Superior vena cava syndrome - changing etiology in the third millennium.

Superior vena cava syndrome (SVCS), is diagnosed following different degrees of central venous system obstruction, which traditionally was caused by infections, tumors or fibrosing mediastinitis. Recently the role of SVC thrombosis secondary to indwelling central venous devices or pacemaker leads as well as different hypercoagulable states have drawn much attention. In the current review we present a 58-year-old female patient who underwent recurrent pacemaker replacements due to recurrent infections. The patient was hospitalized with superior vena cava syndrome and multiple thrombi in the upper body circulation. Additionally the evaluation was conducted for thrombophilia, which revealed the presence of high titers of antiphospholipid antibodies, suggesting the concurrent diagnosis of the antiphospholipid syndrome (APS). This case reflects the changes in the etiology of SVCS, and the need for a comprehensive evaluation of patients, in the search for additional factors that may complicate a pacemaker insertion, such as the presence of antiphospholipid antibodies. We review the relevant literature and highlight the importance for an interdisciplinary approach in the treatment of SVCS nowadays.

Prolactin's role in the pathogenesis of the antiphospholipid syndrome.

Increased levels of serum prolactin have been reported in patients with various autoimmune diseases and have been associated with lupus disease activity. Currently, there is a lack of data regarding hyperprolactinaemia in patients with the antiphospholipid syndrome. Hence, this study was carried out in order to evaluate the prevalence and clinical significance of hyperprolactinaemia in antiphospholipid syndrome. A total of 172 European patients with antiphospholipid syndrome and 100 geographically and sex-matched healthy controls were included in the study; none had obvious causes of hyperprolactinaemia. All patients underwent clinical assessment for disease manifestations, in addition to laboratory assessment for serum prolactin, antiphospholipid antibodies and some other biomarkers of autoimmune diseases. The tests were performed utilizing the LIAISON® Analyzer (DiaSorin, Sallugia Italy). Hyperprolactinaemia was detected in 21/172 patients with antiphospholipid syndrome and 0/100 controls (p < 0.001). This significant difference was present in both genders and was obvious even after subgrouping the patients into primary and secondary antiphospholipid syndrome. When clinical features were compared, hyperprolactinaemia was associated with reproductive failure, including early and late pregnancy loss (p < 0.05), as well as intrauterine growth retardation (p < 0.05). Hyperprolactinaemia was negatively related to arthralgias, venous thrombosis, pulmonary microthrombosis, pulmonary hypertension in both primary antiphospholipid syndrome and antiphospholipid syndrome secondary to other diseases, and to neurological manifestations in primary antiphospholipid syndrome (p<0.05). The data indirectly imply that prolactin may play a role in the pathogenesis of antiphospholipid syndrome, especially antiphospholipid syndrome-related reproductive failure.

Can lupus flares be associated with tuberculosis infection?

Systemic lupus erythematosus (SLE) is an autoimmune disease that frequently requires treatment with high doses of corticosteroids and immunosuppressive drugs. Primary defects in the innate immunity also contribute to an increased susceptibility to infections. Patients with SLE are at an increased risk for infections with several pathogens, among them Mycobacterium tuberculosis, which is a significant cause of morbidity and mortality, especially in endemic regions. TB infection requires awareness for several reasons: first, TB infection thrives under conditions of immunosuppression, may it be secondary to the disease itself or its treatment. Second, shared antigens by mycobacteria and autoantigens have been described, which may be targets for autoantibodies. We present four Brazilian patients, in whom a diagnosis of tuberculosis was determined during or following persistent flares of their disease. The association of SLE and TB is discussed, as well as different aspects of the tuberculosis infection in this selected population, and its possible role in the course of SLE.

Transverse myelitis and vaccines: a multi-analysis.

Transverse myelitis is a rare clinical syndrome in which an immune-mediated process causes neural injury to the spinal cord. The pathogenesis of transverse myelitis is mostly of an autoimmune nature, triggered by various environmental factors, including vaccination. Our aim here was to search for and analyze reported cases of transverse myelitis following vaccination. A systematic review of PubMed, EMBASE and DynaMed for all English-language journals published between 1970 and 2009 was preformed, utilizing the key words transverse myelitis, myelitis, vaccines, post-vaccination, vaccination and autoimmunity. We have disclosed 37 reported cases of transverse myelitis associated with different vaccines including those against hepatitis B virus, measles-mumps-rubella, diphtheria-tetanus-pertussis and others, given to infants, children and adults. In most of these reported cases the temporal association was between several days and 3 months, although a longer time frame of up to several years was also suggested. Although vaccines harbor a major contribution to public health in the modern era, in rare cases they may be associated with autoimmune phenomena such as transverse myelitis. The associations of different vaccines with a single autoimmune phenomenon allude to the idea that a common denominator of these vaccines, such as an adjuvant, might trigger this syndrome.

Infections and autoimmunity: a panorama.

