Improvement and Recovery from Eating Disorders: A Patient Perspective

This study presents a patient perspective on improvement and recovery from eating disorders. Forty-eight women recruited from patient organizations and a university eating disorder unit participated in the study. Participants completed standard questionnaires and a qualitative interview. "A wish to change," professional treatment, nonprofessional care, and important persons in the women's lives were identified as important recovery factors. Recovery included improved acceptance of oneself, interpersonal relations, problem solving, and body satisfaction, which was not entirely dependent on symptom absence. The patient perspective concurred with clinical reasoning about recovery.     

Effect of chronic antipsychotic treatment on striatal phosphodiesterase 10A levels: a [11C]MP-10 PET rodent imaging study with ex vivo confirmation

A number of phosphodiesterase 10A (PDE10) inhibitors are about to undergo clinical evaluation for their efficacy in treating schizophrenia. As phosphodiesterases are in the same signalling pathway as dopamine D₂ receptors, it is possible that prior antipsychotic treatment could influence these enzyme systems in patients. Chronic, in contrast to acute, antipsychotic treatment has been reported to increase brain PDE10A levels in rodents. The aim of this study was to confirm these findings in a manner that can be translated to human imaging studies to understand its consequences. Positron emission tomography (PET) scanning was used to evaluate PDE10A enzyme availability, after chronic haloperidol administration, using a specific PDE10A ligand ([¹¹C]MP-10). The binding of [¹¹C]MP-10 in the striatum and the cerebellum was measured in rodents and a simplified reference tissue model (SRTM) with cerebellum as the reference region was used to determine the binding potential (BP_ND). In rats treated chronically with haloperidol (2 mg kg⁻¹ per day), there was no significant difference in PDE10A levels compared with the vehicle-treated group (BP_ND±s.d.: 3.57±0.64 versus 2.86±0.71). Following PET scans, ex vivo analysis of striatal brain tissue for PDE10A mRNA (Pde10a) and PDE10A enzyme activity showed no significant difference. Similarly, the PDE10A protein content determined by western blot analysis was similar between the two groups, contrary to an earlier finding. The results of the study indicate that prior exposure to antipsychotic medication in rodents does not alter PDE10A levels.     

Determination of [11C]PBR28 binding potential in vivo: a first human TSPO blocking study

Positron emission tomography (PET) targeting the 18 kDa translocator protein (TSPO) is used to quantify neuroinflammation. Translocator protein is expressed throughout the brain, and therefore a classical reference region approach cannot be used to estimate binding potential (BP_ND). Here, we used blockade of the TSPO radioligand [¹¹C]PBR28 with the TSPO ligand XBD173, to determine the non-displaceable volume of distribution (V_ND), and hence estimate the BP_ND. A total of 26 healthy volunteers, 16 high-affinity binders (HABs) and 10 mixed affinity binders (MABs) underwent a [¹¹C]PBR28 PET scan with arterial sampling. Six of the HABs received oral XBD173 (10 to 90 mg), 2 hours before a repeat scan. In XBD173-dosed subjects, V_ND was estimated via the occupancy plot. Values of BP_ND for all subjects were calculated using this V_ND estimate. Total volume of distribution (V_T) of MABs (2.94±0.31) was lower than V_T of HABs (4.33±0.29) (P<0.005). There was dose-dependent occupancy of TSPO by XBD173 (ED50=0.34±0.13 mg/kg). The occupancy plot provided a V_ND estimate of 1.98 (1.69, 2.26). Based on these V_ND estimates, BP_ND for HABs is approximately twice that of MABs, consistent with predictions from in vitro data. Our estimates of [¹¹C]PBR28 V_ND and hence BP_ND in the healthy human brain are consistent with in vitro predictions. XBD173 blockade provides a practical means of estimating V_ND for TSPO targeting radioligands.     

