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OBJECTIVE: Intestinal involvement is frequently observed in systemic sclerosis (SSc) and is associated with malnutrition and a decreased survival rate. Vascular lesions are claimed to underlie and precede these changes. The aim of this study was to establish whether a reduced mesenteric blood flow was present in SSc patients with no signs or symptoms of small bowel involvement. METHODS: Superior mesenteric artery (SMA) blood flow in the fasting state was measured by colour Doppler ultrasonography in 27 SSc patients and in 25 controls. The effect of a balanced liquid meal on mesenteric blood flow was measured in six matched patients and controls. RESULTS: In fasting SSc patients, there were reductions in mean SMA diameter (P<0.001), blood flow (213+/-92 vs 398+/-125 ml/min in controls, P<0.0001) and pulsatility index (3.49+/-1.0 vs 4.13+/-0.97 in controls, P<0.07). In both groups, the meal increased basal flow values and the differences between controls and patients in the fasting state were not significant. CONCLUSIONS: In the absence of symptoms of small bowel involvement, reversible SMA vasoconstriction is demonstrable in the fasting state in SSc patients.

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OBJECTIVE: Iloprost is a stable prostacyclin analogue which has been shown to be effective in the short-term symptomatic treatment of Raynaud's phenomenon (RP) secondary to systemic sclerosis (SSc). The aim of this study was to evaluate the effects of long-term cyclic therapy with iloprost in comparison with nifedipine on the skin score, pulmonary function and Raynaud's severity score in patients with SSc and RP. METHODS: We conducted a 12-month prospective, randomised, parallel-group, blind-observer trial to compare the effects of intravenously infused iloprost (2 ng/kg/min on 5 consecutive days over a period of 8 hours/day and subsequently for 8 hours on one day every 6 weeks) with those of conventional vasodilating therapy with nifedipine (40 mg/day for os) in 46 patients with SSc and RP. RESULTS: At 12 months, iloprost but not nifedipine reduced the skin score (iloprost: from 13.26 +/- 2.05 to 9.26 +/- 1.32, p = 0.002; nifedipine: from 10.83 +/- 2.09 to 12.17 +/- 3.02, p = n.s.; iloprost vs nifedipine: p = 0.016) and the RP severity score (iloprost: from 2.17 +/- 0.2 to 1.22 +/- 0.13, p = 0.02 vs baseline; nifedipine: from 2.08 +/- 0.34 to 1.33 +/- 0.22, p = n.s.). Carbon monoxide diffusing capacity (DLCO), expressed as % of the predicted normal value, worsened significantly in the nifedipine group (from 69.6 +/- 7.4% to 61.5 +/- 6.5%, p = 0.044) and remained stable in patients treated with iloprost (from 53.2 +/- 4.8 to 56.0 +/- 4.6%, iloprost vs nifedipine: p = 0.026). CONCLUSION: In SSc patients, cyclic intravenous iloprost infusion is able to control vasospastic disease. Our results suggest that it might also act as a disease-modifying agent, as it seems to improve the course of the disease. Further studies principally focused on organ involvement and the natural history of the disease are needed to confirm our results.

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Background: allergy to Ambrosia is a disease of growing importance in Europe. Injective and non injective immunotherapy have been recognised as safe and effective but no evidence is currently available for sublingual immunotherapy (SLIT) in patients sensitised to Ambrosia. This study was planned to assess the effects and the safety of SLIT in patients clinically sensitised to Ambrosia. Methods: 19 patients clinically sensitised to Ambrosia and treated with SLIT were compared to 14 patients treated only with drugs. Diary cards with symptoms and drug consumption were filled-in by patients during the pollen season whereas specific nasal challenge and skin prick test were run two months before and after the pollen season. Patients and doctors were also asked to express their subjective assessment about symptoms and drug consumption during the season. Results: SLIT-treated patients had less symptoms and a significantly minor drug intake (p = 0.04) as compared to untreated patients. Nasal challenge test improved significantly in the SLIT group (p = 0.0001) but not in the control group (p = 0.6875) with a significant difference between groups at the end (p = 0.0413) but not at the beginning of the trial (p = 0.213). The decrease in skin reactivity was significant in the control group (p = 0.0186) and highly significant in the SLIT group (p < 0.0001), with no difference between groups (p = 0.2987). Subjective assessment from both patients and doctors was favorable to SLIT (p = 0.0005 for symptoms; p = 0.0019 for drug consumption). Only one minor local side effect was registered during SLIT. Conclusions: according to our data, SLIT in patients allergic to Ambrosia is safe and able to improve both subjective and objective parameters (AU)

