Effect of infusion duration on valproate pharmacokinetics

The pharmacokinetics of intravenously administered valproic acid (VPA) were investigated in 16 healthy male volunteers in a single-dose, fasting, four-period, randomized, double-blind, placebo-controlled, parallel design study. Subjects were randomly assigned to be infused a single dose of sodium valproate equivalent to 1000 mg VPA or placebo over each of four different time periods. Valproate concentrations in plasma were determined using gas chromatography with flame ionization detection. The pharmacokinetic parameters were determined by both non-compartmental and model-dependent techniques. Analyses of variance (ANOVAs) were performed to detect any statistical differences among the regimens. Overall, the pharmacokinetic of valproate were similar after infusions of 5, 10, 30, and 60 min, with an average terminal-phase half-life of 15.9 h. There were modest differences in overall clearances among the regimens, with the 5 min infusion producing a mean area under the plasma concentration-time curve (AUC; 1877 micrograms.h ml-1) that was significantly (13 to 16 per cent) higher than the means for the longer infusions (1614-1656 micrograms.h ml-1). Differences in distribution were also noted as a function of infusion duration. The shortest duration produced a significantly smaller terminal volume of distribution (12.8 vs 14.2-15.1 l) and more rapid tissue equilibration. The alpha-phase rate constant declined from a mean of 5.1 h-1 after the 5 min infusion to a mean of 0.9 h-1 after the 60 min infusion. The distributional differences are almost certainly related to the saturable protein binding of valproate. However, the lower clearance after the 5 min infusion indicates that there may have also been partial saturation of one of the metabolic pathways of valproate during the distributive phase, and that the increase in fu was smaller than the decrease in CL'int, such that the product of fu.CL'int showed a net decrease.     

Wada memory testing and hippocampal volume measurements in the evaluation for temporal lobectomy

We examined the relationship of Wada memory performance and MRI hippocampal volume measurements to laterality of ultimate seizure localization in 20 patients with complex partial seizures who later underwent temporal lobectomy. Discriminant function analysis employing both Wada memory test asymmetries and hippocampal volume asymmetries correctly classified 100% of the patients into left and right temporal lobe groups. Wada memory asymmetries alone correctly classified 90% of the sample (80% of the sample when the discriminant function included all patients except the one being classified), and hippocampal volume asymmetries alone correctly classified 90% of the patients. A significant correlation was present between Wada memory asymmetries and hippocampal volume asymmetries (r = 0.78), indicating that structural evidence of reduced hippocampal volume has a functional correlate reflected by Wada memory performance. These data suggest that the combination of functional and structural measures is of value in the preoperative evaluation for epilepsy surgery.     

Renal physiology series: Part 6 of 8. The aging kidney: structure, function, and nursing practice implications

The effects of normal aging on the kidney are both structural and functional. Morphologic changes involve the renal blood vessels, glomeruli, tubules, and interstitium. Physiologic changes include alterations in renal plasma flow, glomerular filtration rate, filtration fraction, tubular transport, concentrating ability, acidification, the renal handling of electrolytes, and patterns of urine flow and electrolyte excretion. The structural and functional changes that occur in the senescent kidney, and the implications for nursing practice are discussed.     

Phenytoin as a countermeasure for motion sickness in NASA maritime operations

Seasickness is the most prevalent form of motion sickness and is an operational problem during Space Shuttle Solid-fueled Rocket Booster (SRB) retrieval. Phenytoin has been shown to protect against motion sickness induced by Coriolis stress. We exposed SRB recovery personnel to off-vertical rotation and sea motion after phenytoin or placebo. Phenytoin blood levels of at least 9 micrograms/ml were protective against motion sickness at sea. No change in susceptibility to nitrogen narcosis was seen in divers in chamber tests at 460 KPa. Phenytoin was used during performance of critical and hazardous tasks during training and actual SRB recovery operations. Phenytoin is an effective operational countermeasure for motion sickness for selected SRB crewmembers.     

