Autonomic dysfunction in patients with progressive supranuclear palsy

The most important features that characterize and differentiate progressive supranuclear palsy (PSP) from other parkinsonian syndromes are postural instability, supranuclear gaze palsy, pseudobulbar palsy, and cognitive disturbances. Although it has been reported that significant autonomic dysfunction is an exclusionary feature for PSP diagnosis, we could demonstrate in this study using semiquantitative clinical interview and cardiovascular testing that both PSP and idiopathic Parkinson's disease (PD) patients can present with significant autonomic dysfunction. The parasympathetic cardiovascular system seems to be involved to a similar extent in PD and PSP patients, whereas sympathetic cardiovascular dysfunction is more frequent and severe in PD patients, but can also be found in PSP patients. Our findings have a profound implication on the diagnosis and treatment of PSP patients. © 2008 Movement Disorder Society     

Clinical Evaluation of a New Technique for Interdental Enamel Reduction

In orthodontics, reduction of tooth-size by grinding interproximal surfaces (stripping) of teeth is a common procedure. In order to achieve perfectly smooth surfaces, clinicians have carefully tested various methods and progressively improved this therapeutic procedure. In this in-vivo study we used scanning electron microscopy (SEM) to evaluate the morphologic effect of a 3-step technique using an oscillating perforated diamond-coated disc for enamel reduction and 2 Sof-Lex XT discs for polishing. This technique was applied in 32 patients with an average age of 15.5 years. A total of 296 interproximal surfaces was treated and replicas were produced for scanning electron microscopy evaluation. The scanning electron microscopy investigations demonstrated that more than 90% of the reproximated surfaces were very well or well polished, resulting in polished enamel surfaces smoother than untreated enamel. This technique proved to be clinically expedient as it finished each interproximal surface within about 2.2 minutes. At the same time, it was demonstrated to be safe and comfortable for the patient, eliminating the need for lip or cheek protectors and making injuries unlikely. Zusammenfassung: Zahngrößenreduktion durch Beschleifen der Approximalflächen (Strippen) ist ein in der Kieferorthopädie gebräuchliches Verfahren. In dem Bemühen, perfekt glatte Schmelzoberflächen zu erzielen, wurden bereits etliche Methoden gründlich untersucht und immer wieder verbessert. In der vorliegenden In-vivo-Studie wurde mittels Rasterelektronenmikroskopie (REM) das morphologische Ergebnis eines Verfahrens untersucht, bei dem die Schmelzreduktion mit einer oszillierenden perforierten Diamantscheibe erfolgte und die nachfolgende Politur mit zwei Sof-Lex-XT-Scheiben geschah. Diese Technik wurde bei 32 Patienten mit einem Durchschnittsalter von 15,5 Jahren angewendet. Insgesamt wurden 296 Approximalflächen behandelt und anschließend Replikas für die rasterelektronenmikroskopische Untersuchung angefertigt. Die rasterelektronenmikroskopischen Befunde zeigten, dass mehr als 90 % der bearbeiteten Approximalflächen gut oder sehr gut poliert waren; der polierte Schmelz war somit glatter als unbehandelte Zahnoberflächen. Das untersuchte Verfahren erforderte pro Approximalfläche einen Zeitaufwand von 2,2 Minuten und erwies sich somit als klinisch praktikabel. Gleichzeitig war es sicher und komfortabel für den Patienten, indem es Lippenretraktoren überflüssig machte und das Verletzungsrisiko trotzdem sehr klein war.     

Shoulder rheumatoid arthritis associated with chondromatosis, treated by arthroscopy

We present a case of rheumatoid arthritis that affected the right shoulder and was associated with chondromatosis and multiple loose body formation. The arthritis was treated arthroscopically with satisfactory results after a follow-up period of 15 months. In our case, arthroscopic debridement and partial synovectomy not only relieved the pain but also improved the range of motion the night after surgery. The multiple loose bodies irritating the synovium and causing effusion, crepitus, and locking were also removed. One may need to change portals of the scope and suction cannula to remove loose bodies in different joint spaces. The subacromial space must be searched for loose bodies. Thorough cleaning, lavage, and synovectomy are important parts of this surgery. The continuous passive motion (CPM) machine in the immediate postoperative period was helpful.     

Ontogeny of the calcium binding protein calbindin D-28k in the rat nervous system

