Uveitis in childhood--Part III. Posterior

Toxoplasma, nematodes, and cytomegalovirus are the most common causes of uveitis in children involving the posterior pole. Discussion of treatment and management is detailed. Rubella retinitis and subacute sclerosing panencephalitis are specific entities which are limited in their initial presentation in children. Panuveitis including sympathetic ophthalmia, Vogt-Koyanagi-Harada, and Beh?et's syndromes, while relatively rare in their occurrence, demand early treatment intervention. Specific antimicrobial therapy and adrenocorticosteroids as well as therapeutic suggestions are also included. This is the last part of a three-part series of articles.     

Persistent otitis media with effusion: A new experimental model

Objectives/Hypothesis: Numerous mechanical animal models for the creation of otitis media with effusion (OME) have been described since the 1920s. However, there are many problems associated with these models, including high infection rates, unreliability, and high resolution rates. The aim of the current study was to create a suitable mechanical animal model that would produce a sterile and long-lasting effusion. Study Design: A new technique using an external surgical approach on specific pathogen–free rats is described. Method: The eustachian tubes of 56 rats were obstructed in the mid portion along the skull base with gutta percha. Results: All animals developed an effusion within 1 week of the procedure. The resolution rate was 8%, with 80% maintaining sterile effusions for up to 1 year. Conclusions: This new procedure for an OME model has proved consistently reliable in creating a persistent and long-lasting effusion. It has a low infection rate and should benefit future studies on the prolonged effects of OME on the tympanic membrane and middle ear.     

A multi-modal treatment program for childhood trauma recovery:Women Recovering from Abuse Program (WRAP).

This article describes the Women Recovering from Abuse Program (WRAP), an outpatient day-hospital program for women suffering from the sequelae of childhood abuse. WRAP was conceived in 1998 by clinicians who advocated for its development based on a growing need to provide women who had experienced childhood trauma an alternative to an inpatient program. WRAP draws from a Stage 1 treatment approach to address chronic interpersonal trauma and dissociation by incorporating psychopharmacology, individual and group psychotherapy. The program is structured into two phases: a preparatory Building Resources Group (BRG) and an intensive multimodal segment comprised of seven types of group therapy. Each group is described in terms of the treatment rationale and its structure and process. Two research studies to date support the effectiveness of WRAP.     

Neuroimaging of NREM sleep in primary insomnia: a Tc-99-HMPAO single photon emission computed tomography study

STUDY OBJECTIVES: The objectives of this study were to: 1) demonstrate the feasibility of combining polysomnography and SPECT neuroimaging to study NREM sleep in primary insomnia and 2) evaluate possible functional CNS abnormalities associated with insomnia. DESIGN: Patients with insomnia and good sleeper controls were studied polysomnographically for three nights with a whole brain SPECT Scan of NREM sleep on Night 3. Groups were screened for medical/psychiatric history, substance use, and matched on age, body mass index, and education. SETTING: Sleep Research Laboratory and Nuclear Medicine Center PARTICIPANTS: Nine females, 5 patients with chronic psychophysiologic insomnia and 4 healthy good sleepers (mean age 36 years, SD 12, range 27-55). INTERVENTIONS: N/A MEASUREMENTS AND RESULTS: Tomographs of regional cerebral blood flow during the 1st NREM sleep cycle were successfully obtained. Contrary to our expectations, patients with insomnia showed a consistent pattern of hypoperfusion across all 8 pre-selected regions of interest, with particular deactivation in the basal ganglia (p=.006). The frontal medial, occipital, and parietal cortices also showed significant decreases in blood flow compared to good sleepers (p<.05). Subjects with insomnia had decreased activity in the basal ganglia relative to the frontal lateral cortex, frontal medial cortex, thalamus, occipital and parietal cortices (p<.05). CONCLUSIONS: This study demonstrated the feasibility of combining neuroimaging and polysomnography to study cerebral activity in chronic insomnia. These preliminary results suggest that primary insomnia may be associated with abnormal central nervous system activity during NREM sleep that is particularly linked to basal ganglia dysfunction.     

