Recombinant vaccinia virus: immunization against multiple pathogens.

The coding sequences for the hepatitis B virus surface antigen, the herpes simplex virus glycoprotein D, and the influenza virus hemagglutinin were inserted into a single vaccinia virus genome. Rabbits inoculated intravenously or intradermally with this polyvalent vaccinia virus recombinant produced antibodies reactive to all three authentic foreign antigens. In addition, the feasibility of multiple rounds of vaccination with recombinant vaccinia virus was demonstrated.

Driving AMPA receptors into synapses by LTP and CaMKII: requirement for GluR1 and PDZ domain interaction.

To elucidate mechanisms that control and execute activity-dependent synaptic plasticity, alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptors (AMPA-Rs) with an electrophysiological tag were expressed in rat hippocampal neurons. Long-term potentiation (LTP) or increased activity of the calcium/calmodulin-dependent protein kinase II (CaMKII) induced delivery of tagged AMPA-Rs into synapses. This effect was not diminished by mutating the CaMKII phosphorylation site on the GluR1 AMPA-R subunit, but was blocked by mutating a predicted PDZ domain interaction site. These results show that LTP and CaMKII activity drive AMPA-Rs to synapses by a mechanism that requires the association between GluR1 and a PDZ domain protein.

Transient oxygen-glucose deprivation induces rapid morphological changes in rat hippocampal dendrites.

Previous studies have revealed that pyramidal neurons in the CA1 region of the hippocampus are extremely susceptible to ischemia-induced cell damage and undergo selective degeneration 2-4 days after the insult. Little is known about early morphological changes in neurons occurring immediately after ischemic insult. Using two-photon laser scanning microscopy we monitored dendritic morphology of cells expressing enhanced green fluorescent protein in response to a transient hypoxic-ischemic episode in organotypic hippocampal slice preparations. This type of vital imaging provides direct evidence of dendritic rearrangements in rat CA1 pyramidal neurons occurring as soon as 20 min after oxygen-glucose deprivation. We propose that dendritic reorganization, resembling that occurring after tetanic stimulation, may be an early stage response to compensate the loss of synapses caused by ischemia-induced neuronal injury.

Isothermal annealing kinetics of X-irradiated pyrene by electron paramagnetic resonance.

The annealing behavior of X-irradiated stable free radicals found in pyrene (C16H10) single crystals was studied by electron paramagnetic resonance. Two processes of thermal decay kinetics were found, both with the same activation energy: 1.9 +/- 0.1 eV.

Endogenous APP derivatives oppositely modulate apoptosis through an autocrine loop.

We have recently shown that, in rat cerebellar granule cells, apoptosis triggered by KCl deprivation is associated with an amyloidogenic shift in the processing of amyloid precursor protein (APP) resulting in an increase of amyloid beta-protein (A beta) secretion. To further investigate this issue we studied the relationship between secretion of APP metabolites (A beta, APPs) and neuronal degeneration. We postulated that the endogenous products of the APP metabolism may modulate neuronal survival by an autocrine loop. Treatment of cerebellar granule cells with various antibodies raised against different epitopes of APPs and A beta oppositely modulates low potassium apoptotic cell death. Antibodies specific for the N-terminal of A beta (4G8, 6E10, R3659) increased neuronal survival by 30% over controls. On the contrary, treatment of cultures undergoing apoptosis with the monoclonal antibody 22C11 directed against the APP N-terminus reduced neuronal survival by 53%, suggesting that endogenous alpha-APPs contribute to neuronal survival. Moreover low KCl culture medium, conditioned by cerebellar granule cells, attenuated the apoptotic process. This anti-apoptotic effect was abolished by removal of APPs from the conditioned medium. Western blotting of APPs removed from the conditioned medium confirmed the presence of alpha-APPs. These data indicate that APP cleavage products oppositely modulate neuronal survival through an autocrine loop and further strengthen an Alzheimer's disease pathogenetic scheme based on altered metabolism of APP.

Chemo-radiotherapeutic management of advanced head and neck cancer.

Stage III and IV head and neck cancer patients usually achieve poor therapeutic results after radiotherapy. The search for more effective treatment modalities is justified, provided that tolerance is not lower than that of the usual radiation therapy schedules. Chemotherapy has been shown to be effective, and cis-platinum and bleomycin based treatments are reported to result in objective remissions in a substantial proportion of cases. There is also experimental evidence of a radiosensitizing activity of cis-platinum. Thirty-five locally advanced head and neck cancer patients were given combined chemo-radiotherapeutic treatment consisting of a cis-platinum and bleomycin induction followed by a standard radiotherapy course integrated with weekly administrations of cis-platinum. Before radiotherapy, an overall 48.5% objective remission rate was achieved, that rose to 85.8% after completion of the entire treatment, with a 31.5% complete response rate. Incidence and severity of radiation mucositis seem not to be increased, and systemic toxicity is very low, with the adopted drug administration schedule. Overall results do not show any obvious superiority over those of radiotherapy alone.

