Deep venous thrombosis: epidemiologic, diagnostic and therapeutic aspects

Deep vein thrombosis (DVT) has a high social and economic cost disease being its prevalence in the general population elevated and producing possibly fatal (pulmonary embolism) or disabling (post-thrombotic syndrome) complications. Thus, it appears of great importance to know the epidemiological and clinical characteristics of DVT in order to perform the best diagnosis, therapy and prophylaxis. The study population is composed by 146 patients (84 males and 62 females, mean age 60.9 +/- 15.3 years, range 19.92 years), arrived in our Vascular Echography Laboratory with the clinical suspect of DVT confirmed by means of echo color Doppler. The most frequent clinical signs were skin hyperthermia in 118 patients (80.8%) and edema in 116 patients (79.5%), while the most common symptom was pain, 89 patients (61.0%). Eleven patients (7.5%) were asymptomatic. The echo criteria utilized were direct thrombus visualization, vessel diameter higher than the contralateral, reduced or absent vessel wall ability to be compressed, reduced or absent color Doppler venous flow, lack or reduction of respiratory flow modulation, visualization of collateral circulation. DVT was located in 131 patients (89.7%) in inferior limbs (proximal in 122 patients, isolated distal in 9 patients), in 14 patients (9.6%) in superior limbs and in 3 patients (2.1%) in the internal jugular vein. In 130 patients a risk factor or a predisposing condition was identified: secondary DVT; in 16 patients the DVT was considered idiopathic. The most frequent risk factors were: previous surgery 28.1%, immobilization 19.9% trauma 17.1%, tumors 9.6%. A hypercoagulation was detected in 4 patients: antithrombin III deficit in 2, post-splenectomy thrombocytosis in 1 and antiphospholipid antibodies syndrome in the last one. The Pisa territory epidemiologic data showed a male 0.51 and female 0.38/1000 subject/year DVT incidence, with significantly higher values in older than 45-54 males and 55-64 females. One hundred and thirty one patients were treated with 5-11 day heparin infusion and thereafter with warfarin at least for 6 months, 1 year or indefinitely depending on thromboembolic risk. Six patients with distal DVT and 9 patients with hemorrhagic risk were treated with subcutaneous calcic or low weight heparin. In 1 patient with a mobile thrombus judged as at very high risk of embolization, a caval filter was positioned. Anticoagulant therapy complications were: 2 minor bleedings, 1 alopecia, 1 thrombocytopenia. Two patients died for neoplastic complications. Fifty-seven patients completed a 6-month follow-up and were submitted to a control each study that evidenced: total recanalization in 15 (26.3%), partial recanalization in 25 (43.9%) and no recanalization in 17 patients (29.8%). In 6 patients there was a DVT relapse and in 9 pulmonary embolization: almost all these patients were in the partial recanalization group.     

