Surveillance after colorectal cancer surgery

Early diagnosis of local and distant recurrences of colorectal cancer remains difficult and there is no agreement on the effectiveness of follow-up in these patients. The aim of this study is to assess the value of our method of follow-up. We consider 239 patients with colorectal cancer and at least 2 years follow-up following radical resection. A local recurrence appeared in 26 patients (10.9%), a distant metastasis in 41 (17.1%), while in seven (2.9%) local and distant recurrences appeared simultaneously. Local recurrence was detected because of an increase in carcinoembryonic antigen (CEA) level in 15 patients (57.7%), during a scheduled endoscopy in four (15.4%) and because of symptoms in seven (26.9%). In seven patients (26.9%) a radical resection was possible. Distant metastases were detected by CEA levels in 20 patients (48.8%), by ultrasonography (U.S.) in 12 (29.3%) and by chest X-ray in five (12.2%). In 13 of 26 patients with liver metastases a resection was performed. This study shows that few patients benefit from follow-up and only CEA levels and liver U.S. performed intensively between 15 and 36 months after surgery are useful in early detection of recurrences. A modification of the follow-up to the single patient, according to the stage, location and grading of cancer, could improve the results, so lowering the costs of this expensive practice.     

Solution conformation of the Pseudomonas syringae MSU 16H phytotoxic lipodepsipeptide Pseudomycin A determined by computer simulations using distance geometry and molecular dynamics from NMR data

Pseudomycin A is a cyclic lipodepsinonapeptide phytotoxin produced by a strain of the plant pathogenic bacterium Pseudomonas syringae. Like other members of this family of bacterial metabolites, it is characterised by a fatty acylated cyclic peptide with mixed chirality and lactonic closure. Several biological activities of Pseudomycin A are lower than those found for some of its congeners, a difference which might depend on the diverse number and distribution of charged residues in the peptide moiety. Hence, it was of interest to investigate its conformation in solution. After the complete interpretation of the two-dimensional NMR spectra, NOE data were obtained and the structure was determined by computer simulations, applying distance geometry and molecular dynamics procedures. The conformation of the large ring of Pseudomycin A in solution includes three rigid structural regions interrupted by three short flexible regions that act as hinges. The overall three-dimensional structure of the cyclic moiety is similar to that of previously studied bioactive lipodepsinonapeptides produced by other pseudomonads.     

Direct monitoring of the calcium concentration in the sarcoplasmic and endoplasmic reticulum of skeletal muscle myotubes

Direct monitoring of the free Ca2+ concentration in the sarcoplasmic reticulum (SR) was carried out in rat skeletal myotubes transfected with a specifically targeted aequorin chimera (srAEQ). Myotubes were also transfected with a chimeric aequorin (erAEQ) that we have demonstrated previously is retained in the endoplasmic reticulum (ER). Immunolocalization analysis showed that although both recombinant proteins are distributed in an endomembrane network identifiable with immature SR, the erAEQ protein was retained also in the perinuclear membrane. The difficulty of measuring [Ca2+] in 100-1000 microM range was overcome with the use of the synthetic coelenterazine analogue, coelenterazine n. We demonstrate that the steady state levels of [Ca2+] measured with srAEQ is around 300 microM, whereas that measured with erAEQ is significantly lower, i.e. around 200 microM. The effects of caffeine, high KCl, and nicotinic receptor stimulation, in the presence or absence of external calcium or after blockade of the Ca-ATPase, were investigated with both chimeras. The kinetics of [Ca2+] changes revealed by the erAEQ were similar, but not identical, neither quantitatively nor qualitatively, to those monitored with the srAEQ, indicating that at this stage of muscle development, differences exist between SR and ER in their mechanisms of Ca2+ handling. The functional implications of these findings are discussed.     

Efficacy of lonidamine combined with different DNA-damaging agents in the treatment of the MX-1 tumor xenograft

The a.c. conductivity of the proteins lysozyme and subtilisin, both in their active and inactive or inhibited forms were determined theoretically. For this, quantum mechanical calculations and a random walk theory were used. The conclusions are that these enzymatic proteins can easily transport electrons which is most probably important in their role as catalysators of biochemical reactions. The electron transport is sensitive to three-dimensional changes of the active sites of these enzymes which have more flexibility than the whole molecule. Therefore, the flexibility of the active sites of enzyme catalysts is not only important for the conformational fitting with the reactants, but also strongly influences the transport in biochemical reactions.     

Myxomas of the mandible and maxilla

Two cases of congenital absence of a cervical vertebral pedicle are reported. This condition includes hypoplasia of the ipsilateral posterior arch and may predispose to spinal cord injury. The radiographic and computed tomography (CT) findings are reviewed, and the importance of the ipsilateral oblique radiographic view and of CT in diagnosis is stressed.     

Salvage chemotherapy with mitomycin, vindesine, and cisplatin (MiViP) in recurrent carcinoma of the cervix

We report two cases of metastatic non-functioning pancreatic endocrine tumour with very elevated plasma levels of alpha-fetoprotein. In these two cases, serial plasma levels of alpha-fetoprotein, initially normal, correlated well with hepatic tumour progression and were associated with fatal outcome. These results suggest that elevated plasma concentration of alpha-fetoprotein may be caused by metastatic pancreatic endocrine tumour and than alpha-fetoprotein serial measurement may be useful in prognostic evaluation.     

The geometric nature of plasticity laws

This paper concerns the plasticity constitutive laws in small strain. In the thermodynamic approach developed here, the key concept is that of internal variables. The differential nature of plasticity law has been pointed out for a long time. If we unite the invariance condition of these laws in a state variable transformation, this involves, ultimately, that the natural mathematic frame of plasticity theory is Differential Geometry. The system state is defined as a point of a differentiable manifold. The state variable are the local coordinates of this point in a chart. The internal stresses are the components of a covariant vector of the cotangent bundle to internal state manifold and the elastic domain is a convex part of cotangent vector space. The plastic yield criteria such as von Mises condition define a Riemannian structure over the manifold. The metric element is identified with the internal dissipation element. Constitutive laws link the covariant derivatives of the thermodynamic stress with the state variable. Hardening modulus splits up in two parts, kinematic hardening and metric hardening. This last is defined by Christoffel connection coefficients. Applied to von Mises isotropic yield condition, the metric hardening is identified with isotropic hardening. The Baltov-Sawczuk model is also analysed. The use of appropriate polar coordinates simplifies significantly the computations. Generalization to a significant category of non-differentiable yield criteria, such as Tresca condition, is considered by introducting a metric tensor family. The adaptation of Drucker's postulate to the proposed model requires the introduction of parallel transport of the internal stress covector. Generally, this transport is different over distinctive paths joining two points. This fact expresses internal state manifold curvature. The Riemann-Christoffel tensor is computed for von Mises, Baltov-Sawczuk and Tresca models.     

Characterization of an ASIC for CPG sensors with grid-only depth of interaction sensing

A new version of the front-end application specific integrated circuit (ASIC) for co-planar-grid (CPG) sensors is presented. Compared to the first version, the ASIC is optimized for signal/noise performance, modified in peaking time, and it implements timing signals to measure the depth of interaction using the grids signals only. Experimental results using state-of the-art CPG sensors and different approaches for reducing the error due to electron trapping are reported. A new technique that makes use of the sum and difference of the grids signals is also presented.