Child thyroid disruption by environmental chemicals.

Laboratory experiments and animal evidences support the fact that thyroid function can be altered by a large number of chemicals routinely found in the environment and in samples of human and wildlife tissues. Although humans are commonly exposed to low pollutant doses, disrupting effects on endocrine function (e.g. thyroid) from such chemical exposures represent major health concerns. Thyroid is essential for mammalian brain development both before and after birth, and recent clinical evidences strongly suggest that brain development is much more sensitive to thyroid hormone excess or deficit than previously believed. Thyroid hormone deficit or excess during development can have permanent, pervasive and profound effects on the neurological function of the child. In addiction, maternal thyroid hormones play a role in fetal brain development before the onset of fetal thyroid function, and thyroid hormone deficit in pregnant women can produce irreversible neurological effects in their offspring. Considering that thyroid hormones are important in fetal brain development and child neurological outcome, environmental factors affecting maternal/fetal/infant thyroid function, or thyroid hormone action directly, may affect fetal brain development and child neurological outcome. The aim of this paper is to discuss how environmental chemicals can interfere with the normal production, metabolism, and excretion of thyroid hormones, and their known impact on the thyroid system during child development.

Regional cerebral blood flow in juvenile systemic lupus erythematosus: a prospective SPECT study. Single photon emission computed tomography.

OBJECTIVE: Using single photon emission computed tomography (SPECT) we evaluated the presence and evolution of changes in brain perfusion in juvenile systemic lupus erythematosus (JSLE). METHODS: SPECT was performed in 14 patients with active JSLE divided in 2 groups: the first included 7 patients without central nervous system (CNS) involvement and the second 7 patients with minor neuropsychiatric symptoms (headache, reactive depression, cognitive impairment, mood swing). SPECT findings were compared to seroimmunological and magnetic resonance imaging (MRI) data. After 6 month followup, a second SPECT scan was performed in 12 of 14 patients. RESULTS: At baseline, SPECT showed perfusion defects in 2 patients without neuropsychiatric symptoms and in 5 patients with CNS involvement. In one of the 7 patients with altered SPECT, MRI showed focal hyperintensities. MRI alterations were observed in another patient who had a normal SPECT scan. Cortical atrophy was present in 5 of 14 patients. Correlation between neuropsychiatric manifestations and SPECT findings was not clearly evident because the major part of JSLE patients with CNS involvement and with SPECT alterations had multiple symptoms, but showed focal hypoperfusion on SPECT imaging. No significant association was found between seroimmunological data and SPECT findings. At followup, improvement of perfusion alterations was observed in 6 of 7 patients with altered SPECT and, in 3 of them, findings might be attributed to changes in steroid treatment. CONCLUSION: Perfusion abnormalities in SLE may represent reversible lesions or subclinical CNS involvement. Moreover, SPECT imaging appears to be useful in detecting and monitoring CNS involvement in SLE.

Skin-prick-test-induced anaphylaxis.

An anaphylactic reaction occurred in a 57-year-old man after a prick by prick test with fresh kiwi and in a 29-year-old man after prick tests with some species of fish. Both patients had a history of anaphylaxis after ingestion of kiwi and fish, respectively. These cases suggest that, especially in patients with a history of anaphylaxis, all efforts should be made to minimize the risk of systemic reactions, and skin prick testing should be performed only in places equipped to treat anaphylaxis.

MRI and SPECT investigations of the CNS in SLE patients.

Twenty-two SLE patients were examined with Magnetic Resonance Imaging (MRI) and Single Photon Emission Computed Tomography (SPECT). Multifocal areas of cerebral blood flow (CBF) defects were found in 81.8% of the patients. These alterations were present in patients with severe neurological disorders, in those with neuropsychiatric symptoms only, and also in asymptomatic cases. Anticardiolipin antibodies (aCL) were detected in all patients, but no correlation was found between serum aCL positivity and neurological involvement. The high incidence of cerebral blood flow disorders found in asymptomatic patients, and their poor correlation with the MRI alterations suggest a primary defect of CBF in these patients.

Lupus anticoagulant and monocyte procoagulant activity in polyabortive women.

