Thrombolytic therapy or surgery for valve prosthesis thrombosis: systematic review and meta-analysis.

BACKGROUND: Prosthetic heart valve thrombosis is a life-threatening condition for which treatment has not been evaluated by randomized trials. OBJECTIVES: To compare surgery with thrombolytic therapy for the treatment of prosthetic valve thrombosis. METHODS: A comprehensive systematic review was carried out by independent researchers using PubMed, Web of Knowledge, HINARI, LILACS and EMBASE, including papers indexed up to 23 October 2013 with at least 10 patients, evaluating one or both treatment options. Outcomes of interest were death, stroke, bleeding, embolic events and success. Study quality was assessed by the Newcastle-Ottawa Scale (ranges from 0 to 9). Comprehensive Meta Analysis Software was used to pool study results, for publication bias analysis and for meta-regression. RESULTS: Forty-eight studies were included (2302 patients). No randomized study was identified, and all were observational in design. Study quality varied from 4 to 6 stars using the Newcastle-Ottawa Scale. Mortality for surgery was 18.1% (95%CI, 14.6-22.1; I(2) , 62% [42-75]), while mortality for thrombolytic therapy was 6.6% (95% CI, 4.8-8.9; I(2) , 0% [0-13]). Surgical mortality appeared to increase with NYHA-class, according to meta-regression. Other results related to surgery and thrombolytic therapy, respectively, were: embolic events, 4.6% (2.9-7.3) and 12.8% (10.8-15.2); stroke, 4.3%,(2.7-6.6%) and 5.6%,(4.3-7.4%); success rate, 81.9% (77.2-85.8) and 80.7% (75.6-85.0); bleeding, 4.6% (2.9-7.1) and 6.8% (5.4-8.6); and death or stroke, 19.0% (14.8-24.2) and 11.4% (8.7-14.7). CONCLUSION: Mortality in patients treated by thrombolytic therapy for valve prosthesis thrombosis is significantly lower than in patients treated surgically. As we cannot yet ascertain whether this difference is due to the treatment alone, more studies are now necessary to further clarify these findings.

In vitro remineralizing effect of fluoride varnishes containing sodium trimetaphosphate.

This study analyzed the effects of fluoride varnishes supplemented with sodium trimetaphosphate (TMP) on the remineralization of caries-like lesions in vitro. Bovine enamel discs were selected through surface hardness (SH) and caries-like lesions were induced. SH was again determined and the blocks were divided into 7 experimental groups (n = 24/group): placebo (no fluoride or TMP), 5% TMP, 2.5% NaF, 2.5% NaF/5% TMP, 5% NaF, 5% NaF/5% TMP and commercial formulation (Duraphat™, 5% NaF), following a blind protocol. Discs were treated with the varnishes and kept in a remineralizing solution for 4 h and a demineralizing solution for 2 h. Varnishes were then removed and half of the discs were used for analysis of loosely (CaF2) and firmly bound fluoride. The remaining discs were submitted to a pH-cycling regimen for 6 days. The percentage of surface hardness recovery (%SHR), cross-sectional hardness (ΔKHN) and enamel CaF2 and fluoride were determined. Data were analyzed by ANOVA and by Student-Newman-Keuls' test (p < 0.05). A dose-response relationship was observed between fluoride concentrations in the varnishes and %SHR. The 5% TMP varnish led to %SHR similar to that obtained for the placebo. When TMP was used in association with fluoride, however, significantly higher %SHR were observed in comparison with their counterparts without TMP. Moreover, ΔKHN obtained for the 5% NaF/5% TMP was significantly lower among all groups tested. Higher concentrations of CaF2 and fluoride were observed for Duraphat and 5% NaF, followed by 5% NaF/5% TMP, 2.5% NaF and 2.5% NaF/5% TMP (p < 0.05). It was concluded that the supplementation of fluoride varnishes with TMP leads to enhanced remineralizing effect of artificial caries lesions in vitro.

In vitro evaluation of the effect of mouth rinse with trimetaphosphate on enamel demineralization.

OBJECTIVE: The aim of this study was to investigate the effectiveness of sodium trimetaphosphate (TMP) addition to mouth rinses to inhibit enamel demineralization. DESIGN: Bovine enamel blocks (n = 88) were selected by surface hardness and divided into eight treatment groups (n = 11 per group): placebo, 100 or 225 µg F/ml; the rinses with 100 µg F/ml had differing TMP concentrations (range 0-0.6%). The blocks were subjected to pH cycling for 5 days and treated twice a day with mouth rinses. After that, surface and cross-sectional hardness as well as fluoride in enamel were measured. RESULTS: The groups containing both 100 µg F/ml and 0.4% TMP inhibited demineralization most effectively (p < 0.001). This formulation yielded lower values of lesion areas than the formulations containing 100 or 225 µg F/ml but no TMP. The addition of 0.4% TMP increased the fluoride in enamel. CONCLUSION: It is possible to improve the effectiveness of a mouth rinse with 100 µg F/ml by addition of TMP, this being superior in inhibiting enamel demineralization compared with mouth rinses containing 225 µg F/ml.

