Comparison of gas-liquid chromatography and EMIT assay for serum valproic acid

We describe a simple direct extraction method for the gas-liquid chromatography determination of serum valproic acid. The working range for the assay is 2-180 mg/L and our within-run precision was 5.8 and 4.3% at the 40 and 90 mg/L concentrations respectively. Hemolyzed and lipemic sera as well as samples from patients with hyperbilirubinemia and from patients with decreased renal function were put through the assay and no interfering peaks were noted. Interference occurred when teflon-lined screw caps were used during the extraction step. The method was proven to be accurate by linear regression analysis of samples containing weighed-in amounts of valproic acid. The above assay was compared to an enzyme immunoassay technique (EMIT). The working range for the latter is 10-150 mg/L and the with-run precision was 10.8 and 5.9% and 90 mg/L concentration respectively. Samples were run by both the gas-liquid chromatograph and enzyme immunoassay methods and gave very similar results over the range 16-139 mg/L.     

Review of determinants of patients' preferences for adjuvant therapy in cancer.

PURPOSE: Many studies have determined cancer patients' preferences for adjuvant therapy, for example, by asking patients the extent of benefit they would need in order to accept the therapy. However, little is known about the determinants that influence these preferences. Our research goal was to explore which determinants underlie patients' preferences by means of a literature review. METHODS: PubMed searches were conducted to identify studies in which cancer patients' preferences for adjuvant therapy had been elicited by means of a treatment preference instrument. Twenty-three papers were evaluated with regard to reported relationships between preferences and potential determinants. A total of 40 determinants were recorded and classified into one of seven categories: (1) treatment-related determinants, (2) sociodemographic characteristics and current quality of life, (3) clinical characteristics, (4) measurement instrument-related determinants, (5) time-related determinants, (6) cognitive/affective determinants, and (7) specialist-related determinants. Results: The benefit and toxicity of treatment, experience of the treatment, and having dependents (eg, children) living at home were important determinants of patients' preferences. Furthermore, qualitative data suggested that cognitive/affective and specialist-related determinants might have a large impact on patients' treatment preferences. CONCLUSION: Our results show that patients' preferences cannot fully be explained on the basis of treatment-related determinants and patient and clinical characteristics. More research is needed in the area of cognitive/affective and specialist-related determinants because of the lack of quantitative results. Furthermore, we recommend carrying out larger studies in which the (internal) relationships between determinants and preferences are assessed in the context of a cognitive cost-benefit model.     

A muscle spindle model for primary afferent firing based on a simulation of intrafusal mechanical events.

1. A muscle spindle model for primary afferent firing is presented that contains two components representing a gamma d-dependent (bag1) and gamma s-dependent (bag2/nuclear chain) intrafusal fiber. Each of the intrafusal fibers is composed of a linear elastic element representing the sensory part and a muscle fiber representing the muscular part. 2. The muscular part of the bag1 was modeled as a slow twitch, that of the bag2 as a fast twitch muscle fiber. 3. The sensory regions were linear length transducers, generating a rising depolarization on increasing stretch. The input of both bags was fused by taking the largest depolarization to determine a generator potential. The rate of primary afferent firing depended on this generator potential as well as on its rate of change. 4. To simulate the high sensitivity of muscle spindles to small amplitudes of stretching, a model analogue of cross-bridge fixation (or stiction) has been included in the muscular part of the bag1 fiber. This makes use of one hundred cross-bridge regions that release one after the other, provided a certain breaking force is exceeded. 5. The values of the mechanical parameters that defined the model were selected by a computerized search procedure. 6. The values found by means of this procedure allowed the model to provide an accurate simulation of experimental data on ramp-and-hold stretches (for 6 different stretch velocities under variable conditions of fusimotor activity). 7. On sinusoidal stretches at a frequency of 1 Hz the spindle model responded with about one-half the discharge modulation reported in experimental studies. Its phase advance tended to be slightly lower than that observed for real spindles. 8. Frequency response curves showed the same high sensitivities at high frequencies as those observed in real spindles. 9. Close evaluation of the model compared with experimental results in literature reveal its merits as well as its limitations. Because the model is structural rather than phenomenologic, it provides insight into how intrafusal events may contribute to observed firing properties of real muscle spindles.     

