CI 27-63%) for bone loss at femoral neck, 44% (95% CI 27-58%) for lumbar spine, and 56% (95% CI 44-65%) for forearm. CONCLUSIONS: Our data suggest that up to 56% of the between-individual variance in bone loss is due to genes, providing a rationale to identify specific genetic factors for bone loss.

Bone mineral density, osteoporosis, and osteoporotic fractures: a genome-wide association study.

BACKGROUND: Osteoporosis is diagnosed by the measurement of bone mineral density, which is a highly heritable and multifactorial trait. We aimed to identify genetic loci that are associated with bone mineral density. METHODS: In this genome-wide association study, we identified the most promising of 314 075 single nucleotide polymorphisms (SNPs) in 2094 women in a UK study. We then tested these SNPs for replication in 6463 people from three other cohorts in western Europe. We also investigated allelic expression in lymphoblast cell lines. We tested the association between the replicated SNPs and osteoporotic fractures with data from two studies. FINDINGS: We identified genome-wide evidence for an association between bone mineral density and two SNPs (p<5x10(-8)). The SNPs were rs4355801, on chromosome 8, near to the TNFRSF11B (osteoprotegerin) gene, and rs3736228, on chromosome 11 in the LRP5 (lipoprotein-receptor-related protein) gene. A non-synonymous SNP in the LRP5 gene was associated with decreased bone mineral density (rs3736228, p=6.3x10(-12) for lumbar spine and p=1.9x10(-4) for femoral neck) and an increased risk of both osteoporotic fractures (odds ratio [OR] 1.3, 95% CI 1.09-1.52, p=0.002) and osteoporosis (OR 1.3, 1.08-1.63, p=0.008). Three SNPs near the TNFRSF11B gene were associated with decreased bone mineral density (top SNP, rs4355801: p=7.6x10(-10) for lumbar spine and p=3.3x10(-8) for femoral neck) and increased risk of osteoporosis (OR 1.2, 95% CI 1.01-1.42, p=0.038). For carriers of the risk allele at rs4355801, expression of TNFRSF11B in lymphoblast cell lines was halved (p=3.0x10(-6)). 1883 (22%) of 8557 people were at least heterozygous for these risk alleles, and these alleles had a cumulative association with bone mineral density (trend p=2.3x10(-17)). The presence of both risk alleles increased the risk of osteoporotic fractures (OR 1.3, 1.08-1.63, p=0.006) and this effect was independent of bone mineral density. INTERPRETATION: Two gene variants of key biological proteins increase the risk of osteoporosis and osteoporotic fracture. The combined effect of these risk alleles on fractures is similar to that of most well-replicated environmental risk factors, and they are present in more than one in five white people, suggesting a potential role in screening.

Natural history and risk factors for bone loss in postmenopausal Caucasian women: a 15-year follow-up population-based study.

