231 research outputs found
Zonisamide (CI-912) and Cognition: Results from Preliminary Study
Nine patients with refractory partial seizures were evaluated in a pilot study of a new anticonvulsant compound, zonisamide (l,2-benzisoxazole-3-methane-sulfonamide; CI-912). Cognitive functioning was evaluated prior to treatment with zonisamide and repeated after 12 and 24 weeks of treatment with zonisamide. At minimum steady-state plasma concentrations >30 jjug/ml, zonisamide appeared to affect specific cognitive functions such as acquisition and consolidation of new information. Previously learned material, such as vocabulary, and psychomotor performance were not affected. Verbal learning was affected, while visual-perceptual learning was unimpaired. These cognitive effects were observed in the absence of the usual clinical signs and symptoms of toxicity. A linear relationship was found between impairment of cognitive abilities and the minimum plasma concentration (r = -0.73; p < 0.05). Findings also suggest the development of tolerance to the adverse cognitive effects. RESUMEN En un estudio piloto realizado para valorar la eficacia de la zonisamida (1,2-Bencisoxazol-melanosulfonamida [CI-912]), un nuevo compuesto anticonvulsive se han evaluado unos 9 pa-cientes con ataques parciales refractarios al tratamiento. Se de-terminĂ la capacidad cognitiva anterior al tratamiento y se re-pitio 12 y 24 semanas despuĂs del tratamiento con zonisamida. Con concentraciones plasmĂticas mĂnimas estables per encima de 30 mcg/ml, la zonisamida afectĂ las funciones cognitives especĂficas tales como la adquisiciĂn y consolidaciĂn de nueva informaciĂn. El material aprendido previamente, tal como el vo-cabulario, y las funciones psicomotoras no se afectaron. El aprendizaje verbal se modificĂ mientras que el aprendizaje visuo-perfectivo no se modificĂ. Estos efectos cognitivos se ob-servaron en ausencia de los habituales signos y sĂntomas clĂnicos de toxicidad. Se encontrĂ una relaciĂn lineal entre la alteraciĂn de las posibilidades cognitivas y la concentraciĂn plasmĂtica mĂnima (r = -0.73, p < 0.05). Estos hallazgos tambiĂn sugieren el desarrollo de una tolerancia a los efectos cognitivos adversos. ZUSAMMENFASSUNG 9 Patienten mit rezidivierenden Partial-AnfĂllen wurden in einer Pilotstudie mit einer neuen antiepileptischen Substanz: Zonisamide untersucht. Die kognitiven Funktionen wurden vor der Behandlung mit Zonisamide geprtĂft und nach 12 und 24 Therapiewochen mit Zonisamide wiederholt. Bei einem Min-destplasmaspiegel von 30 mcg/ml schien Zonisamide spezifische kognitive FĂhigkeiten wie Aufnahme und Speicherung neuer In-formationen zu beeintrĂchtigen. Vorher gelernte Inhalte wie sprachliche und psychomotorische Fertigkeiten wurden nicht beeinfluĂt. Verbales Lernen war ebenfalls betroffen, wĂhrend visuell, perzeptives Lernen nicht verschlechtert war. Diese BeeintrĂchtigung kognitiver Funktionen wurde bei fehlenden klinischen Intoxikationszeichen beobachtet. Eine lineare Bezie-hung zwischen Verschlechterung kognitiver FĂhigkeiten und Mindest-Plasmaspiegel konnte hergestellt werden (r = -0,73; p < 0,05). Allerdings lassen die Ergebnisse auch auf eine GewĂhnung an diese unerwĂnschten Nebenwirkungen schlieĂen.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65995/1/j.1528-1157.1987.tb03624.x.pd
Pilot Study of Zonisamide (1,2-Benzisoxazole-3-methanesulfonamide) in Patients with Refractory Partial Seizures
