Pharmacokinetics of orally administered hexobarbital in plasma and saliva of healthy subjects

Hexobarbital (HB) concentrations were determined in plasma and saliva of 8 healthy subjects, following oral administration of 500 mg HB-Na. Mean plasma half-lives were 3.2 +/- 0.1 h, and salivary half-lives 3.3 +/- 0.2 h. Mean plasma clearance was 22.9 +/- 2.3 1 h-1. There was a linear relationship between HB concentrations in saliva and plasma (r = 0.92). Mean salivary levels were 34 per cent of plasma levels. Salivary pH was constant throughout the experiment, 7.06 +/- 0.09. There was an inconsistent tendency of the saliva over plasma ratios to increase as a function of time. The percentage of protein binding calculated from saliva over plasma ratios was in reasonable agreement with in vitro data of equilibrium dialysis, 64.1 +/- 2.6 per cent and 65.9 +/- 0.8 per cent, respectively. The experiment was repeated in 4 subjects, and considerable intraindividual differences were shown to exist in saliva over plasma ratio, half-lives, and protein binding. It was concluded that HB elimination half-lives can relatively accurately be determined from salivary concentrations. Oral plasma clearance can only be estimated if the individual saliva over plasma ratios are known; this would require the taking of at least one blood sample during the experiment. When employing HB as a model substrate for drug metabolizing enzyme activity in vivo, the determination of its pharmacokinetic parameters, particularly oral plasma clearance as a reflection of cytochrome P-450 activity, cannot be achieved by taking saliva samples only.     

A theophylline dosage regimen which reduces round-the-clock variations in plasma concentrations resulting from diurnal pharmacokinetic variation

Summary Slower drug absorption at night can leave residual drug from an evening dose of a sustained-release product remaining to be absorbed at the time of the next morning's dose, thereby giving higher plasma concentrations of the drug during the day than the night.When a capsule product releasing theophylline over 12 h after a morning dose was given repetitively at 8 a.m. and 8 p.m. for 4 days, daytime plasma concentrations from 4 h to 8 h after the dose were about 40% greater than corresponding night-time concentrations, and the mean steady-state concentration during the night-time interval was only 81% of that during the daytime interval.Altering the regimen to one capsule at 12 noon and one at 10 p.m. eliminated all significant differences between a.m. and corresponding p.m. plasma concentrations of theophylline and between the mean steady-state concentrations for each of the interdose intervals within a day.     

我省流通领域阿莫西林制剂质量现状

目的:了解流通领域中阿莫西林制剂的质量状况。方法:在全省各市县的部分医药经营企业,抽取阿莫西林胶囊及干糖浆共54批样品,按国家药品标准进行全检后,对其检验结果进行统计分析。结果:不合格的项目有含量、胶囊剂溶出度、干糖浆粒度。该药物制剂的标示百分含量普遍偏低。结论:影响该产品质量的主要项目是含量和溶出度,含量偏低的主要原因是厂家的低限投料,应予以充分重视。     

脊椎滑脱症合并腰椎间盘突出的治疗

1987年6月至1995年1月我院共治疗脊椎滑脱55例,其中17例合并腰椎间盘突出,占31％,临床表现为顽固的腰骶痛和下肢根性放射痛。手术复位、融合不稳定脊椎的同时,均摘除突出的椎间盘髓核组织。经半年以上随访,疗效满意,作者分析了本病的病因病理,认为诊断该病必须综合性检查分析,脊髓造影或CT检查有一定影像学诊断价值,治疗宜早行探查手术。     

非角度稳定性钢板固定治疗桡骨远端关节内背侧移位骨折的结果

Objective Intra-articular fractures of the distal radius in young adults comprise a distinet fracture pattern that is diffficuh to manage and associated with a high frequency of post-traumatic arthritis.Restoration of articular congruency and alignment should improve the outcome.Methods In this study we prospectively re- viewed the results of 21 consecutive cases of dorsally displaced intra-articular distal radius fractures which were treated with internal fixation after failing to achieve articular congruency with closed reduction.Results 3 patients were lost to follow-up.For the rest of 18 patients,follow-up time ranges from 18 to 75 weeks the fractures had healed with highly satisfactory radiographic and functional results.The final volar tilt averaged 4.9°;radial inclination 23.9°;radial length 14mm;and articular incongruity,0.1 mm.Wrist motion at final follow-up examination aver- aged flexion 62°,extension 60°,radial deviation 16°,ulnar deviation 27°,pronation 77°and supination 74°.Grip strength averaged 83% of the uninjured side.The overall outcome of 18 patients(94.4%)had a good or excellent result according to the system of Gartland and Werley and 18 patients(72.2%)had a good result according to the modified system of Green and O'Brien at the most recent evaluation.The only complication in this series was a superficial pin tract infection,which was rapidly resolved with removal of pins at 5th week of external fixation. Conclusion Thus restoration of articular congruency and alignment is possible with minimal complication using modern non-angular stable methods of internal fixation.     

