Gluten-free diet: a new strategy for management of painful endometriosis related symptoms?

AIM: Pelvic pain affects 4% to 39% of women and accounts for 10-40% of all outpatient gynecologic visits. The etiology of painful endometriosis-related has not been fully delineated. No studies have been published concerning gluten-free diet administered to achieved relief of painful symptoms endometriosis-related. The aim of this retrospective study was to evaluate the effectiveness for the outcomes of endometriosis-related pain and quality of life of gluten-free diet in a follow-up of 12 months in patients with chronic pelvic pain endometriosis-related. METHODS: Two hundred seven patients with severe painful endometriosis-related symptoms entered the study. At enrolment time, the baseline values of painful symptoms were assessed by Visual Analogue Scale (VAS) for dysmenorrhoea, non-menstrual pelvic pain, and dyspareunia. According to VAS, pain severity was scored from 0-10; 0 indicating the absence of pain, and 1-4, 5-7 and 8-10 mild, moderate and severe respectively. A gluten-free diet was submitted to all patients and a new evaluation was performed after 12 months of diet. Student t test was used for statistical analysis. RESULTS: At 12 month follow-up, 156 patients (75%) reported statistically significant change in painful symptoms (P<0.005), 51 patients (25%) reported not improvement of symptoms. No patients reported worsening of pain. A considerable increase of scores for all domains of physical functioning, general health perception, vitality, social functioning, and mental health was observed in all patients (P<0.005). CONCLUSION: In our experience, painful symptoms of endometriosis decrease after 12 months of gluten free diet.

T-Cell immune activation in children with vertically transmitted hepatitis C virus infection.

Little is known concerning the clinical features, the histological outcome, and the effects on the maturation of immune system of children with vertically-transmitted hepatitis C virus (HCV) infection. Specifically, no data are available on the peripheral distribution of T-cell subsets. The frequency of naive and memory cells, activated T cells, and cytokine-producing T cells was analyzed in nine HCV-infected children born to HCV-positive mothers. In HCV-infected children, the distribution of naive and memory cells was not significantly altered in the CD4 subset whereas within the CD8 subset, an increase of memory and a decrease of naive cells was observed. The frequency of HLA-DR-positive and Fas-positive T cells was increased in HCV-infected children in both CD4 and CD8 subsets. The distribution of Fas-expressing T cells was directly related to that of HLA-DR cells and inversely related to the frequency of naive T cells. In regard with cytokine production we found increased levels of both CD4 and CD8 interferon-gamma (IFN-gamma)-producing cells whereas no difference in the percentage of interleukin-2 (IL-2)-producing T cells was observed. No meaningful correlation was observed between individual T cell subsets and ALT levels or HCV viral load. In conclusion, our results indicate an increased T-cell activation and a shift to a T(H)1 pattern of cytokine production in children with vertically transmitted HCV infection. The cause of this kind of immune response could reside in the persistent antigenic stimulation by chronic HCV infection.

Flumazenil for hepatic coma in patients with liver cirrhosis: an Italian multicentre double-blind, placebo-controlled, crossover study.

Several factors suggest that endogenous benzodiazepines and gamma-amino-butyric acid may be involved in pathophysiology of hepatic encephalopathy (HE). Contrasting opinions exist on the therapeutic efficacy of flumazenil in the treatment of HE. This study was planned to assess the efficacy of flumazenil by a double-blind, placebo-controlled, crossover design in a large and selected population of cirrhotic patients in stage 4a HE admitted to intensive care units over a 4-year period. Out of 236 patients selected for the study, 132 received flumazenil, whereas 131 patients received placebo. Improvement of the neurological score was documented in 31 patients (23%) of flumazenil group and in two patients (1.5%) of placebo group (p < 0.001) during the first study period, whereas during the crossover period, improvement of the neurological score was documented in seven patients (5.3%) of the flumazenil group and in none of the placebo group (p = 0.022). Improvements in EEG tracings were observed in 44 patients (33.3%) of flumazenil group and in five patients (3.8%) of placebo group (p < 0.001) during the first study period; during the crossover period, improvements in EEG tracings were observed in 10 patients (7.5%) of the flumazenil group and in two patients (1.5%) of the placebo group (p = 0.040). The presence of benzodiazepines was detected in the serum of three responders and in two non-responders. The presence of diazepam and NN-desmethyl diazepam was documented in two responders; prior intake of synthetic diazepam was later confirmed in these patients. The results of our study suggest that flumazenil is beneficial only in a selected subset of cirrhotic patients with severe HE; the applicability of this treatment to unselected patients with hepatic coma or to cirrhotic patients with less severe HE still remains to be determined.