UNLABELLED: In this 15-year follow-up study, we found that the estimated rate of bone loss at the femoral neck (FN) for women aged 45-68 was linear at a rate of 1.67% per year, but quadratic for lumbar spine (LS) at a rate of 3.12% initially, and slowing down with age. We also confirmed the protective role of HRT, increasing weight, and lean mass in long-term bone loss. INTRODUCTION: The objective was to describe the natural history of bone loss and explore the role of environmental factors in postmenopausal women over a 15-year period. METHODS: Bone mineral density (BMD) at the FN and the LS were measured in postmenopausal women from the Chingford Study. Height, weight, HRT status, and calcium/vitamin D supplement were assessed at each visit. Osteoarthritis of hip and spine was assessed by X-ray at baseline and at year 8. RESULTS: A total of 955 postmenopausal women with an average age of 54.7 at baseline were included. Both FN and LS BMD decreased significantly with age (p<0.0001). The decline was larger in the LS (-3.12% per year), which showed a quadratic relationship, than in the FN (-1.67% per year) with a linear relationship. The rate of bone loss was reduced by one third annually for the FN and LS respectively in current HRT users. Change in weight was positively associated with both DeltaFN and DeltaLS BMD (beta=0.16% and 0.09% change in DeltaFN and DeltaLS BMD per kilogramme change in weight respectively, p<0.0001 for both sites). Spine OA and progression were positively associated with DeltaLS BMD (beta=1.22% change in DeltaLS BMD per grade in spine OA and 0.45% change in DeltaLS BMD for patients who progressed, p<0.0001 for spine OA and p=0.002 for spine OA progression). Spine OA (beta=0.54% change in DeltaFN BMD per grade, p<0.0001), but not progression, and hip OA were positively associated with DeltaFN BMD. Furthermore, both age and body weight at baseline were positively associated with both DeltaFN and DeltaLS BMD (beta=0.02-0.04% change in DeltaFN and DeltaLS BMD per year increase in age at baseline and 0.004-0.007% change in DeltaFN and DeltaLS BMD per kilogramme increase in weight at baseline, all p<0.0001). CONCLUSION: This large population-based longitudinal study demonstrated that the decline of BMD over 15 years is linear with age for the FN, but quadratic for the LS. The study confirmed the protective role of HRT, increased weight and lean mass in long-term bone loss.

Homocysteine levels and leukocyte telomere length.

OBJECTIVE: Elevated plasma homocysteine is a risk factor for vascular diseases, possibly due to homocysteine-mediated increase in oxidative stress and inflammation. As leukocyte telomere length (LTL) registers the cumulative oxidative stress and inflammation, we examined the relationship between homocysteine and LTL. METHODS: LTL was measured using the Southern blot method. The relationship between LTL and homocysteine levels was considered for confounding with the following covariates: age, sex, smoking, obesity, physical activity, menopause, hormone replacement therapy use and creatinine clearance. RESULTS: 1,319 healthy subjects were recruited from a population-based cohort. LTL was negatively correlated with plasma homocysteine levels, after adjustment for smoking, obesity, physical activity, menopause, hormone replacement therapy use and creatinine clearance. The difference in multiply-adjusted LTL between the highest and lowest tertile of homocysteine levels was 111 base pairs (p=0.004), corresponding to 6.0 years of telomeric aging. This relationship was further accentuated by decreased concentrations of serum folate and increased levels of C-reactive protein. CONCLUSIONS: Increased homocysteine levels are associated with shortened LTL, further supporting the tenet that LTL is an index of cardiovascular risk.

Lumbar disc disease shows linkage to chromosome 19 overlapping with a QTL for hand OA.

OBJECTIVE: Cervical and lumbar degenerative disc disease (CDD and LDD, respectively) form part of the spine osteoarthritis (OA) phenotype and are known to be influenced by genetic factors. A genome-wide linkage analysis was performed to identify new chromosomal regions of interest. METHODS: Dizygotic healthy female twin volunteers (n = 348) from the TwinsUK register who had magnetic resonance imaging scans 10 years ago coded for degenerative disease, were identified. Multipoint genome-wide linkage analysis was conducted using 737 highly polymorphic markers of approximate spacing 10 cM. RESULTS: The mean age of the twins was 52 years. Significant linkage peaks (log of the odds (LOD) >3) were identified for LDD at three chromosomal regions. These included chromosome 1 (position 285 cM), chromosome 5 (position 175 cM) and chromosome 19 (position 80 cM). The peak on chromosome 19 had LOD = 4.06, and the empirical p = 6.7x10(-4) confirmed reliability of the linkage signal. It lies close to a linkage peak previously obtained by our group for hand OA. CONCLUSIONS: This genome-wide linkage study of CDD and LDD shows evidence of linkage for LDD on chromosome 19. The region of interest is likely to harbour genes that are common to LDD and hand OA.

Is telomere length in peripheral blood lymphocytes correlated with cancer susceptibility or radiosensitivity?

