Biomedical subjects

A Rossi

Publications and source records attributed to A Rossi.

At least 37 records · Page 2Linked to original sources

PubMed2006

Chemotherapy of advanced NSCLC in special patient population.

The elderly and patients with Performance Status (PS) of 2, constitute the so-called special patient population. The tolerability of chemotherapy in this population is globally worse, and treatment approaches should be different. Platinum-based combination chemotherapy is currently recommended as the standard treatment for patients with advanced non-small-cell lung cancer (NSCLC), but its role in special patient population is controversial. The best treatment for elderly patients with advanced NSCLC is still debated. In the first randomized study dedicated to elderly NSCLC patients, single-agent vinorelbine showed superiority over supportive care alone, both in terms of survival and quality of life. In a large randomized trial, gemcitabine plus vinorelbine failed to show any advantage over either agent alone. 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, the role of platin-based chemotherapy needs to be defined in prospective randomised trials. With the current evidence, single-agent chemotherapy with a third-generation drug (vinorelbine, gemcitabine, taxanes) should be the recommended option for non-selected elderly patients with advanced NSCLC. Also for PS2 patients there is no consensus on standard treatment. On the basis of current evidence, chemotherapy treatment appears justified for patients with advanced NSCLC and PS2. Single-agent chemotherapy (gemcitabine, vinorelbine, taxanes) could be the preferred option, although carboplatin-based or low-dose cisplatin-based doublets may represent alternative options. Stronger evidence is expected from new clinical research specifically focused on PS2 patients. High priority should be given to the evaluation of tolerability and efficacy of platinum-based combinations and role of new targeted therapies.

Aged↗

PubMed2006

High serum levels of tumour necrosis factor-alpha and interleukin-8 in severe asthma: markers of systemic inflammation?

BACKGROUND: Severe asthma is characterized by elevated levels of pro-inflammatory cytokines and neutrophilic inflammation in the airways. Blood cytokines, markers of 'systemic' inflammation, may be a feature of amplified inflammation in severe asthma. OBJECTIVE: To detect differences in IL-8, TNF-alpha, IL-16 and IL-13 levels in the serum(s) of stable severe and mild-moderate asthmatics related to blood leucocytes proportion, airway calibre and exhaled nitric oxide (NO) levels. METHODS: We assessed cytokine serum levels by ELISA and blood leucocyte counts by an alkaline peroxidase method in 20 healthy controls, 22 mild-moderate [forced expiratory volume in 1 s (FEV1)(%pred): 89+/-3] and 14 severe asthmatics [FEV1(%pred): 49+/-2]. RESULTS: IL-8 and TNF-alpha levels were higher in severe asthmatics than in mild-moderate asthmatics or in controls (P<0.05). No differences in IL-16 and IL-13 levels were detected. Severe asthmatics showed higher circulating neutrophil and eosinophil number than controls (P<0.05). In severe asthmatics, exhaled NO levels were superior than in controls (P<0.05), but inferior than in mild-moderate asthmatics (P<0.05). We found positive correlation between TNF-alpha levels and exhaled NO (r=0.67; P=0.01) or circulating neutrophil counts (r=0.57; P=0.03) in severe asthmatics. CONCLUSION: sTNF-alpha and sIL-8 are markers of 'systemic' inflammation in severe asthmatics, in conjunction with augmented circulating neutrophils, suggesting the involvement of neutrophil-derived cytokine pattern in severe asthma.

Adult↗

PubMed2006

Decreased hepatic expression of PPAR-gamma coactivator-1 in cholesterol cholelithiasis.