Monocyte stimulation may be induced by various agents. Monocytes generate procoagulant activity (PCA) in response to stimulation; they widely interact with the hemostatic system and participate in thrombin formation. Extensive placental thrombotic infarction has been implicated in fetal death in polyabortive patients with lupus anticoagulant (LA). We investigated 38 polyabortive women: 17 LA negative (LA-) and 18 LA positive (LA+). We compared the results with 25 clinically normal women. After four hours of incubation, the mean value of monocyte PCA in the LA+ women was significantly higher than in either the LA- or the control group (p < 0.0001). The monocyte PCA was out of the range of the controls in 9 of the 18 LA+ women. No correlation was observed between the levels of LA and monocyte PCA (r = 0.02; p = 0.94). No differences were found in monocyte PCA increase when induced by LA-, LA+ or control plasma; in all cases the increase was about five-six fold. Our results indicate that an increased monocyte PCA is present in some LA+ polyabortive women, thus suggesting that monocyte activation might be involved in the formation of thrombotic placental infarction and the consequent fetal loss in some patients. It might also suggest that these patients, in particular, could benefit from corticosteroid treatment, which is known to inhibit the formation of monocyte PCA.

Lupus anticoagulant and anticardiolipin antibodies in young adults with cerebral ischemia.

BACKGROUND AND PURPOSE: Our study evaluates in an unselected young population with cerebral ischemia the frequency of antiphospholipid antibodies; the relationship of antiphospholipid antibodies to conventional risk factors for and pathological mechanisms of cerebral ischemia; and the risk of recurrence of cerebral ischemia or systemic thrombotic events in patients with antiphospholipid antibodies compared with those without. METHODS: We prospectively tested for antiphospholipid antibodies in 55 of 59 young (aged 15-44 years) adults consecutively examined for ischemic stroke (n = 44) or transient ischemic attack (n = 11). These patients underwent a complete clinical and laboratory assessment for cerebral ischemia and had a 3-year mean follow-up. RESULTS: Ten patients (18%), all with stroke, had antiphospholipid antibodies. Antiphospholipid antibodies were significantly more frequent in women than in men (Fisher's test, p = 0.014). Two patients with antiphospholipid antibodies had a new diagnosis of systemic lupus erythematosus. On angiography, none of the patients with antiphospholipid antibodies had extracranial lesions. Patients with antiphospholipid antibodies had significantly more prior cerebral events (Fisher's test, p = 0.014), and, by survival analysis, higher probability of cerebral ischemic or systemic thrombotic events during follow-up than patients without (log rank test, p less than 0.005). CONCLUSIONS: We conclude that the prevalence of antiphospholipid antibodies is rather high in young adults with cerebral ischemia; that patients with cerebral ischemia and antiphospholipid antibodies may have unrecognized systemic lupus erythematosus; and that, among young patients with cerebral ischemia, patients with antiphospholipid antibodies constitute a subgroup at high risk of cerebral ischemic or systemic thrombotic recurrence. Prevention in this latter group may require close follow-up and treatment.

Prevention of miscarriage in antiphospholipid syndrome.

Recurrent adverse pregnancy outcome may be the final result of different causes, including autoimmune diseases, as the Antiphospholipid Syndrome. Antiphospholipid antibodies (lupus anticoagulant and/or anticardiolipin antibodies) were found in 16% of 197 patients with prior unexplained recurrent miscarriages. During our study 22 out of 32 antiphospholipid antibodies positive women became pregnant again. To prevent abortion relapses, 16 of them were treated with acetylsalicylic acid (50 mg x 2/day) and/or fluocortolone (20 mg/day for 5 days/week). Such therapy started as soon as pregnancy was diagnosed in 14 patients. Two patients began the therapeutic regimen during the third month of gestation. Six patients, who didn't accept this therapeutic approach, represent our control group. All the 14 early treated patients ended pregnancy with success. The 2 women that began the therapy later presented abortion relapses. Among the 6 not treated patients, 5 presented spontaneous abortion and only one gave birth to a baby. No side effect was observed neither in treated mothers nor in their babies. In conclusion, even if further studies would be necessary to standardise a therapeutic protocol, our results encourage the clinical care of patients with antiphospholipid antibodies and adverse pregnancy outcomes.

