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Biomedical subjects

G Parisi

Publications and source records attributed to G Parisi.

At least 55 records · Page 3Linked to original sources

High-dose interferon plus ribavirin in chronic hepatitis C not responding to recombinant alpha-interferon.

BACKGROUND: Recently, the combination treatment of recombinant alpha-interferon plus ribavirin has been proposed for chronic hepatitis C patients unresponsive to previous therapy with recombinant alpha-interferon alone. AIM: To determine the effectiveness of the combination therapy for the re-treatment of chronic hepatitis C patients unresponsive to previous interferon therapy. Immediate and long-term follow-up data are reported. PATIENTS AND METHODS: A series of 100 patients with chronic hepatitis C not responding to recombinant alpha-interferon 3 MU tiw, were randomly assigned to two groups of 50 patients each: Group A, treated with recombinant alpha-interferon therapy for an additional six months but at a double dosage (6 MU tiw) in association with ribavirin. Group B, same treatment as group A but without ribavirin. All patients responsive to therapy were then followed-up for at least 12 months. At the end of the treatment and at the end of the follow-up period, we distinguished between complete responses (return to normal of alanine aminotransferase with undetectable serum HCV-RNA] and biochemical responses (return to normal of alanine aminotransferase still with detectable viraemia). RESULTS: Side-effects were observed only in patients treated with recombinant alpha-interferon plus ribavirin: 12% discontinued the therapy due to haemolytic anaemia. In group A, the percentages of end-of-treatment complete response, end-of-treatment biochemical response, sustained complete response, and sustained biochemical response, were 38%, 20%, 8%, and 14%, respectively, whilst in group B, these percentages were 12%, 16%, 6%, and 16%, respectively. CONCLUSION: The results indicate that in patients with chronic hepatitis C unresponsive to previous recombinant alpha-interferon therapy, re-treatment with higher recombinant alpha-interferon doses, either alone or in combination with ribavirin, lead to mild long-term benefit. However, the satisfactory end of treatment complete response in group A suggests that a significant percentage of patients are sensitive to the combination therapy; and that a more aggressive therapeutic protocol in this selected subset of patients could result in a larger number of long-lasting responses leading, in turn, to a more favourable cost-effect ratio.

Alanine Transaminase↗

Interferon plus ribavirin in chronic hepatitis C non-responders to recombinant alpha-interferon.

The aim of this study was to evaluate the most appropriate therapeutic protocol for patients with chronic hepatitis C not responding to a previous course of recombinant interferon alpha-2b (rIFN). Sixty patients were randomly assigned to two groups of 30 subjects each: group A was treated with double dose of the same type of rIFN (6 MU t.i.w.) plus ribavirin for 6 months; group B was treated with the same rIFN dose and duration as group A, but without ribavirin. An end of treatment complete response (ETCR) was defined as alanine transaminase (ALT) normalization with undetectable serum HCV-RNA at the end of the treatment, while an end of treatment biochemical response (ETBR) as ALT normalization with still detectable viraemia. The two groups were homogeneous. The patients with ETCR or ETBR were than followed-up for at least 1 year. A sustained biochemical response (SBR) was defined as the persistence of normal ALT with still detectable viraemia after a 12-month follow-up, and a sustained complete response (SCR) as the persistence of normal ALT with undetectable viraemia. Side-effects were only observed in patients treated with rIFN plus ribavirin: four cases (13%) discontinued the therapy owing to haemolytic anaemia. Combination therapy induced an ETCR in 11 patients (37%) and an ETBR in six (20%), while a SCR was observed in two subjects (7%) and a SBR in four (13%). The use of a double dose of rIFN alone obtained an ETCR in four cases (13%) and an ETBR in five (17%), with a SCR in two (7%) and a SBR in three (10%). Hence, both combination therapy and single treatment with higher rIFN doses were unable to show statistically significant long-term benefits in patients with chronic hepatitis C resistant to a previous course of rIFN treatment.

Adult↗

Does the initial location of Crohn's disease have an influence on the time-to-relapse in patients under maintenance treatment with oral mesalamine?