Skin diseases as extrahepatic manifestations of HCV. Review of some clinical cases.

Among extra-hepatic manifestations of hepatitis C virus (HCV) infection particular interest is focused on some dermatological diseases such as: leukocytoclastic vasculitis, oral lichen planus, pruritus-urticaria, psoriasis. Aim of this paper is to analyze these typical dermatoses in a population of patients with HCV infection and describe the characteristic clinical pictures. These clinical pictures confirm the importance of liver examination in presence of skin diseases not related to other pathogenetic mechanisms.

[Antiphospholipid syndrome in obstetrics]. / Sindrome da anticorpi antifosfolipidi in ostetricia.

BACKGROUND: The purpose of this study was to verify the frequency of antiphospholipid syndrome in pregnancy associated with fetal wastage and maternal hypertension. The antiphospholipid antibody syndrome is a clinical syndrome of venous and arterial thrombotic events, recurrent pregnancy loss, and thrombocytopenia associated with two autoantibodies: the lupus anticoagulant (LAC) and anticardiolipin antibody (ACA). METHODS: A group of 83 pregnant patients with recurrent fetal loss or with maternal hypertension for the presence of autoantibodies has been studied. None of the patients had systemic lupus erythematosus or any other autoimmune disease such as sclerodermia, myasthenia, autoimmune thrombocytopenic purpura. The patients have been divided into two groups: a) 45 women with fetal wastage history; b) 38 women with maternal hypertension. RESULTS: The prevalence of autoantibodies in the first group reaches 31.1% (14/45 patients). Two of these 14 patients (14.3%) had fetal loss (one with treatment and one without). 12 of this 14 patients (85.7%) had a normal delivery and all with treatment. Two treatment scheme were used in this study: one with aspirin and another with aspirin and prednisone. In the group of 45 patients there were 34 normal deliveries: 27 (79.5%) pregnancies were treated with aspirin and 7 (20.6%) were treated with aspirin and prednisone. There were 11 fetal loss and 9 (81.1%) in patients without treatment and 2 (18.2%) in treated pregnancies. The prevalence of autoantibodies in the second group reaches 21%. CONCLUSIONS: In conclusions, it can be suggested that treatment strategies for the prevention of fetal loss in the antiphospholipid syndrome are warranted because treatment appears to alter fetal outcome favorably.

[Modifications to the technic of cesarean section after Stark]. / Modifiche alla tecnica del taglio cesareo secondo Stark.

BACKGROUND: As the operating births (caesarean section) increase, many surgical equipes have been compelled to revise operating techniques in order to reduce fetus extraction times and the whole expense of operation without renouncing, at the same time to beauty advantages. With Stark technique, that we have modified, we have obtained all these aims, improving at the same time patients' postoperative course as well succeeding to extract the fetus in about five minutes. In the '70 Cohen explained the utility of a transiliac incision allowing the access to abdominal cavity with rectus muscles unsticking in an area in which these muscles should present a less adhesiveness. METHODS: Since 1988 Stark has used Cohen's technique changing however uterus closing times, peritoneal membranes and abdominal walls. Our technique is different since we performed the incision according to Pfannestiel. RESULTS: The times are considerably reduced to 4.8 minutes for fetus extraction and in postoperative time the complications are drastically reduced too (infection, pain, hematoma, adhesions). CONCLUSIONS: Therefore we can surely say that this kind of technique can be used with success in all gynaecological surgery, in extrauterine pregnancies and adnexial tumefactions (not malignant). Personal opinion is that spinal anesthesia is the best analgesic technique.

[Food allergy: recent findings]. / Allergia alimentare: recenti acquisizioni.

Food allergy induces in infancy and childhood a large variety of symptoms which may be trivial in many children, chronic and severe in others and even fatal in rare cases. According to double-blind placebo controlled oral food challenges, cow's milk, egg, wheat and fish are the most common offending foods. Elimination of the offending food(s) is imperative for the management of children with food allergy. An appropriate formula without cow's milk proteins and allergenic epitopes should be given to infants with cow's milk allergy. Breast feeding and selected weaning after the sixth month of life are recommended for the prevention of food allergy in atopic prone babies.

Hematopoietic SCT for the Black African and non-Black African variants of sickle cell anemia.

