Venous thromboembolism and hypercoagulability in splenectomized patients with thalassaemia intermedia

Thromboembolic phenomena have been described in patients with thalassaemia intermedia and major, although there are relatively few epidemiological data on the overall frequency of these complications. To obtain more insight into the risk and mechanism of venous thromboembolism in thalassaemia, the aims of this study were: (i) to establish retrospectively the prevalence of thromboembolic events in a large group of adults with thalassaemia intermedia and major during a follow up period of 10 years; (ii) to measure in subgroups of these patients sensitive markers of activation of coagulation and fibrinolysis enzymes; and (iii) to look for possible procoagulant mechanisms. A high prevalence of thromboembolic events was found, particularly in splenectomized patients with thalassaemia intermedia (29%). These patients had high plasma levels of markers of coagulation and fibrinolysis activation. Furthermore, thalassaemic red cells and erythroid precursors from splenectomized patients with thalassaemia intermedia had an enhanced capacity to generate thrombin. To evaluate the role of splenectomy per se on procoagulant activity, we evaluated the capacity to form thrombin in healthy individuals who had been splenectomized for trauma. They produced the same amount of thrombin as non-splenectomized controls. In conclusion, the results of this study show the existence of a hypercoagulable state in splenectomized patients with thalassaemia intermedia and that their red and erythroid cells are capable of acting as activated platelets in thrombin generation.     

Clonally related penicillin-nonsusceptible Streptococcus pneumoniae serotype 14 from cases of meningitis in Salvador, Brazil.

Active hospital-based surveillance in the city of Salvador, Brazil, from December 1995 through October 1998, identified 221 patients with confirmed pneumococcal meningitis. Of these 221 patients, 29 (13%) had isolates with intermediate-level resistance to penicillin. Infection with these penicillin-nonsusceptible isolates was significantly associated with age of <2 years (P<.0019), previous antibiotic use (P<.0006), and coresistance to trimethoprim-sulfamethoxazole (P<.0000). Serotype 14 was the most prevalent serotype (55.2%) of penicillin-nonsusceptible isolates. Strain typing by repetitive element BOX polymerase chain reaction (PCR) analysis showed that penicillin-nonsusceptible serotype 14 isolates had closely related BOX PCR patterns, whereas penicillin-susceptible serotype 14 isolates each had distinct, unrelated patterns. Penicillin-nonsusceptible serotype 14 isolates from Salvador and other Brazilian cities had similar BOX PCR patterns. These observations indicate that in Brazil a large proportion of cases of penicillin-nonsusceptible pneumococcal meningitis appear to be caused by a closely related group of serotype 14 strains that may have disseminated to widely separate geographic areas.     

Urinary incontinence in the elderly: relation to cognitive and motor function

Urinary incontinence is a common problem in older subjects, very often wrongfully accepted as a normal part of the aging process. A total of 520 subjects (208 males and 312 females; mean age 74.8 +/- 11.8 years), from both private- and nursing-home dwelling populations, were included in this study aimed to estimate the incidence of urinary incontinence and identify factors associated with condition, in aged subjects. The incidence and type of urinary incontinence (stress, urge or mixed incontinence) were assessed by structured questionnaires and diagnosis was confirmed by a seven-day consecutive voiding diary. Assessment of physical, cognitive and emotional functions was performed on each subject using the Mini Mental State Examination (MMSE), Instrumental Activities of Daily Living Scale (IADL), Tinetti Scale (gait), Tinetti Scale (balance) and Geriatric Depression Scale (GDS) instruments. In the total population sample the incidence of urinary incontinence was 47.9%. The incontinence cases were classified, according to the different types, as: stress incontinence (males: 3.4%; females: 8.7%; males+females: 6.5%); urge incontinence (males: 27.4%; females: 31.4%; males+females: 29.8%); mixed incontinence (males: 20.2%; females: 5.8%; males+females: 11.5%). In the total population sample, no significant relationship was found between age and prevalence of urinary incontinence. In the elderly female group, age significantly correlated in a direct manner with urge incontinence (P<0.01) and inversely with stress incontinence (P<0.001). Only in the male sex group age significantly correlated with mixed incontinence (P<0.005). Multiple linear regression analysis showed that the dependent variable 'incontinence' could be predicted by MMSE (P<0.001) in the male sex group and by the Tinetti Scale (gait) (P<0.001) in the female sex group.     