The role of interleukin 1, erythropoietin and red cell bound immunoglobulins in the anaemia of rheumatoid arthritis.

Since interleukin 1 (IL-1) and erythropoietin (Epo) are believed to play a role in the pathogenesis of rheumatoid arthritis (RA) anaemia we measured IL-1 alpha and Epo concentrations in 10 RA patients with chronic disease anaemia (CDA) and in 14 RA patients without anaemia. Anaemic RA patients had significantly higher IL-1 alpha concentrations than patients without anaemia. IL-1 alpha correlated negatively with haemoglobin and correlated positively with ESR. The results of a multivariate analysis showed that the best predictors of the presence and absence of anaemia were IL-1 alpha and ESR. No clinical parameters permitted a distinction between these two groups of patients. Epo levels were not different in anaemic and non-anaemic RA patients. No correlation was found between Hb and Epo, indicating the presence of an impaired Epo response in RA patients with CDA. We completed our study with the determination of the mean red cell lifespan and with the quantification of IgG and IgM bound to the surfaces of red blood cells (RBC-IgG and RBC-IgM) using a sensitive ELISA method. We observed a modest reduction in red cell survival in anaemic RA patients compared to normal controls. We did not find any correlation between Hb and red cell lifespan and between Hb and RBC-IgG. RBC-IgG and RBC-IgM were not found to be more elevated in anaemic RA than in non-anaemic patients.

Immunological abnormalities in a group of patients with limited cutaneous systemic sclerosis and prominent vascular disease.

Antinuclear antibodies, circulating immune complexes, rheumatoid factors and anticardiolipin antibodies were detected in the sera of 17 patients affected by the limited cutaneous subset of systemic sclerosis and marked clinical evidence of ischaemic cutaneous lesions (fingertip ulcerations). This study was designed to evaluate the possible role of anticardiolipin (aCL) antibodies and other immunological disorders in the endothelial damage characteristic of the disease. ACL antibodies were found in 41% of the patients. With the exception of a significant connection with positive rheumatoid factor tests (RIA), no notable associations between anticardiolipin antibodies and antinuclear antibodies, circulating immune complexes (CIC), and other serological abnormalities were found. ACL antibodies did not significantly correlate with the presence of vascular lesions in our patients. However, a role of these antibodies in endothelial damage cannot be excluded, possibly in association with other serum factors such as immune complexes and antinuclear antibodies. A positive connection between the incidence of CIC and the severity of lung perfusion impairment was observed, and the previously reported relationship between anticentromere antibodies and calcinosis was indirectly confirmed.

Changes in peripheral blood lymphocytes and immune complexes in splenectomized patients: lack of correlation with residual splenic function.

In 47 patients who had undergone splenectomy (31 post-trauma and 16 elective), the percentage levels of T and B lymphocytes, and the T lymphocyte subsets and circulating immune complexes were studied in peripheral blood and correlated with residual splenic function evaluated by means of the pitted red cell count. The T and B lymphocyte levels in splenectomized patients did not differ significantly from those in controls, while OKT8+ lymphocyte levels were significantly higher both after post-trauma and elective splenectomy; there was no significant difference between the two groups of splenectomized patients. Circulating immune complexes were significantly higher both after post-trauma and elective splenectomy only with the C1qBA and C1qSP methods, while there were no differences between splenectomized patients and controls with the KgBSP method. None of the three methods showed significant differences between post-trauma and electively splenectomized individuals. The pitted red cell levels were significantly lower in post-trauma splenectomized patients with respect to electively splenectomized individuals and 22% of post-trauma splenectomized patients had pitted red cell values within the range compatible with the presence of splenosis. The immunological alterations detected did not correlate with the pitted red cell levels, nor were they less evident after post-trauma splenectomy or in patients with pitted red cells compatible with splenosis: this suggests that the occurrence of splenosis is not sufficient to prevent these alterations. Finally, since in our study the average distance from the operation was 5 yr, it is likely that these alterations can be considered as being stable.

Anticardiolipin antibodies in a case of neuro-Behçet with superior vena caval occlusion.

