Polymer encapsulation of amoxicillin microparticles by SAS process.

Encapsulation of amoxicillin (AMC) with ethyl cellulose (EC) by a supercritical antisolvent process (SAS) was investigated. AMC microparticles obtained previously by an SAS process were used as host particles and EC, a biodegradable polymer used for the controlled release of drugs, was chosen as the coating material. In this work, a suspension of AMC microparticles in a solution of ethyl cellulose in dichloromethane (DCM) was sprayed through a nozzle into supercritical CO2. Scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS) and HPLC analyses were carried out. The effects of AMC:EC ratio, the initial polymer concentration of the solution, temperature and pressure on the encapsulation process were investigated. Although all the experiments led to powder precipitation, the AMC encapsulation was achieved in only half of the cases, particularly when the lower drug:polymer ratios were assayed. In general, it was observed that the percentages of AMC present in the precipitates were higher on increasing the AMC:EC ratio. In these cases composites rather than encapsulates were obtained. The in vitro release profiles of the resulting materials were evaluated in order to ascertain whether composites can be used as encapsulated systems for drug delivery systems.

[Acute myelitis and Lyme disease]. / Myélite aiguë et neuroborréliose.

INTRODUCTION: Acute myelitis accounts for 4 to 5 percent of all cases of neuroborreliosis. In the literature, simultaneous spinal MRI and cerebrospinal fluid (CSF) investigations are presented for only 8 cases. We describe here 3 cases of acute Lyme myelitis. METHOD: In a cohort of 45 patients with neuroborreliosis, diagnosed between January 1998 and January 2005, 3 had acute myelitis. Clinical, biological and radiological data were studied. CASE REPORTS: The three patients had motor, sensorial and sphincter involvement. Extra-spinal involvement, such as fever and headache for one, facial nerve palsy for the second and subarachnoid hemorrhage for the third, was also noted. Pleocytosis varied from 10 to 520 white cells per mm3. Lyme serology was positive in CSF for all. Intrathecal anti-Borrelia antibody index was positive or intermediate for all three patients. Spinal cord MRI revealed a large hyperintense zone involving more than 3 vertebral segments. Myelitis was central, posterior or transverse in the axial plane. The clinical course was favorable after a three-week course of appropriate antibiotics. CONCLUSION: These 3 cases and the others from the literature show the diversity of the clinical and radiological features of acute myelitis: transverse, central or posterior myelitis. Thus, Lyme serology in CSF in indicated for patients presenting acute myelitis, particularly in endemic areas.

[Acute leukaemia in two multiple sclerosis patients treated with mitoxantrone]. / Leucémies aiguës chez deux patients atteints de sclérose en plaques et traités par mitoxantrone.

INTRODUCTION: Mitoxantrone (Mx) is used as a second-line treatment in multiple sclerosis. Since 1998, eight cases of acute leukemia (AL) have been described. We report two new cases of myeloid AL that occurred during treatment with Mx. OBSERVATIONS: The first case concerned a women who was treated with Mx for 3 months. In spite of a very low total dose (58.32 mg), she developed promyelocytic AL. The second patient died of myeloid AL, 27 months after the last injection of Mx. DISCUSSION: All the reported cases of AL occurring after Mx respond to the criteria of leukemia induced by anti-topoisomerases II. Epidemiological data and those from animal experiments suggest that Mx has direct role in the occurrence of leukemia. CONCLUSION: It must be remembered that even if the risk of Mx-induced leukemia is low, blood cell counts must be closely monitored for at least five years after the last injection of this treatment.

[Interferon beta1-a IM once weekly does not modify general psychological function in the first months after therapy in patients with relapsing-remitting multiple sclerosis]. / L'interféron beta1-a IM ne modifie pas le fonctionnement psychologique global de patients atteints de sclérose en plaques rémittente pendant les premiers mois de traitement.