Endothelium and hemorheology

Hemorheological alterations which can be found in ischaemic vascular diseases are well known and widely studied; less clear is the relationship between these alterations and endothelial function. Our studies showed that modifications in endothelial function caused by physical stress are associated with a worsening in hemorheological parameters mainly in patients affected by ischaemic vascular diseases: major vascular alterations have been found in patients with very high levels of plasma markers endothelial dysfunction. The control of the basal tone of the vessels is given by the complex interaction between vasoconstrictor and vasodilator endothelial factors and when this equilibrium is broken we have the endothelial dysfunction. From a methodological point of view we can find an endothelial dysfunction index determining the various substances produced by the endothelium, but it is very difficult to have a value which clearly identifies the real state of the endothelial alteration. The function of the NO, which is one of the more powerful endogenous vasodilators and whose synthesis is catalysed by nitric oxide synthase (NOS), can be determined by the ratio between blood concentrations of citrulline and arginine (the co-product and the precursor of the way of NO synthesis), which represents the level of activity of the enzyme. A very affordable index of the endothelial dysfunction is the asymmetric dimethylarginine (ADMA), a powerful endogenous inhibitor of NOS; in fact several studies demonstrated a strong relationship between ischaemic vascular diseases and high levels of plasma ADMA. Evaluation of these parameters is measured by means of high performance liquid chromatography (HPLC): this technique provides very affordable results and allows to obtain evaluations of substances in very small concentrations, like ADMA.     

Anti-beta 2 glycoprotein I antibodies in centenarians

BACKGROUND: Non-organ-specific autoantibodies are present in centenarians without evidence of autoimmune diseases but conflicting or no data on anti-phospholipid and anti-phospholipid binding proteins were reported. OBJECTIVE: To investigate the presence and antigen specificity of anti-phospholipid and anti-phospholipid binding proteins in centenarians. METHODS: Seventy-seven centenarians, 70 adult controls, 65 unselected elderly subjects, and 38 old SENIEUR volunteers were investigated. Anti-cardiolipin, anti-human beta 2 glycoprotein I, and lupus anticoagulant were detected. Antigen specificity was assayed against plates coated with anionic, neutral and cationic phospholipids and beta 2 glycoprotein I-dependence was also evaluated. RESULTS: 54.3% of the centenarians were positive for IgG and 8.6% for IgM anti-beta 2 glycoprotein I antibodies, while only 20.7% centenarians were positive for anti-cardiolipin IgG and 2.59% for IgM; none resulted positive for lupus anticoagulant. Anti-cardiolipin positive sera cross-reacted with negatively charged phospholipids and displayed decreased binding to serum-free cardiolipin-coated plates that was restored by human beta 2 glycoprotein I or fetal calf serum. CONCLUSIONS: Centenarians display high reactivity against human beta 2 glycoprotein I but low binding to the bovine molecule in the anti-cardiolipin assay. In spite of the presence of antibodies comparable to those found in patients with the anti-phospholipid syndrome, no vascular events were reported suggesting the presence of unknown protective factors and/or the lack of triggering factors.     

Value of ERCP in the diagnosis and management of pre- and postoperative biliary complications in hydatid disease of the liver

Twenty-nine patients with symptomatic hydatid disease of the liver were evaluated preoperatively by endoscopic retrograde cholangiopancreatography (ERCP) in the years 1982-1987. In the same period, 6 patients who previously underwent surgery for the parasitic disease also underwent ERCP because of postoperative symptoms of biliary obstruction. Findings at ERCP excluded biliary tract involvement in 11 cases. Positive findings were shown in 24 patients, including compression of the bile ducts in 4, small cysto-biliary communications in 5, intrabiliary rupture in 9, residual hydatid material in the common bile duct, and sclerosing cholangitis in 3. Endoscopic removal of migrated hydatid debris was achieved in 8 patients, avoiding reoperation in 4.     

Tumor-derived microvesicles: The metastasomes

Metastasis is the leading cause of cancer death, yet it is mechanistically considered a very inefficient process suggesting the presence of some sort of (e.g. systemic) routes for fuelling the process. The pre-metastatic niche formation is described as one such metastasis promoting route. Now, the emerging potentials of tumor-derived microvesicles (TDMVs), not only in formulating the pre-metastatic niche, but also conferring neoplastic phenotypes onto normal cells, has integrated new concepts into the field. Here, we note as an ancillary proposition that, exerting functional disturbances in other sites, TDMVs (we have termed them metastasomes) may aid foundation of the secondary lesions via two seemingly interrelated models: (i) tumor-organ-training (TOTr), training a proper niche for the growth of the disseminated tumor cells; (ii) tumor-organ-targeting (TOTa), contribution to the propagation of the transformed phenotype via direct or indirect (TOTr-mediated disturbed stroma) transformation and/or heightened growth/survival states of the normal resident cells in the secondary organs. Respecting the high content of the RNA molecules (particularly microRNAs) identified in the secretory MVs, they may play crucial parts in such “malignant trait” spreading system. That is, the interactions between tumor tissue-specific RNA signatures, being transferred via metastasomes, and the cell-type/tissue-specific RNA stockrooms in other areas may settle a unique outcome in each organ. Thus, serving as tumor-organ matchmakers, the RNA molecules may also play substantial roles in the seeding and tropism of the process.