The aim of this study was to determine the possible influence of the initial location of Crohn's disease (CD) on the time-to-relapse in patients with quiescent CD treated only with oral mesalamine (5-ASA). We divided 74 consecutive patients in clinical remission into three groups according to the initial location of CD. Group A consisted of 30 cases with an ileal location; group B, 18 with ileocolonic location; and group C, 26 with a colonic location. The patients entered the study if they were in clinical and endoscopic remission for at least 3 months. Relapse was defined by CD Activity Index > or = 150, CD Endoscopic Index of Severity > or =4, and by an abnormal increase of C-reactive protein, white blood cell count, and erythrocyte sedimentation rate; moreover, if it was confirmed by x-ray and/or endoscopy. Time-to-relapse was defined as the interval between the date of enrollment and the date of relapse. The patients with an ileal location showed a relapse within 5 years, with a time-to-relapse of 1 year in 26% of cases, 2 years in 85%, 3 years in 92%, and 4 years in 96%. The patients with ileocolonic location showed a relapse within 4 years, with time-to-relapse of 1 year in 39% of cases, 2 years in 89%, and 3 years in 94%. The cases with a colonic location showed a relapse within 6 years, with time-to-relapse of 1 year in 33% of cases, 2 years in 71%, 3 years in 79%, and 4 years in 87%. Surgical treatment was necessary in 37% of the cases with an ileal location, in 44% with ileocolonic location, and 17% with a colonic location. In conclusion, even if our data lack a statistical significance, we have found that the initial anatomic involvement is not a valid parameter to predict the relapse risk in a homogeneous group under continuous treatment with oral 5-ASA, although ileocolonic location seems to have a more aggressive course.

Administration, Oral↗

Potential energy landscape and long-time dynamics in a simple model glass

We analyze the properties of a Lennard-Jones system at the level of the potential energy landscape. After an exhaustive investigation of the topological features of the landscape of the systems, obtained by studying small size samples, we describe the dynamics of the systems in multidimensional configurational space by means of a simple model. This considers the configurational space as a connected network of minima where the dynamics proceeds by jumps described by an appropriate master equation. Using this model we are able to reproduce the long-time dynamics and the low temperature regime. We investigate both the equilibrium regime and the off-equilibrium one, finding those typical glassy behaviors usually observed in the experiments such as (i) a stretched exponential relaxation, (ii) a temperature-dependent stretching parameter, (iii) a breakdown of the Stokes-Einstein relation, and (iv) the appearance of a critical temperature below which one observes a deviation from the fluctuation-dissipation relation as a consequence of the lack of equilibrium in the system.

Journal Article↗

Dynamical structure factor in disordered systems

We study the spectral width as a function of the external momentum for the dynamical structure factor of a disordered harmonic solid, considered as a toy model for supercooled liquids and glasses. In the contexts of both the single-link coherent potential approximation and a single-defect approximation, two different regimes are clearly identified: if the density of states at zero energy is zero, the usual p(4) law is recovered for small momentum. On the contrary, if the disorder induces a nonvanishing density of states at zero energy, a linear behavior is obtained. The dynamical structure factor is numerically calculated in lattices as large as 96(3) and satisfactorily agrees with the analytical computations.

Journal Article↗

Toy model for the mean-field theory of hard-sphere liquids

We investigate a toy model of liquid, based on simplified hypernetted chain equations in very large spatial dimension D. The model does not exhibit a phase transition, but several regimes of behavior when D-->infinity can be observed in different intervals of the density.

Journal Article↗

Down-regulation of natural killer cells and of gamma/delta T cells in systemic lupus erythematosus. Does it correlate to autoimmunity and to laboratory indices of disease activity?

A depletion of natural killer (NK) cells seems to play a role in the course of systemic lupus erythematosus (SLE) whereas the possible involvement in this disease of T cell receptor (TCR) gamma/delta positive T cells is still debated. The aim of this study was to evaluate the peripheral blood mononuclear cells (PBMCs) that express NK surface markers CD16 and CD56 or gamma/delta TCR antigen in 58 SLE patients, investigating the possible role of these cell subsets involved in non-MHC-restricted cytotoxicity and their relationship with the main clinical and laboratory parameters. SLE patients had, with respect to controls, considerably decreased values of NK cells (P<0.0004 in percentage and P<0.00004 as absolute number), of non-MHC-restricted T cytotoxic lymphocytes (P<0.007 and P<0.0015, respectively) and of T cells expressing gamma/delta TCR (P<0.02 and P<0.004, respectively). The absolute numbers of these cell subsets positively correlated to each other (P<0.009). gamma/delta T cells inversely correlated with higher ESR values, both percentually (P<0. 006; r=-0.367) and in absolute number (P<0.009; r=-0.350). Moreover, the percentage values of this cell subset inversely correlated with higher levels of CRP (P<0.05; r=-0.256) while SLE patients with anti-SSB/La antibodies had lower values of T lymphocytes bearing gamma/delta TCR, both as percentage (P<0.008) and as absolute number (P<0.02). Our study indicates that non-MHC-restricted cytotoxicity, shared by NK, NK-like and gamma/delta T cells, may be down-regulated in SLE patients, owing to a significant reduction of these PBMC subsets. These specific cell subset impairments seem to affect only some aspects of the disease, suggesting a weakening of the regulatory properties of these cells in the control of different immunological and inflammatory features of SLE, that could be of importance in its clinical expression.