INTRODUCTION: Psychological troubles are common in multiple sclerosis but their underlying etiology is still controversial. METHODS: The objective of this open, non comparative, multicenter study was to assess changes in global psychological functioning in new multiple sclerosis patients during the first 3 months of treatment with intramuscular interferon beta-1a once weekly (Avonex). This functioning was rated every 4 weeks with the GAF (Global Assessment Functioning) scale. Depression measured on MADRS (Montgomery & Asberg Depression Rating Scale), clinical global impression (CGI) on patients'psychological status and clinical as well as biological tolerance were also assessed every 4 weeks. RESULTS: Five hundred and ninety-nine patients (71.4 percent women), aged 39.4 years were included. No clinically significant difference in mean GAF score between baseline and the end of the first 3 months of interferon beta-1a IM treatment (main evaluation outcome) was found. Similar results were obtained on MADRS scale. CONCLUSION: No clinically significant alteration of global psychological functioning, including symptoms of depression, was observed during the first 3 months of treatment with interferon beta-1a IM.

Detection of pathological molecular alterations in scrapie-infected hamster brain by Fourier transform infrared (FT-IR) spectroscopy.

In this report a new approach for the identification of pathological changes in scrapie-infected Syrian hamster brains using Fourier transform infrared microspectroscopy is discussed. Using computer-based pattern recognition techniques and imaging, infrared maps with high structural contrast were obtained. This strategy permitted comparison of spectroscopic data from identical anatomical structures in scrapie-infected and control brains. Consistent alterations in membrane state-of-order, protein composition, carbohydrate and nucleic acid constituents were detected in scrapie-infected tissues. Cluster analysis performed on spectra of homogenized medulla oblongata and pons samples also reliably separated uninfected from infected specimens. This method provides a useful tool not only for the exploration of the disease process but also for the development of rapid diagnostic and screening techniques of transmissible spongiform encephalopathies.

[First experiences with the trauma radiologic PACS project at the University of Innsbruck Department of Radiology]. / Erste Erfahrungen mit dem unfallradiologischen PACS-Projekt an der Innsbrucker Universität für Radiodiagnostik.

Radiography in an emergency setting is a demanding task, in technical as well as in logistical terms. Rapid acquisition of high quality radiographs under difficult conditions, for example severely injured patients with multi-organ trauma is important. All image data and radiological reports must be transmitted to the trauma surgeon as soon as possible. To meet these needs with the promising means of modern X-ray technology, we decided to implement a completely digital X-ray division inside the new outpatient trauma department. In the setting of an outpatient emergency department digital radiography and PACS cannot be realised without problems. We present our first experience with the installation and 10 month filmless routine in the X-ray division for traumatology outpatients at the university of Innsbruck department of radiology.

Cerebral targeting indicates vagal spread of infection in hamsters fed with scrapie.

The pathogenesis of scrapie and other transmissible spongiform encephalopathies (TSEs) following oral uptake of agent is still poorly understood and can best be studied in mice and hamsters. The experiments described here further extend the understanding of the pathways along which infection spreads from the periphery to the brain after an oral challenge with scrapie. Using TSE-specific amyloid protein (TSE-AP, also called PrP) as a marker for infectivity, immunohistochemical evidence suggested that the first target area in the brain of hamsters orally infected with scrapie is the dorsal motor nucleus of the vagus nerve (DMNV), rapidly followed by the commissural solitary tract nucleus (SN). The cervical spinal cord was affected only after TSE-AP had been deposited in the DMNV, SN and other medullary target areas. For the first time, these results demonstrate conclusively that, in our animal model, initial infection of the brain after oral ingestion of scrapie agent occurs via the vagus nerve, rather than by spread along the spinal cord.

Evidence for an alternative direct route of access for the scrapie agent to the brain bypassing the spinal cord.

Scrapie is a disease which occurs naturally in sheep and goats and belongs to a group of neurodegenerative disorders known as transmissible spongiform encephalopathies, or TSEs. There is currently no cure for TSEs, and the causative agent has not yet been identified. Numerous experiments, however, have addressed the pathogenetic process following a TSE infection. In this paper we present a study of the spread of the scrapie agent after intraperitoneal infection of hamsters. The accumulation of TSE-specific amyloid protein, TSE-AP (also known as PrP), was used as a marker for infectivity. The data suggested three points of agent entry into the spinal cord: the most important one between thoracic vertebrae T7-9, and two minor ones in the lower cervical spinal cord and between vertebrae T13-L2. Further, strong evidence was found for the existence of a direct route of access to the brain which bypasses the spinal cord and most likely terminates in the medulla oblongata. The indication of an alternative pathway to the brain was confirmed by the data from orally infected hamsters. The spleen appeared to play a potential, but non-essential role in pathogenesis after intraperitoneal infection in our animal model.

