Low molecular weight heparins. Implications in anesthesia and resuscitation

Low molecular weight heparins are a group of drugs that have only recently been introduced in clinical practice. The are widely used for prophylaxis in thromboembolic disease and are being employed increasingly to treat established venous thrombosis. One way in which these drugs are often used is for prophylaxis in the perioperative period for patients at high risk of developing venous thromboembolism, and the anesthesiologist must therefore be familiar with the main aspects of this application. We review pharmacological characteristics of these drugs as well as the literature on low molecular weight heparins, stressing points of main interest to the anesthesiologist and intensive care recovery unit specialist, namely adverse effects (mainly bleeding) and the implications that use of low molecular weight heparin will have on choice of anesthetic (in particular the dilemma of whether to use local/regional anesthesia).     

A shared genetic mechanism for melanotic encapsulation of CM-Sephadex beads and a malaria parasite, Plasmodium cynomolgi B, in the mosquito, Anopheles gambiae

Dialysis dose and malnutrition have a great impact on the clinical out come of chronic hemodialysis patients. The interrelationships between them, however, remain undefined. Thus, we performed a study to determine the effects of increasing the dialysis dose on serum albumin concentrations and mortality in hemodialysis patients. We examined urea kinetic modeling, biochemical nutritional indices, comorbid conditions, patient survival time, and annual mortality rate. Dialysis dose, measured by Kt/V, significantly increased from 1.3 +/- 0.3 in 1987 to 1.5 +/- 0.4 in 1990 and to 1.7 +/- 0.4 in 1993. Serum albumin level also increased from 3.8 +/- 0.4 g/dL in 1987 to 4.0 +/- 0.4 in 1990 and to 1.7 +/- 0.4 in 1993. In 1993, 76% of patients had Kt/V > or = 1.50 compared with 45% in 1990 and 28% in 1987, whereas 82% of patients had a serum albumin level > or 4.0 g/dL in 1993 compared with 58% in 1990 and 29% in 1987. Protein catabolic rate and hematocrit also increased from 1987 to 1993, but not serum cholesterol or triglyceride. The annual mortality rate declined from 16.1% in 1987 to 13.2% in 1990 and to 8.0% in 1993. The decrease in mortality appeared to be unrelated to differences in patient selection or comorbid conditions. Serum albumin levels, hematocrit, Kt/V, and protein catabolic rate were significantly related to patient survival after age, sex, and diabetic status had been adjusted. Furthermore, there was a positive correlation between Kt/Vs and serum albumin concentration (r = 0.216, P < 0.001). Thus it appears that increasing the dose of dialysis improves serum albumin levels and perhaps survival rate in hemodialysis patients as well.     

Molecular basis of resistance to HIV-1 protease inhibition: a plausible hypothesis

The binding thermodynamics of the HIV-1 protease inhibitor acetyl pepstatin and the substrate Val-Ser-Gln-Asn-Tyr-Pro-Ile-Val-Gln, corresponding to one of the cleavage sites in the gag, gag-pol polyproteins, have been measured by direct microcalorimetric analysis. The results indicate that the binding of the peptide substrate or peptide inhibitor is entropically driven; i.e., it is characterized by an unfavorable enthalpy and a favorable entropy change, in agreement with a structure-based thermodynamic analysis based upon an empirical parameterization of the energetics. Dissection of the binding enthalpy indicates that the intrinsic interactions are favorable and that the unfavorable enthalpy originates from the energy cost of rearranging the flap region in the protease molecule. In addition, the binding is coupled to a negative heat capacity change. The dominant binding force is the increase in solvent entropy that accompanies the burial of a significant hydrophobic surface. Comparison of the binding energetics obtained for the substrate with that obtained for synthetic nonpeptide inhibitors indicates that the major difference is in the magnitude of the conformational entropy change. In solution, the peptide substrate has a higher flexibility than the synthetic inhibitors and therefore suffers a higher conformational entropy loss upon binding. This higher entropy loss accounts for the lower binding affinity of the substrate. On the other hand, due to its higher flexibility, the peptide substrate is more amenable to adapt to backbone rearrangements or subtle conformational changes induced by mutations in the protease. The synthetic inhibitors are less flexible, and their capacity to adapt is more restricted. The expected result is a more pronounced effect of mutations on the binding affinity of the synthetic inhibitors. On the basis of the thermodynamic differences in the mode of binding of substrate and synthetic inhibitors, it appears that a key factor to understanding resistance is given by the relative balance of the different forces that contribute to the binding free energy and, in particular, the balance between conformational and solvation entropy.     