Sickle cell anemia (SCA) remains associated with high risks of morbidity and early death. Allogeneic hematopoietic SCT (HSCT) is the only curative treatment for SCA. We report our experience with transplantation in a group of patients with the non-Black African variant and the Black African variant of SCA. This study included 40 consecutive SCA patients (13 patients with the non-Black African variant and 27 with the Black African variant) who underwent BM transplantation from HLA-identical sibling donors between June 2004 and May 2013, following a myeloablative-conditioning regimen. All patients obtained sustained engraftment. One patient (non-Black African variant) became a stable mixed chimera with 25% donor cells more than 6 years after transplantation. The probabilities of survival, SCA-free survival and TRM at 5 years after transplant were 91%, 91% and 9%, respectively. All surviving patients remained free of any SCA-related events after transplantation. Our results confirm that it is possible to offer a greater than 90% chance of cure to children with SCA. HSCT should be considered the standard of care for who have an HLA-identical donor, before complications result from the sickling of RBC.

Radial scar without associated atypical epithelial proliferation on image-guided 14-gauge needle core biopsy: analysis of 49 cases from a single-centre and review of the literature.

The purpose of this study was to evaluate the reliability of image-guided 14-gauge needle core biopsy in the diagnosis of radial scar without associated atypical epithelial proliferation, by comparison with definitive histological diagnosis on surgical excision. The records of 8792 consecutive image-guided 14-gauge needle core biopsy of the breast performed from January 1996 to December 2009 were reviewed. Forty-nine cases of radial scar without associated atypical epithelial proliferation were identified and compared with definitive histological diagnosis on surgical excision. The definitive histological diagnosis on surgical excision confirmed the results of image-guided 14-gauge needle core biopsy in 36 of 49 cases (73.5%), in 9 cases (18.3%) radial scar was associated with atypical epithelial proliferation, while 4 cases out of 49 cases were upgraded to carcinoma (3 cases of ductal carcinoma in situ and one case of invasive lobular carcinoma), with an underestimation rate of 8.2%. A diagnosis of radial scar without associated atypical epithelial proliferation on image-guided 14-gauge needle core biopsy does not exclude a malignancy on surgical excision; consequently during the multidisciplinary discussion further assessment by surgical excision or vacuum-assisted excision, as recently reported, needs to be considered to obtain a definitive histological diagnosis.

Higher CD3(+) and CD34(+) cell doses in the graft increase the incidence of acute GVHD in children receiving BMT for thalassemia.

We evaluated the incidence of GVHD, risk factors and the impact of graft composition on acute GVHD (aGVHD) in 92 children who underwent BMT for thalassemia following busulfan/cyclophosphamide (BUCY)-based conditioning regimens and GVHD prophylaxis with CSA/short-MTX and methylprednisolone. The incidence of grade 2-4 and 3-4 aGVHD was 35% (95% confidence interval (CI) 25-44) and 9% (95% CI 4-16), respectively. We found that CD3(+) and CD34(+) cell doses above the median were associated with high incidence of grade 2-4 aGVHD (49 vs 20%, P=0.005 and 46 vs 23%, P=0.021, respectively). In multivariate analysis, high CD3(+) (hazard ratio (HR) 4.6; 95% CI 1.4-14.7; P=0.010) and CD34(+) (HR 4.3; 95% CI 1.4-12.7; P=0.011) cell doses were associated with grade 2-4 aGVHD. We further examined the effect of CD3(+) and CD34(+) cell doses on aGVHD using quartile cutoff points and found a minimum threshold for CD3(+) (38 × 10(6)/kg) and CD34(+) (4 × 10(6)/kg) cells above which the incidence of grade 2-4 aGVHD is significantly increased. This study shows for the first time a positive correlation between the number of CD3(+) and CD34(+) cells and aGVHD in children receiving sibling BMT, and indicates that using tailored and more intensive post transplant immunosuppression may permit to better control aGVHD.

Allogeneic cellular gene therapy in hemoglobinopathies--evaluation of hematopoietic SCT in sickle cell anemia.

