药物动力学入门(三)

重复给药许多药物不仅投药一次。病人在接受药物治疗时,通常是经多次的药物应用。这样每一剂量给予的次数和多少则称为给药方案。通过给药方案的调整,则可以显著地改变药物治疗的效果。口服给药如果口次剂量每次给药的间隔相当长,则由每一次剂量所给的药物已几乎完全消除,所以这些分次给药的行为相互将无何影响,如图33所示。     

The surgical risk of colectomy in patients with cirrhosis

The records of 54 patients with documented cirrhosis who underwent colectomy between January 1970 and January 1984 were studied to assess the operative risk and to determine the preoperative predictive risk factors. In-hospital mortality was 24 percent (13 patients), and postoperative complications occurred in 48 percent (26 patients). The risk of surgical intervention was significantly increased if encephalopathy, ascites, anemia, or hypoalbuminemia was present before operation. A simple operative risk index involving the presence of encephalopathy and ascites and the levels of hemoglobin and albumin is proposed to help distinguish a low-risk subgroup in whom postoperative mortality was 12.8 percent from a high-risk subgroup in whom postoperative mortality was 53.3 percent.     

Anesthesia for trauma

Trauma is the leading cause of death for persons aged 1 to 38 years. Successful management is facilitated by prehospital endotracheal intubation, transport to regional trauma centers, rapid resuscitation by an on-site team of trained physicians, timely operative intervention, and provision of care by well-prepared anesthesiologists familiar with the potential complications typical of traumatized patients. No particular anesthetic agent or technique is ideal. Causes for intraoperative hypotension include hypovolemia, hemopneumothorax, pericardial tamponade, an intracranial mass, acidosis, and hypothermia. The anesthesiologist should play an active role in all phases of trauma management, including provision of postoperative intensive care and pain relief.     

Cytoprotective actions of 2,4-dimethoxybenzylidene anabaseine in differentiated PC12 cells and septal cholinergic neurons

The potential cytoprotective actions of a novel nicotinic agent 2,4-dimethoxybenzilidene anabaseine (DMXB) were investigated in differentiated PC12 cells and transected rat septal cholinergic neurons in vivo. In NGF-differentiated PC12 cells, removal of both NGF and serum led to cell loss, a reduced % of cells expressing neurites, the release of lactate dehydrogenase, and a decrease in total cellular protein. Cell loss was apparent within 24 h, and remained constant between 4–8 days post-NGF removal. NGF alone (100 ng/ml), DMXB (10 μM), but not nicotine (10 μM), prevented these cell and neurite losses. DMXB-induced cytoprotection was blocked by 1 μM mecamylamine. DMXB (1 mg/kg, ip) injected twice but not once per day protected cholinesterase-staining septal neurons from retrograde degeneration following unilateral fimbrial transections. The twice per day DMXB injection-protocol also decreased cell roundness among cholinesterase-staining cells in the lesioned septal hemisphere compared to saline-injected animals. These studies suggest that DMXB may exert cytoprotective activity in NGF-sensitive neuronal populations. © 1994 Wiley-Liss, Inc.     

N-acetylaspartate is an axon-specific marker of mature white matter in vivo: a biochemical and immunohistochemical study on the rat optic nerve.

Axonal pathology is a major cause of neurological disability in multiple sclerosis. Axonal transection begins at disease onset but remains clinically silent because of compensatory brain mechanisms. Noninvasive surrogate markers for axonal injury are therefore essential to monitor cumulative disease burden in vivo. The neuronal compound N-acetylaspartate, as measured by magnetic resonance spectroscopy, is currently the best and most specific noninvasive marker of axonal pathology in multiple sclerosis. The possibility has been raised, however, that N-acetylaspartate is expressed also by oligodendroglial lineage cells. In order to investigate N-acetylaspartate specificity for white matter axons, transected rat optic nerves were analyzed by high-performance liquid chromatography and immunohistochemistry. In transected adult nerves, N-acetylaspartate and N-acetyl aspartylglutamate decreased in concordance with axonal degeneration and were undetectable 24 days posttransection. Nonproliferating oligodendrocyte progenitor cells, oligodendrocytes, and myelin were abundant in these axon-free nerves. At 24 days posttransection, N-acetylaspartate was increased (42%; p = 0.02) in nontransected contralateral nerves. After transection at postnatal day 4, total N-acetylaspartate decreased by 80% (P14; p = 0.002) and 94% (P20; p = 0.003). In these developing axon-free nerves, 25 to 33% of oligodendrocyte progenitor cells were proliferating. These data validate magnetic resonance spectroscopy measurements of N-acetylaspartate as an axon-specific monitor of central nervous system white matter in vivo. In addition, the results indicate that neuronal adaptation can increase N-acetylaspartate levels, and that 5 to 20% of the N-acetylaspartate in developing white matter is synthesized by proliferating oligodendrocyte progenitor cells.     

Body pain and treatment response in late-life depression.

OBJECTIVE: The authors investigated the influence of body pain on 1) time to treatment response and 2) suicidal ideation, in late-life depression. They hypothesized that higher levels of body pain would predict a longer time to and lower likelihood of response, and increased levels of suicidal ideation. METHODS: Subjects (N=187) were older adult outpatients (age > or =69 years), with current episodes of major depression, who were openly treated with paroxetine up to 40 mg daily and weekly interpersonal psychotherapy. Response was defined as 3 consecutive weeks of Hamilton Rating Scale for Depression at < or =10. Body pain was measured with the Bodily Pain Index of the SF-36 quality-of-life assessment. Authors used survival-analysis models on the responder sample to test the effect of body pain on response, after controlling for severity of depression. RESULTS: Overall response rate was 75.4%. Nonresponders reported more severe pain at baseline. After covarying for severity of baseline depression, no effect was found for physical pain on time-to-response or degree of suicidality. Bodily pain remained stable during acute treatment for responders, independent of depression response to combination psychotherapy and antidepressant treatment. CONCLUSIONS: Older adult patients with higher levels of physical pain can still respond to antidepressant treatment; however, reported bodily pain may be associated with a more difficult-to-treat depression.     

Alpha-contingent EEG feedback reduces SPECT rCBF variability.

EEG feedback methods, which link the occurrence of alpha to the presentation of repeated visual stimuli, reduce the relative variability of subsequent, alpha-blocking event durations. The temporal association between electro-cortical field activation and regional cerebral blood flow (rCBF) led us to investigate whether the reduced variability of alpha-blocking durations with feedback is associated with a reduction in rCBF variability. Reduced variability in the rCBF response domain under EEG feedback control might have methodological implications for future brain-imaging studies. Visual stimuli were randomly presented to seven subjects, contingent upon the occurrence of alpha (alpha-contingent stimulation (ACS)) or alpha-blocking (not-alpha-blocking-contingent stimulation (NACS)) events. We employed a within-subjects design. rCBF was measured from multiple, cortical and sub-cortical regions. The primary dependent variables were the Mean, Standard Deviation and the ratio of Mean/Standard Deviation of: 1) the alpha-blocking response durations and 2) the temporally summated rCBF responses within the Visual Associative regions of interest (ROIs). Additional within-subjects rCBF measures were derived to quantify the variance-reducing effects of ACS across multiple, distributed areas of the brain. Both EEG and rCBF measures demonstrated decreased variability under ACS. This improved control was seen for localized as well as anatomically distributed rCBF measures.