Serotonin transporter binding after recovery from eating disorders

RATIONALE: Several lines of evidence suggest that altered serotonin (5-HT) function persists after recovery from anorexia nervosa (AN) and bulimia nervosa (BN). OBJECTIVES: We compared 11 subjects who recovered (>1 year normal weight, regular menstrual cycles, no binging or purging) from restricting-type AN (REC RAN), 7 who recovered from bulimia-type AN (REC BAN), 9 who recovered from BN (REC BN), and 10 healthy control women (CW). MATERIALS AND METHODS: Positron emission tomography (PET) imaging with [11C]McN5652 was used to assess the 5-HT transporter (5-HTT). For [11C]McN5652, distribution volume (DV) values were determined using a two-compartment, three-parameter tracer kinetic model, and specific binding was assessed using the binding potential (BP, BP=DVregion of interest/DVcerebellum-1). RESULTS: After correction for multiple comparisons, the four groups showed significant (p<0.05) differences for [11C]McN5652 BP values for the dorsal raphe and antero-ventral striatum (AVS). Post-hoc analysis revealed that REC RAN had significantly increased [11C]McN5652 BP compared to REC BAN in these regions. CONCLUSIONS: Divergent 5-HTT activity in subtypes of eating disorder subjects may provide important insights as to why these groups have differences in affective regulation and impulse control.     

Influenza Virus H5 DNA Vaccination Is Immunogenic by Intramuscular and Intradermal Routes in Humans

Avian influenza virus causes outbreaks in domestic and wild birds around the world, and sporadic human infections have been reported. A DNA vaccine encoding hemagglutinin (HA) protein from the A/Indonesia/5/05 (H5N1) strain was initially tested in two randomized phase I clinical studies. Vaccine Research Center study 304 (VRC 304) was a double-blinded study with 45 subjects randomized to placebo, 1 mg of vaccine, or 4 mg of vaccine treatment groups (n = 15/group) by intramuscular (i.m.) Biojector injection. VRC 305 was an open-label study to evaluate route, with 44 subjects randomized to intradermal (i.d.) injections of 0.5 mg by needle/syringe or by Biojector or 1 mg delivered as two 0.5-mg Biojector injections in the same deltoid or as 0.5 mg in each deltoid (n = 11/group). Injections were administered at weeks 0, 4, and 8 in both studies. Antibody responses to H5 were assessed by hemagglutination inhibition (HAI) assay, enzyme-linked immunosorbent assay (ELISA), and neutralization assay, and the H5 T cell responses were assessed by enzyme-linked immunospot and intracellular cytokine staining assays. There were no vaccine-related serious adverse events, and the vaccine was well tolerated in all groups. At 1 mg, i.d. vaccination compared to i.m. vaccination induced a greater frequency and magnitude of response by ELISA, but there were no significant differences in the frequency or magnitude of response between the i.d. and i.m. routes in the HAI or neutralization assays. T cell responses were more common in subjects who received the 1- or 4-mg dose i.m. These studies demonstrated that the DNA vaccine encoding H5 is safe and immunogenic and served to define the proper dose and route for further studies. The i.d. injection route did not offer a significant advantage over the i.m. route, and no difference was detected by delivery to one site versus splitting the dose between two sites for i.d. vaccine administration. The 4-mg dose (i.m) was further investigated in prime-boost regimens.     

Psychological distress of patients undergoing intensified conditioning with radioimmunotherapy prior to allogeneic stem cell transplantation

This is a pilot study comparing the emotional distress of patients receiving an intensified conditioning regimen (radioimmunotherapy=RIT) with patients receiving conventional conditioning for allogeneic stem cell transplantation. In total, 53 patients (18 received RIT) were given two questionnaires designed to measure emotional distress (HADS, POMS) before starting conditioning (t1) and at discharge (t2). During the in-patient period, patients answered questions daily relating to physical distress, psychological distress, and how they were "coping with the situation". At t2, the transplant team assessed the manner in which the patients were coping. The data displayed no relevant differences with regard to emotional distress between the two groups, both at t1 and t2. For both groups, anxiety and vigor decreased and fatigue increased between t1 and t2. On average, perceived distress was higher for those patients being treated with RIT during the in-patient time, but the differences between both groups were significant only regarding physical distress during the recovery period. No difference was found for the transplant team's assessment. We hypothesize that an intensified conditioning regimen with RIT per se has only a small distressing effect on the patients' psyche during their stay at the hospital. Differences between both groups probably result from independent factors such as, for example, the patients' pre-existing health conditions.     

Serotonin transporter binding after recovery from bulimia nervosa

Objective:

Physiological and pharmacological studies indicate that altered brain serotonin (5‐HT) activity could contribute to a susceptibility to develop appetitive and behavioral alterations that are characteristic of bulimia nervosa (BN).

Method:

Eight individuals recovered from BN (REC BN) and eight healthy control women were scanned with [11C]DASB and positron emission tomography imaging of the 5‐HT transporter (5‐HTT). Logan graphical analysis was applied, and parametric binding potential (BP_{nondisplaceable (ND)}) images were generated. Voxel‐by‐voxel t‐tests and a region of interest (ROI) analysis were conducted.