Many patients with thalassemia have been cured with BMT since the first successful transplant in 1981. Allogeneic stem cell gene therapy is the only treatment option for patients with sickle cell anemia (SCA). A total of 11 patients with a median age of 12 years (range, 2-16), affected by SCA, received hematopoietic SCT from HLA-identical, related donors following a myeloablative-conditioning regimen. Indications for transplantation were vaso-occlusive crisis, acute chest syndrome, avascular bone necrosis, chronic RBC transfusions, or hemorrhagic stroke. All patients had sustained engraftment. One patient became a stable mixed chimera with 25% of donor cells at 4 years after transplantation. One patient died at 1 year after transplantation. The probability of survival, SCA-free survival and TRM at 5 years after transplant were 90, 90 and 10%, respectively. All 10 surviving patients remained free of any SCA-related events after transplantation. In conclusion, these data confirm SCT from a suitable HLA-matched, related donor should become the primary option for curing children with SCA. There is an excellent survival rate and a return to normal life, free of SCA-related events.

Second hematopoietic SCT in patients with thalassemia recurrence following rejection of the first graft.

There is a substantial incidence of graft failure in patients with thalassemia after myeloablative conditioning regimens especially in class 3 patients in whom its incidence could be as high as 8-38.5%. Most patients with graft failure have recurrence of thalassemic marrow. Historically, results of second transplants for thalassemia were poor because of a high rejection rate and/or increased TRM. Sixteen patients with thalassemia recurrence following rejection of the first graft and with a median age of 9 years (range, 4-20) were given second transplants using BM (n=7) or PBSC (n=9) after preparation with a new treatment protocol. All but two patients received stem cells from the same donor. The median interval between two transplants was 28 months (range, 8-204). The sustained engraftment rate was high (94%) with only one patient having primary graft failure. The probability of overall survival, event-free survival, TRM and graft failure were 79, 79, 16 and 6%, respectively. There were three transplant-related deaths. Thirteen patients are alive with Lansky/Karnofsky score of 100. This intensified treatment protocol was well tolerated with no significant increase in toxicity. The excellent results obtained with this new preparative regimen allow us to recommend it for second transplantation for patients with thalassemia recurrence.

[From atopic dermatitis to asthma]. / Dalla dermatite atopica all'asma.

Atopic dermatitis (AD) is the most common chronic skin disorder in infancy and childhood and is the main hallmark of atopic constitution. The disease is multifactorial, and although genetic predisposition is certainly a prerequisite, a number of environmental factors modulate the phenotypic expression of AD. The majority of affected children shows IgE sensitisation towards a large variety of foods and aeroallergens. Since at least 1600, it has been recognized that patients with AD have a high predisposition to develop asthma. Recent epidemiological studies show that AD is commonly seen in individuals from families with a history of asthma. In addition, in population where asthma is uncommon, AD is also uncommon. The sex distribution of AD and asthma is the same, with boys affected significantly more often by these two atopic diseases and in similar proportions. The ETAC project (Early Treatment of the Atopic Child) is a large multicenter, multi-national, double blind, placebo controlled, randomised trial. The main objective of the study is to stop the progression from AD to asthma in young children with AD using early therapeutic intervention with Cetirizine and the second objective is to investigate the main risk factors for the onset of asthma. The results of this study indicate that exposure to potent allergens such as cat or mite significantly increased the risk of sensitisation to these allergens. Prolonged breast feeding was associated with a lowest sensitisation rate to cow milk proteins and to egg. Therefore environmental factors seem to play a crucial role in IgE sensitisation in children with AD.

Low-dose IL-2 reduces lymphocyte apoptosis and increases naive CD4 cells in HIV-1 patients treated with HAART.

During HIV disease an increased in vitro apoptosis of peripheral blood mononuclear cells has been demonstrated. This can be reversed in vitro by interleukin (IL)-2. Recent trials with highly active antiretroviral therapy (HAART) and IL-2 in HIV-1-infected patients showed promising immunological and clinical results. Here we investigated the effects of subcutaneous low-dose IL-2 administration in combination with HAART on in vitro apoptosis and the relationship between apoptosis, CD4(+) counts, and HIV replication. Twenty-two asymptomatic HIV patients were randomized for HAART (arm I) and HAART plus IL-2 (arm II). Spontaneous apoptosis was decreased in both arms after 28 weeks of therapy but the reduction was highly significant only in arm II (P = 0.05 vs P = 0.001). As the percentage of apoptosis decreased, there was a significantly higher increase of both CD4(+) and CD4(+) naive T cells in arm II vs arm I. HIV plasma viremia was reduced in all patients after therapy. Our data suggest that intermittent therapy with low-dose subcutaneous IL-2 in addition to HAART induces a positive immunomodulation in asymptomatic HIV-infected patients.