Subspace-based signal analysis using singular value decomposition

A unified approach is presented to the related problems of recovering signal parameters from noisy observations and identifying linear system model parameters from observed input/output signals, both using singular value decomposition (SVD) techniques. Both known and new SVD-based identification methods are classified in a subspace-oriented scheme. The SVD of a matrix constructed from the observed signal data provides the key step in a robust discrimination between desired signals and disturbing signals in terms of signal and noise subspaces. The methods that are presented are distinguished by the way in which the subspaces are determined and how the signal or system model parameters are extracted from these subspaces. Typical examples, such as the direction-of-arrival problem and system identification from input/output measurements, are elaborated upon, and some extensions to time-varying systems are given     

Treatment of radiation-induced nervous system injury with heparin and warfarin

When radiation is used to treat nervous system cancer, exposure of adjacent normal nervous system tissue is unavoidable, and radiation-induced injury may occur. Acute injury is usually mild and transient, but late forms of radiation-induced nervous system injury are usually progressive and debilitating. Treatment with corticosteroids, surgery, and antioxidants is often ineffective. We treated 11 patients with late radiation-induced nervous system injuries (eight with cerebral radionecrosis, one with a myelopathy, and two with plexopathies, all unresponsive to dexamethasone and prednisone) with full anticoagulation. Some recovery of function occurred in five of the eight patients with cerebral radionecrosis, and all the patients with myelopathy or plexopathy. Anticoagulation was continued for 3 to 6 months. In one patient with cerebral radionecrosis, symptoms recurred after discontinuation of anticoagulation and disappeared again after reinstitution of treatment. We hypothesize that anticoagulation may arrest and reverse small-vessel endothelial injury--the fundamental lesion of radiation necrosis--and produce clinical improvement in some patients.     

Nanocell logic gates for molecular computing

Molecular electronics seeks to build electrical devices to implement computation - logic and memory - using individual or small collections of molecules. These devices have the potential to reduce device size and fabrication costs, by several orders of magnitude, relative to conventional CMOS. However, the construction of a practical molecular computer will require the molecular switches and their related interconnect technologies to behave as large-scale diverse logic, with input/output wires scaled to molecular dimensions. It is unclear whether it is necessary or even. possible to control the precise regular placement and interconnection of these diminutive molecular systems. This paper describes genetic algorithm-based simulations of molecular device structures in a nanocell where placement and connectivity of the internal molecular switches are not specifically directed and the internal topology is generally disordered. With some simplifying assumptions, these results show that it is possible to use easily fabricated nanocells as logic devices by setting the internal molecular switch states after the topological molecular assembly is complete. Simulated logic devices include an inverter, a NAND gate, an XOR gate and a 1-bit adder. Issues of defect and fault tolerance are addressed.     

Acute aortic outflow obstruction by diminution of bulboventricular foramen size after volume unloading in univentricular physiology

A young child with [S, L, L] segmental anatomy, double-inlet left ventricle, transposition of the great arteries, rudimentary right ventricle, and mildly restrictive bulboventricular foramen is reported, in whom intraoperative temporary snaring of the modified Blalock-Taussig shunt resulted in instantaneous and dramatic volume contraction of the left ventricle, decrease in bulboventricular foramen size, and increase of the gradient across the latter from 10 mm Hg preoperatively to 50 mm Hg. A modified Damus-Stansel-Kaye procedure using autogenous aortic tissue resulted in unobstructed aortic outflow; in addition, a bidirectional cavopulmonary shunt was performed. The importance of early relief of actual or potential aortic outflow obstruction in hearts with restrictive bulboventricular foramen is emphasized.