Summary Calbindin D-28k immunoreactivity appeared at embryonal day 14 (E14) in the central nervous system as well as in the sensory organs and at E15 in the peripheral nervous system of the rat. At E14 the infundibular process of the diencephalon, cells of the posterior hypothalamus and of the dorsal thalamus were the only structures strongly immunostained in the brain, whereas neurons of the basal plate of the spinal cord, medulla oblongata and of the out-ermost layer of the cerebral cortex were only faintly labeled. Calbindin positive cerebellar Purkinje cells could be discerned at E15 together with a few cells in the hippocampus and in ganglia of the cranial nerves. At E19 various mesencephalic and metencephalic structures, spinal ganglion cells and basal ganglia displayed calbindin immunoreactive cells. The adult pattern of calbindin immunoreactivity (Garcia Segura et al. 1984) was reached before birth in most brain regions. In general, cells which displayed calbindin during brain development were also calbindin positive in the adult animal. Exceptions to this rule were cells of the deep nuclei of the cerebellum and non-neuronal cells which transiently expressed calbindin during development. Calbindin appeared in a given brain region almost invariably 1 or 2 days after the cessation of cell division and the beginning of neuronal migration and extension of neuronal processes. The calcium binding protein calbindin might influence these Ca²⁺-dependent processes.Abbreviations A Axon - ac anterior commissure - Acq Aqueductus cerebri - AH Adenohypophysis - AMY Amygdala - aV anterior vermis - BG Basal Ganglia - BO Bulbus olfactorius - BPG basal pontine grey - C Cortex - CA Crista ampullaris - cer Cerebellum - CO otic cyst - CP choroid plexus - CPT Caudatoputamen - DCN deep cerebellar nuclei - DT dorsal thalamus - E foregut epithelium - ec external capsule - eml external medullary lamina - ENP entopeduncular nucleus - EP Ependym - ET Epithalamus - EY eye - F Fimbria - fo Fornix - fr Fasciculus retroflexus - GP Globus pallidus - gr granular laver of the cerebellum - Gsp ganglion spirale cochlea - HI Hippocampus - HYP Hypothalamus - I hippocampal interneurons - ic internal capsule - IE inner ear - IH inner hair cells of the cochlea - IO inferior olive - IS internal sulcus cells of the cochlea - LD laterodorsal thalamus - LV lateral ventricle - MB mamillary body - MH medial habenular nucleus - mol molecular layer of the cerebellum - mt mamillo-thalamic tract - mtt mamillo-tegmental tract - N nose - n olfactory nerve - NBM Nucleus basalis of Meynert - NE nose epithelium - NH Neurohypophysis - NRT Nucleus reticularis tegmenti pontis - ON olfactory nuclei - OR optic recess - PC posterior commissure - PG Epiphysis - PI inferior cerebellar peduncle - PS superior cerebellar peduncle - PU Purkinje cell - PV paraventricular hypothalamic nucleus - pV posterior vermis - PVP paraventricular thalamic nucleus - PY pyramidal cells of the hippocampus - RA Raphe nuclei - RE Nucleus reuniens - RH Nucleus rhomboideus - RN reticular nucleus - RP Rathke's pouch - sc spinal cord - SG substantia gelatinosa Rolandi - slm Stratum-lacunosum molecular - sm Stria medullaris - SN Substantia nigra - SO supraoptic nucleus - Sol Nucleus of the solitary tract - Tect Tectum - Teg Tegmentum - TG tegmental nucleus of Gudden - Tg tongue - TO tuberculum olfactorium - VT ventral thalamus - WH white matter - ZI Zona incerta - 3 third ventricle - 4 fourth ventricle - II _N Nervus opticus - Vg Trigeminal ganglion - Vsp spinal trigeminal nucleus - VIIG Ganglion geniculi - VIIIG Ganglion vestibulare - IXGI interior ganglion of IX - IXGS superior ganglion of IX - XGI inferior ganglion of X Submitted by S.E. as her doctoral thesis at the medical faculty of the University of Zürich     

Immunization with a recombinant MAGE-A3 protein after high-dose therapy for myeloma

MAGE-A3 is frequently expressed in high-risk multiple myeloma (MM). We immunized a healthy donor with MAGE-A3 protein formulated in AS02B to transfer immunity to her identical twin, diagnosed with MAGE-A3-positive MM. After a melphalan 200 mg/m syngeneic peripheral blood stem cell transplant, primed donor cells collected after immunizations were transferred and followed by repeated patient immunizations. MAGE-A3 immunizations were well tolerated. Strong MAGE-A3-specific antibody, cytotoxic T-lymphocyte (CTL), and T-helper responses were induced in both twins. A humoral response was transferred to the patient with the donor peripheral blood stem cells and increased by booster immunization. The CTL response targeted a previously undescribed HLA-A*6801 binding MAGE-A3115-123 peptide. MAGE-A3115-123 CTLs were detected in the patient more than 1 year after the last immunization. Multiple T-helper cellular responses were detected with the dominant response to an HLA-DR11 restricted MAGE-A3 epitope. The patient remains in remission 2.5 years after the second transplant. This report shows for the first time that immunization of a healthy donor with a defined cancer-testis protein induces immune responses that can be transferred and expanded posttransplant in the recipient. MAGE-A3 immunization may be a useful adjunct to high dose melphalan-based peripheral blood stem cell transplant, providing a new therapeutic option for high-risk MM.     

Changes in FiO<Subscript>2</Subscript> affect PaO<Subscript>2</Subscript> with minor alterations in cerebral concentration of oxygenated hemoglobin during liquid ventilation in healthy piglets

Objective To measure the impact of changes in the fraction of inspired oxygen (FiO₂) on systemic and cerebral oxygen supply in gas and liquid ventilated healthy animals.Design Interventional prospective animal study.Setting University research laboratory.Participants Ten healthy, new-born piglets.Interventions Variations in FiO₂ during conventional mechanical ventilation (CMV) followed by partial liquid ventilation (PLV) with two different filling volumes of PF 5080 (10 vs. 30 ml/kg).Measurements and results Arterial blood gases were obtained 15 min after changing FiO₂ and concentrations of cerebral oxygenated and total hemoglobin were determined with near infrared spectroscopy. During CMV an increase in FiO₂ 1.0 was associated with a constant rise in PaO₂ but only a small increase in the cerebral concentration of oxygenated Hb. Initiation of PLV (at FiO₂ of 1.0) caused a rapid drop in PaO₂ towards values that were similar to CMV at FiO₂ of 0.5. At FiO₂ of 0.5 a reduction in oxygenated Hb was found in the 30 ml/kg filling group. Complete filling of the lungs with PFC caused a significant drop in total cerebral Hb concentration.Conclusions According to our data, PLV in healthy lungs should be performed with a FiO₂ of 1.0 and a small filling volume to avoid deterioration in cerebral oxygen supply.Financial support: The study was supported by a grant of German Ministry of Education and Research (BMBF Perinatale Lunge-01ZZ9511). NIRO 300 was kindly supplied by Hamamatsu Germany.