20 research outputs found
Dynamic Critical Behavio(u)r of a Cluster Algorithm for the Ashkin--Teller Model
We study the dynamic critical behavior of a Swendsen--Wang--type algorithm
for the Ashkin--Teller model. We find that the Li--Sokal bound on the
autocorrelation time ()
holds along the self-dual curve of the symmetric Ashkin--Teller model, but this
bound is apparently not sharp. The ratio
appears to tend to infinity either as a logarithm or as a small power (0.05
\ltapprox p \ltapprox 0.12).Comment: 51062 bytes uuencoded gzip'ed (expands to 111127 bytes Postscript); 4
pages including all figures; contribution to Lattice '9
Universal ratios along a line of critical points. The Ashkin--Teller model
The two-dimensional Ashkin-Teller model provides the simplest example of a
statistical system exhibiting a line of critical points along which the
critical exponents vary continously. The scaling limit of both the paramagnetic
and ferromagnetic phases separated by the critical line are described by the
sine-Gordon quantum field theory in a given range of its dimensionless
coupling. After computing the relevant matrix elements of the order and
disorder operators in this integrable field theory, we determine the universal
amplitude ratios along the critical line within the two-particle approximation
in the form factor approach.Comment: 31 pages, late
Dynamic Critical Behavior of a Swendsen-Wang-Type Algorithm for the Ashkin-Teller Model
We study the dynamic critical behavior of a Swendsen-Wang-type algorithm for
the Ashkin--Teller model. We find that the Li--Sokal bound on the
autocorrelation time ()
holds along the self-dual curve of the symmetric Ashkin--Teller model, and is
almost but not quite sharp. The ratio appears
to tend to infinity either as a logarithm or as a small power (). In an appendix we discuss the problem of extracting estimates of
the exponential autocorrelation time.Comment: 59 pages including 3 figures, uuencoded g-compressed ps file.
Postscript size = 799740 byte
Innate Immune Function in Placenta and Cord Blood of Hepatitis C – Seropositive Mother-Infant Dyads
Vertical transmission accounts for the majority of pediatric cases of hepatitis C viral (HCV) infection. In contrast to the adult population who develop persistent viremia in ∼80% of cases following exposure, the rate of mother-to-child transmission (2–6%) is strikingly low. Protection from vertical transmission likely requires the coordination of multiple components of the immune system. Placenta and decidua provide a direct connection between mother and infant. We hypothesized that innate immune responses would differ across the three compartments (decidua, placenta and cord blood) and that hepatitis C exposure would modify innate immunity in these tissues. The study was comprised of HCV-infected and healthy control mother and infant pairs from whom cord blood, placenta and decidua were collected with isolation of mononuclear cells. Multiparameter flow cytometry was performed to assess the phenotype, intracellular cytokine production and cytotoxicity of the cells. In keeping with a model where the maternal-fetal interface provides antiviral protection, we found a gradient in proportional frequencies of NKT and γδ-T cells being higher in placenta than cord blood. Cytotoxicity of NK and NKT cells was enhanced in placenta and placental NKT cytotoxicity was further increased by HCV infection. HCV exposure had multiple effects on innate cells including a decrease in activation markers (CD69, TRAIL and NKp44) on NK cells and a decrease in plasmacytoid dendritic cells in both placenta and cord blood of exposed infants. In summary, the placenta represents an active innate immunological organ that provides antiviral protection against HCV transmission in the majority of cases; the increased incidence in preterm labor previously described in HCV-seropositive mothers may be related to enhanced cytotoxicity of NKT cells
Pregnant patient with dermatomyositis successfully treated with intravenous immunoglobulin therapy
Introduction
The idiopathic inflammatory myopathies (IIMs) comprise
a heterogeneous group of diseases of unknown etiology
characterized by chronic inflammation of the skeletal muscles.
IIMs are rare in subjects of reproductive age and very
few cases of pregnancy in women affected by IIMs have
been reported in the literature. Furthermore, these have
generally been associated with a poor pregnancy outcome
and relapses of disease activity, suggesting a negative effect
of pregnancy on disease activity and vice versa (1–7).
Here we describe the case of a woman with classic dermatomyositis
(DM) that developed at the beginning of her
pregnancy. She was treated with intravenous immunoglobulin
therapy (IVIG) and corticosteroids and was delivered
of a healthy 3,180-gm boy at 35 weeks’ gestation.
Case report
A 32-year-old woman affected by dermatomyositis was
referred to the Rheumatology Unit of Pisa University in
June 2002, when she was 17 weeks pregnant. Disease onset
dated to March 2002 with the appearance of diffuse myalgias,
increasing proximal muscle weakness, and skin rash;
blood tests at the time showed a marked increase in
transaminases and creatine phosphokinase (CPK; 3,560
IU/liter, normal values 180 IU/liter). During the same
timeframe, she underwent a pregnancy test, which proved
positive. The patient was admitted to a local hospital
where the diagnosis of DM was made on the basis of the
findings of a heliotrope rash and Gottron’s papules, an
increase in muscle enzyme plasma levels, and a positive
electromyogram (8). Moderate-dose steroid therapy (methylprednisolone
40 mg/day) was instituted, with a prompt
improvement of the serologic markers (CPK 1,836 IU/liter).