Adolescent↗

Continuous phase transition in a spin-glass model without time-reversal symmetry.

We investigate the phase transition in a strongly disordered short-range three-spin interaction model characterized by the absence of time-reversal symmetry in the Hamiltonian. In the mean-field limit the model is well described by the Adam-Gibbs-DiMarzio scenario for the glass transition; however, in the short-range case this picture turns out to be modified. The model presents a finite temperature continuous phase transition characterized by a divergent spin-glass susceptibility and a negative specific-heat exponent. We expect the nature of the transition in this three-spin model to be the same as the transition in the Edwards-Anderson model in a magnetic field, with the advantage that the strong crossover effects present in the latter case are absent.

Journal Article↗

Age-related decline of bone mass and intestinal calcium absorption in normal males.

Although about 25% of all hip fractures occur in men, little is known about the pattern of their age-related bone loss and its main determinants. The aim of this cross-sectional study was to evaluate the age-related changes of intestinal calcium absorption, bone mass, and bone turnover in normal men. In 70 normal males (age 17-91 years), we measured spinal and forearm bone density (FBD) (by DXA), fractional intestinal calcium absorption (by oral test), serum immunoreactive parathyroid hormone (PTH), dietary calcium intake (diet records), biochemical markers of bone turnover (serum alkaline phosphatase (ALP), osteocalcin, urine calcium, creatinine, and hydroxyproline), and 1,25(OH)2D3 serum levels. Vertebral bone density (VBD) showed a modest decline before age 50 and a greater decline after age 50, whereas FBD presented a significant decrease with advancing age starting at age 40, suggesting a predominant age-related cortical bone loss. Intestinal calcium absorption (47CaFA) and serum 1,25(OH)2D3 also presented an age-related decline similar to FBD. Simple correlation analysis revealed that age was significantly related to 47CaFA (r = 0.60), calcium intake (r = 0.32), VBD and FBD (r = 0.79 and 0.63, respectively), serum 1,25(OH)2D3 (r = 0.69), and serum iPTH (r = 0.72). No significant correlation was found between age and biochemical markers of bone remodeling. Partial correlation and stepwise variable selection analyses, using 47CaFA and bone mass as dependent variables, showed that in normal males, serum 1,25(OH)2D3 and dietary calcium intake were the main contributors (64%) to 47CaFA variability, whereas only age accounted for 63% of VBD and age and dietary calcium accounted for 45% of FBD variability. These results indicate that bone loss in men accelerates after age 50 years and that among other factors, intestinal calcium malabsorption and 1,25(OH)2D3 serum levels play a role.

Adolescent↗

Colonic disease in cirrhotic patients with portal hypertension: an endoscopic and clinical evaluation.

Fifty cirrhotic patients with portal hypertension but without colonic or systemic disease underwent lower gastrointestinal endoscopy in order to investigate the effects, if any, of portal hypertension on the colon. Fifty patients without liver or systemic disease, examined by colonoscopy because of irritable bowel syndrome in the same period served as controls. Rectosigmoid varices were observed in 34% of the cirrhotic patients and 2% of the controls. Hemorrhoids were observed in 70% of the cirrhotic patients and 48% of the controls. Multiple vascular-appearing lesions were found in 16% of the cirrhotic patients and 6% of the controls. Nonspecific inflammatory changes were noted in 10% of the cirrhotic patients and 4% of the controls. Simultaneous presence, in the same patient, of rectosigmoid varices, hemorrhoids, multiple vascular-appearing lesions, and nonspecific inflammatory changes, was observed in only five (10%) of the cirrhotic patients. We found polyps in 12% of the cirrhotic patients and 14% of the controls, and a malignant tumor in 4% of the cirrhotic patients. The patients with normal colonoscopic findings were 8% of the cirrhotic patients and 36% of the controls. All patients and controls were followed up for 1 year; there was no gastrointestinal hemorrhage among controls, whereas 34% of the cirrhotic patients had an upper gastrointestinal hemorrhage (88% from esophageal varices, 12% from the stomach) and 4% had a lower gastrointestinal hemorrhage (one from rectosigmoid varices and one from nonspecific inflammatory lesions). Colonic lesions were significantly more frequent in the cirrhotic patients (92%) than in the control group (64%); however, such lesions did not seem specific to the disease and were not statistically correlated with the degree of esophageal varices by Child's grading, the etiology of cirrhosis, or the bleeding risk from the lower gastrointestinal tract.