Mean terminal restriction fragment (TRF) lengths in white blood cells (WBCs) have been previously found to be associated with breast cancer. To assess whether this marker could be used as a test for breast cancer susceptibility in women, TRF length was measured in 72 treated female breast cancer patients and 1696 unaffected female controls between the ages of 45 and 77 from the Twin Research Unit at St Thomas' Hospital, as well as 140 newly diagnosed breast cancer cases and 108 mammographically screened unaffected controls from Guy's Hospital. Mean TRF was also tested for correlation with chromosome radiosensitivity and apoptotic response in the Guy's Hospital patients. After adjusting for age, smoking and body mass index, there was no significant difference in TRF lengths between the treated breast cancer patients and unaffected controls (P=0.71). A positive correlation between age-adjusted apoptotic response and mean TRF in newly diagnosed untreated breast cancer patients (P=0.008) was identified but no significant difference in TRF lengths between breast cancer patients and unaffected controls was detected (P=0.53). This suggests that TRF lengths in WBC, is not a marker of breast cancer susceptibility and does not vary significantly between affected women before and after treatment.

Association between KLOTHO gene and hand osteoarthritis in a female Caucasian population.

OBJECTIVE: Osteoarthritis (OA) is a common complex disease with strong heritable components. In this study, we investigated the association between four putatively functional genetic variants in KLOTHO gene, a strong ageing-related gene, and hand OA in a large female Caucasian population. METHODS: Subjects (n=1015, age range 33-74 years) were selected from the TwinsUK Registry. Radiographs of both hands were taken for each individual with standard posteroanterior view. The presence/absence of radiographic OA, osteophyte and joint space narrowing (JSN) was assessed using a standard atlas. Four putatively functional single nucleotide polymorphisms (SNPs) in KLOTHO gene were genotyped using allelic discrimination assay. Association was initially estimated using Pearson's chi(2) or Fisher's exact test at allelic and genotypic levels. The direction and magnitude of significant association were further investigated by robust logistic regression with age as a covariate. RESULTS: We found significant association between SNP G-395A and the presence/absence of radiographic hand OA and osteophyte, but not JSN. Allele G significantly increased the risk for radiographic hand OA and osteophytes with odds ratios (ORs) of 1.44 (P=0.008, 95% confidence interval (CI) 1.09-1.91) and 1.36 (P=0.006, 95% CI 1.09-1.70), respectively. From logistic regression modelling, genotype GG showed more than three-fold increased risk for both radiographic hand OA (OR=3.10, 95% CI 1.10-8.76) and osteophyte (OR=3.10, 95% CI 1.10-8.75) when compared to genotype AA. After adjustment for age, ORs for genotype GG further increased to 4.39 (P=0.006, 95% CI 1.51-12.74) for radiographic hand OA and to 4.47 (P=0.005, 95% CI 1.56-12.77) for osteophytes. CONCLUSIONS: Our results suggest that one variant in KLOTHO gene is associated with the susceptibility of hand OA and appears to act through osteophyte formation rather than cartilage damage.

Genetic influence on the progression of radiographic knee osteoarthritis: a longitudinal twin study.

