Biomedical subjects

A Rossi

Publications and source records attributed to A Rossi.

At least 19 recordsLinked to original sources

PubMed2026

CRISPR/Cpf1-mediated knockout of FLG in human induced pluripotent stem cells generates a model for studying epidermal barrier dysfunction.

Loss of filaggrin (FLG) function impairs skin barrier formation and contributes to common inflammatory skin diseases. In this study, we established a FLG knockout human induced pluripotent stem cell (iPSC) line based on KOLF2.1 J using CRISPR/Cas12a (Cpf1)-mediated genome editing. A guide RNA targeting exon 2 introduced a homozygous mutation, which was confirmed by sequencing. The edited cells maintained typical pluripotent stem cell morphology, expressed key undifferentiated markers, and retained the ability to differentiate into all three germ layers. Karyotype and copy number variation (CNV) analyses confirmed genomic stability and parental origin; the cells were free of mycoplasma. This cell line enables studies of FLG-associated skin biology and pathology.

Humans↗

PubMed2006

Is the human masticatory system devoid of recurrent inhibition?

The aim of the present study was to investigate the existence or otherwise of a functional recurrent inhibitory system (Renshaw cell system) in the motoneurons that innervate human masticatory muscles. In a previous study, L: -acetylcarnitine (L: -Ac), a substance known to potentiate recurrent inhibition in humans was found to alter, in a specific way, the discharge variability, and the synchronous activity of motor units depending on the presence or absence of recurrent inhibition in the corresponding motoneuron pool. Using a similar paradigm, we have recorded the tonic discharge activity of motor unit pairs from the masseter muscle during voluntary isometric contraction while subjects were undergoing continuous intravenous saline (SAL, NaCl 0.9%) perfusion. Following a brief baseline-recording period, the subjects were given a test injection of either L: -Ac or isotonic saline (SAL) in a double blind manner. The variability, synchronization, and coherence between the motor unit discharges were analysed during three successive periods: pre-injection, during injection, and post-injection, each lasting 2-3 min. Neither L: -Ac nor SAL injection induced a significant change in the inter-spike interval (ISI) or the coefficient of variation of the ISIs in the motor units tested. There were also no significant changes in the pattern of synchronous activity or in the coherence, which reflects the common frequency content of the unit discharges. Reminiscent of what had been observed previously with motoneurons without recurrent inhibition in the Abductor Digitorum Minimi muscle, the lack of effects of L: -Ac injection on the firing behaviour of masseter motoneurons may suggest that classical Renshaw cell inhibition is lacking in this motoneuron pool.

Acetylcarnitine↗

PubMed2006

Changes in the recruitment curve of the soleus H-reflex associated with chronic low back pain.

OBJECTIVE: We investigated whether patients with chronic low back pain (CLBP) manifest changes in the excitability of the soleus H-reflex. METHODS: H-reflex stimulus-response curve was studied in 14 CLBP patients and 14 age-matched healthy subjects. H-threshold, H-maximum size, H-steepness and H-latency were determined for both legs. Homosynaptic depression (HD), following a train of H-reflexes, and presynaptic inhibition (PI) from flexor afferents onto soleus Ia afferents were also evaluated. RESULTS: H-threshold was significantly increased, H-size as a function of stimulus intensity was significantly different, and H-recruitment curve steepness was significantly lower in CLBP patients compared to healthy subjects. No significant difference in the amount of HD and PI of the H-reflex was found between the two groups. H-latency and Hmax/Mmax ratio was comparable between the subjects groups. CONCLUSIONS: In CLBP there is a reduced excitability of group Ia afferent fibres from the soleus muscle to which presynaptic factors do not seem to contribute and that presumably depend on changes in the peripheral sensory input. SIGNIFICANCE: Changes in H-reflex excitability may underlie a decrease in the gain of a peripheral sensor in CLBP. Estimation of soleus H-threshold and H-recruitment curve may contribute to the diagnostic evaluation of CLBP and may be used to monitor the efficacy of treatment.

Adult↗

PubMed2006

Gloves and socks syndrome caused by parvovirus B19 infection.

The papular purpuric gloves and socks syndrome (PPGSS) is an uncommon dermatosis with a typical purpuric exanthem limited to hands and feet; it occurs mainly in young adults. We report a case of a 19-year-old man with an acute febrile illness accompanied by purpuric and papular lesions located mostly on the dorsal areas of his hands and feet. Serologic analysis for parvovirus B19 yielded positive results. The diagnosis of PPGSS was made. The eruption cleared without therapy in 12 days with plantar and palmar desquamation. Parvovirus B19 and some other viral infections have been proven to be causative agents of this syndrome.

