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.     

硫酸多糖对体外人脐静脉内皮细胞损伤的保护作用

研究表明,硫酸多糖体外对多聚阳离子和氧自由基损伤的人脐静脉内皮细胞有保护作用。肝素、硫酸软骨素A抗多聚阳离子损伤作用比同浓度低分子肝素和甘糖酯强。肝素、硫酸软骨素A、甘糖酯抗氧自由基损伤作用优于同浓度低分子肝素。结果显示硫酸多糖有保护血管内皮的作用,其作用可能与所带阴离子基团有关。     

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.      

Detection of ethambutol-resistant Mycobacterium tuberculosis strains by multiplex allele-specific PCR assay targeting embB306 mutations

We describe a multiplex allele-specific (MAS)-PCR assay to detect simultaneously mutations in the first and third bases of the embB gene codon 306ATG. These mutations are known to confer ethambutol (EMB) resistance in the majority of clinical Mycobacterium tuberculosis isolates worldwide. The mutated bases are revealed depending on the presence or absence of the respective indicative fragments amplified from the embB306 wild-type allele. Initially optimized on purified DNA samples, the assay was tested on crude cell lysates and auramine-stained sputum slide DNA preparations with the same reproducibility and interpretability of the generated profiles in agarose gel electrophoresis. Since EMB resistance is generally linked to multiple-drug resistance (MDR), the MAS-PCR assay for EMB resistance detection can be used in clinical laboratory practice in areas with a high prevalence and a high transmission rate of MDR-EMB-resistant tuberculosis.