OBJECTIVE: Genetic influences on rates of osteoarthritis (OA) progression are unknown. Our aim was to estimate the heritability of progression of radiographic knee OA using a longitudinal twin study. METHODS: Unselected monozygotic (MZ) and dizygotic (DZ) twin pairs from the TwinsUK registry were utilized. Anteroposterior radiographs were performed on both knees at baseline and follow-up using the same protocol. Radiographic features of knee OA including osteophyte and joint space narrowing (JSN) were assessed on a four-point scale using a standard atlas. Progression of knee osteophyte and JSN was defined as the difference in the corresponding score between follow-up and baseline > or =1. Liability threshold modelling using logistic regression was utilized for heritability estimation. RESULTS: A total of 114 MZ pairs and 195 DZ pairs were studied. The average follow-up time was 7.2 years. Medial progression of osteophyte and JSN was more common than lateral progression. Prevalence of progression was generally higher in the MZs than the DZs. Similarly, concordances and tetrachoric correlations for both osteophyte and JSN were higher in the MZs than the DZs although only significant for overall and medial JSN and osteophyte. The heritability estimates were 69% [95% confidence interval (CI) 42-97%] and 80% (95% CI 50-100%) for medial osteophyte and JSN, respectively. The estimates were reduced by 7-15% after adjustment for age, body mass index (BMI), and the severity of osteophyte/JSN at baseline. CONCLUSION: Our data documented a substantial genetic influence on the progression of knee OA--as seen in the medial compartment, providing a solid basis to search for genes involved in this highly relevant clinical trait.

The big finger: the second to fourth digit ratio is a predictor of sporting ability in women.

BACKGROUND: The second to fourth finger length ratio (2d:4d) is thought to be related to diverse traits including cognitive ability, disease susceptibility, and sexuality. OBJECTIVE: To examine the relationship between 2d:4d and sports ability in women. METHODS: Hand radiographs from 607 women (mean age 54 years) were used to estimate 2d:4d. Ranking of sports ability was on a scale (1-5). RESULTS: The highest achieved level of participation in any sport was significantly negatively associated with 2d:4d (b = -4.93, p = 0.01) as was the relationship between 2d:4d and running level (b = -6.81, p = 0.034). Ability in other sports also showed a negative relationship albeit non-significant. CONCLUSIONS: These results suggest that a low 2d:4d ratio is related to increased female sports ability. It can be postulated that this ratio may predict potential sports ability. Understanding the mechanisms underpinning this relationship may give important insights into musculoskeletal fitness, health and disease.

Heritability of DNA-damage-induced apoptosis and its relationship with age in lymphocytes from female twins.

Apoptosis is a physiological form of cell death important in normal processes such as morphogenesis and the functioning of the immune system. In addition, defects in the apoptotic process play a major role in a number of important areas of disease, such as autoimmune diseases and cancer. DNA-damage-induced apoptosis plays a vital role in the maintenance of genomic stability by the removal of damaged cells. Previous studies of the apoptotic response (AR) to radiation-induced DNA damage of lymphoid cells from individuals carrying germline TP53 mutations have demonstrated a defective AR compared with normal controls. We have also previously demonstrated that AR is reduced as individuals age. Results from the current study on 108 twins aged 18-80 years confirm these earlier findings that the AR of lymphoid cells to DNA damage is significantly reduced with increasing age. In addition this twin study shows, for the first time, that DNA-damage-induced AR has a strong degree of heritability of 81% (95% confidence interval 67-89%). The vital role of DNA-damage-induced apoptosis in maintaining genetic stability, its relationship with age and its strong heritability underline the importance of this area of biology and suggest areas for further study.

Evaluating quality of life after endolymphatic sac surgery: The Ménière's Disease Outcomes Questionnaire.

OBJECTIVE: To develop a disease-specific instrument to measure the quality of life in patients with Ménière's disease and to assess quality-of-life outcomes after endolymphatic sac decompression. STUDY DESIGN: Retrospective survey. PATIENTS: Patients with Ménière's disease who underwent endolymphatic sac decompression from June 1996 to June 2001, after failing a course of medical management. Two hundred fifteen potential subjects were identified; completed questionnaires were returned by 159 patients. MAIN OUTCOME MEASURES: The Ménière's Disease Outcomes Questionnaire was developed, and consists of questions in three domains that determine quality of life: physical, emotional, and social well-being. The Ménière's Disease Outcomes Questionnaire consisted of 18 multiple-choice questions that were paired for pre- and postoperative conditions, and one global quality-of-life question. The preoperative quality-of-life score (total score for preoperative items) was compared with the postoperative quality-of-life score. The main outcomes measure was the change in quality-of-life score. RESULTS: Overall, the mean change in quality-of-life score was +25.6 points (range, -34 to 83) (p < 0.001). The change in Ménière's Disease Outcomes Questionnaire quality-of-life score was highly correlated with the change in the global question score (p < 0.01). Quality of life was improved in 87% of respondents, unchanged in 3% of patients, and poorer in 9% of patients after endolymphatic sac decompression. CONCLUSIONS: The Ménière's Disease Outcomes Questionnaire is a new disease-specific quality-of-life tool that is a valid measure of quality of life in patients with Ménière's disease, and is responsive to measuring change in quality of life after treatment. Significant improvement in quality of life was reported by 87% of patients after endolymphatic sac decompression.