Effects of magnesium sulphate and nitric oxide in pulmonary hypertension induced by hypoxia in newborn piglets

AIM: To examine the haemodynamic effects of intravenous magnesium sulphate on an animal model of neonatal pulmonary hypertension induced by hypoxia. METHODS: The cardiac index (Q), pulmonary arterial pressure (PAP), systemic arterial pressure (SAP), and pulmonary (PVRI) and systemic (SVRI) vascular resistance indices were measured in nine newborn piglets (including three controls). Pulmonary hypertension was induced by lowering the FIO2 to 0.12-0.14, after which there was a significant increase in PAP and PVRI (37% and 142%, respectively; p < 0.01) and a significant fall in SAP and Q (30% and 33%, respectively; p < 0.01). RESULTS: Magnesium sulphate was infused intravenously as four doses of 25 mg/kg, 15 minutes apart, which resulted in a significant mean (SD) increase in serum magnesium (0.83 (0.07) mmol/l to 1.82 (0.19) mmol/l; p < 0.01). After the initial dose SAP, SVRI, PAP and PVRI decreased, but not significantly. Each subsequent dose of (50, 75, 100 mg/kg) was accompanied by further significant reductions in these variables from control baseline (p < 0.05). The PVRI:SVRI ratio remained unchanged throughout. Inhaled nitric oxide (NO) 40 ppm was administered after the last dose of magnesium sulphate. The PVRI:SVRI significantly decreased (p < 0.05), indicating that reversible pulmonary hypertension remained after a maximum dose of magnesium sulphate. CONCLUSIONS: Unlike NO, magnesium sulphate is not a selective pulmonary vasodilator and may lead to deleterious effects on systemic pressures in critically ill newborns.     

Measurement and global analysis of the absorbance changes in the photocycle of the photoactive yellow protein from Ectothiorhodospira halophila

The photocycle of the photoactive yellow protein (PYP) from Ectothiorhodospira halophila was examined by time-resolved difference absorption spectroscopy in the wavelength range of 300-600 nm. Both time-gated spectra and single wavelength traces were measured. Global analysis of the data established that in the time domain between 5 ns and 2 s only two intermediates are involved in the room temperature photocycle of PYP, as has been proposed before (Meyer T.E., E. Yakali, M. A. Cusanovich, and G. Tollin. 1987. Biochemistry. 26:418-423; Meyer, T. E., G. Tollin, T. P. Causgrove, P. Cheng, and R. E. Blankenship. 1991. Biophys. J. 59:988-991). The first, red-shifted intermediate decays biexponentially (60% with tau = 0.25 ms and 40% with tau = 1.2 ms) to a blue-shifted intermediate. The last step of the photocycle is the biexponential (93% with tau = 0.15 s and 7% with tau = 2.0 s) recovery to the ground state of the protein. Reconstruction of the absolute spectra of these photointermediates yielded absorbance maxima of about 465 and 355 nm for the red- and blue-shifted intermediate with an epsilon max at about 50% and 40% relative to the epsilon max of the ground state. The quantitative analysis of the photocycle in PYP described here paves the way to a detailed biophysical analysis of the processes occurring in this photoreceptor molecule.     

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) accelerates differentiation of murine preimplantation embryos in vitro

The effects of antioxidant-rich foods as adjuncts to a prudent diet were compared for 12 weeks in a randomized, single-blind and controlled trial in 204 (group A) and 202 (group B) patients with acute myocardial infarction. There was a significant decrease in cardiac end points in group A compared to group B (37 vs 58, p < 0.01) after 12 weeks. Within intervention group A, those 108 patients with greater adherence to the intervention program showed a greater reduction in cardiac end points (14 vs 58, p < 0.001), and a significant decrease in total mortality (6 vs 28, p < 0.001), including cardiac mortality (6 vs 25, p < 0.01) compared to group B. Underlying these beneficial effects, antioxidant-rich foods caused a significantly smaller rise in lactate dehydrogenase (LDH) cardiac enzyme in group A than in group B (427.8 vs 561.6 IU/dL), indicating that the protective influence of such a diet may be observed within 1 week. The subset of group A patients showing reduction in mortality also had a lesser rise in LDH and greater reduction in blood lipids, blood glucose and blood pressures. Antioxidant-rich foods also caused a significant decrease in blood lipids with a lower decrease in high-density lipoprotein cholesterol in group A than in group B. Assay of serum level of antioxidants and long-term follow-up may confirm our observations.     

Modified technique of blunt cannula retrobulbar anesthesia for vitreoretinal surgery

We prospectively evaluated a modified version of a previously reported technique of retrobulbar anesthesia for vitreoretinal surgery involving the use of a blunt 19-gauge cannula to directly infuse anesthetic into the retrobulbar space. Using this method, 60 consecutive patients undergoing scleral buckling surgery had effective anesthesia and akinesia, with no complications.