[Comparative effects of low and medium molecular hydroxyethyl starch (HES) solutions on hemorrhagic shock in rats].

BACKGROUND: Hydroxyethyl starch (HES) solutions are frequently used plasma expanders. We examined the effects of medium-HES (mean molecular weight of 130,000 dalton) and low-HES (mean molecular weight of 70,000 dalton) on the survival rates (Exp. I), colloid osmotic pressure (COP) (Exp. II) and coagulation (Exp. III) with rats in hemorrhagic shock. METHODS: Hemorrhagic shock was induced by removing 55% (Exp. I) and 20% (Exp. II and III) of the circulating blood volume. Saline, low-HES or medium-HES of the same volume with the removed blood was intravenously infused immediately after bleeding. RESULTS: Exp. I: In survival rate, effect of medium-HES was significantly superior to that of saline. Exp. II: The COP of medium-HES group was significantly higher than that of saline group 3 hrs after hemorrhagic shock. Exp. III: There were no changes in von Willerbrand factor and factor VIII 3 hrs after hemorrhagic shock among saline, low-HES and medium-HES. CONCLUSIONS: Medium-HES and low-HES are efficacious plasma volume substitutes; however, the ability of medium-HES to prolong maintenance of COP better than low-HES is a finding that would be significant in a clinical setting involving preoperative blood management and extreme blood loss.

Single dose of rituximab for refractory steroid-dependent nephrotic syndrome in children.

We conducted a multicenter prospective trial to evaluate the efficacy, safety and pharmacokinetics of a single dose of rituximab (375 mg/m(2) body surface area) for the treatment of children with refractory steroid-dependent nephrotic syndrome (SDNS). All patients (n = 12) were able to discontinue steroids at a median of 74 days after treatment. The frequency of relapses per 6 months was significantly reduced and the steroid-free period per 6 months was significantly increased after treatment compared with those before treatment. The condition in nine of the patients (75%) relapsed at a median of 129 days after treatment, and seven patients were given additional rituximab due to steroid dependency. Most of the relapses developed simultaneously with recovery of B-cells. However, three patients (25%) did not have a relapse with B-cell recovery and the disease was kept in remission for more than 1 year. None of the patients developed life-threatening adverse events. This is the first report of a prospective study of a single dose of rituximab for refractory SDNS. Treatment with a single dose of rituximab may be effective for refractory SDNS, but its efficacy to prevent relapses was transient in most of the patients.

Cerebral salt wasting in subarachnoid hemorrhage rats: model, mechanism, and tool.

Cerebral salt wasting (CSW) frequently occurs concomitantly with aneurysmal subarachnoid hemorrhage (SAH). CSW induces excessive natriuresis and osmotic diuresis, and reduces total blood volume. As a result, the risk of symptomatic cerebral vasospasm may be elevated. Therefore, it is important to determine the mechanism of CSW. The purpose of this study was to evaluate whether the rat SAH model exhibits CSW and to investigate the relationship between CSW and natriuretic peptides. A SAH model was produced in 24 rats by perforating a cerebral artery with a nylon thread up through the common carotid artery. To evaluate CSW, urine was cumulatively collected from SAH onset to 12 hours and sodium (Na) excretion was analyzed. Body weight and hematocrit were analyzed before and after SAH onset. Concentrations of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in plasma were also analyzed. Urine volume and total Na excretion of SAH rats were significantly higher than those of sham rats (p<0.05). Body weight of SAH rats significantly decreased and hematocrit significantly increased (p < 0.05). ANP concentration was significantly decreased in SAH rats (p<0.05). However, BNP concentrations did not change. This study demonstrated for the first time that a rat SAH model exhibited CSW. It was suggested that the cause of CSW was neither ANP nor BNP. In addition, this rat SAH model will be useful for study of CSW after SAH.

Differential pharmacokinetics of theophylline in elderly patients.

The clinical use of theophylline as a first-line bronchodilator has declined during the last two decades. However, in many clinical settings, such as an emergency bronchial asthma attack, theophylline may have a first-line role, in combination with beta(2)-adrenoreceptor agonists and corticosteroids, for improving the asthmatic status. Furthermore, many therapeutic mechanisms of theophylline for bronchial asthma have been reported, and recent studies have suggested that theophylline therapy may have a beneficial role in the management of chronic stable asthma as well as exacerbated disease. However, theophylline has a low therapeutic index because the bronchodilation it produces has a linear relationship with logarithmic increases in serum concentration for the therapeutic range of 5-20 mg/L. Thus, the knowledge of its basic pharmacokinetics and the factors that can alter its clearance is clinically relevant for physicians. Especially when used in elderly asthmatic patients, dosage adjustment of theophylline is a requisite since the elderly have several risk factors that may increase the plasma theophylline level, such as reduced clearance, various underlying diseases and multiple coadministered drugs. After theophylline treatment has been initiated, therapeutic drug monitoring is required.