1,706 research outputs found
Molecular Dynamics simulation of sucrose coated and trehalose coated carboxy-myoglobin
No full textWe performed a room temperature
molecular dynamics (MD) simulation on a system
containing 1 carboxy-myoglobin (MbCO) molecule
in a sucrose–water matrix of identical composition
(89% [sucrose/(sucrose water)] w/w) as for a previous
trehalose–water–MbCO simulation (Cottone et
al., Biophys J 2001;80:931–938). Results show that, as
for trehalose, the amplitude of protein atomic meansquare
fluctuations, on the nanosecond timescale, is
reduced with respect to aqueous solutions also in
sucrose. A detailed comparison as a function of
residue number evidences mobility differences along
the protein backbone, which can be related to a
different efficacy in bioprotection. Different heme
pocket structures are observed in the 2 systems. The
joint distribution of the magnitude of the electric
field at the CO oxygen atom and of the angle between
the field and the CO unit vector shows a
secondary maximum in sucrose, absent in trehalose.
This can explain the CO stretching band profile (A
substates distribution) differences evidenced by infrared
spectroscopy in sucrose- and trehalose-coated
MbCO(Giuffrida et al., J Phys ChemB2004;108:15415–
15421), and in particular the appearance of a further
substate in sucrose. Analysis of hydrogen bonds at the
protein–solvent interface shows that the fraction of
water molecules shared between the protein and the
sugar is lower in sucrose than in trehalose, in spite of
a larger number of water molecules bound to the
protein in the former system, thus indicating a lower
protein–matrix coupling, as recently observed by Fourier
transform infrared (FTIR) experiments (Giuffrida
et al., J Phys Chem B 2004;108:15415–15421)
Clinical course of ulcerative colitis
No full text. Dig Liver Dis. 2008 Jul;40 Suppl 2:S247-52.
Clinical course of ulcerative colitis.
Cottone M, Scimeca D, Mocciaro F, Civitavecchia G, Perricone G, Orlando A.
Department of Medicine, Pneumology and Nutrition Clinic, V. Cervello Hospital,
University of Palermo, Palermo, Italy.
AIM: To provide a review of studies on prognosis in ulcerative colitis by
reviewing the relevant population-based cohort studies. On the basis of incidence
and population studies, ulcerative colitis has a favourable clinical course, with
good quality of life, a chronic course characterized by at least one relapse, and
a surgery rate of 30% after 10 years from diagnosis. Patients affected by severe
ulcerative colitis have a higher risk of colectomy, and some clinical variables
may predict the disease's clinical course. Most patients respond to steroids and
only a low percentage become dependent, or non-responders to steroids. Patients
who have a long-lasting ulcerative colitis (>10 years) or are affected by an
extensive disease have an increased risk of developing colorectal cancer, while
those treated with immunosuppressants for long period of time may have an
increased risk of developing lymphomas. Data on mortality in ulcerative colitis
patients are not homogeneous, but if a real risk exists it is in patients with
extensive or severe disease. The evidence that patients with severe ulcerative
colitis are often non-smokers may explain why in one study the mortality rate was
lower
Radiofrequency thermal ablation vs percutaneous ethanol injection for small hcc in cirrhosis:metanalysis of randomized controlled trials
No full text1. Am J Gastroenterol. 2009 Feb;104(2):514-24. Epub 2009 Jan 13.
Radiofrequency thermal ablation vs. percutaneous ethanol injection for small
hepatocellular carcinoma in cirrhosis: meta-analysis of randomized controlled
trials.
Orlando A, Leandro G, Olivo M, Andriulli A, Cottone M.
Department of Medicine, Pneumology and Nutrition Clinic, V. Cervello Hospital,
University of Palermo, Piazza Mameli 1, Palermo, Italy. [email protected]
OBJECTIVES: Radiofrequency thermal ablation (RF) and percutaneous ethanol
injection (PEI) have been employed in the treatment of small hepatocellular
carcinoma (HCC) as curative treatments. The aim of the study was to review the
available evidence comparing RF to PEI for small HCC.
METHODS: Search strategy: Cochrane, MEDLINE, CANCERLIT, and ENBASE databases were
used. Selection criteria: randomized clinical trials evaluating RF vs. PEI. Data
were extracted from each randomized controlled trial (RCT). Primary outcomes were
overall survival and local recurrence. Meta-analysis software was used and risk
differences (RDs) and their 95% confidence intervals and Q-test for heterogeneity
were calculated.
