Recurrent miscarriages in women not fulfilling classification criteria for antiphospholipid antibody syndrome.

Obstetric antiphospholipid antibody syndrome (APS), is well defined by classification criteria. It is well known that women with APS should receive prophylactic anticoagulation therapy with subcutaneous low weight heparin all throughout pregnancy and in the first 6 weeks postpartum. However, the optimal treatment for pregnant women having positive anti-phospholipid antibodies, but not fulfilling classification criteria for APS is still unclear. In this retrospective study we report pregnancy outcomes of 10 patients affected by recurrent miscarriages and positive anti-cardiolipin or aß2GP1 antibodies with titers ranging from 10 to 20 GPL/MPL demonstrated at least twice before pregnancy.

Granuloma annularis revealing Wegener's granulomatosis.

Skin manifestations are often associated with systemic autoimmune diseases (SAD). Some SAD, such as systemic lupus erythematosus, psoriatic arthritis and scleroderma display pathognomonic dermatological features, whereas other systemic diseases such as sarcoidosis, vasculitis and rheumatoid arthritis can present with non-specific skin manifestations that range from erythema nodosum to necrotic lesions. Here we report the case of a 25-year-old man with uveitis, polyarthrirtis, pulmonary involvement, nephrotic syndrome, cutaneous granuloma and pneumonia by E. coli.

The evaluation of the intracavitary effusions by a bedside ultrasound examination.

OBJECTIVE: This study aims to evaluate the bedside use of the pocket-sized ultrasound (US) device for the detection of the intracavitary effusions. METHODS: We randomly enrolled 40 patients admitted to S. Andrea Hospital of Rome. Every patient received a clinical and biochemical evaluation and a bedside US examination to detect and estimate the intracavitary (pleural, pericardial and intra-abdominal) effusions; the US measurements have been compared to the computed tomography (CT) scans (as gold standard). RESULTS: The patients presented a high prevalence of effusions: right pleural 16/40 = 40% (esteemed volume 236.3±500.7 ml, mean±standard deviation m±SD), left pleural 8/40 = 20% (127.0±377.4 ml), pericardial 12/40 = 30% (47.5±72.8 ml) and intra-abdominal effusions 5/40 = 12.5% of cases (110.9±600.6 ml). Linear regression analysis showed a significant correlation between US and CT measurements: pleural r = 0.973 p <  1×10-38, pericardial r = 0.927 p <  1×10-39, intra-abdominal space r = 0.921 p <  1×10-59. The accuracy of the bedside US at the pleural, pericardial and abdominal level was respectively 98%, 93% and 96% (Cohen's kappa coefficient 0.966, 0.841 and 0.833). CONCLUSIONS: The present study showed a high prevalence of the intracavitary effusions and a high accuracy of the bedside US. The bedside US by a pocket-sized device is promising tool for its advantages of reproducibility and non-invasiveness of the device.

Hypercalcaemia in systemic lupus erythematosus.

Hypercalcaemia is found in more than 90% of the cases of primitive hyperparathyroidism and malignancies. Rarely, D hypervitaminosis, sarcoidosis, other granulomatous diseases, some drugs, and endocrine diseases may be responsible. Nine patients with systemic lupus erythematosus (SLE) and hypercalcaemia, without evidence of primary hyperparathyroidism, have been previously described. Here we report the 10th patient with SLE and hypercalcaemia, along with a brief review of the literature.

Lag3+ regulatory T lymphocytes in critical carotid artery stenosis.

