Valproate-associated coagulopathies in children during short-term treatment.

Valproic acid is one of the most frequently prescribed antiepileptic drugs for the therapy of generalized and focal epilepsies. Valproate induces a variety of hemostatic disorders such as thrombocytopenia, abnormal platelet function, hypofibrinogenemia, and decreased concentrations of von Willebrand factor, and it rarely causes serious bleeding complications. It may also lead to atherosclerosis and thrombosis. However, there is still lack of knowledge about the incidence and occurrence of these particular side effects. In this prospective systematic study, we assessed the early effects of sodium valproate on both pro- and anticoagulatory factors, homocysteine, and lipoprotein (a) in 24 newly diagnosed epileptic children treated with valproate. Valproate causes decreased factor VII levels, platelet count, factor VIII, Protein C, fibrinogen, and increased lipoprotein (a) levels. To the best of our knowledge, our report is the first in the medical literature, which describes that valproate significantly reduces factor VII levels even during short-term therapy.

Pseudohyponatremia in a patient with HIV and hepatitis C coinfection.

Pseudohyponatremia refers to low serum sodium in the presence of normal plasma tonicity. Whereas pseudohyponatremia secondary to hyperlipidemia is a commonly recognized occurrence, falsely low sodium levels secondary to elevated protein are less frequently observed. We present in this paper the case of a man coinfected with HIV and hepatitis C who had pseudohyponatremia from hypergammaglobulinemia. As hypergammaglobulinemia is a frequent occurrence in both HIV and HCV, we suggest that pseudohyponatremia is an important and likely underdiagnosed phenomenon in this patient population. Clinicians need to be aware of the electrolyte exclusion effect and become familiar with the techniques used by their local laboratory in the measurement of serum electrolytes. Pseudohyponatremia should also be included in the differential diagnosis of an elevated osmolal gap, as the falsely lowered sodium level will lead to a falsely low calculated serum osmolality.

The immunoglobulinopathies: from physiopathology to diagnosis.

The diversity of immunoglobulins (Igs) results mainly from recombinations of numerous genes within the heavy (V(Heavy), D, and J(Heavy)) and within the light (V(Light), J(Light)) chain gene loci, and from somatic hypermutations occurring during the immune response of B-cells. Igs production is controlled by complex cellular and humoral mechanisms. Plasma of healthy individuals contains polyclonal Igs. Clonal expansion of cells producing antigen-specific Igs may result from physiological as well as from pathological immune events. Exquisitely sensitive and specific molecular biology techniques have been used to evaluate the clonal diversity of cells producing antigen-specific Ig. However, the application of such techniques is hampered by the necessity to collect the totality of antigen-specific B-cells for subsequent analysis, which is impossible to perform routinely in humans. In addition, these techniques do not provide quantitative information about the concentration of the circulating Igs. It is therefore necessary to use tools allowing study of the quantity of the circulating Igs, and more particularly to detect overproduction of a single homogeneous Ig resulting from the expansion of a B-cell clone secreting Igs. Here, we review the mechanisms of B-cell differentiation and Ig synthesis, discuss the diseases associated with clonal Ig production and review the methods available in the clinical laboratory for Ig analysis.

Renal hemodynamic, fluid volume, and arterial pressure changes during hyperproteinemia.

The chronic effects of hyperproteinemia on renal hemodynamics, fluid volume, and arterial pressure were determined in six conscious dogs over a 32-day period. Plasma protein concentration was increased by intravenous infusion of approximately 300 ml/day of previously collected autologous plasma, and the responses to changes in sodium intake were studied. By the end of a 9-day period of hyperproteinemia and normal sodium intake, plasma protein concentration had increased 2.2 g/dl, plasma colloid osmotic pressure had increased 7-8 mmHg, mean arterial pressure had increased 12 mmHg, glomerular filtration rate (GFR) had increased 15%, estimated renal plasma flow (ERPF) had increased 51% primarily due to renal vasodilatation, and filtration fraction had decreased 23%. Also, sodium balance was negative, water balance was positive, sodium iothalamate space had increased, plasma sodium concentration had decreased, and the relationship between mean arterial pressure and urinary sodium excretion was shifted to the right along the arterial pressure axis. In conclusion, long-term increases of plasma protein concentration result in a marked increase in ERPF as well as significant increases in GFR, extracellular fluid volume, and arterial pressure.

[Fundamental data in hemorheology. II. Hyperviscosity syndromes]. / Données fondamentales en hémorhéologie. II. Les syndromes d'hyperviscosité.

Whole blood behaves like a deformable colloidal particle suspension in a macromolecular medium. Pathological variations in the rheological properties of blood and the clinical symptoms they produce form the "hyperviscosity syndromes". The term "hyperviscosity" was originally used for characterising the plasma hyperviscosity observed during macroglobulinemia and it is only recently that the chapter covering hyperviscosity syndromes has been enlarged to describe the syndromes as a state in which the increased blood viscosity and increase in flow resistance must be considered as the result of the rheological behaviour of blood taken as a whole (plasma and blood cells). The etiology of hyperviscosity syndromes can be: an increase in total plasma protein levels, or the appearance of a monoclonal protein, the increase in the number of blood cells, the increase in the erythrocyte's internal viscosity, the changes in the erythrocyte's viscoelastic properties, the excessive aggregating tendency of the erythrocytes and perhaps that of the platelets.

Pulmonary function in nonsmoking subjects with alpha1 antitrypsin deficiency (MZ phenotype).

We measured pulmonary functions in 10 nonsmoking asymptomatic subjects, ages 40.5 years +/- 9.2 years, with alpha1 antitrypsin heterozygous deficiency (phenotype MZ). The subjects were longstanding residents of the greater Los Angeles area. The range of physiologic studies and per cent of normal predicted values were forced vital capacity (FVC), 2.8 to 7.0 liters (86 to 124 per cent predicted); ratio of the forced expiratory volume in 1 second to the FVC, 70 to 86 per cent (86 to 104 per cent predicted); the ratio of the residual volume to total lung capacity, 28 to 44 per cent (94 to 119 per cent predicted); total lung capacity, 4.8 to 9.8 liters (80 to 119 per cent predicted); flow at 50 per cent FVC, 3.1 to 7.8 liters per second (69 to 140 per cent); and volume of isoflow, 7.3 to 26 per cent of forced vital capacity (38 to 137 per cent predicted). In eight patients studied, static deflation pressure volume curves were normal, and at respiratory rate of 60 breaths/min the ratio of dynamic compliance to static compliance did not fall below 84 per cent. We have found that these nonsmoking heterozygotes with alpha1 antitrypsin deficiency have normal pulmonary functions (within 1.67 SD of predicted mean).