RESULTS: Five RCTs were identified including 701 patients. The overall survival
was significantly higher in patients treated with RF than in those treated with
PEI (RD 0.116, 95% CI 0.173/0.060; heterogeneity not present). Local recurrence
rate is significantly higher in patients treated with PEI than in those treated
with RF. In the RF group the 1, 2, and 3 years cancer-free survival rates were
significantly better than in the PEI-treated patients (respectively: RD 0.098-95%
CI 0.006/0.189; heterogeneity P=0.57; RD 0.187, 95% CI 0.082/0.293; heterogeneity
P=0.98; RD 0.210, 95% CI 0.095/0.325; heterogeneity P = 0.78). A small number of
adverse events were reported in the two treatments.
CONCLUSIONS: RF ablation is superior to PEI in the treatment of small HCC with
respect to overall survival, 1, 2, and 3 years survival rates, 1, 2, and 3
cancer-free survival rates, and tumor response. RF shows a significantly smaller
risk of local recurrence
UNRESECTABLE HEPATOCELLULAR CARCINOMA:META-ANALYSIS OD ARTERIAL EMBOLIZATION
No full text. Radiology. 2002 Jul;224(1):47-54.
Transarterial chemoembolization for unresectable hepatocellular carcinoma:
meta-analysis of randomized controlled trials.
Cammà C, Schepis F, Orlando A, Albanese M, Shahied L, Trevisani F, Andreone P,
Craxì A, Cottone M.
National Council of Research, Istituto Metodologie Diagnostiche Avanzate,
Palermo, Italy. [email protected]
Comment in
Radiology. 2003 May;227(2):611-2; author reply 612-3.
Radiology. 2004 Jan;230(1):300-1; author reply 301-2.
PURPOSE: To review the available evidence of chemoembolization for unresectable
hepatocellular carcinoma (HCC).
MATERIALS AND METHODS: Computerized bibliographic searches with MEDLINE and
CANCERLIT databases from 1980 through 2000 were supplemented with manual
searches, with the keywords "hepatocellular carcinoma," "liver cell carcinoma,"
"randomized controlled trial [RCT]," and "chemoembolization." Studies were
included if patients with unresectable HCC were enrolled and if they were RCTs in
which chemoembolization was compared with nonactive treatment (five RCTs) or if
different transarterial modalities of therapy (13 RCTs) were compared. Data were
extracted from each RCT according to the intention-to-treat method. Five of the
RCTs with a nonactive treatment arm were combined by using the random-effects
model, whereas all 18 RCTs were pooled from meta-regression analysis.
RESULTS: Chemoembolization significantly reduced the overall 2-year mortality
rate (odds ratio, 0.54; 95% CI: 0.33, 0.89; P =.015) compared with nonactive
treatment. Analysis of comparative RCTs helped to predict that overall mortality
was significantly lower in patients treated with transarterial embolization (TAE)
than in those treated with transarterial chemotherapy (odds ratio, 0.72; 95% CI:
0.53, 0.98; P =.039) and that there is no evidence that transarterial
chemoembolization is more effective than TAE (odds ratio, 1.007; 95% CI: 0.79,
1.27; P =.95), which suggests that the addition of an anticancer drug did not
improve the therapeutic benefit.
CONCLUSION: In patients with unresectable HCC, chemoembolization significantly
improved the overall 2-year survival compared with nonactive treatment, but the
magnitude of the benefit is relatively small
REPRESENTATION OF STATIONARY MULTIVARIATE GAUSSIAN PROCESSES. FRACTIONAL DIFFERENTIAL APPROACH
No full textIn this paper, the fractional spectral moments method (H-FSM) is used to generate stationary Gaussian
multivariate processes with assigned power spectral density matrix. To this aim, firstly the N-variate process
is expressed as sum of N fully coherent normal random vectors, and then, the representation in terms of HFSM
is used
Statistics of nonlinear stochastic dynamical systems under Lévy noises by a convolution quadrature approach
No full textThis paper describes a novel numerical approach to find the statistics of the non-stationary response of scalar nonlinear systems excited by Lévy white noises. The proposed numerical procedure relies on the introduction of an integral transform of the Wiener–Hopf type into the equation governing the characteristic function. Once this equation is rewritten as partial integro-differential equation, it is then solved by applying the method of convolution quadrature originally proposed by Lubich, here extended to deal with this particular integral transform. The proposed approach is relevant for two reasons: (1) statistics of systems with several different drift terms can be handled in an efficient way, independently from the kind of white noise; (2) the particular form of Wiener–Hopf integral transform and its numerical evaluation, both introduced in this study, are generalizations of fractional integro-differential operators of potential type and Grünwald–Letnikov fractional derivatives, respectively
Incidence of HSV and HPV with azathioprine
No full textIBd
Incidence of HSV and HPV
with azathioprine
Mario Cottone and Sara Renna
severe infections are an established risk of immunosuppressive therapy;
however, the risk of opportunistic infections in patients with IBd who
receive immunosuppressive therapy has so far only been studied
retrospectively. the increased incidence of herpes flares and development
or worsening of viral warts in patients with IBd who receive azathioprine
has now been demonstrated for the first time in a prospective study.