A new anticonvulsant compound, zonisamide (1,2 benzioxazole-methanesulfonamide), was studied in 10 adults with medically refractory partial seizures. Following a single oral dose of 400 mg, peak plasma levels occurred an average of 2.8 h after dosing, and the mean clearance from plasma was 2.34 L/h. Whole blood concentrations were high than plasma concentrations because of red blood cell binding. steady-state plasma concentrations were high than predicted from a linear kinetic model. In most patients, seizure frequency was reduced after zonisamide was substituted for a standard antiepileptic drug. Dose-related reversible side effects in the central nervous and gastrointestinal system were observed. Most patients tolerated doses between 5.2 and 12.5 mg/kg/day. RĂSUMĂ Un nouveau produit anticonvulsivant, le zonisamide (1,2 benziosoxazole-methylsulfonamide) a ĂtĂ administrĂĂ 10 adultes atteints de crises partielles non contrĂlĂes par le traitement mĂdical. AprĂs une dose unique orale de 400 mg, le pic du taux plasmatique survient en moyenne 2 h 1/2 aprĂs l'ingestion, et la clairance plasmatique moyenne est de 2,34 litres par heure. les concentrations sanguines totales sont plus ĂlevĂes que les concentrations plasmatiques, en raison de la liaison aux globules rouges, les concentrations plasmatiques Ă l'Ătat d'equilibre sont plus ĂlevĂes que celles que l'on peut dĂdurie d'un modĂle de cinĂtique linĂaire. Chez la plupart des patients, la frĂquence des crises a ĂtĂrĂduite par la substitution du zonisamide au traitement antiĂpileptique standard. Des effets secondaires doses-dĂpendants et rĂversibles ont ĂtĂ observĂs au niveau du systĂme nerveux central et du tube digestif. La plupart des patients ont tolĂrĂ des doses entre 5,2 et 12,5 mg/kg de poids par jour. RESUMEN En 10 adultos con ataques parciales refractarios a1 tratamiento mĂdico, se ha estudiado la acciĂn de un nuevo compuesto anticonvulsivo, la zonisamida (1,2 benzisoxazol-metanosulfonamida). Tras la ingestiĂn de una sola dosis oral de 400 mg., se alcanzaron los niveles pico en plasma en un promedio de 2.8 horas desputs de la dosis y el aclaramiento medio del plasma fuĂ de 2, 34 litros/hora. Las concentraciones en sangre fueron mĂs altas que las plasmĂticas debido a que la medicaciĂn se ligaba a los hematies. Las concentraciones plasmĂticas estables fueron mĂs altas que las previsibles de un modelo cinĂtico lineal. En la mayorĂa de los pacientes la frecuencia de los ataques se redujo despuĂs de cambiar la medicaciĂn antiepilĂptica standard por la zonisamida. TambiĂn se observaron los efectos colaterales sobre el tracto gastrointestinal y el sistema nervioso central que estaban relacionadas con la dosis y eran reversibles. La mayor parte de los pacientes tolerĂ dosis que oscilaban entre 5.2 y 12.5 mg/kg/dĂa. ZUSAMMENFASSUNG Ein neues Antikonvulsivum, Zonisamid (1,2 Benzisoxazol-Methansulfonamid) wurde bei 10 Envachsenen mit therapieresistenten PartialanfĂllen gesucht. Nach einer oralen Einzeldosis von 400 mg wurden Plasmaspitzenwerte im Durchschnitt nach 2, 8 Stunden erreicht. Die mittlere Clearance aus dem Plasma betrug 2, 34 L/Stunde. Ganzblutkonzentrationen waren hĂher als Plasmakonzentrationen aufgrund der Bindung an die roten BlutkĂrperchen. Die steady-state Plasmakonzentrationen waren hĂher als bei einem linearen kinetischen Modell zu envarten. Bei den meisten Patienten konnte die Anfallsfrequenz nach Substitution eines Standardantiepileptikums durch Zonisamid reduziert werden. Es bestanden dosisabhĂngige, reversible, zentral-nervĂse und gastrointestinale Nebenwirkungen. Die meisten Patienten tolerierten Dosen zwischen 5, 2 und 12, 5 mg/kg/Tag.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65938/1/j.1528-1157.1985.tb05407.x.pd
Post-traumatic diaphragma hernia
W niniejszym artykule przedstawiono przypadek 22-letniego mÄĹźczyzny z pourazowÄ
przepuklinÄ
przeponowÄ
,
do powstania ktĂłrej doszĹo w nastÄpstwie tÄpego urazu klatki piersiowej i nadbrzusza. Na podstawie
przeprowadzonych badaĹ diagnostycznych rozpoznano pourazowÄ
przepuklinÄ przeponowÄ
lewostronnÄ
.