Aspecific membranous laryngitis after infectious mononucleosis.

Aspecific membranous laryngitis is an unusual but very serious complication of viral infections. Here, we report the uncommon finding of infectious mononucleosis characterized by aspecific membranous laryngitis with fever, dysphonia and severe dyspnea in a 12-year-old girl. Endoscopy showed mucopus and sloughed epithelium forming a pseudomembrane covering almost all the supraglottal region and a supraglottal swelling including the epiglottis and arytenoids. The importance of suspecting diphtheria, epiglottitis, viral or bacterial croup and laringo-tracheo-bronchitis and including them in the differential diagnosis is emphasized.

[Four years of clinical experience with the cardio-eurhythmic action of verapamil in intravenous administration]. / Quattro anni di esperienze cliniche sull'azione cardioeuritmizzante del verapamil per somministrazione endovenosa

Personal clinical experience using Verapamil intravenously in 200 patients with a number of arrhythmia conditions is reported. The effectiveness of the drug in controlling supraventricular paroxysmal tachycardia and high ventricular frequency atrial fibrillation in particular is pointed out. Good results were also obtained in atrial flutter, in sinus tachycardia, in extrasystole conditions and, at times, in ventricular paroxysmal tachycardia. Clinical experience limits contraindications to atrioventricular block, severe shock, excessive digitalization, and the associated use of beta block substances.

[Educating patients about heart failure in community hospitals: it is possible...]. / Education des patients concernant l'insuffisance cardiaque en centre hospitalier général: c'est possible....

Prognosis for heart failure is linked to patient's compliance. Compliance is also dependent from patient education about his disease and treatment. Therapeutic education could be done in a community hospital but needs a lot of time. However, therapeutic education for heart failure patients becomes more and more essential in clinical practice and improves patient knowledge and implication and hospitalization duration.

[Nasal dimorphism and respiratory dysfunction. Preoperative selection of patients and follow-up using computerized rhinomanometry]. / Dismorfismi nasali e disfunzione respiratoria. Selezione preoperatoria dei pazienti e follow-up mediante rinomanometria computerizzata.

Indications and results of corrective nasal surgery are at times uncertain with the traditional clinical evaluation. To find more certain parameters a study was made with active anterior computerized rhinomanometry (C.R.) pre- and post-operatively in 50 patients randomly chosen from those proposed for rhinoseptoplasty during 1990. The level of total basal resistance (TR) and total residual resistance after pharmacological decongestion were used as objective indicators of respiratory stenosis. Clinically these patients showed some degree of nasal deformity, usually associated with septal deviation. Difficulty in breathing did not always correspond to the level of TR recorded. At times habit or psychological factors related to nasal aesthetics could play an important role. Using CR it was possible to divide the patients into three categories: a) the first (9 patients with normal total basal resistance) required treatment for exclusively aesthetic reasons; b) the second (18 patients with increased basal TR but normal residual TR) required treatment of the conchae and medical therapy; c) the third (23 patients with increased basal and residual TR) had the broadest functional and aesthetic indications. Six months after surgery normal residual TR was found in 96% of these cases. Only 12% of the patients were functionally unsatisfactory, with residual anatomical alteration (4%), phlogosis (4%) or sensations "sine materia" (4%). The present experience confirms the value of CR as an objective test for surgical selection and functional results.

[Nasal respiratory stenosis and maxillary hypoplasia. Changes after orthodontic treatment with rapid palatal expansion]. / Stenosi respiratoria nasale ed ipoplasia mascellare. Modificazioni dopo trattamento ortodontico con espansione rapida palatale.

The relationship between hypoplasia of the upper maxillary bone and nasal respiratory insufficiency in a group of twenty infants with malocclusion being treated by rapid maxillary expansion (RME) were studied. Prior to treatment all patients presented endognatia with discrepancies of from -4 to -7 mm in the transverse basal skeleton. These were often associated with adenoid hypertrophy (70% of the cases), increased total nasal resistance (70%), oral respiration (80%) and middle ear diseases (30%). RME led to resolution of occlusion alterations in all cases and often also brought about a regression in adenoid hypertrophy (57% of the cases), normalization of the total nasal resistance (70%) and respiration (80%). These effects were achieved alone without association with any other form of medical or surgical E.N.T. treatment. The functional results confirmed by the radiological and clinical findings indicate an increase in the diameters of the nasal fossa and in the distance between the canines, between premolars and between molars as well as reduction in adenoid vegetation and in the diffuse hypertrophic tissues lining the naso-pharyngeal space. Nonetheless, hypoplasia of the upper maxillary bone and nasal respiratory insufficiency remain strictly linked and are bound to a variable, and at times uncertain, cause-effect relationship. Is nasal stenosis the moving force of maxillary-mandibular dysmorphism and gnatological dysfunction or does it result from an overall genetic conditioning of facial skeleton development? During their vast experience in adenoid and metadenoid pathologies in infancy the authors have, at times, observed significant maxillo-facial dysmorphisms. They have likewise found that "facies adenoidea" were not always associated with hypertrophy of the pharyngeal tonsil.(ABSTRACT TRUNCATED AT 250 WORDS)