The patient, a 55-year-old man with neuro-Behçet, developed superior vena caval occlusion. Antibodies to cardiolipin were detected in high titres in his serum and a decreased fibrinolysis was also found. It is suggested that anticardiolipin antibodies, perhaps decreasing fibrinolysis, may play an important pathogenic role in some patients with Behçet's disease.

HTLV-III seropositivity in symptom-free Italian haemophiliacs. Correlation with consumption of commercial concentrate and abnormalities of T and B lymphocytes.

Various immunological parameters exploring both T- and B-cell functions were determined in a group of 74 symptom-free Italian haemophiliacs treated with commercial concentrate imported from the USA and were correlated with the presence in their serum of antibody to HTLV-III. There was a strong correlation between HTLV-III seropositivity and the amount of concentrate consumed. A significant correlation between HTLV-III seropositivity and T-cell alterations, such as T4/T8 ratio less than 1 and reduction in the absolute number of T4+ lymphocytes, or B-cell alterations such as hypergammaglobulinaemia and enhanced spontaneous IgG synthesis in vitro, was also observed.

Autoantibodies to human nuclear antigen(s)-HNA-in connective tissue diseases and other disorders.

Autoantibodies reacting with nuclear antigen(s) on human cells (HNA) with weak or without reactivity on nuclei of other species have been found by the indirect immunofluorescence technique used in routine tests for the diagnosis of autoimmune diseases. Precipitin lines were obtained by counterimmunoelectrophoresis (CIE) only when human lymphocyte extracts were used and not with rabbit thymus acetone powder. By comparison with reference sera, the autoantibodies directed to HNA were found to be different from SSA/Ro antibodies and did not give the fluorescence pattern of anti nuclear mitotic apparatus (NuMA) antibodies on HEp-2 cells. The prevalence of sera with anti-HNA antibodies not associated with other antinuclear antibodies (ANA) is low (about 0.7% of ANA found in routine assay). In association with ANA of other specificities, the prevalence of anti-HNA antibodies, demonstrated after absorption of sera with rat liver acetone powder, was higher (about 1% of ANA positive sera). By treatment with physicochemical agents and enzymes, the HNA was found to be a DNA (glyco)-protein complex extractable with saline solution, resistant to 56 degrees C for 6 h and stable at pH values ranging from 3 to 10. Anti-HNA antibodies were found in patients with mild connective tissue diseases, but also in idiopathic interstitial pneumonia and in chronic hepatitis.

Plasma exchange in the treatment of acute systemic lupus erythematosus without circulating immune complexes.

One patient affected by systemic lupus erythematosus with recurrent phlebothrombosis and peripheral neuropathy is described. False positive VDRL test, anticardiolipin antibodies, and high titres of antinuclear antibodies were present. Circulating immune complexes were not found. The effect of plasma exchange on clinical symptoms and on serological abnormalities was rapid and striking.

A solid phase immunoradiometric assay for gastric parietal cell antibodies.

We recently described a solid phase immunoradiometric assay (IRMA) for anti-thyroglobulin and anti-thyroid microsomal antibodies. In the present study a similar IRMA for gastric parietal cell antibodies (PCA) has been developed. Samples to be tested are incubated within wells of polyvinyl microtitre plates coated with solubilized gastric microsomal antigen. After removal of unbound material, PCA is detected by adding purified 125I-anti-human IgG antibody. A good correlation was found with the results of PCA assays obtained by indirect immunofluorescence. In contrast, negative PCA by IRMA were consistently obtained in sera containing high titres of several other organ specific and non-organ specific autoantibodies. PCA determinations by IRMA were than carried out in a series of normal controls and patients with autoimmune or non-autoimmune thyroid disorders. Positive results were obtained in three of 70 (4.3%) apparently normal subjects, in 16 of 87 (18.4%) patients with Hashimoto's thyroiditis, in 10 of 48 (20.8%) with idiopathic myxoedema, in 25 of 95 (25.6%) with Graves' disease and in five of 64 (7.8%) with other non-autoimmune thyroid disorders. Preliminary results showed that quantitative measurements of PCA by IRMA could be performed using a serum containing high levels of PCA as standard reference. In conclusion, PCA may be easily and specifically detected using the same IRMA procedure previously developed for anti-thyroid antibodies. We therefore suggest that the present IRMA may be proposed as a general technique for the detection of different organ specific autoantibodies.