Assessment of thymic output in common variable immunodeficiency patients by evaluation of T cell receptor excision circles.

Common variable immunodeficiency (CVID) is a heterogeneous syndrome characterized by repeated infections and hypogammaglobulinaemia. Additionally, T-cell abnormalities including lymphopenia, decreased proliferation to mitogens and antigens, and the reduced production and expression of cytokines, have also been observed. In this study we have investigated the expression of naive, memory and activation markers in T-cell subpopulations in 17 CVID patients in comparison to age-matched normal controls. The numbers of CD4+ T cells, including CD45RA+CD62L+ and, to a lesser extent, CD45RA-CD62L+/RA+CD62L- were significantly reduced in patients, whereas CD8+ T cells were within normal range. In contrast, HLA-DR+ cells were increased both in CD4+ and CD8+ T cells. To assess the thymic output, we analysed the presence of T-cell receptor excision circles (TRECs) in CD4+ and CD8+ T cells by quantitative PCR. TRECs were decreased significantly in patients and the rate of TREC loss was higher with increasing age. TRECs correlated with naive CD4+ T cells, whereas there was an inverse relationship between TRECs and CD8+HLA-DR+ and CD8+CD45RA-CD62L+/RA+CD62L- T cells. Our results suggest the presence of a defect in the naive T cell compartment with origin at the thymic level in CVID, and indicate that TREC may be a useful marker to monitor thymic function in this primary immunodeficiency.

T cell receptor repertoire and function in patients with DiGeorge syndrome and velocardiofacial syndrome.

DiGeorge syndrome (DGS) and velocardiofacial syndrome (VCFS) are associated with chromosome 22q11.2 deletion. Limited information is available on the T cell receptor (TCR) Vbeta repertoire. We therefore investigated TCR Vbeta families in lymphocytes isolated from blood and thymic samples of seven patients with DGS and seven patients with VCFS, all with 22q11.2 deletion. We also studied activities related to TCR signalling including in vitro proliferation, anti-CD3-induced protein tyrosine phosphorylation, and susceptibility to apoptosis. Reduced CD3+ T cells were observed in most patients. Spontaneous improvement of T cell numbers was detected in patients, 3 years after the first study. Analysis of CD4+ and CD8+ TCR Vbeta repertoire in peripheral and thymic cells showed a normal distribution of populations even if occasional deletions were observed. Lymphoproliferative responses to mitogens were comparable to controls as well as anti-CD3-induced protein tyrosine phosphorylation. Increased anti-CD3-mediated apoptosis was observed in thymic cells. Our data support the idea that in patients surviving the correction of cardiac anomalies, the immune defect appears milder than originally thought, suggesting development of a normal repertoire of mature T cells.

Decreased CD95 expression on naive T cells from HIV-infected persons undergoing highly active anti-retroviral therapy (HAART) and the influence of IL-2 low dose administration. Irhan Study Group.

The functional recovery of the immune system in HIV-infected persons receiving HAART and the role of adjuvant immune therapy are still matters of intensive investigation. We analysed the effects of HAART combined with cytokines in 22 naive asymptomatic individuals, randomized to receive HAART (n = 6), HAART plus a low dose (1000 000 U/daily) of rIL-2 (n = 8), and HAART plus rIL-2 after previous administration of granulocyte colony-stimulating factor (n = 8). After 3 months of therapy, increased CD4+ T cell counts and diminished viral loads were observed in all patients, independently of cytokine addition. A decreased expression of CD95 (Apo 1/Fas) was evident in all groups when compared with values before therapy. The percentages of peripheral blood mononuclear cells (PBMC) expressing CD95 after therapy decreased by 15%, 22% and 18% in the three treatment groups, respectively (P < 0.05). Analysis of PBMC subsets demonstrated that CD95 expression was significantly reduced on CD45RA+CD62L+ naive T cells (25.3%, 22.4%, and 18.6%, respectively; P < 0.05) in each group, after therapy. Accordingly, all patients showed a reduced rate of in vitro spontaneous apoptosis (P < 0.05). Another effect induced by HAART was a significant increase in IL-2Ralpha expression on total PBMC (P < 0.05), independently of cytokine addition. Altogether, our results suggest that very low dose administration of rIL-2 (1000 000 U/daily) may be not enough to induce a significant improvement in the immune system as regards HAART alone. The employment of higher doses of recombinant cytokines and/or different administration protocols in clinical trials might however contribute to ameliorate the immune reconstitution in patients undergoing HAART.