After this initial positive response in May 2002, however,
the patient presented with a progressive increase in muscle
weakness, a worsening of the cutaneous manifestations,
and a further increase in CPK levels (up to 3,650
IU/liter). Her steroid dosage was increased to 60 mg/day
methylprednisolone and she was transferred to the Rheumatology
Unit of the University of Pisa.
Examination on admission revealed the presence of a
heliotrope rash, Gottron’s papules, and severe proximal
muscle weakness in the shoulder and hip girdles. There
was no peripheral edema, and her blood pressure values
and chest and cardiac examinations were normal. The
results of her laboratory tests were as follows: CPK 1,163
IU/liter; aspartate aminotransferase 141 U/liter (normal
values 45 U/liter), alanine aminotransferase 91 U/liter
(normal values 45 U/liter), normal renal function, no
proteinuria, and a negative Coombs test. She was positive
for antinuclear antibodies by indirect immunofluorescence
(1/160 with a diffuse pattern), whereas assays for
anti-Ro/SSA, anti-La/SSB, anti-Sm, anti-RNP, and anti-Jo1
antibodies by CIE were negative as were anticardiolipin
antibodies and lupus anticoagulant. Capillaroscopy
showed the presence of diffuse abnormalities with a polydermatomyositis
pattern.
The obstetric evaluation was unremarkable. Sonography
showed a viable fetus with body measurements within the
normal range for gestational age.
Treatment with high-dose steroids (60 mg/day) was
maintained and IVIG therapy at a dose of 1 gm/day for 2
consecutive days was instituted. The patient responded
well, with a reduction of CPK levels to 669 IU/liter after 2
weeks, and a progressive increase in muscle strength and
disappearance of the skin lesions. She was discharged and
admitted to our pregnancy clinic for followup. This consisted
of frequent monitoring of muscle enzyme, hemochrome,
and uric acid levels and urine analysis every 15
days; IVIG infusion once per month; and monthly obstetric
evaluations.
In July, clinical and laboratory examinations showed a
dramatic improvement with a complete recovery of muscle
strength and normalization of muscle enzyme levels. In
M. Mosca, MD, F. Strigini, MD, A. Carmignani, MD, A.
d’Ascanio, MD, A. R. Genazzani, MD, S. Bombardieri, MD:
University of Pisa, Pisa, Italy.
Address correspondence to M. Mosca, MD, Rheumatology
Unit, Department of Internal Medicine, University of
Pisa, Via Roma 67, 56126 Pisa, Italy. E-mail: marta.mosca@
int.med.unipi.it.
Submitted for publication January 13, 2004; accepted in
revised form July 11, 2004.
Arthritis & Rheumatism (Arthritis Care & Research)
Vol. 53, No. 1, February 15, 2005, pp 119–121
DOI 10.1002/art.20913
© 2005, American College of Rheumatology
CASE REPORT
119
view of the good clinical response, steroids were rapidly
tapered to a maintenance dose of 8 mg/day by September
2002, with no worsening of the patient’s status.
Monthly ultrasound examinations showed normal fetal
growth and echoanatomy. Uterine artery Doppler velocimetry
was normal at 20 weeks’ gestation. Umbilical artery
and middle cerebral artery velocimetry were also measured
monthly from 28 weeks’ gestation onward, and normal
systolic/diastolic and pulsatility index, respectively,
were obtained. Because of the increased risk of gestational
diabetes mellitus linked to the use of steroids, a 100-gm
oral glucose load was performed at 28 weeks and yielded
normal results. Toxoplasma-specific IgG antibodies were
detected at 25 weeks’ gestation, whereas negative results
had been obtained in previous monthly tests. Because IgM
antibodies were not detectable, it was concluded that the
IgG antibodies against toxoplasma had been passively administered
with the IVIG therapy.
At 35 weeks’ gestation, the patient presented at a local
hospital with premature rupture of membranes and preterm
labor with 4-cm cervical dilatation. The baby was
delivered by cesarean section with epidural analgesia, as
previously planned (see discussion below). The 3,180-gm
boy had no neonatal complications and did not require
neonatal intensive care; only a transient increase in CPK
was observed.
After being delivered, the patient was discharged in
good clinical condition, with instructions to continue
maintenance therapy consisting of 4 mg methylprednisolone
daily and IVIG every 8 weeks. No recurrence of
her disease was observed during puerperium or after
breastfeeding.
IVIG therapy was discontinued on March 2003. At her
last checkup in June 2003 the patient was in good health
and her disease was still inactive. No signs of disease have
been observed in her son.