the rate of opportunistic infections
in patients with iBD is dependent on the
patient’s nutritional status, degree of innate
immune system activity, whether the
patient has undergone surgery and their
use of immunosuppressive drugs or biological
therapy.1 severe infections are a
welldocumented
risk in patients who are
treated with immunosuppressive therapy;2
however, use of immunosuppressants
as maintenance therapy in patients with
iBD is becoming increasingly common.
in a 2004–2005 crosssectional
study of
20,000 patients with iBD, conducted in
France, >50% of patients with Crohn’s
disease and approximately 25% of patients
with ulcerative disease had received the
immuno suppressant azathioprine.3
infections with varicellazoster
virus and
herpes simplex virus (Hsv) are common,
nonfatal conditions characterized by a unilateral,
painful, vesicular rash in a dermatomal
distribution. Patients with iBD are
hypothesized to be at increased risk of
these viral infections because of diseaserelated
alterations in immune function
and frequent use of immunosuppressive
medications. Data on infection with human
papillomavirus (HPv) species in patients
with iBD are scarce but seem to show
an increased incidence of this infection
in such patients.4 Different studies have
used various metho dological approaches
to evaluate the risk of these three viral
infections in patients with iBD but no
studies have evaluated the incidence of all
three viruses.
Korelitz et al.5 reported the incidence of
varicellazoster
infection in patients with
iBD who were treated with 6mercaptopurine
to be 2.2%. However, the researchers
did not provide a comparison with the
incidence of this infection in a control
population, which limits the conclusions
that can be drawn.
a case–control study by toruner et al.1
sought to identify the factors associated
with iBD and infection by comparing 100
consecutive patients with iBD who had
opportunistic infections to patients with
iBD who did not have a history of opportunistic
infection. although the relative
risk of infection was greatest in patients
>50 years of age (compared with those
≤24 years of age) and was independent
of immuno suppressant treatment, use of
cortico steroids, azathioprine and infliximab
was also associated with a significantly
increased risk of opportunistic infection.
the researchers reported a higher incidence
of varicellazoster,
Candida albicans and
Hsv infections in patients who received
immunosuppressant treatment than in
those who did not receive this therapy, but
did not provide values for the risk of any
single infection.
Gupta et al.6 carried out a similar but
larger study, in which the incidence of
varicellazoster
infections in 7,823 patients
with Crohn’s disease and 1,930 patients with
ulcerative colitis was compared with its
Practice points
■ The incidence of opportunistic infections,
for example with varicella-zoster virus
and human papillomavirus species,
are increased in patients with iBD who
receive immunosuppressant therapy
■ Concomitant treatment of the
opportunistic infection or suspension of
immunosuppressive medication are two
possible therapeutic strategies
■ vaccination for human papillomavirus
species is recommended for women
with iBD
© 2009 Macmillan Publishers Limited. All rights reserved
nature reviews | gastroenterology & hepatology volume 6 | auGust 2009 | 445
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incidence in 79,563 individuals without
iBD. Patients with Crohn’s disease or
ulcerative colitis had a higher risk of
varicellazoster
infection than indivi duals
in the control group. in a nested, case–
control study, 185 patients with Crohn’s
disease and varicellazoster
infections
and 266 patients with ulcerative colitis and
varicellazoster
infections were compared
with 1,787 patients with iBD but without
varicellazoster
infection. Patients who
received immuno suppressant medications
had a greater risk of varicellazoster
infection than those who did not receive
such therapy. the unadjusted and adjusted
odds ratios for receipt of a prescription
for azathioprine or 6mercapto
purine and
varicellazoster
infection were both 3.1.
unfortunately, this study did not investigate
the incidence of other opportunistic
infections, such as Hsv.
the studies described above are all
retrospec tive and are, therefore, constrained
by the usual limitations of this study type.
retrospective analyses of safety data cannot
accurately assess the true incidence of
benign infections because they are transient
conditions. such analyses, therefore,
rely on accurate recall of information by the
patient and can result in an underestimation
of incidence of infection. thus, the information
available from case–control studies
is of limited value; no direct way exists to
estimate the incidence or prevalence of
disease, nor the attributable or excess risk
of particular groups of patients.
the study by seksik et al.7 is the first
prospec tive study to investigate the
incidence of opportunistic infection in
patients with iBD who receive azathioprine
therapy. in this study, 230 patients with
iBD received either azathioprine (n = 169)
or nonimmuno suppressive therapy (n = 61).
the patients underwent a comprehensive
skin examination and completed a questionnaire
every 3–6 months, and the number
of opportunistic infections, including ear,
nose, and throat infections, bronchitis and
oral or genital Hsv flares was recorded.