压迫及非压迫因素在实验性神经根性疼痛中的作用

目的：探讨压迫及非压迫因素在实验性椎间盘源性神经根性疼痛中的作用。方法：取大鼠白体脊椎关节突修剪后放置在L5神经根下．造成对L5神经根的直接压迫（压迫组）；取大鼠白体尾椎椎间盘组织无压迫下放置在L5神经根表面（非压迫组）：同时设立对照组。术后不同时间点测定各组大鼠后足底机械刺激疼痛阈值的变化。结果：压迫组与非压迫组大鼠后足底均产生了一个长时程机械刺激疼痛阈值的降低；与压迫组相比．非压迫组大鼠术后1天就开始出现了疼痛阈值降低（P〈0．05），明显早于压迫组大鼠，并且疼痛阈值降低更加显著：而压迫组大鼠术后1周时才出现明显的疼痛阈值降低（P〈0．05）。对照组大鼠疼痛阈值没有发生明显的改变。结论：尽管压迫和非压迫因素都参与椎间盘源性神经根性疼痛的发生．但二者作用的时间不同＋在椎间盘突出的早期阶段非压迫因素可能在疼痛中起着重要的作用：随后压迫因素可能逐渐成为致痛的主因。     

Interobserver variation in the evaluation of neurological signs: observer dependent factors.

Introduction - Interobserver variation among four observers in evaluation of eight selected neurological signs was investigated. Material & methods - Two hundred and two consecutive unselected inpatients were examined by two senior neurologists and two trainees, all without knowledge of the neurological case history. The signs examined were: anisocoria, jerky eye movements, facial palsy, elbow extension force, finger-nose test, Barré sign, knee jerk, and extensor plantar reflex. Observed agreement rates and kappa coefficients were calculated in order to compare the interobserver variability among neurologists and trainees, and to evaluate differences in the interobserver variability between signs. Results - Observed agreement rates varied from 0.80 to 0.95 for neurologists and from 0.65 to 0.98 for trainees. For neurologists kappa coefficients ranged from 0.40 to 0.67 and for trainees from 0.22 to 0.81. The neurologists had higher kappa values than the trainees in 5 signs, but this difference was only statistically significant for jerky eye movements. For the individual signs the observed agreement rates were between 0.50 and 0.93 for all four examiners combined, and overall kappa values varied from 0.32 to 0.71 with highest agreement for facial palsy and lowest for knee jerk. Conclusion - The magnitude of the interobserver and intersign variation indicates that the interpretation of the neurological signs tested, without knowledge of the case history, should be done with some caution.     

Link protein shows species variation in its susceptibility to proteolysis.

Human cartilage link protein exists as three native components, while equine, bovine, and porcine cartilage link protein exist as two and Swarm rat chondrosarcoma link protein exists as only one component. These nonhuman link protein components represent intact protein structures, and there is little evidence for proteolytically modified forms in nonhuman tissues. In human cartilage, the proteolytic production of modified link proteins increases with age, whereas high amounts of such products were not seen in the nonhuman tissues. However, the small amounts of link protein fragments that were observed in the nonhuman cartilages were of a similar size to their human counterparts. On digestion of human proteoglycan aggregate with stromelysin, rapid modification of the link protein components occurred, whereas the aggregates from nonhuman cartilages showed incomplete cleavage of their link protein components. The relative resistance of nonhuman link protein to stromelysin may in part be due to a unique amino acid substitution present near the enzymic cleave site.     

Pharmacokinetic Study of Mitomycin C with Emphasis on the Influence of Aging

Mitomycin C (MMC) at a dose of 8 mg/m² was administered by short intravenous infusion to 14 cancer patients. All patients had normal renal, hepatic, cardiac and bone marrow functions. The plasma level of MMC, which was determined by high-performance liquid chromatography over a 24–h period after the infusion, fitted the 2-compartment model curve except for one patient. There was a significant correlation between the area under the time versus concentration curve (AUC) of MMC and the age of patients ( r = 0.558, P < 0.05). Pharmacokinetic parameters in one of the older (a 69-year-old male) patients were extremely different from those of the other 13 patients. This patient experienced severe myelosuppression, probably due to the markedly increased AUC of MMC. Our results suggest that a patient's age has a significant influence on the pharmacokinetics of MMC in patients with normal major organ functions and that in some patients, MMC pharmacokinetics may be altered, possibly due to interpatient variation in the activation or metabolic pathway of MMC.     

学龄儿童掌指骨发育某些正常变异的观察

１９８０年和１９９０年对１２５９名城乡７～１２岁学龄儿童掌指骨发育的正常变异进行了观察。结果证实，小指中节骨发育变异的检出率最高（总检出率１４．７％），且男女儿童１９９０年此率均高于１９８０年（Ｐ＜０．０５），反映城市儿童该变异近１０年有增高的趋势；１９９０年男女学龄儿童小指中节骨变异检出率城市明显高于农村（Ｐ＜０．０１）；Ⅱ掌骨副骨骺总检出率３．８％，指骨骺核硬化总检出率２．２％，这两种变异男性明显高于女性．且无城乡差异。本观察各年龄组小指中节骨的变异同骨龄无规律性联系。