Results:

REC BN had significantly lower [11C]DASB BP_ND in midbrain, superior and inferior cingulate and significantly higher [11C]DASB BP_ND in anterior cingulate and superior temporal gyrus in the voxel‐based analysis. ROI analysis indicated lower [11C]DASB BP_ND in midbrain (p = .07), containing the dorsal raphe, in REC BN, consistent with our earlier studies.

Discussion:

These preliminary findings of a small‐scale study confirm and extend previous data suggesting that ill and recovered BN have altered 5‐HTT measures, which potentially contribute to BN symptomatology and/or differential responses to medication. © 2011 by Wiley Periodicals, Inc. (Int J Eat Disord 2012;)     

Trauma experience in individuals with idiopathic environmental intolerance and individuals with somatoform disorders

OBJECTIVE: Results from previous studies suggest that past trauma experience increases the risk for medically unexplained somatic symptoms and somatoform disorders (SFD). This cross-sectional study examined the link between various lifetime traumas, idiopathic environmental intolerance (IEI), and SFD. METHODS: Two clinical groups of 54 subjects with IEI and 44 subjects with SFD were compared to 54 subjects (comparison group, CG) free from both IEI and SFD regarding self-reported traumas. The subjects were mainly recruited via advertisements in local newspapers. From 970 individuals screened for IEI and multiple somatic symptoms, 152 were included through a two-step selection procedure consisting of screening questionnaires, a medical examination, and structured interviews for IEI and mental disorders. RESULTS: In all three groups at least one potential traumatic event was reported rather frequently (CG: 70%; IEI: 82%; SFD: 73%). But contrary to our expectation, significant group differences were neither found in regard to the proportion of subjects with any trauma, nor traumas fulfilling DSM-IV criteria (CG: 41%; IEI: 48%; SFD: 59%), nor multiple traumas (CG: 43%, IEI: 56%, SFD: 39%). Only two trauma categories were endorsed more frequently by the two clinical groups than by the CG: the unspecified 'other' category (IEI, SFD>CG) and 'life-threatening illness' (IEI>CG). CONCLUSION: No clear evidence was found for increased rates of trauma experience in IEI and SFD. However, the results of this exploratory study should be considered as preliminary. Comparing larger IEI and SFD groups with a representative population-based sample may yield different results.     

Sample size requirements for studying small populations in gerontology research

Calculating sample sizes required to achieve a specified level of precision when estimating population parameters is a common statistical task. As consumer surveys become increasingly common for nursing homes, home care agencies, other service providers, and state and local administrative agencies, standard methods to calculate sample size may not be adequate. Standard methods typically assume a normal approximation and require the specification of a plausible value of the unknown population trait. This paper presents a strategy to estimate sample sizes for small finite populations and when a range of possible population values is specified. This sampling strategy is hierarchical, employing first a hypergeometric sampling model, which directly addresses the finite population concern. This level is then coupled with a beta-binomial distribution for the number of population elements possessing the characteristic of interest. This second level addresses the concern that the population trait may range over an interval of values. The utility of this strategy is illustrated using a study of resident satisfaction in nursing homes.     

Characterizing uncertainty and variability in physiologically based pharmacokinetic models: state of the science and needs for research and implementation.

Physiologically based pharmacokinetic (PBPK) models are used in mode-of-action based risk and safety assessments to estimate internal dosimetry in animals and humans. When used in risk assessment, these models can provide a basis for extrapolating between species, doses, and exposure routes or for justifying nondefault values for uncertainty factors. Characterization of uncertainty and variability is increasingly recognized as important for risk assessment; this represents a continuing challenge for both PBPK modelers and users. Current practices show significant progress in specifying deterministic biological models and nondeterministic (often statistical) models, estimating parameters using diverse data sets from multiple sources, using them to make predictions, and characterizing uncertainty and variability of model parameters and predictions. The International Workshop on Uncertainty and Variability in PBPK Models, held 31 Oct-2 Nov 2006, identified the state-of-the-science, needed changes in practice and implementation, and research priorities. For the short term, these include (1) multidisciplinary teams to integrate deterministic and nondeterministic/statistical models; (2) broader use of sensitivity analyses, including for structural and global (rather than local) parameter changes; and (3) enhanced transparency and reproducibility through improved documentation of model structure(s), parameter values, sensitivity and other analyses, and supporting, discrepant, or excluded data. Longer-term needs include (1) theoretical and practical methodological improvements for nondeterministic/statistical modeling; (2) better methods for evaluating alternative model structures; (3) peer-reviewed databases of parameters and covariates, and their distributions; (4) expanded coverage of PBPK models across chemicals with different properties; and (5) training and reference materials, such as cases studies, bibliographies/glossaries, model repositories, and enhanced software. The multidisciplinary dialogue initiated by this Workshop will foster the collaboration, research, data collection, and training necessary to make characterizing uncertainty and variability a standard practice in PBPK modeling and risk assessment.