the incidence of Hsv flares was significantly
greater in the group of patients who
received azathioprine than in patients
who did not do so (1.0 ± 2.6 versus 0.2 ± 0.8
per year, P = 0.04). similarly, significantly
more patients who received azathioprine
treatment experienced newonset
or
worsening viral warts (17.2% versus 3.3%
P = 0.004). these findings are in line with
those from other studies that have reported
an increased incidence of warts in immunosuppressed
patients—an observation that
was initially reported in renal transplant
recipients.8 Contrary to other studies in
the literature,1,5,6,9 however, seksik et al. did
not show an increase in the incidence of
varicellazoster
or cytomegalovirus infection
in patients with iBD who received
immunosuppressant therapy.
what are the implications of seksik et al.’s
findings? a detailed history of herpes infection
should be collected before immunosuppressive
treatment is initiated in
patients with iBD. However, no agreement
exists on what to do when an Hsv or other
infection is diagnosed during immunosuppressive
therapy. viget et al.10 suggest
that immunosuppressant therapy should
be withdrawn as soon as possible after the
identification of an opportunistic infection,
but seksik et al. suggest azathio prine
treatment should be maintained and concomitant
treatment with antiHsv
drugs
should be initiated. no data on the risk
of anogenital cancer related to persistent
HPv infection exist; therefore, in the case
of warts, suspension of immuno suppressive
treatment is advisable.
importantly, the findings from this
study suggest that gynecological examination
and cervical cancer screening should
be planned for women with iBD before
and after immuno suppressant treatment.
HPv vaccination is safe, immunogenic
and highly effective against infection with
specific species of HPv. Predictive data
also indicate that implementation of HPv
vaccination within a national screening
program is likely to be more costeffective
than current clinical practice methods.
the increasing incidence of HPv infection
in young women with iBD also indicates
that, in the future, emphasis may be placed
on the new generation of recombinant
HPv vaccines.
Dipartimento di Medicina, Pneumologia e
Fisiologia della Nutrizione, Università di
Palermo, Palermo, Italy (M. Cottone, S. Renna).
Correspondence: M. Cottone, Dipartimento di
Medicina, Pneumologia e Fisiologia della
Nutrizione, Università di Palermo. Ospedale V.
Cervello, Via Trabucco 180, 90146 Palermo,
Italy
[email protected]
doi:10.1038/nrgastro.2009.110
competing interests
The authors declare no competing interests.
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infections in patients with inflammatory bowel
disease. Gastroenterology 134, 929–936
(2008).
2. Lichtenstein, G. R. et al. serious infections and
mortality in association with therapies for
Crohn’s disease: TReAT registry. Clin.
Gastroenterol. Hepatol. 4, 621–630 (2006).
3. Beaugerie, L. et al. The use of
immunomodulators and biologics in
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2005 [Abstract]. Gastroenterology
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4. Kane, s., Khatibi, B. & Reddy, D. Higher
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Gastroenterol. 103, 631–636 (2008).
5. Korelitz, B. i., Fuller, s. R., warman, J. i. &
Goldberg, M. D. shingles during the course of
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Gastroenterol. 94, 424–426 (1999).
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incidence and risk factors for herpes zoster
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7. seksik, P. et al. incidence of benign upper
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cutaneous infections in inflammatory bowel
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Aliment. Pharmacol. Ther. 29, 1106–1113
(2009).
8. spencer, e. s. & Andersen, H. K. viral
infections in renal allograft recipients treated
with long-term immunosuppression. Br. Med. J.
2, 829–830 (1979).
9. warman, J. i., Korelitz, B. i., Fleisher, M. R. &
Janardhanam, R. Cumulative experience with
short- and long-term toxicity to
6-mercaptopurine in the treatment of Crohn’s
disease and ulcerative colitis. J. Clin.
Gastroenterol. 37, 220–225 (2003).
10. viget, n., vernier-Massouille, G., salmon-
Ceron, D., Yazdanpanah, Y. & Colombel, J. F.
Opportunistic infections in patients with
inflammatory bowel disease: prevention and
diagnosis. Gut 57, 549–558 (2008).
Credit: CDC images
© 2009 Macmillan Publishers Limited. All rights reserve
Rossella Saetta Cottone (éd.), Penser les dieux avec les présocratiques
No full textCet ouvrage trilingue, issu du séminaire présocratique mené depuis 2017 au centre Léon-Robin par R. Saetta Cottone et G. Journée, rassemble d’éclairantes contributions de spécialistes internationaux interrogeant à nouveaux frais le rapport des premiers penseurs grecs au divin. D’une grande précision, avec une attention particulière à la langue, toutes ouvrent d’intéressantes pistes de recherche, dont la variété permet de croiser les perspectives et les champs. Il s’agit de sortir de l’alterna..
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