Permanent inflation of detachable balloons with a low-viscosity, hydrophilic polymerizing system

A polymer system was developed for use in permanent inflation of detachable balloons, to avoid long-term reliance on the integrity of balloon shells or valve mechanisms. This system is based on 2-hydroxy-ethyl methacrylate (HEMA) as the monomer, in combination with a cross-linking agent and a water-soluble curing system. The low-viscosity, hydrophilic mixture can be exchanged through a small-bore catheter into a detachable balloon and polymerizes in 40-60 minutes at body temperature. Partially polymerized HEMA can cause vascular occlusion; hence, careful timing of balloon detachment is required. The evolution of the radiographic appearance of HEMA-filled balloons is predictable. The balloons remain radiopaque on plain radiographs as long as the balloon shell and valve mechanisms are competent. After rupture of the shell or failure of the valve mechanism, the balloons become invisible on plain radiographs but remain hyperattenuating on computed tomography scans.     

Technique for axillary radiotherapy using computer‐assisted planning for high‐risk skin cancer†

High‐risk skin cancer arising on the upper limb or trunk can cause axillary nodal metastases. Previous studies have shown that axillary radiotherapy improves regional control. There is little published work on technique. Technique standardization is important in quality assurance and comparison of results especially for trials. Our technique, planned with CT assistance, is presented. To assess efficacy, an audit of patients treated in our institution over a 15‐month period was conducted. Of 24 patients treated, 13 were treated with radical intent, 11 with this technique. With a follow up of over 2 years, the technique had more than a 90% (10/11) regional control in this radical group. Both of the radical patients who were not treated according to the technique had regional failure. One case of late toxicity was found, of asymptomatic lymphoedema in a radically treated patient. This technique for axillary radiotherapy for regional control of skin cancer is acceptable in terms of disease control and toxicity as validated by audit at 2 years.     

Identification of thyroxine-binding globulin-San Diego in a family from Houston and its characterization by in vitro expression using Xenopus oocytes

T4-binding globulin (TBG) is a liver glycoprotein that transports iodothyronines in serum. Several TBG variants with reduced T4 binding affinity have been described, all of which are also characterized by reduced serum TBG concentrations and reduced heat stability. Their loss of binding thus appears to be due to a general defect of the molecule. We now report the occurrence of a variant TBG, detected in a family from Houston, TX, with half the normal T4 binding affinity and heat stability but normal serum concentration and isoelectric focussing pattern. The propositus was identified by reduced total T4 and T3 serum levels. All family members were euthyroid, and inheritance followed an X-linked pattern. Sequence analysis of the TBG gene of the propositus and his heterozygous mother revealed two amino acid substitutions: serine 23 with threonine (S23T), and the known polymorphism leucine 283 with phenylalanine (L283F). These substitutions are identical to those of TBG-San Diego (TBG-SD), a variant with similar properties except for a reduced serum concentration. Expression of recombinant TBG-SD/H with the S23T substitution in Xenopus oocytes reproduced the binding defect and heat lability. The amount of TBG-SD/H synthesized and secreted by the oocytes was not different from that of normal TBG. The difference in serum TBG concentrations in affected members of the San Diego and Houston families thus does not appear to be due to an error in the measurement of TBG, but may be related to differences in the rates of degradation.     

Vitamin A levels and severity of measles. New York City.

Recent studies show that vitamin A levels decrease during measles and that vitamin A therapy can improve measles outcome in children in the developing world. Vitamin A levels of children with measles have not been studied in developed countries. We therefore measured vitamin A levels in 89 children with measles younger than 2 years and in a reference group in New York City, NY. Vitamin A levels in children with measles ranged from 0.42 to 3.0 mumol/L; 20 (22%) were low. Children with low levels were more likely to have fever at a temperature of 40 degrees C or higher (68% vs 44%), to have fever for 7 days or more (54% vs 23%), and to be hospitalized (55% vs 30%). Children with low vitamin A levels had lower measles-specific antibody levels. No child in the reference group had a low vitamin A level. Our data show that many children younger than 2 years in New York City have low vitamin A levels when ill with measles, and that such children seem to have lower measles-specific antibody levels and increased morbidity. Clinicians may wish to consider vitamin A therapy for children younger than 2 years with severe measles. Additional studies of vitamin A in measles and other infectious diseases, and in vaccine efficacy trials, should be done.