Radiolabeled nucleoside analogs in cancer diagnosis and therapy

Radiolabeled nucleosides, specifically 5-iodo-2'-deoxyuridine (IUdR) radioiodinated with the Auger-electronemitting 123I or 125I, have been shown to produce extensive DNA damage in mammalian cell systems in vitro. Such nucleosides are cycle-dependent agents that are taken up by mitotically dividing cells in the S phase of the cell cycle. The degree of damage that occurs is related to the fact that these nucleosides bind covalently to DNA bringing the decaying Augerelectron-emitting radionuclide in close proximity to the genome. The use of these radiohalogenated nucleosides in vivo is associated with several problems. The first relates to their extremely short biologic half-life in blood (T1/2 of minutes in humans). The second involves achieving therapeutic ratios in tumor cells in the face of efficient hepatic dehalogenation. The third concerns the uptake of these radiopharmaceuticals by actively proliferating normal cell renewal systems, thus potentially causing toxic side effects. The fourth, one shared with other cycle-dependent drugs, relates to the matter of labeling the whole tumor cell population. To facilitate targeting to tumors, investigators have been examining the direct introduction of these agents into the targeted area or into an arterial blood supply that immediately precedes the target. For example, radiopharmaceutical administration could be intracavitary (bladder, spinal fluid, peritoneum), intralesional (brain tumor, breast mass) or intra-arterial (liver, pancreas). In all these situations, the following conditions must be met: (a) once within the vicinity of the tumor the agent can freely diffuse through the tissues and is selectively taken up by cancerous cells; (b) once the agent has left the target area it is converted quickly into a nontoxic form and/or excreted from the body; and finally, (c) the biologic behavior of the agent is not altered by repeated injections. We report herein our experience and that of others with [123I/125I/131I]IUdR in cultured cells, animal tumor-model systems, and patients. In vitro, DNA incorporation of 123I- and 125I-labeled IUdR leads to an exponential decrease in cell survival (no shoulder on the survival curve). However, the total number of decays needed to produce a given lethal effect with [123I]IUdR is approximately twice that required with [125I]IUdR. In vivo, the scintigraphic and antineoplastic capabilities of radioiodinated IUdR have been demonstrated in an intraperitoneal murine ovarian tumor model following intraperitoneal injection; in an intracerebral rat gliosarcoma model after intracranial administration; in an intrathecal rat gliosarcoma model after intrathecal infusion; and in a rat transitional cell bladder cancer model following intravesicular infusion. [123I]IUdR, [125I]IUdR, and/or [131I]IUdR have been administered to patients with brain, breast, colorectal, or gastrointestinal cancers (intratumorally); ovarian cancer (intraperitoneally); bladder cancer (intravesically); liver metastases from colorectal cancer (through the hepatic artery, permanent intra-arterial catheter). These studies have confirmed the observations made in animal models. The data indicate that 5-iodo-2'-deoxyuridine radiolabeled with an Auger electron emitter (123I or 125I) may be a useful agent for the scintigraphic diagnosis and/or therapy of neoplastic diseases that are accessible to direct radiopharmaceutical administration. This radiopharmaceutical should serve as a prototype for, and facilitate the development of, other radiolabeled nucleoside analogs. Further investigations are certainly warranted.     

Symbolic analysis of linear polyhedra

This paper concerns several analytical problems related to linear polyhedra in euclidean three-dimensional-space. Symbolic formulas for line, surface, and volume integration are given, and it is shown that domain integrals are computable in polynomial time. In particular, it is shown that mass, first and second moments, and products of inertia are computable inO(E) time, whereE is the number of edges of the boundary. Simple symbolic expressions for the normal derivatives of domain integrals are also derived. In particular, it is shown that they are closely linked to the topology of the integration domain, as well as that they are expressible as combinations of domain integrals over lower-order domains (faces, edges, and vertices). The symbolic results presented in this paper may lead to an easy incorporation of integral constraints, for example, concerning mass and inertia, in the engineering designing process of solid objects.     

Synthesis and Evaluation of Voltage-Gated Sodium Channel Blocking Pyrroline Derivatives Endowed with Both Antiarrhythmic and Antioxidant Activities

Under the hypothesis that cardioprotective agents might benefit from synergism between antiarrhythmic activity and antioxidant properties, a small series of mexiletine analogues were coupled with the 2,2,5,5-tetramethylpyrroline moiety, known for its antioxidant effect, in order to obtain dual-acting drugs potentially useful in the protection of the heart against post-ischemic reperfusion injury. The pyrroline derivatives reported herein were found to be more potent as antiarrhythmic agents than mexiletine and displayed antioxidant activity. The most interesting tetramethylpyrroline congener, a tert-butyl-substituted analogue, was at least 100 times more active as an antiarrhythmic than mexiletine.     

Lipofilling in Breast Oncological Surgery: A Safe Opportunity or Risk for Cancer Recurrence?

