Construction and validation of a Parkinson's disease mutation genotyping array for the Parkin gene.

Parkin mutations account for the majority of familial and sporadic early onset Parkinson's disease (EOPD) cases with a known genetic association. More than 100 mutations have been described in the Parkin gene that includes homozygous, compound heterozygous, and single heterozygous mutations. We have designed a Parkin mutation genotyping array (gene chip) that includes published Parkin sequence variants and allows their simultaneous detection. The chip was validated by screening 85 PD cases and 47 controls previously tested for Parkin mutations. Similar genotyping microarrays have been developed for other genetically heterogeneous diseases including age-related macular degeneration. Here, we show the utility of a genotyping array for Parkinson's disease by analysis of 60 subjects from the Genetic Epidemiology of Parkinson Disease (GEPD) study that includes 15 early-onset PD case probands and 45 relatives.     

Biological and physical properties of autogenous vascularized fibular grafts in dogs

The biological and biomechanical properties of normal fibulae, fibulae that had had a sham operation, and both vascularized and non-vascularized autogenous grafts were studied in dogs at three months after the operation. The study was designed to quantify and correlate changes in these properties in orthotopic, stably fixed, weight-bearing grafts and to provide a baseline for additional studies of allografts. The grafts were eight centimeters long and internally fixed. The mechanical properties of the grafts were studied by torsional testing. Metabolic turnover of the grafts was evaluated by preoperative labeling of the dogs with 3H-tetracycline for resorption of bone mineral and with 3H-proline for turnover of collagen. Cortical bone area and porosity were measured. Postoperative formation of bone was evaluated by sequential labeling with fluorochrome. The vascularized grafts resembled the fibulae that had had a sham operation and those that had not had an operation with regard to the total number of osteons and the remodeling process, as measured both morphometrically and metabolically. The vascularized grafts were stronger and stiffer than the non-vascularized grafts and were not different from the bones that had had a sham operation. In contrast, the non-vascularized grafts were smaller, weaker, less stiff, and more porotic, had fewer osteons, and demonstrated increased turnover and resorption compared with the vascularized grafts, the bones that had had a sham operation, and the bones that had not been operated on.     

Case report: Concordant traumatic brainstem contusion delayed diagnosis in a young man with Wilson's disease

Wilson's disease is a hereditary autosomal recessive disorder of copper metabolism. The corresponding gene locus has been localized on the long arm of chromosome 13. Three different clinical variants of the disease can be distinguished: hepato-cerebral, abdominal/hepatic, and central nervous type. The heterogeneity of symptoms can cause problems in differential diagnosis, especially when another concordant disorder can also explain the pathogenesis of symptoms. The case report of a young man who suffered from brainstem contusion demonstrates the possibilities of misinterpretation because presenting symptoms could be attributed either to traumatic brain injury followed by adjustment disorder or Wilson's disease. Clinical signs included leftsided hemiparesis, bilateral gaze direction nystagmus, marked dysarthria with consecutive pervasive mutism, choreo-athetoid movements, spasmodic torticollis and diplopia dependent on gaze direction. Slit lamp examination showed Kayser-Fleischer's corneal ring. EEG- and computer assisted tomography investigations revealed non-specific findings. The patient was treated with D-Penicillamine. Alternative treatment with oral zinc preparations is discussed.

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Zusammenfassung Beim Morbus Wilson handelt es sich um eine autosomal rezessiv vererbte Störung des Kupferstoffwechsels. Der Genort konnte auf dem langen Arm des Chromosoms 13 lokalisiert werden. Klinisch können aufgrund ihrer Symptomatik drei Verlaufsformen (hepato-zerebraler, abdominalhepatischer und zerebraler Typ) unterschieden werden. Die Vielfalt der Symptome kann differentialdiagnostische Schwierigkeiten bereiten. Das Beispiel eines jungen Mannes mit einer traumatischen Hirnstammkontusion zeigt, wie die Diagnose der hepato-lentikulären Erkrankung dadurch erschwert wurde, daß die Pathogenese der Symptome durch die Hirnstammkontusion und darauf folgende Anpassungsstörungen erklärt worden war. Die Symptomatik bestand aus linksseitiger Hemiparese, lateralem Blickrichtungsnystagmus, Dysarthrie mit nachfolgendem universalem Mutismus, choreo-athetodischen Bewegungsstörungen, Torticollis spasmoidicus und blickrichtungsabhängigem Auftreten von Doppelbildern. Bei der Spaltlampenuntersuchung stellte sich der Kayser-Fleischer Ring dar. EEG- und computertomographische Untersuchungen erbrachten nur unspezifische Befunde. Die Behandlung erfolgte mit D-Penicillamin. Die alternative Behandlung mit oraler Gabe von Zinksalzen wird diskutiert.