Mutations in the human melanocortin-4 receptor gene associated with severe familial obesity disrupts receptor function through multiple molecular mechanisms

Mutations in the melanocortin-4 receptor gene (MC4R) represent the commonest monogenic cause of human obesity. However, information regarding the precise effects of such mutations on receptor function is very limited. We examined the functional properties of 12 different mutations in human MC4R that result in severe, familial, early-onset obesity. Of the nine missense mutants studied, four were completely unable to generate cAMP in response to ligand and five were partially impaired. Four showed evidence of impaired cell surface expression and six of reduced binding affinity for ligand. One mutation in the C-terminal tail, I316S, showed reduced affinity for alpha-MSH but retained normal affinity for the antagonist AgRP. None of the mutations inhibited signaling through co-transfected wild-type receptors. Thus, in the most comprehensive study to date of the functional properties of naturally occurring MC4R mutations we have (1) established that defective expression on the cell surface is a common mechanism impairing receptor function, (2) identified mutations which specifically affect ligand binding affinity thus aiding the definition of receptor structure-function relationships, (3) provided evidence against the notion that these receptor mutants act as dominant-negatives, and (4) identified a potentially novel molecular mechanism of receptor dysfunction whereby a mutation alters the relative affinities of a receptor for its natural agonist versus antagonist.     

Review of tethered cord syndrome with a radiological and anatomical study: Case report

Summary The primary tethered cord syndrome has been documented mainly in children and adolescents but also in adults, and patients may present with backache, neuromuscular skeletal changes such as club-foot, scoliosis, muscular atrophy, disturbances of gait, or dysfunction of bladder and rectum, or a combination of these conditions. The cadaveric case presented describes plain film radiographic and anatomical findings of spina bifida occulta at the first and second sacral levels, and an enlarged spinous process of the fifth lumbar vertebra, in a 78 year old male cadaver with a tethered spinal cord terminating at the first sacral level. During life, this man had not undergone surgery for tethered spinal cord.

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Revue du syndrome de moelle attachée: étude radiologique et anatomique à propos d'un cas

Résumé Le syndrome de moelle attachée primaire a souvent été décrit chez l'enfant et l'adolescent mais aussi chez l'adulte, les patients pouvant se présenter avec des douleurs du dos, des modifications neuro-musculaires et squelettiques comme un pied bot, une scoliose, une atrophie musculaire, des anomalies de la marche, des dysfonctionnements de la vessie et/ou du rectum, ou une combinaison de ces différents symptômes. L'observation rapportée ici est l'étude anatomique et radiologique d'un spina bifida oculta des première et deuxième vertèbres sacrées associé à l'élargissement du processus épineux de la cinquième vertèbre lombaire chez un cadavre mâle de 78 ans ayant une moelle épinière attachée au niveau de la première vertèbre sacrée. Durant sa vie ce patient n'avait pas subi de chirurgie pour cette moelle attachée.

     

APOE is a potential modifier gene in an autosomal dominant form of frontotemporal dementia (IBMPFD).

PURPOSE: Inclusion-body myopathy, Paget's disease of bone and frontotemporal dementia is an adult-onset autosomal dominant illness (IBMPFD) caused by mutations in the valosin-containing protein (VCP) on chromosome 9p21.1-p12. The penetrance of the gene is 82% for myopathy, 49% for Paget's disease, but may be as low as 30% for frontotemporal dementia. Modifier genes could account for decreased frontotemporal dementia penetrance. In this study apolipoprotein-E (APOE) was evaluated for this role in IBMPFD families based on its known modifier effect in Alzheimer's disease. METHODS: From a database of 231 members of 15 families, 174 had APOE genotype available for analysis. Logistic regressions on APOE genotype and frontotemporal dementia were performed, using appropriate covariates. RESULTS AND CONCLUSION: FTD was associated with APOE 4 genotype (P=0.0002), myopathy (P=0.0006), and age (P=0.01), but not microtubule associated protein tau (MAPT) H2 haplotype (P=0.5) or gender (0.09) after adjustment for membership in pedigrees with at least one APOE 4 genotype. These data suggest a potential link between APOE 4 genotype and the specific form of frontotemporal dementia found in IBMPFD. The molecular basis of this link bears further investigation. We did not observe an association of frontotemporal dementia and H2 MAPT haplotype.