Chorego operowano w trybie planowym. W trakcie laparotomii stwierdzono rozerwanie lewej kopuĹy przepony,
przez ktĂłre ĹźoĹÄ
dek zostaĹ w wiÄkszej czÄĹci przemieszczony do klatki piersiowej. ĹťoĹÄ
dek odprowadzono
do jamy brzusznej i wykonano plastykÄ przepukliny pourazowej przepony, zeszywajÄ
c jÄ
przy rozprÄĹźonym
pĹucu. W przebiegu pooperacyjnym wystÄ
piĹa odma opĹucnowa lewostronna, ktĂłrÄ
leczono, wykonujÄ
c
drenaĹź lewej jamy opĹucnowej. DrenaĹź usuniÄto w 4. dobie po operacji, po uzyskaniu upowietrznienia
dolnego pola lewego pĹuca. Pacjenta wypisano z kliniki w 5. dobie po operacji w stanie dobrym.A case of a 22 year-old male with post-traumatic diaphragmatic hernia resulting from a blunt injury of
chest and epigastrium is presented. Based on diagnostic procedures, left-sided posttraumatic diaphragmatic
hernia was diagnosed. A scheduled surgical procedure was performed in the patient. A laparotomy
revealed a rupture of the left diaphragmatic dome which allowed the displacement of the major part of
the stomach to the thoracic cavity. The stomach was replaced in the abdominal cavity and a hernioplasty
was performed by suturing the diaphragm while keeping the lungs expanded. During the postoperative
course, left-sided pneumothorax occurred which was treated with left thoracic cavity drainage. The drain
was removed on the fourth day after the operation when aeration of the lower field of the left lung was
achieved. The patient was discharged in good condition on the fifth day after operation
Moment inversion problem for piecewise D-finite functions
We consider the problem of exact reconstruction of univariate functions with
jump discontinuities at unknown positions from their moments. These functions
are assumed to satisfy an a priori unknown linear homogeneous differential
equation with polynomial coefficients on each continuity interval. Therefore,
they may be specified by a finite amount of information. This reconstruction
problem has practical importance in Signal Processing and other applications.
It is somewhat of a ``folklore'' that the sequence of the moments of such
``piecewise D-finite''functions satisfies a linear recurrence relation of
bounded order and degree. We derive this recurrence relation explicitly. It
turns out that the coefficients of the differential operator which annihilates
every piece of the function, as well as the locations of the discontinuities,
appear in this recurrence in a precisely controlled manner. This leads to the
formulation of a generic algorithm for reconstructing a piecewise D-finite
function from its moments. We investigate the conditions for solvability of the
resulting linear systems in the general case, as well as analyze a few
particular examples. We provide results of numerical simulations for several
types of signals, which test the sensitivity of the proposed algorithm to
noise
Local modes, phonons, and mass transport in solid He
We propose a model to treat the local motion of atoms in solid He as a
local mode. In this model, the solid is assumed to be described by the Self
Consistent Harmonic approximation, combined with an array of local modes. We
show that in the bcc phase the atomic local motion is highly directional and
correlated, while in the hcp phase there is no such correlation. The correlated
motion in the bcc phase leads to a strong hybridization of the local modes with
the T phonon branch, which becomes much softer than that obtained
through a Self Consistent Harmonic calculation, in agreement with experiment.
In addition we predict a high energy excitation branch which is important for
self-diffusion. Both the hybridization and the presence of a high energy branch
are a consequence of the correlation, and appear only in the bcc phase. We
suggest that the local modes can play the role in mass transport usually
attributed to point defects (vacancies). Our approach offers a more overall
consistent picture than obtained using vacancies as the predominant point
defect. In particular, we show that our approach resolves the long standing
controversy regarding the contribution of point defects to the specific heat of
solid He.Comment: 10 pages, 10 figure
Distinct RNA profiles in subpopulations of extracellular vesicles: apoptotic bodies, microvesicles and exosomes
Introduction: In recent years, there has been an exponential increase in the number of studies aiming to understand the biology of exosomes, as well as other extracellular vesicles. However, classification of membrane vesicles and the appropriate protocols for their isolation are still under intense discussion and investigation. When isolating vesicles, it is crucial to use systems that are able to separate them, to avoid cross-contamination. Method: EVs released from three different kinds of cell lines: HMC-1, TF-1 and BV-2 were isolated using two centrifugation-based protocols. In protocol 1, apoptotic bodies were collected at 2,000×g, followed by filtering the supernatant through 0.8 µm pores and pelleting of microvesicles at 12,200×g. In protocol 2, apoptotic bodies and microvesicles were collected together at 16,500×g, followed by filtering of the supernatant through 0.2 µm pores and pelleting