For more than 2,000 years, it was thought that malignant spirits caused diseases. By the end of nineteenth century, these beliefs were displaced by more modern concepts of disease, namely, the formulation of the "germ theory," which asserted that bacteria or other microorganisms caused disease. With the emergence of chronic degenerative and of autoimmune diseases in the last century, the causative role of microorganisms has been intensely debated; however, no clear explanatory models have been achieved. In this review, we examine the current available literature regarding the relationships between infections and 16 autoimmune diseases. We critically analyzed clinical, serological, and molecular associations, and reviewed experimental models of induction of and, alternatively, protection from autoimmune diseases by infection. After reviewing several studies and reports, a clinical and experimental pattern emerges: Chronic and multiple infections with viruses, such as Epstein-Barr virus and cytomegalovirus, and bacteria, such as H. pylori, may, in susceptible individuals, play a role in the evolvement of autoimmune diseases. As the vast majority of infections pertain to our resident microbiota and endogenous retroviruses and healthy carriage of infections is the rule, we propose to focus on understanding the mechanisms of this healthy carrier state and what changes its configurations to infectious syndromes, to the restoration of health, or to the sustaining of illness into a chronic state and/or autoimmune disease. It seems that in the development of this healthy carriage state, the infection or colonization in early stages of ontogenesis with key microorganisms, also called 'old friends' (lactobacilli, bifidobacteria among others), are important for the healthy living and for the protection from infectious and autoimmune syndromes.

Application of a static fluorescence-based cytometer: the CellScan in clinical immunology.

The CellScan system is a laser scanning cytometer which enables repetitive fluorescence intensity (FI) and polarization (FP) measurements in living cells, as a means of monitoring lymphocyte activation. By monitoring FP changes in peripheral blood lymphocytes (PBL) following exposure to antigenic stimuli, the CellScan may have a role in the diagnosis of autoimmune diseases. Monitoring changes in FI and FP in PBLs from patients with atherosclerosis following exposure to various stimuli, has illustrated the role of the immune system in the atherosclerotic process. The CellScan has also been evaluated as a diagnostic tool for drug-induced allergy, based on FP reduction in PBLs following incubation with the suspected drugs. FI and FP changes in cancer cells have been found to correlate with the cytotoxic effect of different anti-neoplastic drugs, illustrating the potential role of the CellScan system in clinical oncology. In conclusion, the CellScan is a promising new tool with a variety of applications in cell biology, immunology, cancer research and clinical pharmacology.

Pulmonary leukostasis: role of perfusion lung scan in diagnosis and follow up.

A patient with hyperleukocytic myelomonocytic leukemia who presented to the emergency room with sudden pleuritic chest pain and dyspnea is reported. Clinical manifestations included dyspnea tachypnea and hyperventilation. Blood gas analysis revealed hypoxemia, hypocarbia, and respiratory alkalosis. Chest X ray was normal, and perfusion lung scan revealed a diffuse vascular occlusive pattern compatible with pulmonary leukostasis. The patient underwent immediate leukapheresis with subsequent mitigation of symptoms. A second perfusion lung scan showed evidence of significant improvement. To our knowledge this is the first published case of hyperleukocytosis presenting with pulmonary leukostasis that was successfully diagnosed and followed by serial perfusion lung scan.

Tricuspid valve endocarditis in adult patients without known predisposing factors.

Four patients with no known predisposing conditions developed tricuspid valve endocarditis. All patients had community-acquired infection with a rapidly progressive course that was complicated by right heart failure and respiratory insufficiency. Pulmonary involvement was prominent in all cases. The infectious process was due to Staphylococcus aureus in three patients and to Streptococcus intermedius in one patient. Three patients underwent early surgical intervention; the outcome was favourable in all cases. It is clear that tricuspid valve endocarditis can occur in the absence of known predisposing factors, and when Staphylococcus aureus is involved, the course of the disease may be acute and rapidly progressive.

Early invasive pulmonary aspergillosis in a leukemia patient linked to aspergillus contaminated marijuana smoking.

46-year-old patient with acute myeloid leukemia (AML) whose disease manifested as fever, chills and dry cough is reported here. Despite broad antibiotic coverage he remained acutely ill with spiking fever, shaking chills, and hypoxemia. His initial chest radiograph was normal but chest computed tomography (CT) scan disclosed bilateral focal infiltrates. Hypoxemia and severe thrombocytopenia precluded invasive diagnostic procedures. A thorough epidemiological investigation revealed that before becoming acutely ill the patient smoked daily tobacco mixed with marijuana from a "hookah bottle". While waiting for tobacco and "hookah water" cultures, we started antifungal therapy. Resolution of fever and hypoxemia ensued after 72 hours. Tobacco cultures yielded heavy growth of Aspergillus species. We suggest that habitual smoking of Aspergillus-infested tobacco and marijuana caused airway colonization with Aspergillus. Leukemia rendered the patient immunocompromised, and allowed Aspergillus to infest the lung parenchyma with early occurrence of invasive pulmonary aspergillosis. Physicians should be aware of this potentially lethal complication of "hookah" and marijuana smoking in immunocompromised hosts.

Induction of the chemokine stromal-derived factor-1 following DNA damage improves human stem cell function.

The chemokine stromal-derived factor-1 (SDF-1) controls many aspects of stem cell function. Details of its regulation and sites of production are currently unknown. We report that in the bone marrow, SDF-1 is produced mainly by immature osteoblasts and endothelial cells. Conditioning with DNA-damaging agents (ionizing irradiation, cyclophosphamide, and 5-fluorouracil) caused an increase in SDF-1 expression and in CXCR4-dependent homing and repopulation by human stem cells transplanted into NOD/SCID mice. Our findings suggest that immature osteoblasts and endothelial cells control stem cell homing, retention, and repopulation by secreting SDF-1, which also participates in host defense responses to DNA damage.