Sequential appearance and accumulation of pathognomonic markers in the central nervous system of hamsters orally infected with scrapie.

Both infectivity and TSE-specific amyloid protein (also referred to as protease resistant- or prion protein, PrP) are pathognomonic markers for transmissible spongiform encephalopathies (TSE). This paper presents a new densitometric method for the quantification of TSE-specific amyloid protein and its application to studying the pathogenesis of scrapie in Syrian hamsters after infection with scrapie strain 263K. A first study established a close correlation between infectivity and TSE-specific amyloid protein with a doubling time of 2-2.6 days in the brain and cervical spinal cord for both markers. The ratio of infectivity and TSE-specific amyloid protein was relatively constant at a mean value of about 10(6) protein molecules per infectious unit during the course of infection. A subsequent study addressed the temporal-spatial spread of infection in the central nervous system by tracing the accumulation of the pathological protein. The pathogenetic process was first detected in the spinal cord between vertebrae T4 and T9, and then showed an anterograde and retrograde spread with a rate of 0.8-1.0 mm/day. There were also some indications for a possible alternative route of spread of infection from the periphery to the brain, other than via the spinal cord. Involvement of the spleen did not appear essential for the early pathogenesis in hamsters orally infected with the 263K strain of scrapie.

Western blot mapping of disease-specific amyloid in various animal species and humans with transmissible spongiform encephalopathies using a high-yield purification method.

SAF-protein, an amyloid, is the main constituent of scrapie-associated fibrils (SAF) and a specific marker for transmissible spongiform encephalopathies (TSE). Using an improved extraction method and Western blot detection, the disease-specific amyloid was found in various parts of the central nervous system of hamsters orally infected with scrapie, of squirrel monkeys orally infected with kuru, sporadic Creutzfeldt-Jakob disease (CJD) and scrapie, of human patients with sporadic CJD, of a sheep with natural scrapie and of a cow with bovine spongiform encephalopathy (BSE). In human CJD samples, the concentration of TSE-specific amyloid was estimated to be 1000- to 10 000-fold lower than in the central nervous system of hamsters with scrapie. The extraction method has a yield of 70% and allows Western blot detection of the TSE-specific amyloid in samples representing 1-10 micrograms of brain tissue from intracerebrally infected hamsters, as well as in individual spleens from hamsters with terminal scrapie infected by the intracerebral, oral or intraperitoneal route. A 20-100 mg sample of material is sufficient for the extraction of the pathological protein from different rodent, monkey, ovine, bovine and human tissues. The results reported here demonstrate the potential suitability of the method for the routine diagnosis of TSE as well as for the detailed analysis of distribution patterns of the TSE-specific amyloid in experimental approaches to the investigation of these diseases.

Small virus-like structure in brains from cases of sporadic and familial Creutzfeldt-Jakob disease.

We have previously observed small virus-like particles in the brain of hamsters with experimental scrapie. Here we report that small virus-like structures can be isolated from brains of patients with Creutzfeldt-Jakob disease and identified by electronmicroscopy.

[A new treatment of Huntington's chorea. Report of three cases (author's transl)]. / Un nouveau traitement de la chorée de Huntington. A propos de trois observations.

The authors report their experience in three cases of Huntington's chorea treated with tiapride (Tiapridal). A real efficacy and an interesting effect of the drug were observed on choreic hyperkinesias. No regression of the other symptoms were noted and the course of the disease not changed.

[Effect of tiapride on the side effects of cerebrospinal fluid depletions in spinal puncture, pneumoencephalography and air myelography]. / Action du tiapride sur les eefets secondaires des soustractins de liquide céphalo-rachidien par ponction lombaire, encéphalographie et myélographie gazeuse.

The authors report their experience of the treatment post-cerebrospinal fluid loss syndrom, following subtraction by lumbar puncture, pneumoencephalography and air myelography. The study of 70 patients, divided in two equal groups, one receiving classic therapy, one receiving tiapride, a new molecule of original conception, lead to emphasize the interest of this drug. Tolerance in general is good, despite the administration of high doses and effects on the syndrom are positive and remarkable in preventive and curative treatment.