Lipofilling (LF) is a largely employed technique in reconstructive and esthetic breast surgery. Over the years, it has demonstrated to be extremely useful for treatment of soft tissue defects after demolitive or conservative breast cancer surgery and different procedures have been developed to improve the survival of transplanted fat graft. The regenerative potential of LF is attributed to the multipotent stem cells found in large quantity in adipose tissue. However, a growing body of pre-clinical evidence shows that adipocytes and adipose-derived stromal cells may have pro-tumorigenic potential. Despite no clear indication from clinical studies has demonstrated an increased risk of cancer recurrence upon LF, these observations challenge the oncologic safety of the procedure. This review aims to provide an updated overview of both the clinical and the pre-clinical indications to the suitability and safety of LF in breast oncological surgery. Cellular and molecular players in the crosstalk between adipose tissue and cancer are described, and heterogeneous contradictory results are discussed, highlighting that important issues still remain to be solved to get a clear understanding of LF safety in breast cancer patients.     

A new short-path distillation system applied to the reduction of cholesterol in butter and lard

A molecular distillation plant, built particularly to increase the separation efficiency and to obtain safer working conditions, was tested to remove cholesterol from anhydrous butter and lard. A preliminary experiment was carried out with butter to evaluate the fractionation obtained at temperatures between 190 and 250°C and residual pressures between 10⁻³ and 10⁻⁴ torr. A second experiment was carried out at 185°C and at the maximum operational vacuum, evaluating the fractionation achieved within a time scale between 30 and 180 min. Cholesterol was almost completely removed during the second hour with minimal loss of low-molecular weight triglycerides. An experiment was carried out with lard at 250°C and maximum achievable operational vacuum (10⁻⁴ Torr), lasting approximately 6 h, and cholesterol was removed almost completely during the second hour without significant modifications in the triglyceride composition. This situation remained constant throughout the duration of the test.     

On requirement verification for evolving Statecharts specifications

Software development processes have been evolving from rigid, pre-specified, and sequential to incremental, and iterative. This evolution has been dictated by the need to accommodate evolving user requirements and reduce the delay between design decision and feedback from users. Formal verification techniques, however, have largely ignored this evolution and even when they made enormous improvements and found significant uses in practice, like in the case of model checking, they remained confined into the niches of safety-critical systems. Model checking verifies if a system’s model \(\mathcal{M}\) satisfies a set of requirements, formalized as a set of logic properties \(\Phi\) . Current model-checking approaches, however, implicitly rely on the assumption that both the complete model \(\mathcal{M}\) and the whole set of properties \(\Phi\) are fully specified when verification takes place. Very often, however, \(\mathcal{M}\) is subject to change because its development is iterative and its definition evolves through stages of incompleteness, where alternative design decisions are explored, typically to evaluate some quality trade-offs. Evolving systems specifications of this kind ask for novel verification approaches that tolerate incompleteness and support incremental analysis of alternative designs for certain functionalities. This is exactly the focus of this paper, which develops an incremental model-checking approach for evolving Statecharts. Statecharts have been chosen both because they are increasingly used in practice natively support model refinements.     

Effect of Enameling on the Strength and Dynamic Fatigue of Soda–Lime–Silica Float Glass

The effect of a glass enamel coating on the strength and fatigue behavior of float glass was investigated. Commercially available enamel that was comprised of Cu₂Cr₂O₄ pigment particles in a bismuth-zinc borosilicate glass matrix was applied to a soda–lime–silica float glass via screen printing, followed by fusion at elevated temperature. Strengths of the enameled specimens were evaluated in biaxial flexure using a ring-on-ring (ROR) test geometry, and the data were analyzed using a conventional two-parameter Weibull distribution. Enameling was found to significantly degrade the strength of the float glass. There was no statistical difference in the characteristic strengths of samples enameled on the air side (66 MPa) compared with samples enameled on the tin side (61 MPa) of the float glass. Fractographic analysis revealed that the failures in the enameled float glass samples initiated at pores and pigment aggregates in the enamel, whereas failures in float glass samples initiated solely from surface flaws. Dynamic fatigue tests were performed on enameled float glass and indented float glass samples to determine the effect of the enamel on the stress corrosion behavior of the enameled components. There was no statistically significant difference between the stress corrosion exponents for the float glass and enameled float glass specimens.