BACKGROUND: Cholesterol cholelithiasis (gallstone disease) is a common disease in the Western world. The aim of the present study was to analyze the hepatic expression of a number of nuclear receptors involved in bile acid metabolism in human cholesterol gallstone disease. MATERIALS AND METHODS: Surgical liver biopsies were obtained from 11 patients with untreated cholesterol cholelithiasis and nine gallstone-free subjects; mRNA levels of cholesterol 7alpha-hydroxylase (CYP7A1) and related nuclear receptors and coactivators were assayed by quantitative real-time RT-PCR. RESULTS: No differences between the two groups were detected in mRNA levels of CYP7A1 and related nuclear receptors, with the exception of peroxysome proliferator-activated receptor-gamma coactivator 1 (PGC-1), which was significantly (P < 0.01) less expressed in gallstone subjects. Expression of PGC-1 was linearly correlated with farnesoid X receptor (FXR) in gallstone patients (r = 0.87 on a log scale, P < 0.01), but not in control subjects; in gallstone patients PGC-1 expression was also correlated with hepatocyte nuclear factor 4 (HNF-4) (r = 0.78, P < 0.01). CONCLUSION: These findings suggest that PGC-1 can play a role in the prevention of cholesterol gallstone disease in humans; this might take place via interaction with the bile acid receptor FXR, whose protective role in cholelithiasis has been suggested by recent evidence in animal models and other coactivators. The present data might help to understand the pathophysiology and possibly focus on new therapeutical targets in cholesterol gallstone disease.

Bile Acids and Salts↗

PubMed2006

Molecular characterisation of six patients with prolidase deficiency: identification of the first small duplication in the prolidase gene and of a mutation generating symptomatic and asymptomatic outcomes within the same family.

Prolidase deficiency (PD) is a rare autosomal recessive connective tissue disorder caused by mutations in the prolidase gene. The PD patients show a wide range of clinical outcomes characterised mainly by intractable skin ulcers, mental retardation and recurrent respiratory infections. Here we describe five different PEPD mutations in six European patients. We identified two new PEPD mutant alleles: a 13 bp duplication in exon 8, which is the first reported duplication in the prolidase gene and a point mutation resulting in a change in amino acid E412, a highly conserved residue among different species. The E412K substitution is responsible for the first reported phenotypic variability within a family with severe and asymptomatic outcomes.

Adult↗

PubMed2006

Concurrent radiotherapy does not affect adjuvant CMF delivery but is associated with increased toxicity in women with early breast cancer.

We evaluated whether concurrent radiotherapy (RT) affected delivery and toxicity of adjuvant intravenous CMF (cyclophosphamide, methotrexate and 5-fluorouracil) in women with operable breast cancer. The medical charts of 321 consecutive breast cancer patients who received CMF either alone for 6 cycles, or for 4 cycles following of an anthracycline (A-CMF) were reviewed. One hundred forty-four women underwent radiotherapy concurrently with CMF. Optimal CMF delivery (success as opposite to failure) was defined as the combined achievement of an average relative dose intensity (aRDI) > or = 85% and an average percent of the total dose (aPTD) > or = 90% for the three drugs in the CMF regimen. Multivariate logistic regression analysis showed that concurrent-RT did not affect CMF delivery (OR for success 1.391 p=0.230). The sequential A-CMF regimen (OR for success 0.208, 95% C.I. 0.120-0.360, p<0.001) and age > or = 56 (OR for success 0.351, 95% C.I. 0.200-0.161, p<0.001) were independently associated with suboptimal CMF delivery. Moreover, concurrent RT was independently associated with increased leukopenia, thrombocytopenia, upper abdominal pain, mucositis and fatigue. Our retrospective analysis suggests that concurrent-RT has no impact on optimal CMF delivery, but it increases the burden of CMF-related toxicity.

Adult↗

PubMed2006

Management of acute lower limb ischemia following percutaneous arterial closure device application: our experience.

INTRODUCTION: The Authors report their experience in the management of acute lower limb ischemia following percutaneous arterial closure device application. PATIENT AND METHODS: Five patients required an emergency vascular operations for acute lower limb ischemia. The symptoms onset was < 1 hour in 1 case, 4-12 hours in 2 cases and > 24-36 hours in 2 cases. A preoperative angiography was performed in all the cases. A transfemoral embolectomy was carried out. Direct suture repair were performed in three cases, vein patch angioplasty was carried out in two cases. In one case, a common femoral artery endarterectomy was performed. RESULTS: No post-operative mortality and limb loss occurred. CONCLUSIONS: Acute lower limb ischemia due to closure devices required an extensive approach with reconstruction in high risk septic area. Angiography is mandatory for surgical strategies. We prefer direct suture repair and vein path angioplasty for vascular reconstruction.

Acute Disease↗

PubMed2006

Indications and results of endovenous laser tratment (EVLT) for greater saphenous vein incompetentce. Our experience.

