Expression of glutamate transporter,GABRA6, serine proteinase inhibitor 2 and low levels of glutamate and GABA in the brain of knock-out mouse for Canavan disease

Canavan disease (CD) is an autosomal recessive leukodystrophy characterized by spongy degeneration of the brain. The clinical features of CD are hypotonia, megalencephaly, and mental retardation leading to early death. While aspartoacylase (ASPA) activity increases with age in the wild type mouse brain, there is no ASPA activity in the CD mouse brain. So far ASPA deficiency and elevated NAA have been ascribed with the CD. Other factors affecting the brain that result from ASPA deficiency may lead pathophysiology of CD. The NMR spectra and amino acid analysis showed lower levels of glutamate and gamma-aminobutyric acid in the CD mouse brain compared to the wild type. Microarray gene expression on CD mouse brain showed glutamate transporter-EAAT4 and gamma-aminobutyric acid-A receptor, subunit alpha6 (GABRA6) were lower 9.7- and 119.1-fold, respectively. Serine proteinase inhibitor 2 (Spi2) was 29.9-fold higher in the CD mouse brain compared to the wild type. The decrease of GABRA6 and high expression of Spi2 in CD mouse brain were also confirmed by real-time RT-PCR. This first report showing abnormal expression of EAAT4, GABRA6, Spi2 combined with lower levels of glutamate and GABA are likely to be associated with the pathophysiology of CD.     

AlloDerm tympanoplasty of tympanic membrane perforations

PURPOSE: To study the effectiveness of AlloDerm (LifeCell Corporation, Branchburg, NJ) as a graft material in underlay tympanoplasty by comparison to autologous fascia in a chronic tympanic membrane perforation animal model. MATERIALS AND METHODS: Seventeen chinchillas underwent creation of bilateral chronic tympanic membrane perforations over a 6-week period. Twenty-two stable perforations were divided equally between the experimental AlloDerm and control fascia graft groups. The grafts were surgically placed through a postauricular tympanomeatal flap. The tympanic membranes were examined at 4 and 10 weeks and then harvested for histopathological analysis. Tympanoplasty operative times, perforation closure rates, and gross and histological analyses were compared between the AlloDerm and fascia grafts. RESULTS: A statistically significant difference in mean surgical time was recorded between the AlloDerm (47 minutes) and fascia (68 minutes) grafting procedures (t test, P =.001). Perforation closure was achieved in 90% of the AlloDerm and 100% of the fascia treated tympanic membranes. Gross and histopathologic inspections revealed no significant differences. Microscopically, AlloDerm and fascia grafts had similar inflammatory responses, but AlloDerm showed increased fibroblast infiltration and neovascularization. CONCLUSION: The avoidance of donor site morbidity, reduction of surgical time, and excellent gross and histologic outcomes in this animal model reveal that AlloDerm could be a safe, cost-effective alternative to autologous fascia. Further study would be necessary in human clinical trials.     

Retrospective targeted HCV lookback using centralized contracted notification service

BACKGROUND: Mandated HCV 2.0 lookback significantly challenged the human and financial resources available to the six Los Angeles County Department of Health Services (DHS) hospital blood banks. To comply with FDA requirements, DHS developed a centralized process that utilized the services of a contract vendor for performing HCV lookback. STUDY DESIGN AND METHOD: A DHS public health nurse acted as HCV lookback coordinator and as liaison with the vendor. Cases were electronically forwarded to the vendor, who then reviewed the patient's chart to obtain information necessary for tracking the patient through commercial databases. The vendor was responsible for notifying the recipient for pretest counseling and for providing documentation of all efforts. RESULTS: In total, 411 recipients were identified, of which, 168 cases were completed by the hospitals, 243 were forwarded to the vendor, 50 percent were deceased, 21 percent were contacted, and 28 percent could not be contacted, and 1 percent could not be located on any databases. The vendor contacted 35 of 66 cases that the hospitals had unsuccessfully attempted to contact. Of the cases forwarded to the vendor, 82 percent were completed on time. Delays were attributable to the vendor in less than 2 percent of cases. The cost per case forwarded to the vendor was 322 US dollars. CONCLUSION: Utilizing a professional service to conduct HCV recipient notifications is an effective strategy for meeting FDA deadlines and for freeing transfusion service staff to perform critical functions. It remains to be seen whether such strategies offer a cost savings.     

The chronic effects of an extract of Bacopa monniera (Brahmi) on cognitive function in healthy human subjects

RATIONALE: Extracts of Bacopa monniera have been reported to exert cognitive enhancing effects in animals. However, the effects on human cognition are inconclusive. OBJECTIVE: The current study examined the chronic effects of an extract of B. monniera (Keenmind) on cognitive function in healthy human subjects. METHODS: The study was a double-blind placebo-controlled independent-group design in which subjects were randomly allocated to one of two treatment conditions, B. monniera (300 mg) or placebo. Neuropsychological testing was conducted pre-(baseline) and at 5 and 12 weeks post drug administration. RESULTS: B. monniera significantly improved speed of visual information processing measured by the IT task, learning rate and memory consolidation measured by the AVLT (P<0.05), and state anxiety (P<0.001) compared to placebo, with maximal effects evident after 12 weeks. CONCLUSIONS: These findings suggest that B. monniera may improve higher order cognitive processes that are critically dependent on the input of information from our environment such as learning and memory.     