Maturation of long-term potentiation in the hippocampal dentate gyrus of the freely moving rat

The ability of the perforant path/dentate granule cell synapse of the hippocampal formation to establish and maintain enhanced levels of synaptic transmission in response to tetanization (long-term potentiation, LTP) was investigated in freely moving rats at 15, 30, and 90 days of age. Measures of (1) the slope of the population excitatory postsynaptic potential (EPSP), and (2) the population spike amplitude (PSA) obtained before, and at several times following tetanization, were used to evaluate the magnitude and duration of LTP as a function of age. Significant enhancement of both EPSP slope and PSA measures was obtained from animals of all three ages in response to perforant path tetanization. The initial degree of enhancement was essentially the same across the age groups, ranging from +27% to +38% of pretetanization levels for EPSP slope measures and +60% to +75% of pretetanization levels for PSA measures, obtained 15 min after tetanization. The duration of this enhancement obtained from animals of the preweaning group was significantly longer than that obtained from either 30- or 90-day-old animals. Enhanced measures of both EPSP slope and PSA decayed to baseline levels in these older animals 18 to 24 h after tetanization, while animals tetanized at 15 days of age maintained potentiated levels of both measures for a period of 5 days following tetanization. Tetanization of 15-day-old animals resulted in a significant reduction in the latency to EPSP onset without affecting the time-based relationships among the other measured parameters, which included latency of the population spike onset, population spike minimum, and population spike offset. Tetanization had no effect on the latency measure of any of these parameters in either of the two older age groups. The primarily postnatal development of the dentate granule cell population suggests that both functionally immature GABAergic modulation of granule cell activity and the differential development of components of the N-methyl-D-aspartate receptor complex may be involved in the age-related differences in the induction and expression of the LTP phenomenon. This study represents the first developmental characterization of LTP in the perforant path/dentate granule cell synapse in freely moving rats during early development. The results indicate that LTP can be reliably established and maintained in behaving rats as young as 15 days of age. Whereas the degree of potentiation at this age is equivalent to that obtained from juveniles and young adults, the duration of the effect significantly outlasts that obtained from older animals in which development of the dentate gyrus is more functionally mature. © 1994 Wiley-Liss, Inc.     

Surgical pain is followed not only by spinal sensitization but also by supraspinal antinociception

Nociception can produce segmental spinal sensitization or descending supraspinal antinociception. We assessed both types of sensory change after surgery during isoflurane-nitrous oxide anaesthesia with or without fentanyl before nociception. Patients undergoing back surgery received fentanyl 3 micrograms kg-1 (n = 15) or placebo (n = 15) before anaesthesia in a prospective, randomized, blinded study. Sensation, pain detection and tolerance thresholds to electrical stimulation were measured before operation at the arm, incision and herniated disc dermatomes (HDD) and 1, 2, 4, 6, 24 h and 5 days after operation, together with pain scores and patient-controlled morphine consumption (duration 24 h). For segmental effects, thresholds were normalized to the thresholds at a distant dermatome (arm). Raw pain thresholds were increased after operation (fentanyl > placebo) and were maximal at 4 h (pain tolerance in HDD: fentanyl +5.2 mA (+62.7%), placebo, +3.8 mA (+44.2%); P < 0.05 vs baseline for both). Normalized sensation thresholds decreased for placebo only (HDD/4 h: placebo, -1.8 (-44.8%), P < 0.05; fentanyl, +0.1 (+5.5%) ns). All changes returned to baseline by 24 h except for the placebo group normalized HDD sensation (d5: placebo, -2.4 (-59.7)%, P < 0.05; fentanyl -0.1 (-5.5%) ns). Pain scores and morphine consumption were similar. The study demonstrated both supraspinal analgesia and spinal sensitization after surgery. Fentanyl administration before operation augmented the former while decreasing the latter, and hence sensitization, especially if neuropathic, may particularly benefit from pre-emptive analgesia.      

Severe early malnutrition and DRL performance in the rat

Rats with a history of severe early malnutrition (6% casein) were compared to well-fed control animals on an ascending series of DRL values ranging from 5 to 60 seconds. The 6% rats who were dietarily-rehabilitated at weaning did not differ from control animals in efficiency, responses per reinforcement or response rate. In contrast, rats chronically exposed to 6% diets performed so poorly during training with continuous reinforcement that they did not advance to even the first DRL (5-sec) condition. These findings show that severely-undernourished rats can perform within normal limits on even high DRL values, provided they are well trained and that they have adequate nutritional rehabilitation.