Adult↗

A numerical study of the critical line of Kauffman networks.

Kauffman networks were introduced in 1969 as a model of genetic regulatory systems. One of the most striking successes of this model is its ability to reproduce, for a critical value of its parameters, the observed scaling laws of the average cell replication time and of the average number of cell types in a given organism vs. the number of genes. Yet, the numerical evidence for such scaling laws in the model is still unsatisfactory, and restricted to a particular critical point, while we expect that the scaling behaviour is universal along the critical line. In this paper we try to sharpen the evidence for the scaling behaviour of critical systems, carrying on a detailed numerical investigation of their properties. We measure the length of the cycles (which in the model represents the period of cell cycles) and their number (which represents the number of cell types) for a point of the critical line different from the only one previously studied. Our results seem to confirm that such quantities scale as radicalN for all critical systems, at least for lengths and numbers small enough. On the other hand, we found that their probability distributions are very broad (power-law like) and become broader with system size. This means that there is an effective scale of the length and of the number of cycles that increases much faster than radicalN, and in the infinite size limit the biological analogy found by Kauffman may be lost. A numerical study of the modular structure of critical networks supports this conclusion. The implications of this fact for the biological interpretation of the model are briefly discussed. Finally, we found that the typical weight of the attraction basins tends to zero as a power law in the infinite size limit, with an exponent which seems to be universal along the whole critical line.

Animals↗

[Giant fibrovascular polyp of the esophagus].

Fibrovascular polyps of the oesophagus are rare tumor-like lesions characterized by development of the peduncolated intraluminal masses that can reach gigantic size and may have spectacular clinical presentation including regurgitation of a fleshy mass into the mouth and can lead to sudden death for occlusion of the larynx. Starting from a case observed and successfully treated by transoral resection we review the clinical radiographic and pathological findings of benign oesophageal tumor that requires surgical removal because of the progressive nature of the symptoms and the small, just known, risk of sudden death. The approach depends on the pedicule site.

Aged↗

Evaluation of clinical patterns in ulcerative colitis: a long-term follow-up.

The aim of this prospective research was to compare, in a seven-year follow-up, the clinical outcome of ulcerative pancolitis with that of non-progressive ulcerative colitis. The activity of the disease was evaluated by a Clinical Activity Index and an Endoscopic Index. Of 112 cases of ulcerative colitis observed, 95 showed no change in extent and were studied as examples of non-progressive UC, and in this group the extension of the disease was: pancolitis in 19%, left-sided colitis in 39%, proctosigmoiditis in 17% and proctitis in 25%. A colectomy had to be performed in 5%. None of the enrolled cases developed a cancer during the follow-up. The patients with ulcerative pancolitis or left-sided colitis were treated with 5-ASA 1.6 g/day in a delayed-release formulation, while the cases with proctosigmoiditis or proctitis were treated with 5-ASA enemas 4 g/day. The cases with more than one relapse/year were 39%. The proportion of patients with only one relapse/year was 53%. The patients with steady remission for all the seven years of the trial were only 8%, but with a statistically significant difference between the groups with initial diagnosis of proctosigmoiditis or proctitis and the group with initial diagnosis of pancolitis or left-sided colitis (12% versus 5%). Among the cases with continuous remission, 37% showed colonic alterations, with an endoscopic score higher than 4 but a clinical score less than 6. Side-effects were observed in 6% patients but without treatment withdrawal. Non-progressive ulcerative colitis throughout the colon has a relatively good prognosis which seems to be independent of the location of the disease, even if we have found a statistically significant higher percentage of cases with steady remission among the patients with more distal disease.

Administration, Oral↗

[A case report of reversible biliary pseudolithiasis caused by ceftriaxone in childhood: does the problem deserve greater attention?].

The authors report the case of a nine-year-old girl admitted to hospital with signs of meningeal irritation during the course of hyperpyretic phlogosis of the upper airways who presented, after 6 days' treatment with CFTX, at a dose of 50 mg/kg/day (1.5 g/day), therefore at the maximum recommended dose for the antibiotic in question, symptomatic cholecystic "pseudolithiasis" which resolved two weeks after the suspension of the drug. This case appears to concord with recent reports of "pseudolithiasis" in childhood that appeared with doses not regarded as being at risk, and it draws attention to the etiopathogenetic importance of other factors, including familial recurrence. The authors recommend a reasonable use of CFTX and the need to be "vigilant" both in relation to the onset and evolution of the clinical condition described above.

Ceftriaxone↗