Antecedentes: la alergia a Ambrosia, es una enfermedad de importancia creciente en Europa. Tanto la inmunoterapia subcutánea como la no inyectada, han demostrado ser seguras y eficaces, pero actualmente no se dispone de evidencia sobre la inmunoterapia sublingual (ITSL) en pacientes sensibles a Ambrosia. Este estudio se desarrolló para valorar los efectos y la seguridad del ITSL en pacientes clínicamente sensibles a Ambrosia.Métodos: 19 pacientes sensibles a Ambrosia y tratados con ITSL, se compararon con 14 pacientes tratados solamente con medicación antialérgica. Durante la época de polinización los pacientes rellenaron diariamente cartillas indicando los síntomas y la medicación consumida. Se realizaron pruebas del pinchazo cutáneo y pruebas de provocación nasal específica dos meses antes y después de la polinización. Tanto los pacientes como los médicos evaluaron subjetivamente los síntomas y medicación durante este período.Resultados: los pacientes tratados con ITSL mostraron menor sintomatología y una reducción significativa del consumo de medicamentos (p = 0,04) comparado con los pacientes no tratados. La provocación nasal mejoró significativamente en el grupo tratado con ITSL (p = 0,0001) pero no en el grupo control (p = 0,6875) con una diferencia significativa al final (p = 0,0413) pero no al principio del ensayo (p = 0,213). La disminución de la reactividad de la piel fue significativa en el grupo control (p = 0,0186) y altamente significativa para el grupo ITSL (p < 0,0001), con poca diferencia entre ambos grupos (p = 0,2987). La valoración subjetiva tanto de médicos como de pacientes fue favorable para la ITSL (p = 0,0005 en los síntomas, y p = 0,0019 en el consumo de medicamentos). Solo se registró un caso de reacción local leve con la ITSL.Conclusiones: según nuestros datos, la ITSL en pacientes alérgicos a Ambrosia es seguro, y capaz de mejorar tanto los parámetros subjetivos como los objetivos. (AU)

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We have previously detected autoantibodies against topoisomerase II alpha (anti-topo II alpha) in sera from patients with idiopathic pulmonary fibrosis. To determine whether anti-topo II alpha is also present in systemic sclerosis (SSc) patients with pulmonary involvement, we screened sera from 92 patients and 34 healthy controls. Presence of anti-topo II alpha was investigated with respect to clinical and serological features, including the frequencies of HLA class I and II alleles. Anti-topo II alpha was detected in 20/92 (21.7%) patients. No association was found with either anti-topoisomerase I (Scl-70 or anti-topo I) or anti-centromere antibodies. However, anti-topo II alpha was associated with the presence of pulmonary hypertension (PHT) (as opposed to pulmonary fibrosis), and with a decrease of carbon monoxide diffusing capacity. Anti-topo II alpha was strongly associated with the presence of the class I antigen HLA-B35. No significant association was found with HLA class II antigens. HLA-B35 also turned out to be associated with the presence of PHT. These results indicate that in SSc patients, the presence of anti-topo II alpha is associated with PHT, and that the simultaneous presence of HLA-B35 seems to add to the risk of developing PHT.

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BACKGROUND: Allergy to Ambrosia is a disease of growing importance in Europe. Injective and non-injective immunotherapy have been recognised as safe and effective but no evidence is currently available for sublingual immunotherapy (SLIT) in patients sensitised to Ambrosia. This study was planned to assess the effects and the safety of SLIT in patients clinically sensitised to Ambrosia. METHODS: 19 patients clinically sensitised to Ambrosia and treated with SLIT were compared to 14 patients treated only with drugs. Diary cards with symptoms and drug consumption were filled-in by patients during the pollen season whereas specific nasal challenge and skin prick test were run two months before and after the pollen season. Patients and doctors were also asked to express their subjective assessment about symptoms and drug consumption during the season. RESULTS: SLIT-treated patients had less symptoms and a significantly minor drug intake (p = 0.04) as compared to untreated patients. Nasal challenge test improved significantly in the SLIT group (p = 0.0001) but not in the control group (p = 0.6875) with a significant difference between groups at the end (p = 0.0413) but not at the beginning of the trial (p = 0.213). The decrease in skin reactivity was significant in the control group (p = 0.0186) and highly significant in the SLIT group (p < 0.0001), with no difference between groups (p = 0.2987). Subjective assessment from both patients and doctors was favorable to SLIT (p = 0.0005 for symptoms; p = 0.0019 for drug consumption). Only one minor local side effect was registered during SLIT. CONCLUSIONS: According to our data, SLIT in patients allergic to Ambrosia is safe and able to improve both subjective and objective parameters.