Acrodermatitis↗

PubMed2006

Prevalence of HCV infection in nongastric marginal zone B-cell lymphoma of MALT.

BACKGROUND: Hepatitis C virus (HCV) infection is frequently associated with B-cell non-Hodgkin's lymphomas. We investigated the prevalence of HCV infection in nongastric marginal zone lymphomas of mucosa-associated lymphoid tissue (MALT) in order to define the relationship between the viral infection and the presenting features, treatment, and outcome. METHODS: We retrospectively studied 172 patients with a histological diagnosis of marginal zone B-cell lymphoma of MALT, except for stomach, and with available HCV serology, among a series of 208 patients. RESULTS: HCV infection was documented in 60 patients (35%). Most HCV-positive patients (97%) showed a single MALT organ involvement. HCV-positive patients showed a more frequent involvement of skin (35%), salivary glands (25%), and orbit (15%). The majority of stage IV HCV-positive patients (71%) had a single MALT site with bone marrow involvement. The overall response rate was similar in HCV-positive (93%) and HCV-negative patients (87%). Overall survival (OS) and event-free survival (EFS) did not differ according to HCV infection. In multivariate analysis, advanced disease (stage III-IV) was associated with a poorer OS (P = 0.0001), irrespective of HCV serostatus. CONCLUSIONS: This study shows that nongastric marginal zone lymphomas are characterized by a high prevalence of HCV infection. Patients with involvement of a single MALT site have the highest prevalence of HCV. HCV-positive nongastric lymphomas of MALT show an indolent course similar to HCV-negative patients and seem an ideal target for exploiting the antilymphoma activity of antiviral treatments.

Antibodies, Viral↗

PubMed2006

Recurrence quantification analysis of surface EMG detects changes in motor unit synchronization induced by recurrent inhibition.

The systemic injection of L-Acetylcarnitine (L-Ac) induces a reversible increase in recurrent inhibition. In addition, L-Ac potentiation of recurrent inhibition has been found to increase the synchronous activity of single motor units, as detected by traditional linear analysis in the time domain. This result has been recently confirmed using a nonlinear method based on the analysis of embedded determinism (%DET) extracted from the surface EMG. The present study aimed at testing the general applicability of RQA methodology, as a viable tool for assessing motor unit synchronization, by extending the analysis of surface EMG, as revealed by changes in %DET induced by L-Ac, to many upper and lower limb muscles and to muscles that are not easily studied by needle electrodes, such as the orbicularis oculi. Subjects performed brief periods of tonic contractions, alternated to periods of rests to avoid muscle fatigue. Pharmacological enhancement of recurrent inhibition was obtained by a short-lasting intravenous injection of L-Ac. Control experiments were performed replacing L-Ac injection with saline injection. The average %DET showed a significant increase during L-Ac injection in the deltoid, biceps brachii, extensor carpi radialis, while no effect was observed in the opponens pollicis and abductor digiti minimi for the upper limb muscles. Similarly, the average %DET showed a significant increase during L-Ac injection in the quadriceps, soleus, and tibialis anterior, while no effect was observed in the abductor hallucis for the lower limb muscles. RQA of orbicularis oculi muscle activity showed no increase in %DET during L-Ac injection in analogy to what found in the intrinsic muscles of the hand and foot, known to be devoid of recurrent inhibition. The presence or absence of drug-induced increase in motor unit synchronization agrees with the known distribution of recurrent inhibition in the various motor nuclei. The overall significance of these findings is the potential application of RQA methodology as a reliable and independent tool for generally assessing motor unit synchronization from surface EMG under strictly controlled experimental condition.

Acetylcarnitine↗

PubMed2006

Genetic abnormalities and CNS tumors: report of two cases of ependymoma associated with Klinefelter's Syndrome (KS).