AIM: Endovenous laser treatment (EVLT) seems to be a safe and less invasive method for the treatment of the great saphenous vein (GSV) incompetence. The aim of our study was to evaluate the indications and results of EVLT. METHODS: Between January 2003 and October 2004, 77 patients (55 C3 and 22 C4) underwent EVLT. In 23 cases phlebectomy was performed, in 16 patients a subfascial perforator vein ligations occurred. In 62 patients we used a percutaneous access to the distal GSV, in 15 cases a surgical isolation was performed. In all cases a 600 nm with 1 mm diameter laser was used. RESULTS: Follow-up was performed for a period of 6 months and showed GSV recanalization in 2 cases; 18 patients (23.3%) developed a transient postoperative pain along GSV, in 4 (5.1%) of them the pain persisted for 3 months. In 6 cases a reversible paresthesia due to a lesion of the saphenous nerve were recorded (7.7%) and in 1 case (1.2%) a skin burn occurred. No deep vein thromboses were observed. CONCLUSIONS: EVLT is a safe technique, with low incidence of recanalizations and postoperative complications. Our opinion is to extend the indication in selected cases of GSV incompetence.

Female↗

PubMed2006

[Acute urinary retention in a child with acute disseminated encephalomyelitis].

Acute disseminated encephalomyelitis (ADEM) is an immune-mediated inflammatory demyelinating encephalomyelitis with often monosymptomatic abrupt onset, followed by multifocal neurologic symptomatology depending on lesion-site. Diagnosis is made on the basis of characteristic magnetic resonance imaging (MRI) signal alterations. ADEM is sensitive to steroid therapy, immunoglobulins and plasmapheresis, presents usually a monophasic course and disappears completely after 2 or 3 weeks. Resolution of MRI lesions appears usually within 6 months of presentation. We report on a 14-year-old male, admitted to our Emergency Unit because of fever and acute urinary retention with a normal neurological examination. Urinary tract ultrasonography and mictional cystography were normal; electrophysiology showed a mild involvement of the peripheral nervous system and brain and spine MRI revealed disseminated areas of increased signal on T2-weighted sequences suggestive of ADEM. Steroid therapy brought about clinical recovery in a few days. Resolution of lesions on MRI after 4 months and absence of relapses during four-year clinical follow-up confirmed definitive diagnosis. Our case is interesting because, to our knowledge, this is the first literature report with acute urinary retention as predominant symptom in monosymptomatic forms. Another peculiar feature is the absence of associated neurologic symptomatology despite MRI evidence of important brain and spine alterations.

Acute Disease↗

PubMed2005

Changes in coordination of postural control during dynamic stance in chronic low back pain patients.

The human postural system operates on the basis of integrated information from three independent sources: vestibular, visual and somatosensory. It is conceivable that a derangement of any of these systems will influence the overall output of the postural system. The peripheral proprioceptive system or the central processing of proprioceptive information may be altered in chronic low back pain (CLBP). We therefore investigated whether patients with CLBP exhibited an altered postural control during quiet standing. Dynamic posturography was performed by 12 CLBP patients and 12 age-matched controls. Subject's task was to stand quietly on a computer-controlled movable platform under six sensory conditions that altered the available visual and proprioceptive information. While the control of balance was comparable between the two groups across stabilized support surface conditions (1-3), CLBP patients oscillated much more than controls in the anterior-posterior (AP) direction in platform sway-referenced conditions (4-6). Control experiments ruled out that increased sway was due to pain interference. In CLBP patients, postural stability under challenging conditions is maintained by an increased sway in AP direction. This change in postural strategy may underlie a dysfunction of the peripheral proprioceptive system or the central integration of proprioceptive information.

Adaptation, Physiological↗

PubMed2005

Homozygosity for the p.K136E mutation in the SLC17A5 gene as cause of an Italian severe Salla disease.

