Comparative evaluation in nonhuman primates of five PET radiotracers for imaging the serotonin transporters: [11C]McN 5652, [11C]ADAM, [11C]DASB, [11C]DAPA, and [11C]AFM.

The recent introduction of a number of new radiotracers suitable for imaging the serotonin transporters (SERT) has radically changed the field of SERT imaging. Whereas, until recently, only one selective SERT radiotracer was available ([11C]McN 5652) for SERT imaging with positron emission tomography (PET), several new C-11-labeled radiotracers of the -dimethyl-2-(arylthio)benzylamine class have been described as appropriate imaging agents for the SERT. The aim of this study was to conduct a comparative evaluation of four of the most promising agents in this class ([11C]ADAM, [11C]DASB, [11C]DAPA, and [11C]AFM) with the reference tracer [11C]McN 5652 under standardized experimental conditions. This evaluation included in vitro measurements of affinity and lipophilicity, and in vivo PET imaging experiments in baboons. In vitro, DASB displayed significantly lower affinity for SERT than the other four tracers. In the blood, [11C]DASB and [11C]AFM display faster clearance and higher free fractions. Brain uptake was analyzed with kinetic modeling using a one-tissue compartment model and the metabolite-corrected arterial input function. The kinetic uptake of [11C]DASB was significantly faster compared with the other compounds, and the scan duration required to derive time-independent estimates of regional distribution volumes was shorter. [11C]DAPA exhibited the slowest brain kinetic. Regional-specific-to-nonspecific equilibrium partition coefficient (V3") was the highest for [11C]AFM, followed by [11C]DASB and [11C]DAPA, which in turn provided higher V3" values than [11C]ADAM and [11C]McN 5652. From these experiments, two ligands emerged as superior radiotracers that provide a significant improvement over [11C]McN 5652 for PET imaging of SERT: [11C]DASB, because it enables the measurement of SERT availability in a shorter scanning time, and [11C]AFM, because its higher signal-to-noise ratios provide a more reliable measurement of SERT availability in brain regions with relatively low density of SERT, such as in the limbic system.     

Five‐year retrospective review of guideline‐based management of fungal endophthalmitis

Purpose: Guidelines were introduced in 2000 at the Bristol Eye Hospital (BEH) for the management of fungal endophthalmitis. A 5‐year retrospective audit re‐evaluated the guidelines and monitored the management of this rare condition. Clinical effectiveness and management costs were considered in light of visual outcome. Methods: Cases were identified through a 5‐year retrospective review of theatre logbooks, Patient Administration System coded admissions with primary diagnosis of purulent endophthalmitis and pharmacy logbooks of patients receiving antifungal therapy. Data correlation and review of patient management were carried out in light of the findings. Results: Twenty‐three cases were included, based on clinical disease and/or positive smears or cultures. Age range was 13–74 years, with a male : female ratio of 16 : 7 and right eye : left eye ratio of 14 : 9. Risk factors for fungal endophthalmitis included septicaemia caused by intravenous drug use (78%), presence of indwelling lines (9%), postocular surgery (9%) and post‐trauma (4%). Guidelines were rigidly followed in 56% of cases, with improved visual acuity in 9/13 patients compared to 4/10 where management deviated from guidelines. Deviation from guidelines occurred with incomplete use of the recommended drug regimen for the disease severity or use of drugs that were alternative to the suggested guidelines. Treatment was initiated on clinical judgement in 91% of cases and laboratory diagnosis in 9%. Conclusion: The BEH guidelines provided a useful reference when managing this uncommon condition. Voriconazole, a newer broad‐spectrum agent with good ocular penetration (used in 9%), has been added to the revised guidelines. Monitoring rare conditions over prolonged time frames supports evidence‐based medicine.     

Training status and interest in certification of nondiplomate faculty teaching predoctoral dental public health

OBJECTIVES: A survey was conducted to better understand the training needs of faculty members without dental public health (DPH) specialty board certification who teach DPH to dental students. METHODS: An 11-item questionnaire was sent to 193 non-DPH diplomate faculty members at US dental schools who were dentists and at least one of the following: a member of the American Association of Dental Schools Community and Preventive Dentistry Section, a referral from an academic American Board of Dental Public Health diplomate, a DPH faculty listed on the school's Web pages, a DPH contact from the AADS Institutional Directory, or the school's dean if no other contact. RESULTS: A 70 percent response rate was obtained. Seventy-nine percent of the respondents taught at least one national board-related DPH topic. Among these faculty members, 67 percent have or are in training for the master of public health, 26 percent have completed or are in a DPH residency, and 63 percent desire training in one or more of the DPH topics. The majority (64%) does not plan to take the specialty exam, while 28 percent plan to take the exam within five years. About half reported no personal incentives to take the exam and 39 percent perceived no institutional incentives. CONCLUSIONS: These nondiplomate teachers of predoctoral DPH desire training, but appear to have barriers and perceive few benefits to achieving DPH board certification.     