The aim of this study was to evaluate CD25+ and Lag3+ T regulatory subpopulations in patients with critical carotid artery stenosis (CAS) and Stanford-A acute aortic dissection (AAD). CD25+ and Lag3+ were measured in 36 patients affected by CAS and 24 patients with Stanford type A AAD. Based on neurological symptoms, patients affected by CAS were further divided in 25 asymptomatic (CAS-A) and 11 symptomatic (CAS-S) subjects. Twenty-five patients with traditional cardiovascular risk factors (RF), matched for age and sex, were used as control group. Interleukin (IL)-10, IL-6 and transforming growth factor-ß-levels were also measured. CD25+ T cells were significantly increased in CAS-S versus CAS-A (p > 0.05), AAD (p > 0.05) and RF (p > 0.05). Moreover, a significant increase in Lag3+ Tregs was observed in CAS e CAS-S versus AAD (p < 0.05) and RF (p < 0.05), whereas no significant difference was observed between CAS-S and CAS-A. IL-6 was higher in AAD compared to the other groups. Patients with neurological symptoms display a peculiar expansion of CD25+ T cells, strongly confirming a relationship between ischemic brain damage and this regulatory subpopulation, whereas Lag3+ Tregs early distinguish CAS from AAD and probably exert protective actions against aortic wall rupture throughout their anti-inflammatory functions.

In vitro fertilization and autoimmunity: Evidence from an observational study.

INTRODUCTION: The aim of this study was to evaluate the prevalence of antiphospholipid antibodies (aPLs) in infertile women undergoing in vitro fertilization (IVF). METHOD OF STUDY: From January 2012 to December 2017, 520 consecutive clinical records of infertile women undergoing IVF were evaluated. Among them, 100 consecutive clinical records of patients with positive autoantibodies were selected. RESULTS: In 100/520 (19.23%) women, positive auto-antibodies were detected: 35/520 (6.73%) fulfilled classification criteria for a systemic disease. Positive aPLs were observed in 43 women (8.27%): 17/520 (3.27%) fulfilled diagnostic criteria for PAPS/APS, whereas patients with positive aPLs, who fulfilled diagnostic criteria for a systemic autoimmune disease other than APS were 18/520 (3.46%). LA and aCL were the main aPLs detected 53.49% and 44.19% respectively, whereas aB2GPI were found in 25.58%. CONCLUSIONS: we suggest that women with infertility may represent a subpopulation of patients with underhanded systemic autoimmune syndromes in which the main symptoms represented are obstetrical complications. We, therefore, recommend evaluating aPLs in all patients undergoing IVF with the aim of recognizing women at a higher risk of miscarriage or pregnancy morbidity.

Systemic lupus erythematosus and myelofibrosis: A case report and revision of literature.

Blood cytopenia represents one of the diagnostic criteria for systemic lupus erythematosus (SLE) and may occur as the first symptom of the disease. Antibody-mediated peripheral destruction of blood cells is the main cause of cytopenia observed in patients affected by SLE, however, inflammatory anemia, nutritional deficiencies, immunosuppressive therapy and, more rarely, myelofibrosis (MF) have also been documented. In the literature, 45 cases of autoimmune MF (AIMF) and SLE have been previously reported. Here the 46 th case of a 43-year-old female with a SLE and an underhand cytopenia, with a review of the literature.

[Ulcerative colitis and thrombocytopenia: a clinical case of fortuitous association?]. / Rettocolite ulcerosa e piastrinopenia: un caso clinico di associazione fortuita?

Ulcerative colitis (UC) is an inflammatory bowel disease of unknown etiology, involving primarily the rectum with major intestinal symptoms. Additionally, UC is often associated with extraintestinal manifestations, especially arthropathies, as well as with some autoimmune disorders. Vice versa, UC is rarely described in association with hematologic abnormalities, such as autoimmune hemolytic anemia and immune thrombocytopenic purpura with antiplatelet antibodies positive. Usually UC precedes the onset of thrombocytopenia by days or years or coincides with it. We report a case of UC and thrombocytopenia with negative anti-platelet antibodies in which an immunosuppressive therapy with corticosteroids obtained significant remission of intestinal symptoms along with a rapid increase of platelet count.

Contribution of immunological mechanism in a case of ochronotic arthropathy.

We have studied cell mediated and humoral response on the synovial fluid and peripheral blood of a 60-year-old man affected by ochronosis. Results showed raised percentages of CD3+, CD8+, HLA-DR+ and CD25+ T cells, presence of TNF, enhanced levels of immunoglobulins and low levels of C3 in the synovial fluid, and a higher rate of HLA-DR+ and CD25+ T lymphocytes in peripheral blood. These data suggest a possible role of immunological response the evolution of an ochronotic arthropathy.