of exosomes at 120,000×g. Extracellular vesicles were analyzed by transmission electron microscopy, flow cytometry and the RNA profiles were investigated using a Bioanalyzer®. Results: RNA profiles showed that ribosomal RNA was primary detectable in apoptotic bodies and smaller RNAs without prominent ribosomal RNA peaks in exosomes. In contrast, microvesicles contained little or no RNA except for microvesicles collected from TF-1 cell cultures. The different vesicle pellets showed highly different distribution of size, shape and electron density with typical apoptotic body, microvesicle and exosome characteristics when analyzed by transmission electron microscopy. Flow cytometry revealed the presence of CD63 and CD81 in all vesicles investigated, as well as CD9 except in the TF-1-derived vesicles, as these cells do not express CD9. Conclusions: Our results demonstrate that centrifugation-based protocols are simple and fast systems to distinguish subpopulations of extracellular vesicles. Different vesicles show different RNA profiles and morphological characteristics, but they are indistinguishable using CD63-coated beads for flow cytometry analysis
Can we continue research in splenectomized dogs? Mycoplasma haemocanis: Old problem - New insight
We report the appearance of a Mycoplasma haemocanis infection in laboratory dogs, which has been reported previously, yet, never before in Europe. Outbreak of the disease was triggered by a splenectomy intended to prepare the dogs for a hemorrhagic shock study. The clinical course of the dogs was dramatic including anorexia and hemolytic anemia. Treatment included allogeneic transfusion, prednisone, and oxytetracycline. Systematic follow-up (n=12, blood smears, antibody testing and specific polymerase chain reaction) gives clear evidence that persistent eradication of M. haemocanis is unlikely. We, therefore, had to abandon the intended shock study. In the absence of effective surveillance and screening for M. haemocanis, the question arises whether it is prudent to continue shock research in splenectomized dogs. Copyright (C) 2004 S. Karger AG, Basel
Renal cell carcinoma metastasizing to solitary fibrous tumor of the pleura: a case report
<p>Abstract</p> <p>Introduction</p> <p>A tumor metastasizing to another malignancy is an uncommon phenomenon. Since it was first described in 1902, there have been fewer than 200 cases reported in the literature, with lung cancer metastasizing to renal cell carcinoma being the most frequently described pattern. Here we report a case of a solitary fibrous tumor of the lung acting as the recipient for a renal cell carcinoma. To our knowledge, this is the first reported case of such a combination and the second case involving a solitary fibrous tumor.</p> <p>Case presentation</p> <p>A 58-year-old Caucasian man who developed a persistent dry cough presented to our hospital. Imaging studies revealed a large pleural-based mass in the left lung. A biopsy of the mass showed a spindle-cell lesion consistent with a solitary fibrous tumor. The patient underwent surgical excision of the 13 cm mass. The pathological examination confirmed the diagnosis of a solitary fibrous tumor but also demonstrated discrete foci of metastatic renal cell carcinoma. Until that point, a primary renal cell carcinoma tissue diagnosis had not been made and the initial radiological work-up was inconclusive.</p> <p>Conclusion</p> <p>Awareness of the unusual phenomenon of tumor-to-tumor metastasis is important for practicing surgical pathologists, particularly in the evaluation of a mass lesion showing bimodal histology. This case also highlights the importance of careful examination of surgical specimens, as minute and unusual findings can direct patient care.</p
Protection against glucose-induced neuronal death by NAAG and GCP II inhibition is regulated by mGluR3
Glutamate carboxypeptidase II (GCP II) inhibition has previously been shown to be protective against long-term neuropathy in diabetic animals. In the current study, we have determined that the GCP II inhibitor 2-(phosphonomethyl) pentanedioic acid (2-PMPA) is protective against glucose-induced programmed cell death (PCD) and neurite degeneration in dorsal root ganglion (DRG) neurons in a cell culture model of diabetic neuropathy. In this model, inhibition of caspase activation is mediated through the group II metabotropic glutamate receptor, mGluR3. 2-PMPA neuroprotection is completely reversed by the mGluR3 antagonist (S)-Îą-ethylglutamic acid (EGLU). In contrast, group I and III mGluR inhibitors have no effect on 2-PMPA neuroprotection. Furthermore, we show that two mGluR3 agonists, the direct agonist (2 R ,4 R )-4-aminopyrrolidine-2, 4-dicarboxylate (APDC) and N -acetyl-aspartyl-glutamate (NAAG) provide protection to neurons exposed to high glucose conditions, consistent with the concept that 2-PMPA neuroprotection is mediated by increased NAAG activity. Inhibition of GCP II or mGluR3 may represent a novel mechanism to treat neuronal degeneration under high-glucose conditions.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65724/1/j.1471-4159.2003.02321.x.pd
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