Inhibition of human LAK-cell activity by the anti-depressant trifluoperazine.

The anti-depressive drug trifluoperazine (TFP) was studied on in vitro immune responses. TFP proved to be an inhibitor of lymphokine-activated killer (LAK) cells in its generative step, as well as in its effector phase. Natural killer (NK) activity and interleukin-2 (IL-2) or mitogen-induced lymphocyte proliferation were just as sensitive to the drug effects, whereas the division of tumor cells was more resistant. The mechanism through which TFP suppresses these lymphocytic systems remains unclear. It does not, however, affect an early stage of cellular activation as the addition of the drug as late as 24 h after the start of the culture was still inhibitory for lymphocyte mitogenesis. Neither the expression of CD25, nor that of CD56 was affected by TFP, and exogenous IL-2 was unable to overcome the suppression of proliferation. In relation to cell-mediated cytotoxicity, TFP partially interfered with the effector/target binding. However, addition of lectin to the assay did not overcome the inhibition of lysis produced by the drug. Although further work remains to be done, the effect of TFP on immune responses must be taken into consideration when treating immunosuppressed patients.

Effect of ouabain on lymphokine-activated killer cells.

A large amount of evidence points towards the potential role of lymphokine activated killer (LAK) cells as tools in the treatment of chronically stressed conditions, such as cancer. The modulation of this activity by biologically active endogenous compounds of the HPA (hypothalamic-pituitary-adrenal) axis, however, is not completely understood. Ouabain, a specific inhibitor of Na(+)-K(+)-ATPase, and now recognized as an endogenous component present in human plasma, was tested on IL-2 and TPA-activated killer cells. Ouabain was able to inhibit the generation of LAK activity, as well as to suppress either PHA or TPA-induced lymphocyte proliferation. Once the cells were triggered for cytotoxicity, however, ouabain was not able to interfere with their effector phase, as it did not show any effect when present only during the assay. TPA-induced "LAK-simile" cells displayed the same sensitivity towards ouabain as LAK cells did. Although the physiological relevance of endogenous ouabain secretion remains elusive, these effects of ouabain on LAK cytotoxicity should be considered in patients undergoing this kind of immunotherapy.

Ultrastructural study on the spermiogenesis and spermatozoon of the metacercariae of Microphallus primas (Digenea), a parasite of Carcinus maenas.

The thread-like spermatozoon of the crab parasite Microphallus primas was studied by electron microscopy. A survey of the head region of the spermatozoon reveals three features hitherto unknown in Platyhelminthes spermatozoa. The first is the aberrant inclusion of the nucleus within one of the two axonemes, limited to the head end region. The second is the coexistence, in the same axoneme, of two patterns, 9 + 0 (doublets without dynein arms) and 9 + "1". The third is the presence of a layer of cortical microtubules running longitudinally from the zone where the nucleus goes from axoneme to the tail region (where the two flagella start). The sequence of events in spermatogenesis is similar to that described for most of the Digenea trematodes, and the spermiogenesis process conforms to a common plan in nearly the whole group.

Ultrastructural and cytochemical studies in the mantle of Anodonta cygnea.

The large central region of the mantle of Anodonta cygnea was studied using transmission and scanning electron microscopy (TEM and SEM) for ultrastructural analysis and light microscopy (LM) and TEM for cytochemical analysis. X-ray diffraction studies of the organic matrix pellicle deposited on the inner surface of the shell were also carried out. Two groups of columnar cells presenting desmosomes on the apical region were observed in the outer epithelium. One group secretes a structural and neutral mucopolysaccharide (MPS) identified with chitin, normally excreted to form the organic matrix of the shell. Another group presents numerous cytoplasmic vesicles and constitutes the predominant cells of this epithelium. Two different types of mucous cells were found in the inner epithelium. One type secretes a faintly acid mucopolysaccharide (MPS) with sulphate groups and another type secretes an association of this polysaccharide with a neutral MPS. Staining for sulfhydryl groups (probably cysteine) was also positive, suggesting the presence of proteoglycans in these secretions. A third type of cells was also observed presenting a very different ultrastructural aspect (columnar form) without large secretion masses. They may correspond to the replacing cells in this highly secretory epithelium. Elastic fibers were found on the base of the outer epithelium and amoebocytes were observed in the interepithelial tissue.