HLA antigens in alkaptonuric patients.

BACKGROUND: In alkaptonuric patients a disabling ochronotic arthropathy develops, due to the deposit of a pigmented polymer of homogentisic acid. Since in inherited diseases the clinical expressions may be multifactorial, involving genetic and environmental factors, where the HLA system may play a role, we studied HLA antigens in ochronotic patients. METHODS: The study was carried out in 21 members of three families of six ochronotic patients and in two isolated ochronotic patients. The HLA typing has been done testing for antigens from loci A, B and C, by international standard microlymphocytotoxicity method, and for loci DR and DQ, by fluorescence method on immunologically isolated cells by means of antibody-coated microspheres. The chi square test was used for statistical analysis, with Yates correction due to the low number of observations. RESULTS: Despite the limited number of subjects, due to the rarity of the disease, a significantly higher prevalence of HLA-DR7 antigen was found in the alkaptonuric patients when compared to a general population (p<0.02), suggesting a possible association, while the prevalence of HLA A, B, C and DQ showed no significant differences. CONCLUSIONS: It might play a role in the pathophysiology and in the clinical expression of the disease.

Role of monocytes in the early phase of acute myocardial infarction.

BACKGROUND: In acute myocardial infarction peripheral leucocytosis occurs early and fibrinogen levels increase in response to the tissue injury, expressed by the enhanced enzyme plasma levels. The aim of the present study has been to investigate if a unifying link between these modifications might be found. METHODS: In 325 patients, 246 men and 79 women, 61.46 +/- 11.00 and 70.03 +/- 11.30 years mean age respectively, at admission for myocardial infarction and before treatment, we simultaneously measured plasma fibrinogen (FBG), hemochromocytometric parameters and plasma enzyme aspartate and alanine transaminase (AST and ALT), lactate dehydrogenase (LDH) and creatine phosphokinase (CPK). The statistical analysis was performed by using standard multiple regression for dependent variable FBG and for the variables white blood cells (WBC), monocyte number, large unstained cells (LUC) and CPK. RESULTS: The results showed that FBG was significantly correlated with monocyte (p < 0.001) and LUC (p < 0.05) counts; assumed as dependent variable, further on with FBG, monocyte number was correlated with WBC count, LUC and CPK; further on with monocyte number, WBC with neutrophile and lymphocyte counts, LUC with CPK, CPK with LDH. CONCLUSIONS: The study seems to show that monocyte modifications occur already in the early phase of myocardial infarction. These modifications are directly related to damage extension, as deducible from CPK levels, and seem to mainly modulate FBG and WBC, since the cytokines and hematopoietic growth factors production by activated monocytes.

Heat inactivable fraction of alkaline phosphatase in marrow and peripheral blood.

We measured the total alkaline phosphatase activity and their heat-inactivable and heat-stable fractions both in marrow and in peripheral blood, collected from 16 patients undergoing bone marrow aspiration for diagnostic purposes. Total enzymatic activity and the heat-inactivable fraction, of bone source, were significantly higher in serum from medullary blood (p < 0.001). Although the heat-stable fraction, of non-bone source, was higher in serum from peripheral blood (p < 0.05), the inactivable fraction showed there the greater component (51.56 +/- 11.91%). Results seem to indicate that the quantification of the enzymatic fractions and of the ratios between them in comparison with marrow and peripheral blood may be useful in cases that pose diagnostic difficulties.

Lactate dehydrogenase and its isoenzymes in the marrow and peripheral blood from haematologically normal subjects.