Discussion
Pregnancy in association with an IIM is a rare event, and as
a consequence the published data are based primarily on
case reports or very small groups of patients (1–7). In a
recent article, Silva et al (1) retrospectively examined their
patient records and reviewed the existing literature on this
subject. They concluded that, as with many other chronic
conditions and autoimmune diseases (such as systemic
lupus erythematosus), the pregnancy outcome appeared to
be closely correlated with the health status of the mother:
most pregnancies occurring during an active phase of the
disease showed a negative outcome, whereas pregnancies
appeared to have good fetal and maternal outcomes when
the disease was inactive (1). However, in the case described
above, pregnancy outcome was favorable for both
mother and fetus in spite of the activity and severity of
DM.
Many questions had to be addressed as we were planning
the management and followup of this patient. First of
all, what was the optimal therapy, one that would minimize
the risks to the mother and the fetus? Corticosteroids
are generally acknowledged to be very effective in the
treatment of IIMs, but medium to high doses may be required
to control disease activity, and therefore corticosteroid-
sparing immunosuppressive drugs (methotrexate, cyclophosphamide,
cyclosporine, azathioprine) are often
used (9). Although some immunosuppressive drugs, such
as azathioprine and cyclosporine, are used in pregnancy,
their administration may carry adjunctive risks for the
patients. Certainly, the administration of corticosteroids
during pregnancy is considered to be relatively safe for
both the mother and fetus, however caution must be exercised
because the long-term use of medium to high doses
carries the risk of complications, such as gestational diabetes
mellitus, hypertension, osteoporosis, infection, and
premature rupture of the membranes (10).
IVIG therapy has been shown to be very effective in the
treatment of IIMs, in particular DM, and is widely used for
various autoimmune conditions during pregnancy (11). It
also is used in the treatment of other pregnancy complications,
such as idiopathic thrombocytopenic purpura and
recurrent miscarriages, and appears to be safe and well
tolerated by pregnant patients (11,12). In our patient, treatment
with IVIG was aimed at maintaining disease remission
while decreasing the corticosteroid dosage. Treatment
with medium to low doses of steroids in combination with
IVIG proved effective in controlling her disease, although
she experienced premature rupture of the membranes.
This occurred at 35 weeks’ gestation, and the successfully
delivered infant showed no signs of respiratory problems
and did not require intensive care. His birth weight was
above the 90th percentile for male infants, which might
have been due to imperfect glucose control in the mother,
although results of an oral glucose loading test were normal
at 28 weeks’ gestation, when she still was taking
medium-dose steroids.
As the pregnancy progressed, we had to face a second
problem—the route of delivery most suitable for this patient.
Most of the cases reported in the literature involved
either patients with active disease who underwent cesarean
section because of maternal or fetal complications, or
patients with longstanding inactive disease who had an
uneventful vaginal delivery. However, our case did not fit
either of these 2 situations: the disease was not active at
the time of parturition, but remission had been achieved
only recently.
Because there have been reports of increased CPK levels
during physiologic labor, with the suggestion that this may
be due to skeletal muscle damage associated with labor
(13), and taking into consideration the recent onset of the
disease, the risk of rhabdomyolisis and myoglobinuria
seemed relevant (14). We decided to recommend an elective
cesarean section to avoid excessive muscle exercise.
No signs of disease were observed in the son at birth or
in the following months. The only abnormality found—a
transient increase in CPK serum levels—is known to occur
during the first 3 to 4 days in full-term infants as well,
reaching a peak just a few hours after birth and normalizing
within a few days (3).
Finally, this clinical case raises questions with regard to
the pathogenesis of IIMs. Recently, cells of maternal origin
have been observed in the inflamed muscles of subjects
with juvenile IIM, suggesting maternal microchimerism.
Furthermore, some authors have hypothesized that fetal
120 Mosca et al
cells circulating in the mother may to some extent be
correlated with the development of autoimmune diseases
in the mothers (4,15,16). Because the dermatomyositis was
diagnosed during the first weeks of pregnancy in our patient,
a correlation between fetomaternal cell trafficking
and the pathogenesis of maternal disease does not seem
likely.
Interestingly, the onset of disease during pregnancy may
also suggest a pathogenetic role of sex hormones. During
pregnancy, in fact, a rise in estrogen and progesterone
concentrations is observed and the influence of these hormones
on immune response has been described in animal
models as well as in patients with other autoimmune
diseases, such as systemic lupus erythematosus and rheumatoid
arthritis (17).
In conclusion, we have described the case of a pregnant
patient with DM who was successfully treated with IVIG
and was delivered of a healthy infant at 35 weeks’ gestation.
To our knowledge this represents the first reported
case of DM with onset during the first trimester of pregnancy,
in which treatment with IVIG resulted in remission
of the maternal disease as well as a positive pregnancy
outcome. In view of the rarity of pregnancy in active IIM,
we suggest consideration of IVIG therapy as a possible
therapeutic option, given its corticosteroid-sparing effect
and the reduced risk of steroid-related side effects