Lysosomal free sialic acid storage diseases are recessively inherited allelic neurodegenerative disorders that include Salla disease (SD) and infantile sialic acid storage disease (ISSD) caused by mutations in the SLC17A5 gene encoding for a lysosomal membrane protein, sialin, transporting sialic acid from lysosomes. The classical form of SD, enriched in the Finnish population, is related to the p.R39C designed Salla(FIN) founder mutation. A more severe phenotype is due both to compound heterozygosity for the p.R39C mutation and to different mutations. The p.R39C has not been reported in ISSD. We identified the first case of SD caused by the homozygosity for p.K136E (c.406A>G) mutation, showing a severe clinical picture, as demonstrated by the early age at onset, the degree of motor retardation, the occurrence of peripheral nerve involvement, as well as cerebral hypomyelination. Recently, in vitro functional studies have shown that the p.K136E mutant produces a mislocalization and a reduced activity of the intracellular sialin. We discuss the in vivo phenotypic consequence of the p.K136E in relation to the results obtained by the in vitro functional characterization of the p.K136E mutant. The severity of the clinical picture, in comparison with the classical SD, may be explained by the fact that the p.K136E mutation mislocalizes the protein to a greater degree than p.R39C. On the other hand, the presence of a residual transport activity may account for the absence of hepatosplenomegaly, dysostosis multiplex, and early lethality typical of ISSD and related to the abolished transport activity found in this latter form.

Brain↗

PubMed2005

Raloxifene reduces urokinase-type plasminogen activator-dependent proliferation of synoviocytes from patients with rheumatoid arthritis.

Extracellular fibrinolysis, controlled by the membrane-bound fibrinolytic system, is involved in cartilage damage and rheumatoid arthritis (RA) synovitis. Estrogen status and metabolism seem to be impaired in RA, and synoviocytes show receptors for estrogens. Our aims in this study were to evaluate in healthy and RA synoviocytes the effects of Raloxifene (RAL), a selective estrogen receptor modulator (SERM), on: proliferation; the components of the fibrinolytic system; and chemoinvasion. The effects of RAL were studied in vitro on synoviocytes from four RA patients and four controls. Proliferation was evaluated as cell number increase, and synoviocytes were treated with 0.5 microM and 1 microM RAL with and without urokinase-plasminogen activator (u-PA) and anti-u-PA/anti-u-PA receptor (u-PAR) antibodies. Fibrinolytic system components (u-PA, u-PAR and plasminogen activator inhibitor (PAI)-1) were assayed by ELISA with cells treated with 0.5 microM and 1 microM RAL for 48 h. u-PA activity was evaluated by zymography and a direct fibrinolytic assay. U-PAR/cell and its saturation were studied by radioiodination of u-PA and a u-PA binding assay. Chemoinvasion was measured using the Boyden chamber invasion assay. u-PA induced proliferation of RA synoviocytes was blocked by RAL (p < 0.05) and antagonized by antibodies alone. The inhibitory effect of RAL was not additive with u-PA/u-PAR antagonism. RA synoviocytes treated with RAL showed, compared to basal, higher levels of PAI-1 (10.75 +/- 0.26 versus 5.5 +/- 0.1 microg/10(6) cells, respectively; p < 0.01), lower levels of u-PA (1.04 +/- 0.05 versus 3.1 +/- 0.4 ng/10(6) cells, respectively; p < 0.001), and lower levels of u-PAR (11.28 +/- 0.22 versus 23.6 +/- 0.1 ng/10(6) cells, respectively; p < 0.001). RAL also significantly inhibited u-PA-induced migration. Similar effects were also shown, at least partially, in controls. RAL exerts anti-proliferative and anti-invasive effects on synoviocytes, mainly modulating u-PAR and, to a lesser extent, u-PA and PAI-1 levels, and inhibiting cell migration and proliferation.

Arthritis, Rheumatoid↗

PubMed2005

Intercalation of the radical scavenger ferulic acid in hydrotalcite-like anionic clays.

Hydrotalcite is a biocompatible lamellar anionic clay formed by double hydroxide layers with a metal cation coordinating four OH groups. The different layers are held together by anionic hosts that can be replaced by a simple ion-exchange process. The synthetic Mg-Al-hydrotalcite was used to intercalate ferulic acid, a compound that shows antioxidant properties due to its free radical scavenger capacity. Analysis of the intercalated compound showed a good intercalation percentage (35.53%) accompanied by an increase of the interlayer space from 7.8A (chloride form) to 17.1A due to the presence of the ferulate. The intercalation product was stable in water, did not show any significant degradation after UV-irradiation, had a higher capacity of UV absorption in comparison to both the pure ferulic acid and ferulic acid-hydrotalcite chloride physical mixture. The intercalated compound was formulated in a siliconic cream and the ferulate in vitro release profiles determined.