OBJECTS: Genetic syndromes associated with ependymoma are uncommon, with the exception of NF2. We describe two cases of ependymoma presenting with Klinefelter's Syndrome (KS) as co-morbid condition. MATERIALS AND METHODS: The first patient was diagnosed for KS during pregnancy; he also presented a thyroid agenesis and a deficit of methyltetrahydrofolate reductase (MTHFR); at 30 months of age he was operated on for a grade II ependymoma of IV ventricle; after a multiple-stage surgery, he underwent oral chemotherapy and stereotactic radiotherapy, but after 15 months he presented a local recurrence and died. The second patient was diagnosed for KS at the age of 16 months; at 10 years of age, due to back pain, he underwent an MRI, which showed a cauda equine tumor. He underwent surgery and radiotherapy. Histology was of mixopapillary ependymoma. CONCLUSION: In a review of literature, various neoplasms have been described in association with KS. To our knowledge, these are the first two cases reported of ependymoma associated to KS. A retrospective study of 44 monoinstitutional ependymoma cases demonstrated association with genetic syndromes in 22%.

Central Nervous System Neoplasms↗

PubMed2006

Changes in motor axon recruitment in the median nerve in mild carpal tunnel syndrome.

OBJECTIVE: To determine whether patients with mild carpal tunnel syndrome (CTS) and conventional electrodiagnostic evidence of selective involvement of sensory conduction show changes in motor axon recruitment in the median nerve. METHODS: Wrist-to-abductor pollicis brevis (APB) motor axon conduction was studied by analysing the relationship between the intensity of electrical stimulation and the size of motor response (input-output curve) in 30 CTS patients with conventional electrodiagnostic evidence of selective involvement of sensory conduction. Parameters (threshold, slope and plateau) of input-output curves were compared with those obtained in 30 controls. RESULTS: The slope of the input-output curve of CTS patients was less steep than that of controls. For stimulus intensity above M-wave threshold (MTh), fewer motor axons were recruited in patients than controls. CONCLUSIONS: Motor fibres are affected in CTS when conventional electrodiagnostic tests show normal motor conduction. Altered recruitment of motor axons could mainly be due to impairment of energy-dependent processes which affect temporal dispersion of the compound volley or axonal conduction block. SIGNIFICANCE: In mild CTS, motor fibres are more often affected than was originally thought. The sensitivity of wrist-to-APB motor conduction studies may be increased by using submaximal stimulus intensities.

Action Potentials↗

PubMed2006

Identification of non-specific alkaline phosphatases in hyphal cells of the fungus Neurospora crassa by in situ histochemistry.

The present study was designed to identify alkaline phosphatases in non-permeabilized hyphal cells of the fungus Neurospora crassa by staining these enzymatic activities with a modified azo dye coupling method. Our strategy allowed the identification of three non-specific alkaline phosphatase activities, one of them possibly being a novel putative enzyme, which is not responsive to either Mg(2+) or EDTA. Another alkaline phosphatase activity, whose location in the hyphal cell is regulated by phosphate, is stimulated by Mg(2+), inhibited by EDTA, and somehow dependent on the expression of the pho-2(+) -encoded Pi-repressible alkaline phosphatase.

Alkaline Phosphatase↗

PubMed2006

Nephronophthisis type 1 deletion syndrome with neurological symptoms: prevalence and significance of the association.

Type 1 nephronophthisis (NPHP) with homozygous deletions of nephrocystin [NPHP1, DEL] has been considered a pure renal disorder, but co-occurrence of extrarenal symptoms, mainly retinitis pigmentosa, is observed in a subset of patients. Recently, [NPHP1, DEL] has been detected in three patients with Joubert syndrome-related disorders (JSRDs), who associated neurological signs with a peculiar neuroradiological malformation known as the 'molar tooth sign' (MTS). To define the frequency of JSRD spectrum in NPHP1 patients, we re-examined 56 cases with [NPHP1, DEL] and found an overall incidence of 8.9% (five out 56 patients). All had small hyperechoic kidneys and had developed advanced renal failure within 15 years. Two patients presented the complete features of JSRD with cerebello-renal-retinal association and MTS. Two others showed, instead, severe intentional tremor and thick superior cerebellar peduncles on brain magnetic resonance imaging (MRI), and one of them had associated retinopathy. The fifth patient presented with hypotonia, developmental delay, central deafness, and ataxia associated with Leber congenital amaurosis and liver fibrosis but with normal brain MRI. Marked intrafamilial variability of associated extrarenal symptoms was observed in familial cases. Deletion extension did not differ in patients with isolated renal phenotype and in those with associated neurological symptoms. In conclusion, neurological defects varying from subtle involvement of cerebellum with thickened peduncle to both JSRD and diffuse central hypotonia are frequent in [NPHP1, DEL] patients. Prevalence of such association may justify systematic neurological and neuroradiological evaluation.

Adolescent↗

PubMed2006

Peripheral benzodiazepine receptors on platelets of fibromyalgic patients.