Lactate dehydrogenase (LDH) activity and its isoenzymatic fractions were measured in bone marrow blood and in peripheral venous blood from 16 haematologically normal subjects. Total LDH activity was significantly higher in marrow than in venous blood (428.8 +/- 98.4 vs 260.1 +/- 40.2 mU/l, p < 0.0001). The same was true for the absolute values of its isoenzymatic fractions. The percentage fractions LDH 1 and LDH 5 were similar in the two regions, while LDH 3 and LDH 4 were higher in medullary blood (p < 0.05) and LDH 2 was higher in peripheral blood (p < 0.05). The Spearman test showed a limited correlation between marrow and peripheral total LDH activity values (p < 0.05). This seems to be at least in part sustained by the highly significant correlations existing in LDH 3 and LDH 4 values, reported to be pre-eminent isoforms in maturing haematopoietic cells (p < 0.005 and p < 0.001, respectively). These findings could be attributed to an apoptotic regulation of marrow cell production.

Hormone metabolism in the pulmonary circulation.

We measured hormonal levels in blood samples from pulmonary and radial arteries in 117 patients undergoing aorto-coronary by-pass surgery with the aim of investigating the role of the pulmonary vessel endothelium in hormone metabolism. Insulin and glucagon concentrations were significantly higher in pulmonary artery blood with respect to radial artery blood (73 +/- 65 vs. 65 +/- 47 pmol/l, p < 0.005, and 80 +/- 49 vs. 73 +/- 51 ng/l, p < 0.01, respectively), while no difference was found for growth hormone, prolactin, C peptide, insulin-like growth factor I, follicle stimulating hormone, luteinizing hormone, thyroid stimulating hormone, parathyroid hormone, thyroglobulin, triiodothyronine, thyroxine, free triiodothyronine, and free thyroxine. Moreover, prolactin concentrations were more than twice the normal levels, this being an effect of propafol and the opiate fentanyl used for the general anesthesia. Assuming that the arteriovenous differences observed are a marker of peptide hormone degradation, our study has demonstrated that with similar kinetics insulin and glucagon secreted into portal circulation and escaping from hepatic extraction undergo further homeostatic removal of about 9-10 % in the pulmonary circulation before entering the general circulation.

Platelet and hemocoagulative changes in elderly atherosclerotic patients after treatment with the antiaggregating drug picotamide.

The effects of the antiaggregating drug picotamide on platelet and hemocoagulative parameters were evaluated in a group of 28 elderly atherosclerotic patients. After 1 month of treatment, consisting of one 300 mg tablet three times per day, a significant inhibition of platelet aggregability in response to ADP, adrenaline, arachidonic acid and collagen and a reduction of the mean platelet volume (-4.62+/-7.46%, P<0.003) was observed. Fibrinogen plasma levels, unchanged at the 15th day, were significantly reduced at the 30th day, from 445.6+/-145.95 to 382.72+/-110.56 mg/dl (P<0.01), while no changes were observed in antithrombin III, factor VII, D-dimer plasma levels and in plasmatic and urinary fibrin(ogen) degradation products values. The results seem to indicate a reduction after antiaggregating treatment of the interaction between the platelets and the vessel wall, that may be responsible for the changes observed.

Renal limited Wegener's granulomatosis.

Differential diagnosis in patients presenting with fever of unknown origin (FUO) is often difficult because infectious diseases, neoplasms, infective endocarditis or systemic autoimmune diseases may all be responsible for the condition. Furthermore, vasculitis may generate typical, atypical or limited syndromes depending on the extent of vascular involvement. Here, we report the case of a 73-year-old man with FUO and renal failure due to a rare variant of Wegener's granulomatosis, limited to the kidneys.

[Splenic infarction after warfarin discontinuation during atrial fibrillation]. / Infarto splenico: rara complicanza tromboembolica di fi brillazione atriale.

We describe a case of patient with splenic infarction, admitted to our department for sudden abdominal pain and fever after discontinuation of anticoagulant therapy for atrial fibrillation, complicating a dilated myocardiopathy and mechanical prosthetic valve. Diagnosis of splenic infarction was made by enhanced-contrast computed tomography, while ultrasounds and radiography were negative. Anticoagulant therapy, gold-standard treatment, was followed by fast clinical improvement. Moreover, splenic infarction should be considered in all cases of acute or chronic pain in left hypochondrium and especially in patients with emboligenous cardiopathies or atrial fibrillation, the most common arrhythmia source of peripheral embolism in clinical practice.