Hemodialysis leukopenia and complement function with different dialyzers.

The relationship between leukopenia and the complement system during hemodialysis was re-examined by studying not only the in vivo effects of four different dialyzer membranes (cellulose hydrate, cuprophan, cellulose acetate, and polyacrilonitrile) on leukocyte counts and complement levels, but especially by investigating the effects of these membranes on complement function in vitro. Whereas from in vivo studies no definite conclusions could be drawn, in vitro investigations provided clear-cut information. When more sophisticated technical approaches were undertaken, it became evident that hemodialysis leukopenia has to be thought of in terms of chemotactic factor generation. In fact, a strict correlation was demonstrated between the degree of leukopenia induced by the dialyzers tested and the ability of the relative membrane to generate chemotactic activity in vitro. Moreover, the previously observed ability of polyacrilonitrile membrane to induce a decrement in complement function was due to the ability of polyacrilonitrile to adsorb complement activity and did not correspond to effective complement consumption. This finding explained why polyacrilonitrile dialysis is not accompanied by a decrease in circulating granulocytes. Taken together, our data strongly point to a pivotal role of complement system in the pathogenesis of hemodialysis leukopenia.

Circulating immune complexes in haemophilia and von Willebrand's disease.

Sera from 63 patients with haemophilia A, 21 with haemophilia B and 29 with von Willebrand's disease were screened for the presence of circulating immune complexes (CICs), serological markers of hepatitis A and B virus, autoantibodies and factor VIII or factor IX inhibitors. CICs were detected by the 125J Clq binding assay (ClqBA), the solid phase conglutinin assay (KgBSP) and the solid phase Clq assay (ClqSP). The incidence of CICs detected by the ClqBA and the ClqSP methods in haemophiliacs and in von Willebrand patients was higher than that observed in normal subjects, while the prevalence of CICs detected by the KgBSP method was not. The presence of CICs was not correlated with patient age, severity of disease, presence of hepatitis B virus serological markers, abnormal liver function tests or factor VIII inhibitors. A significant connection was demonstrated between CICs detected by the ClqBA method and replacement therapy when the dose administered over 1 year was over 20 000 U of factor VIII or IX concentrates. The high proportion of CICs in von Willebrand's disease, not connected with the replacement therapy or the presence of serological markers of hepatitis virus, is in agreement with the possibility that immune complexes may be related to the disease itself and independent, at least in part, of exogenous agents.

[Acute viral hepatitis in the Florence area: I. Epidemiologic study]. / L'epatite virale acuta nell'area di firenze: I--Studio epidemiologico.

The sera of 401 patients admitted to the Department of Infectious Diseases [U.S.L. (Unità Sanitaria Locale) 10 D] in Florence in one year were screened for the presence of markers of hepatitis A and B viruses. On the basis of clinical and serological data, the diagnosis of viral hepatitis was confirmed for 302 patients. Among the se, 73 (24.18%) were affected by hepatitis A, 182 (60.26%) by hepatitis B and 47 (15.56%) by nonA nonB hepatitis. The prevalence of B nonA nonB hepatitis in 133 drug addicts was 69.37% and 25.51% respectively. A previous infection with hepatitis A virus, as demonstrated by the presence of anti A antibodies of the IgG idiotype in the sera, was demonstrated in 201 of 328 patients (62.03%) not affected by hepatitis A. Only 14% of them reported data related to a possible former acute hepatitis. Markers of B virus were found in 62 of 167 sera of patients (37.12%) not affected by acute B hepatitis or chronic HBsAg positive hepatitis. However the prevalence of virus B markers increases up to 50% in the sera of drug addicts. According to our data the spreading of virus hepatitis in the area of Florence is similar to that observed in other Regions of Central and Northern Italy with fairly good social and hygienic conditions. High prevalence of nonA nonB hepatitis and of HBsAg carriers among the drug addicts are noteworthy.