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Résumé La maladie de Wilson est une affection héréditaire autosomale recessive concernant le métabolisme cuivré. Le locus du gène a été situé sur le bras long du chromosome 13. Du point de vue clinique on distingue trois formes symptomatologiques: le type hepato-cérébral, hepato-abdominal et cérébral. La diversité des signes cliniques peut poser des problèmes de diagnostic différentiel, car d'autres affections peuvent se présenter avec cette même Symptomatologie. Nous rapportons ici l'exemple d'un homme jeune, porteur d'une maladie de Wilson et victime d'une contusion traumatique du tronc cérébral, dont les signes cliniques ainsi que les troubles du comportement pouvaient été autant rapportés à la contusion du tronc cérébral qu'à l'affection métabolique.La Symptomatologie comprenait une hemiparesie gauche, un nystagmus lateralisé, une dysarthrie avec mutisme secondaire universel, des mouvements choréo-athétosiques, un torticolis spasmodique et une diplopie dépendante de la direction du regard. L'examen à la lampe à fente permettait à mettre en evidence un anneau de Kayser Fleischer. L'EEG et le scanner cérébral ne montraient pas d'anomalies specifique.Le traitement a consisté en l'administration de D-Penicillamine. Traitment alternative avec les sels de zinc est discuté.

     

La psychothérapie de l'enfant : la symbolisation accompagnée

The psychotherapy of children may be carried out by psychiatrists and psychologists, but also by psychomotricians, language therapists, etc. It varies according to age, pathology, context, expectancies. Symptoms, language use, introspection capacities, capacities in various domains such as language, body expression, etc. are taken into account. Treatment is indicated according to each individual situation. Psychotherapy is conceived as a method for accompanying symbolisation. It is meant to help children use playing and creativity as methods of symbolisation. It does not aim at searching unconscious significations. Art therapy may now be used in the field of social interventions or teaching, as a way to reduce the violence of contemporary society.     

Congenital cervical atresia: Report of seven cases and review of the literature

OBJECTIVE: Our aim was to evaluate the clinical course and management of congenital cervical atresia. STUDY DESIGN: This retrospective analysis included 7 patients referred to our clinic and a review of the medical literature. RESULTS: Including this case series, 58 cases of congenital cervical atresia have been reported in the literature. Forty-eight percent of patients had isolated congenital cervical atresia with a normal vagina whereas the remainder had either complete or partial vaginal atresia (“shortened blind vaginal pouches”). Surgical management has included abdominal hysterectomy or uterovaginal cannulation with or without vaginoplasty. In 59% of patients who underwent uterovaginal canalization procedures (23/39), normal menstrual bleeding was achieved. Four of these patients subsequently became pregnant and were delivered at term. CONCLUSION: Surgical canalization in selected patients with congenital cervical atresia can be successfully performed to provide patients an opportunity for conservative management, resulting in normal menstrual bleeding, resolution of cyclic pelvic pain, and some potential (albeit limited) for fertility.(Am J Obstet Gynecol 1997;177:25)     

Fluoxetine in panic disorder

Twenty-five patients with a primary DSM-III-R diagnosis of panic disorder with or without agoraphobia were treated openly with the serotonin uptake inhibitor fluoxetine for up to 12 months. For most patients, treatment was initiated at 5 mg/day to minimize adverse effects previously reported with initiation at higher doses. Nineteen (76%) experienced moderate to marked improvement in panic attacks. Four (16%) were unable to tolerate fluoxetine due to adverse effects. Initiating treatment of panic disorder with low doses of fluoxetine may increase its acceptability and permit more patients to benefit from fluoxetine.