Aluminum Hydroxide↗

PubMed2005

Cortico-motoneuronal output to intrinsic hand muscles is differentially influenced by static changes in shoulder positions.

We investigated whether shoulder position influenced the recruitment properties of the abductor digiti minimi muscle (ADM) and first dorsal interosseous muscle (FDI). ADM and FDI motor evoked potentials (MEPs) in response to transcranial magnetic stimulation (TMS) were obtained in seven healthy volunteers at two different static positions of the shoulder joint (30 degrees adduction vs 30 degrees abduction) while the arm was passively supported at shoulder level (90 degrees in the horizontal plane) and the elbow joint was fixed at 90 degrees . ADM and FDI voluntary activity was also examined during (1) externally paced finger abductions at 2 Hz in the two different shoulder positions (EMG(ADM) and EMG(FDI) was back-averaged time-locked to the end of finger abduction) and (2) maximal voluntary abduction of the little finger and the index finger. Maximal EMG power and force were analysed in the two shoulder positions. H-reflexes from ADM and FDI were also obtained in two subjects. The ADM stimulus-response curve to TMS showed that the slope and plateau level were significantly reduced with the shoulder at 30 degrees abduction. In contrast, the FDI stimulus-response curve to TMS was not influenced by shoulder position. The back-averaged EMG(ADM) showed a significant decrease in peak amplitude and area with the shoulder at 30 degrees abduction, while no change in EMG(FDI) was observed under the same condition. Similarly, maximal EMG(ADM) and force exertion by the little finger were significantly reduced with the shoulder at 30 degrees abduction, while no such effect was observed for FDI. ADM H-reflex, but not FDI, was also decreased with shoulder abduction. These results indicate that the corticospinal pathway to ADM is less accessible to TMS and to voluntary command when the shoulder is placed at 30 degrees abduction. In contrast, activation of FDI, whether by TMS or by volition, is not influenced by shoulder position. This finding suggests that there are differences in the corticospinal innervation to ADM and FDI, possibly due to the different role of these muscles in hand function.

Adult↗

PubMed2005

Validity and reliability of the Italian version of the Quality of Life, Enjoyment and Satisfaction Questionnaire.

The Quality of Life, Enjoyment and Satisfaction Questionnaire (Q-LES-Q) is increasingly used in psychiatry because it gives emphasis to the subjective perspective of patients on physical, psychological and social domains. This paper reports on the validation of the Italian version of the Q-LES-Q in a large multicenter study (EQUIP) conducted at five Italian sites on outpatients in treatment for anxiety disorders. Study participants underwent a broad assessment of psychopathology including the MINI-International Neuropsychiatric Interview, the Symptom Checklist (SCL-90) and the Clinical Global Impression (CGI). Cronbach's alpha was used to determine the internal consistency of the Q-LES-Q areas and Pearson's r was used to analyze the correlation between the areas of Q-LES-Q and those of the other instruments. The internal consistency of the Q-LES-Q proved to be substantial (>0.80 in each of the areas) as well as the test-retest reliability. The convergent validity of the Q-LES-Q vs. the Work and Social Adjustment Scale was examined. High correlations were found between scales measuring similar constructs in the two instruments and lower correlation between scales measuring different constructs. In conclusion, the Italian version of the Q-LES-Q proved to be as valid and reliable as the original English version.

Adult↗

PubMed2005

Do ASGE guidelines for the appropriate use of colonoscopy enhance the probability of finding relevant pathologies in an open access service?