OBJECTIVE: The aim of the present study was to analyze if alterations of peripheral-type benzodiazepine receptor (PBR) characteristics occurred in platelet membranes of patients affected by primary fibromyalgia (FM). DESIGN AND METHODS: Platelets were obtained from 30 patients with FM. Evaluation of kinetic parameters of PBR was performed using [(3)H] PK11195 as specific radioligand compared with 16 healthy volunteers. RESULTS: The results showed a significant increase of PBR binding sites value in platelet membranes from FM patients (B(max) was 5366+/-188 fmol/mg vs. controls, 4193+/-341 fmol/mg, mean+/-SEM) (**p<0.01) but not for affinity value (K(d) was 4.90+/-0.39 nM vs. controls, 4.74+/-0.39 nM, mean+/-SEM) (p>0.05). Symptom severity scores (pain and tiredness) were positively correlated with B(max). CONCLUSIONS: Our results showed an up-regulation of PBR in platelets of FM patients, and this seems to be related to the severity of fibromyalgic symptoms.

Blood Platelets↗

PubMed2006

New antiangiogenetic agents and non-small cell lung cancer.

New blood vessel formation, known as angiogenesis is a fundamental event in the process of tumor growth and metastatic dissemination. Due to its central role in tumor angiogenesis, the vascular endothelial growth factor (VEGF) and its receptor have been a major focus of basic research and drug development in the field of oncology, including the treatment of non-small cell lung cancer (NSCLC). Approaches targeting VEGF include monoclonal antibodies and vascular endothelial growth factor receptor-tyrosine kinase inhibitors (VEGFR-TKIs). Bevacizumab (Avastin) is an anti-VEGF recombinant humanized monoclonal antibody. A very recent randomized phase III trial demonstrated a statistically significant advantage in median survival favouring the combination of bevacizumab plus chemotherapy versus chemotherapy alone in the treatment of advanced non-squamous NSCLC. This study represents the first evidence of superior efficacy of targeted therapy combined with chemotherapy over chemotherapy alone in the treatment of NSCLC. ZD6474 is an orally bioavailable inhibitor of VEGFR-2 tyrosine kinase. First evidences of antitumor activity and its excellent toxicity profile make it a promising targeted agent for the treatment of NSCLC. A recent phase I/II study examined the combination of Epidermal Growth Factor Receptor (EGFR)-TKI erlotinib and bevacizumab in patients with non-squamous stage IIIB/IV NSCLC. Data on antitumor activity of this combination have to be considered very promising. Clinical trials of multiple targeted therapy may represent the second generation studies in the treatment of NSCLC.

Angiogenesis Inhibitors↗

PubMed2006

Formation of self-organized nanoparticles by lecithin/chitosan ionic interaction.

In this work the production of auto-assembled nanoparticles obtained by the mixing of chitosan and lecithin is presented. The size and surface charge of the nanoparticles were studied as function of the weight ratio between components, the viscosity of the polysaccharide and the pH of the colloidal suspension. In order to elucidate the structure of nanoparticles, micro-FT-IR and elastic neutron scattering experiments have been performed. Results evidenced a strong electrostatic interaction between components and a structure that is neither that of homogeneous spheres nor of coated unilamellar vesicles. Preliminary encapsulation experiments with progesterone, as model lipophilic drug, showed good encapsulation efficiencies.

Algorithms↗

PubMed2006

Expanding the clinical spectrum of POMT1 phenotype.

Mutations in POMT1 have been identified in Walker-Warburg syndrome and in patients with limb-girdle muscular dystrophy and mental retardation (LGMD2K). The authors report new POMT1 mutations in three unrelated children with severe motor impairment, leg hypertrophy, and mental retardation but without brain and ocular malformations. These patients are similar to LGMD2K but have earlier onset and more severe motor disability. The current findings expand the spectrum of POMT1-associated phenotypes.

Adolescent↗

PubMed2006

Motor unit synchronous firing as revealed by determinism of surface myoelectric signal.