[Otorhinological evaluations of patients undergoing rapid disjunction of the median palatine suture]. / Valutazioni otorinologiche in pazienti sottoposti a disgiunzione rapida della sutura mediana palatina.

Seven young patients, who had been diagnosed to be oral breathers by an orthodontist, have been submitted to an ETN specialist examination, before and after the rapid expansion of the mid-palatal suture. Five of these patients had an actual reduction of nasal breathing capacity. Four patients presented a significant enlargement of the adenoids. One patient showed a transmission auditive deficiency. The ETN examination, two months after the maxillary expansion, has permitted to find out that all the patients who had an impaired nasal breathing before the maxillary expansion, had normalized their respiratory capacity. Moreover, those subjects who had enlarged adenoids, showed a normal adenoids volume in the second ETN examination. Finally also the patient with an auditive deficiency presented a normalization of this function at the second ETN examination.

[Morphofunctional correlations in children with upper maxillary endognathia]. / Corrélations morpho-fonctionnelles chez les enfants atteints d'endognathie maxillaire supérieure.

In this study 23 oral breathing children suffering from maxillary hypoplasia (endognathia associated with skeletal class II or III), selected for rapid maxillary expansion (RME) have been investigated by active anterior rhinometry. None of these patients presented O.R.L. pathologies during clinical examination except for some sporadic cases of adenoid hypertrophy (5 cases). Rhinomanometric and cephalometric examinations carried out before and after RME treatment showed a good correlation between the nasal respiratory function parameters and the structural cephalometric elements investigated by means of teleradiography. In particular, an important reduction in nasal respiratory resistance in all patients with conversion from oral to nasal respiration in the majority of cases corresponds, together with cross-bite resolution, to increased transversal dimension of the maxilla produced by RME. A clear regression in adenoid hypertrophy, where present, is also noted without any type of O.R.L. treatment. The improved respiratory situation could therefore produce benefits on the trophism of the nasal mucous and the lymphatic rhinopharyngeal tissue. Agreement between clinical, radiological and rhinomanometric findings confirm the usefulness of this method in diagnosing and following-up patients with this problem.

MCI patients declining and not-declining at mid-term follow-up: FDG-PET findings.

Patients with Mild Cognitive Impairment (MCI) not converted to dementia at one to three years follow-up represent a heterogeneous group across studies, by including 'late converters' but also patients without any neurodegenerative disease. We tested the hypothesis that the combination of memory and brain metabolic assessment could identify subgroups of memory decliners (MCI/Decl) and non-decliners (MCI/noDecl) before a long follow-up time is available. From twenty-nine patients with amnestic MCI (aMCI) at baseline, three groups were identified at follow-up: 10 patients who converted to AD (MCI/AD); 10 patients either showing episodic memory worsening or reaching the floor effect on memory and declining in other key tests (MCI/Decl) and 9 patients showing no memory worsening or even improvement (MCI/noDecl). They were compared with a group of fourteen elderly controls (CTR) by means of basal FDG-PET voxel-based analysis (SPM2). Two hypometabolic clusters were found in MCI/AD versus CTR, including the bilateral posterior cingulate cortex, the left parietal precuneus and the left fusiform gyrus. MCI/AD showed also a large hypometabolic region, mainly including the left medium and superior temporal gyri and inferior parietal lobule, when compared to MCI/noDecl. The MCI/Decl showed a hypometabolic region in the left medial temporal lobe versus both CTR (hippocampus) and MCI/noDecl (parahippocampal gyrus and hippocampus). No significant difference was found in the comparison between CTR and MCI/noDecl, neither in the comparison between MCI/Decl and MCI/AD. Thus, non converter MCI patients comprised a sub-group of 'decliners' with AD-like metabolic and cognitive patterns, likely including 'late converters', and a sub-group lacking this pattern, with stable or improving memory function and a brain metabolic picture similar to that in healthy controls. Combining neuropsychological and FDG-PET information could be used for prognostic purposes in aMCI patients at medium-term follow-up.