Responses to lost letters about a 2000 General Election amendment to abolish prohibition of interracial marriages in Alabama.

A field study using 621 "lost" letters was conducted in the city of Mobile and in small towns in mostly rural Baldwin County, Alabama. Milgram's lost letter technique was validated against the actual votes cast during the November 7, 2000 General Election. The technique was successful as an unobtrusive measure useful for predicting patterns of voting behavior. Rates of return of lost letters "in favor of and opposed to legalizing interracial marriage" agreed with the actual election returns (chi-square "goodness of fit"). Community size seemed associated with return of lost letters.

Dopamine and serotonin uptake inhibitors on the release of dopamine and serotonin in the nucleus accumbens of young and aged rats.

Nucleus accumbens (ACC) of young (4 months old) and aged (24 months old) Wistar rats were perfused with dopamine (DA) uptake blocker, cocaine, or the serotonin (5-HT) selective reuptake inhibitor, fluoxetine, through the microdialysis probe membrane, used to assess the dopamine transporter (DAT) or serotonin transporter (SERT) modulation. The basal extracellular DA release in the ACC was significantly lower in aged rats than young rats. Analysis of DA and 5-HT concentrations in the ACC with increased positive GFAP revealed that DA and DOPAC levels of aged rats were decreased to 55 and 60% of those in young rats, respectively. After co-perfusion with cocaine, both DA and 5-HT releases in the ACC were increased in the young and aged groups. However, the magnitude of the increased DA release was lower in aged rats than young rats. Co-perfusion with fluoxetine showed lower magnitude of the increased DA release in aged rats. It appears that the DAT and SERT system responds initially to ACC cell loss with age, and that especially ACC DAT in the aged rat is more degenerative compared with the young rats. These findings suggest that the serotonergic system with SERT in the remaining ACC neurons show an early adaptive response and resistance to the normal aging and maintain the multiple regulatory system in the ACC despite neural loss since the dopaminergic neurons in the aged animals are vulnerable to aging.

Electroacupuncture stimulation suppresses the increase in alcohol-drinking behavior in restricted rats.

BACKGROUND: Although a number of studies on traditional eastern or Chinese medicine, such as acupuncture, moxibustion, and herbal drugs, have been reported, few reports describe electroacupuncture (EAC) effects on drug- and alcohol-seeking behaviors in animal models. The purpose of the present study was to investigate the effect of EAC on changes in alcohol-drinking behavior in rats challenged with restriction and immobilization stress. MATERIAL AND METHODS: Male Sprague Dawley rats (260-280 g) were tightly hung and immobilized in restriction models for 10 min. These immobilization stresses were performed twice a week for 1 week and for 3 consecutive weeks for the short- and long-restricted stress groups, respectively. EAC was applied for 10 min to the hindlimb point, Tsu-San-Li (ST 36), and the lumbar point, Shen-Shu (BL 23). These points are used to treat mental and psychosomatic disorders and are known clinically to produce a sedation effect. Time-access alcohol-drinking behavior was determined at 24 hr after the termination of EAC. Finally, brain dopamine (DA) levels were assayed in the two groups. A sham-control group underwent only restricted stress without EAC. RESULTS: Time-access alcohol-drinking behavior increased significantly in the long-restricted group compared with the short-restricted group and controls. EAC applied to the ST 36 (Tsu-San-Li) point suppressed the increased alcohol-drinking behavior in restricted rats. However, EAC applied to the Shen-Shu (BL 23) point was not effective, because alcohol-drinking behavior was significantly increased in long-restricted rats compared with short-restricted rats. Striatal DA levels of restricted rats with EAC stimulated at Tsu-San-Li were increased significantly compared with the rats with EAC applied to the Shen-Shu point. CONCLUSION: These findings suggest that EAC applied at ST 36 (Tsu-San-Li) was more effective for reducing the increased alcohol-drinking behavior in restricted rats, and they showed that a point specific in EAC procedure was associated with an increase of striatal DA levels. These findings provide new information for understanding alcohol-drinking behavior and for treating human alcoholics.