Prenatal genetic diagnosis of retinoblastoma and report of RB1 gene mutation from India

Background: Retinoblastoma is the most common intraocular malignancy of childhood. There is a paucity of genetic testing and prenatal genetic diagnosis from India, which has the highest incidence worldwide.

Materials and methods: RB1 gene screening of an 8-month-old female child with bilateral retinoblastoma was accomplished using next generation sequencing. The results were used for prenatal testing in this family.

Results: A heterozygous germline mutation (chr13: 48951119delA; c.1281delA) was detected, which resulted in premature termination of a protein product (p.Glu428Argfs*29). Prenatal testing in maternal DNA revealed carrier status of the mother. Further clinical examination in the family members revealed retinocytomas in both eyes of the mother and maternal grandmother. Prenatal genetic testing of the developing fetus showed positivity for the mutation. As the family preferred to continue the pregnancy, serial 3-D ultrasounds were carried out every 2 weeks in the third trimester. Ten days after delivery, small extrafoveal tumors developed in both eyes, which were then treated successfully with transpupillary thermotherapy.

Conclusion: We report the significance of genetic testing in the early detection and management of retinoblastoma from India.     

In vivo sectional imaging of the retinal periphery using conventional optical coherence tomography systems

Optical coherence tomography (OCT) has transformed macular disease practices. This report describes the use of conventional OCT systems for peripheral retinal imaging. Thirty-six eyes with peripheral retinal pathology underwent imaging with conventional OCT systems. In vivo sectional imaging of lattice degeneration, snail-track degeneration, and paving-stone degeneration was performed. Differences were noted between phenotypes of lattice degeneration. Several findings previously unreported in histopathology studies were encountered. Certain anatomic features were seen that could conceivably explain clinical and intraoperative behavior of peripheral lesions. Peripheral OCT imaging helped elucidate clinically ambiguous situations such as retinal breaks, subclinical retinal detachment, retinoschisis, choroidal nevus, and metastasis. Limitations of such scanning included end-gaze nystagmus and far peripheral lesions. This first of its kind study demonstrates the feasibility of peripheral retinal OCT imaging and expands the spectrum of indications for which OCT scanning may be clinically useful.     

Amphetamine induced dopamine release increases anxiety in individuals recovered from anorexia nervosa

Objective:

Genetic, pharmacologic, and physiological data suggest that individuals with anorexia nervosa (AN) have altered striatal dopamine (DA) function.

Method:

We used an amphetamine challenge and positron emission tomography [¹¹C]raclopride paradigm to explore DA striatal transmission in 10 recovered (REC) AN compared with 9 control women (CW).

Results:

REC AN and CW were similar for baseline, postamphetamine [¹¹C]raclopride binding potential (BP_ND) and change (Δ) in BP_ND for all regions. In CW, ventral striatum Δ BP_ND was associated with euphoria (r = ?0.76; p = 0.03), which was not found for REC AN. Instead, REC AN showed a significant relationship between anxiety and Δ BP_ND in the precommissural dorsal caudate (r = ?0.62, p = 0.05).

Discussion:

REC AN have a positive association between endogenous DA release and anxiety in the dorsal caudate. This finding could explain why food‐related DA release produces anxiety in AN, whereas feeding is pleasurable in healthy participants. © 2011 by Wiley Periodicals, Inc. (Int J Eat Disord 2012)

     

The key informant strategy to determine the prevalence and causes of functional low vision among children in South India

Purpose: To report the prevalence and causes of functional low vision (FLV) in school-age children in Coimbatore District, Tamil Nadu, India and to report our experience using the key informant (KI) method in this setting.

Methods: Children suspected of having low vision were identified by KIs or Aravind Eye Hospital personnel in Coimbatore District. All identified children underwent a cycloplegic refraction and full eye exam. A primary cause of decreased vision was determined for each child. The prevalence of FLV was calculated for children 6–14 years old. Spectacles and low vision devices were provided free of charge.

Results: 345 children aged 6–14 years were referred and 231 had FLV. The positive-predictive value of KI referrals was 64.5%. The prevalence of FLV was 0.071% (7.1 per 10,000; 95% CI 0.062–0.080%) and ranged from 0.026% to 0.141% across the district’s blocks. Older children (age 11–14 years; OR 1.41; 95% CI 1.09–1.82) and males (OR 1.52; 95% CI 1.16–1.98) had greater odds of being diagnosed with FLV. The most common causes of FLV were retinal disorders (30.0%) and amblyopia (25.5%). Low vision devices were provided to 169 children who had a mean near and distance visual acuity improvement of 0.31 and 0.63 logMAR, respectively (p < 0.001).

Conclusions: This study reports a moderate prevalence of FLV and demonstrates the ability of KIs to identify school-age children with FLV in South India. The provision of basic low vision services can improve visual outcomes in this population.