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The aim of the present study was to analyse the in vitro proliferation and cytokine production by alloantigen-stimulated peripheral blood mononuclear cells (PBMC) obtained from patients affected by systemic sclerosis (SSc) and patients with Raynaud's phenomenon (RP). In SSc patients the proliferation of PBMC stimulated in vitro with alloantigens was significantly increased compared with healthy subjects, while no differences were observed for RP patients. Lymphocytes from SSc patients also produced larger amounts of IFN-gamma compared with healthy controls. However, patients with clinically active disease had lower IFN-gamma levels than those found in clinically stable patients. Patients affected by RP showed significantly higher levels of IFN-gamma than healthy subjects. Analysis at the clonal level of the lymphocyte subsets involved in alloantigen stimulation in one patient affected by active SSc, and one subject with RP confirmed the results obtained using PBMC. In particular, in the RP patient but not in the SSc patient, we observed a population of CD4+ T cells which proliferated to alloantigens in vitro and produced high levels of IFN-gamma. We suggest that T lymphocytes producing high levels of IFN-gamma might play a protective role in RP patients and in established scleroderma.

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OBJECTIVE: To investigate the effect of iloprost, a stable prostacycline analog, on kidney blood flow in patients with systemic sclerosis (SSc), using color flow Doppler sonography. METHODS: The acute effect of the drug was studied in 10 patients with SSc with elevated resistance index (RI) levels (all RI values reported are multiplied by 100). Iloprost was administered intravenously (2 ng/kg/min for a period of 8 h). To study the effects of chronic drug administration, 16 patients with SSc were randomly assigned to 2 groups of 8 cases each. The first group was treated with 9 infusions of iloprost in 6 mo. The second group was treated with slow release nifedipine (40 mg/day) for 6 mo. RESULTS: Interlobar artery RI (median 67 vs 61; p = 0.02) and cortical vessel RI (median 65 vs 54; p = 0.001) were reduced after acute treatment. In chronic drug administration, RI values were not modified by nifedipine, while iloprost reduced the RI of the interlobar (median 69 vs 61; p < 0.03) and cortical arteries (median 66 vs 58: p < 0.01). CONCLUSION: Our findings suggest iloprost might be useful for treatment of scleroderma renal vasospasm.

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A prospective study was undertaken to evaluate urinary iodine excretion and changes of maternal thyroid function during pregnancy in healthy women living in the southwest of France. The cohort included a total of 347 pregnant women (mean age 28.0+/-0.5 years). Iodine concentration in a random urine sample and thyroid tests (free thyroxine [FT4], free triiodothyronine [FT3], thyrotropin (TSH), thyroxine-binding globulin [TBG], and thyroglobulin [Tg]) were measured at initial presentation (before 12 weeks of gestation), and during the ninth month of pregnancy. A thyroid ultrasound was performed 1 to 5 days after delivery in 246 mothers. Mean urinary iodine levels were low during the first trimester (6.9+/-0.4 microg/dL), as well as during the ninth month of pregnancy (8.6+/-0.6 microg/dL). During pregnancy, FT4 and T3 concentrations decreased (p < .001), and TSH and Tg concentrations increased (p < .001). Thyroid hypertrophy (thyroid volume greater than 18 mL) was present in 15.4% of women whose first trimester urinary iodine concentration was less than 5 microg/dL, but was present in only 3.5% of women whose urinary iodine concentration was greater than 10 microg/dL. A goiter (thyroid volume greater than 22 mL) was present in 11% of the mothers. In conclusion, this prospective study shows that urinary iodine excretion is low in pregnant women living in the southwest of France. This low iodine intake is associated with reduced circulating thyroid hormone levels and growth of the thyroid gland. These data point to the need of an increased iodine supply in these pregnant women to reduce the potential consequences of low iodine intake on maternal thyroid economy.

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