Meta-analysis in otolaryngology.

OBJECTIVE: To examine the results of meta-analyses in otolaryngology and compare these results with the individual component studies that constitute each meta-analysis. DESIGN: A retrospective review of the literature. MAIN OUTCOME MEASURES: Studies that conducted pooled statistical systematic analyses indexed on MEDLINE for the 10-year period from January 1989 to January 1999 were selected for keyword or subject headings of meta-analysis and otolaryngology (N = 22). Analysis consisted of a modified funnel graph depiction of the individual studies that made up each meta-analysis. Each meta-analysis was evaluated for consistency among these individual studies and comparison of the median result with the weighted mean meta-analysis result. In addition, the methodologic quality of each meta-analysis was assessed in terms of the rigor with which component studies were evaluated. RESULTS: Ten (46%) of the 22 meta-analyses did not provide the individual study results that made up their meta-analyses. The results of 10 studies (46%) were similar to the median result of their individual component studies. The results of 2 studies (9%) differed from this median result, with widely heterogeneous component study results. CONCLUSIONS: A large proportion of meta-analyses in otolaryngology (46%) fail to provide the individual study results necessary to analyze the meta-analysis result critically. Most remaining studies do provide results that accurately compare with the median of their component study results. Only a small proportion of meta-analyses were found to have disparate results, and each appropriately discusses the heterogeneity of the individual studies that comprise their meta-analysis.

Alcohol enhances characteristic releases of dopamine and serotonin in the central nucleus of the amygdala.

The amygdaloid complex (AMY) is implicated in emotional and motivational aspects of behavior, including the formation of positive reinforcement association. AMY may also associated with brain rewarding circuitry. In the present study, the effect of ethanol (EtOH) on the release of dopamine (DA) and serotonin (5-HT) was studied in the central amygdaloid nucleus (CeAMY), and projecting excitatory afferents to the ventral tegmental area (VTA), of freely moving Wistar rats by brain microdialysis. Within 20 min of i.p. injection of EtOH (2 g/kg), the levels of DA and 5-HT in the CeAMY dialysate increased over the baseline value by 270 and 160% (N = 6-7), respectively. Addition of EtOH (25, 50 and 100 mM) to the microdialysis perfusion medium for 1 h caused a 115-150% dose-related increase in the extracellular level of DA in the CeAMY. 100 mM EtOH-induced CeAMY DA release continued to increase for 1 h after the perfusion medium was returned to normal perfusion medium. In contrast, the CeAMY 5-HT level was increased only by the addition of 100 mM EtOH for 1 h to 130% for 80 min. The stimulation of the CeAMY by EtOH through the microdialysis membrane showed delayed responses of DA and 5-HT compared with the i.p. injection of EtOH. Overall, the present findings are not sufficient to conclude whether EtOH acts directly or indirectly on the major monoamine nerve cells in the CeAMY, but the degree of acute EtOH action affected the differences in time at the peak response on EtOH-induced DA and 5-HT releases in the CeAMY via VTA.