Novelty seeking as a predictor of treatment retention for heroin dependent cocaine users

This study examined the relationship between novelty seeking between treatment retention and among heroin dependent cocaine users. Participants were treated with buprenorphine maintenance and contingency management. The Tridimensional Personality Questionnaire's (TPQ) Novelty Seeking scale was administered to 68 participants prior to buprenorphine induction. Demographics, mood and anxiety disorders, antisocial personality disorder, and substance use were also assessed. Variables with significant relationships with overall retention were entered into a logistic regression analysis. In addition, using a survival analysis, all variables with significant relationships with time to drop-out were entered into a multivariate proportional hazards regression with time dependent covariates. Results demonstrated that although high novelty seekers, in comparison to low novelty seekers, were more likely to drop-out by the end of treatment, they had higher retention rates during the early phases of treatment. It is suggested that buprenorphine and contingency management were viewed by participants as novel treatment components and thus facilitated high novelty seekers' success early in treatment. If replicated, results suggest that inclusion of novel treatment components might facilitate retention among this at-risk group.     

Adenosine A1 Agonist at Reperfusion Trial (AART): Results of a Three-Center, Blinded, Randomized, Controlled Experimental Infarct Study

Adenosine A₁ receptor agonists given prior to myocardial ischemia limit ischemic injury in several species. However, the ability of adenosine receptor agonists to limit infarct size when given at reperfusion has proved controversial. We designed a three-center experimental study using a blinded, randomized treatment protocol to test the hypothesis that adenosine A₁ receptor activation during early reperfusion can attenuate lethal reperfusion injury, thereby reducing infarct size. Sixty anesthetized rabbits (20 in each laboratory) underwent 30 minutes coronary artery occlusion followed by 120 minutes reperfusion. The selective adenosine A₁ receptor agonist GR79236 (10.5 g/kg, a dose shown to limit infarction in this model when given before ischemia) or vehicle were administered IV 10 minutes before reperfusion. Infarct size was assessed by tetrazolium staining and, after the randomization code was revealed, data from the three laboratories were pooled for statistical analysis. Infarct size was not modified by administration of GR79236. In the vehicle-treated group, the infarct-to-risk ratio was 28.9 ± 2.7% (n = 24) compared with 31.9 ± 2.6% (n = 26) in the GR79236-treated group (not significant). Risk zone volume was similar in the two groups (1.06 ± 0.05 cm³ vs 1.00 ± 0.05 cm³, respectively). A modest reduction in rate-pressure product was noted following the administration of GR79236, but this effect was transient. The same dose of GR79236 was found to limit infarct size when given prior to coronary artery occlusion. We conclude that A₁ receptor activation does not modify lethal reperfusion injury in myocardium.     

Three dimensional transrectal ultrasound imaging of the prostate: initial experience with an emerging technology

PURPOSE: A three-dimensional ultrasound system (3-D US) was evaluated for its clinical utility in transrectal prostate imaging, in comparison with the current standard 2-dimensional transrectal ultrasound (TRUS) imaging system. METHODS AND MATERIALS: The computer program developed in our laboratory was coupled with a commercially available ultrasound transducer. Geometric validation and volumetric assessment was performed with "stretched-string" wire models and solution-containing balloons respectively. Anatomic correlation of 3-D TRUS images was performed with cadaveric prostates. Intraprostatic lesion localization by 3D-TRUS was assessed clinically by 2 observers in 11 patients prior to radical prostatectomy and the data compared with those yielded by 2-D TRUS. RESULTS: Geometric assessment by 3D TRUS in comparison with the "between strings in the phantom" model (true dimensions) had an error of up to 1.2%. Volume measurement by 3-D TRUS had an error, compared to the true volume, of 0.9%. The correlation coefficient (r) was 0.99985 for the end-firing probe and 0.978 for side firing. The 3-D images provided accurate representation of the true anatomy in the sagittal, transverse and most uniquely, the coronal plane. Two observers achieved better diagnostic accuracies with intraprostatic abnormalities using 3-D instead of standard 2-D TRUS. The negative predictive value and the specificity were improved. CONCLUSION: 3-D TRUS appears to provided accurate representation of the true anatomy with geometric and volumetric validation. Areas of potential clinical application of 3-D TRUS include treatment monitoring with volume measurements and various intervention and therapeutic procedures for both benign and malignant prostatic disorders.     

Laparoscopic management of foreign body perforation in diverticular disease

A case is described where laparoscopic principles in the management of spontaneous sigmoid diverticular perforation are applied to foreign body perforation.