Information on motor strategies can be extracted from the surface electromyogram (EMG) by non-linear methods. The percentage of determinism (%DET) obtained from recurrence quantification analysis (RQA) may be a sensitive variable to detect synchronous motor unit behaviour. The purpose of the present study was to validate this methodology by comparing it with an established technique estimating the degree of synchronization of pairs of voluntary activated motor units from the correlation of their firing in the time-domain. Single motor unit activity was recorded in extensor carpi radialis (ECR) muscle by pairs of tungsten microelectrodes inserted into the muscle belly. Cross-correlation analysis was performed in order to determine synchronization peak area by computing synchronous impulse probability. Surface EMG activity was recorded in parallel by electrodes placed over the skin of the same muscle and %DET was used as a measure of synchronous activity. The %DET appeared to be a valid measure of synchronization yielding results comparable to those obtained with cross-correlation analysis. Increases in %DET (t = 64.59, P < 0.0001) highly correlated (r2 = 0.70, P = 0.0013) with pharmacologically induced increases in the synchronization activity of pairs of ECR motor units (t = 8.71, P < 0.0001). RQA may be used as an alternative methodology for testing synchronous motor unit behaviour from surface EMG under physiological and pathological conditions.

Acetylcarnitine↗

PubMed2006

Prenatal diagnosis of a nasal glioma in the mid trimester.

We report a case of fetal nasal glioma diagnosed at 21 weeks of gestation. The glioma appeared as a moderately hypoechoic mass arising from the junction between the medial aspect of the left orbit and the lateral aspect of the nose, and showing no internal vascularization on color and power Doppler ultrasonography. Fetal magnetic resonance imaging (MRI) excluded the possibility of an encephalocele by ruling out underlying bone defects. After an uneventful pregnancy, the nasal glioma was resected without complications at 4 months of age. The differential diagnosis of fetal paranasal facial masses is discussed.

Adult↗

PubMed2006

Implementation of sedation guidelines in clinical practice in Italy: results of a prospective longitudinal multicenter study.

BACKGROUND AND STUDY AIMS: Following publication in 2000 of the Italian Guidelines for Sedation in Digestive Endoscopy, the authors carried out a dissemination program and an audit of the impact of the Guidelines in clinical practice. The primary aim was to evaluate any changes in sedation methods at the start of and during the study period (at 0, 6, and 12 months). Secondary study aims were detailed analyses of endoscopies regarding sedation, complications, and patient satisfaction. PATIENTS AND METHODS: The prospective, observational, multicenter study was commenced in 60 centers (31 first- and 29 second-level) which opted to have seminars on the Guidelines; results concerning sedation practices in relation to endoscopic procedure, complications, and patient satisfaction were recorded at the start of the study (phase 0) and at 6 and 12 months. Over a 1-year period, 5261 sedated and unsedated patients undergoing endoscopic procedures were enrolled (with data collection between December 1999 and June 2002). The results were analyzed using the chi-squared test. RESULTS: Data were available for all three assessment time points from 29 of the 60 centers. The sedation rate, between phase 0 and 2, increased by 12.75% in first-level centers and 0.73% in second-level centers with midazolam use increasing from 34% to 41%. For colonoscopy, sedation usage increased from 52% to 56%. Adverse events occurred in 0.47% of the patients, without long-term sequelae or death, and patient satisfaction was only slightly, but not significantly higher with sedation (90.4% of sedated patients were "very satisfied" vs. 87% of unsedated patients who were "satisfied"), but the examination was more likely to be complete in sedated patients and this difference was statistically significant ( P < 0.001). CONCLUSIONS: We conclude that if sedation is used as recommended by the Guidelines, it is possible to control clinical risk by using high quality endoscopic procedures.

Adult↗

PubMed2006

Chemotherapy of advanced non-small cell lung cancer in elderly patients.

Non-small cell lung cancer (NSCLC) may be considered typical of advanced age. More than 50% of NSCLC patients are diagnosed over the age of 65 and approximately one-third of all patients are over the age of 70. Elderly patients tolerate chemotherapy poorly compared to their younger counterpart because of the progressive reduction of organ function and comorbidities related to age. For this reason, these patients are often not considered eligible for aggressive platinum-based chemotherapy, the standard medical treatment for advanced NSCLC. With the current evidence, in clinical practice, single-agent chemotherapy with a third-generation drug (vinorelbine, gemcitabine, taxanes) should be the recommended option for non-selected elderly patients with advanced NSCLC. Subset analyses suggest that the efficacy of platinum-based combination chemotherapy is similar in fit older and younger patients, with an acceptable increase in toxicity for elderly patients. However, feasibility of platinum-based chemotherapy remains an open issue and has to be proven in prospective randomised trials. High priority should be also given to the evaluation of the role of new targeted therapies. Moreover, a comprehensive geriatric assessment for individualized treatment choice in NSCLC elderly patients is mandatory.

Age Factors↗