BACKGROUND: This prospective study examined the appropriate use of colonoscopy in an open-access system with the American Society for Gastrointestinal Endoscopy guidelines and determined whether the American Society for Gastrointestinal Endoscopy guidelines were associated with relevant endoscopic findings. METHODS: In a cohort of 2221 consecutive patients referred for colonoscopy, the proportion of patients who underwent colonoscopy for appropriate indications was prospectively assessed. The relationship between appropriateness and the presence of clinically relevant endoscopic diagnoses was assessed by calculating (1) the positive and negative likelihood ratio of the indications; and (2) the change in the probability of relevant endoscopic diagnoses in the presence of the American Society for Gastrointestinal Endoscopy criteria. RESULTS: The rate for 'generally not indicated' colonoscopies was 37%. Relevant endoscopic diagnoses were present in 28.5% of cases with American Society for Gastrointestinal Endoscopy indications versus 20.1% of patients without appropriate indications. However, the risk of finding relevant diagnoses was significantly increased by American Society for Gastrointestinal Endoscopy criteria application (odds ratio (OR) 1.58; 99% CI 1.20-2.07; p<0.01). Furthermore, in both endoscopic situations (appropriate and not appropriate), the likelihood ratio, positive and negative, varied very little, suggesting a low predictivity for serious pathologies by the appropriate procedure. CONCLUSIONS: The use of an appropriateness evaluation system makes it possible to increase the probability of finding relevant endoscopic diseases. However, the exclusive use of such a system for selecting patients to undergo colonoscopy involves a relatively high risk of colorectal neoplasms going undetected.

Adenomatous Polyps↗

PubMed2005

Hashimoto's encephalopathy with selective involvement of the nucleus accumbens: a case report.

Hashimoto's encephalopathy (HE) is an acute or subacute relapsing disorder usually affecting euthyroid patients with evidence of autoimmune thyroiditis. The neurological manifestations are non-specific, with subacute cognitive impairment, movement disorders, generalized seizures, focal neurological symptoms such as stroke-like episodes, or psychiatric disturbances. Autoimmune phenomena are likely to play an etiological role. Magnetic resonance imaging (MRI) findings are usually normal or show non-specific changes. We report the case of an 11-year-old girl with autoimmune thyroiditis who presented acutely with a complex neuropsychiatric disorder in association with MRI evidence of focal involvement of the nucleus accumbens (NA). The NA, a ventral striate nucleus, is part of a complex dopaminergic network. Lesions to the NA result in several psychiatric symptoms, such as attention-deficit hyperactivity disorders. In this patient, we observed alternating phases of stupor and hyperkinetic-anxious behavior, with marked instability. The pathogenetic mechanism and the anatomic and functional correlations are briefly discussed.

Child↗

PubMed2005

Different molecular mechanisms leading to white matter hypomyelination in infantile onset lysosomal disorders.

Hypomyelinating leukoencephalopathies may be related to a primary disturbance in the formation of myelin or may be caused by neuronal, oligodendrocytic or astrocytic dysfunction, leading to a failure of myelination. Abnormal myelination related to a direct metabolic damage on oligodendrocytes has been shown to occur in some animal models of lysosomal storage diseases. To demonstrate that cerebral white matter hypomyelination may occur also in humans affected by early-onset lysosomal storage diseases, we report three cases with infantile-onset lysosomal storage disorders (type 1 GM1 gangliosidosis, globoid cell leukodystrophy or Krabbe's disease, and type A Niemann-Pick disease) showing white matter hypomyelination. Hypomyelinating leukoencephalopathy may therefore represent a feature of lysosomal storage disorders with onset in the first months of life, when the process of myelination is particularly active, indicating that neuronal storage disorders may be primarily responsible for central nervous system hypomyelination.

Age of Onset↗

PubMed2005

Italian clinical research in non-small-cell lung cancer.

Lung cancer is the most common cause of cancer deaths in both men and women worldwide and has a poor prognosis. Non-small-cell lung cancer (NSCLC) represents approximately 80% of all lung cancers. Surgery is the only curative treatment of NSCLC but only 15-20% of tumours can be radically resected with a survival of about 40% at 5 years. Considering these disappointing results NSCLC is one of the most frequent subjects of clinical research worldwide. Italy is playing an important role in the clinical research of NSCLC performing phase I, II and III trials, prevalently by cooperative groups, and achieving important results that contributed to define the standard treatment for NSCLC patients. In particular, Italy is leader in the clinical research of the treatment of advanced NSCLC elderly patients. Today, large controlled clinical trials are ongoing. In this paper we analyse and discuss the main trials performed by Italian groups in the fields of NSCLC.

Aged↗