2007年·第120卷第22期

In the recent editorial comment, Duboule1 emphasized that "animal development is, in fact, nothing but time".That a circadian timing system is apparently universal in biology is the evidence for the important physiological role that rhythmicity plays。

The practice of modern anaesthesiology has extended into perioperative medicine. Due to their expertise in analgesic drug pharmacology and peripheral nerve blocking, anaesthesiologists have pioneered in the management of acute postoperative pain. Effective postoperative analgesia reduces the incidence of postoperative chronic pain, improves the functioning of organs following surgery and shortens the hospital stay.1,2 Although a variety of analgesic techniques and preventative approaches are at the disposal of modem aneasthesiologists, including patient controlled epidural analgesia (PCEA), patient controlled intravenous analgesia, multimodal analgesia and pre-empty analgesia.Despite this array of strategies, these predominantly opioid based techniques are still limited by side-effects such as vomiting, nausea, itching and urinary retention.To optimize further the management of acute postoperative pain, basic mechanisms of postoperative pain must be explored and new treatments must continue to be developed。

Abstract：Background The high incidence of neuropsychologic deficits after cardiac surgery, including cognitive dysfunction and mood status, has significantly influenced the prognosis, outcome of treatment and long-term quality of life of patients. With a circadian secretion pattern, melatonin and cortisol are capable of modulating the human physiological processes and neuropsychological status, whereas disorder of their secretion pattern may lead to many diseases. However, it is unclear whether neuroendocrine variations are related to the neuropsychologic status in patients undergoing coronary artery bypass grafting (CABG). Methods Forty male patients scheduled for CABG with hypothermic cardiopulmonary bypass (CPB) (n=20) or off-pump coronary artery bypass (OPCAB) (n=20) were studied. Blood samples were taken intraoperatively at specific time-points and every 3 hours within the first postoperative 24 hours to determine plasma concentrations of melatonin and cortisol. A neuropsychologic test battery including depression and anxiety was administered preoperatively and 7 to 10 days postoperatively. Statistical methods included the nonparametric analysis, multiple linear regression and cosinor analysis. Results The patients in the CPB group exhibited more severe neuropsychologic deficits and more anxious than those in the OPCAB group after surgery. In both groups, patients were more depressed postoperatively than preoperatively and recovered 3 months after surgery. Depression and anxiety were correlated with some factors of cognitive dysfunctions. In the postoperative 24 hours, 2 patients in the CPB group, and 6 patients in the OPCAB group showed a circadian rhythm of melatonin secretion. As for cortisol secretion, there were 3 patients in the CPB group and 7 in the OPCAB group respectively. Parameters of circadian rhythm of melatonin in the CPB group and those of secretion rhythm of cortisol in both groups were correlated with depression and some neuropsychologic tests. Conclusions The incidence of neuropsychological deficits was higher in patients receiving CABG with CPB than in those without CPB. The status of mood may contribute to the perioperative cognitive dysfunctions. The disordered circadian rhythm of melatonin secretion in patients undergoing CABG with CPB and the disordered cortisol secretion may correlate directly or indirectly through mood with neuropsychological deficits。

Abstract：Background Our previous in vivo study in the rat demonstrates that Shenfu injection, a clinically used extract preparation from Chinese herbs, attenuates neural and cardiac toxicity induced by intravenous infusion of bupivacaine, a local anesthetic. This study was designed to investigate whether bupivacaine could induce a toxic effect in primary cultured mouse spinal cord neuron and if so, whether the Shenfu injection had a similar neuroprotective effect in the cell model. Methods The spinal cords from 11- to 14-day-old fetal mice were minced and incubated. Cytarabine was added into the medium to inhibit the proliferation of non-neuronal cells. The immunocytochemical staining of β-tubulin was used to determine the identity of cultured cells. The cultured neurons were randomly assigned into three sets treated with various doses of bupivacaine, Shenfu and bupivacaine+Shenfu, for 48 hours respectively. Cell viability in each group was analyzed by methyl thiazoleterazolium (MTT) assay. Results The viability of the cultured neurons treated with bupivacaine at concentrations of 0.01%, 0.02%, 0.04% and 0.08% was decreased in a dose-dependent manner. Although the Shenfu injection at concentrations ranging from 1/50 to 1/12.5 (V/V) had no significant influence on the viability of cultured neurons (P＜0.05 vs control), the injection significantly increased the cellular viability of cultured neurons pretreated with 0.03% bupivacaine (P＜0.05). Conclusion Although Shenfu injection itself has no effect on spinal neurons, it was able to reduce the bupivacaine induced neurotoxicity in vitro。

Abstract：Background There have been many studies investigating the impact of the model for end-stage liver disease (MELD) score on predicting post-transplant outcome. But it is unclear whether MELD is correlated to intraoperative fluid therapy and coagulation status. We investigated the relationship between the severity of liver diseases as measured by MELD score and intraoperative fluid requirements and the changes of coagulation characteristics. Methods Ninety patients were included in this retrospective study. The patients were stratified into three groups according to the MELD scores: ＜15 (low), 15-25 (medium) and ＞25 (high). Intraoperatively, volume was restored with allogeneic and/or salvaged red blood cells (RBC), fresh-frozen plasma (FFP), platelet and other types of fluids according to hemodynamic data, hematocrit, and clotting data. Intraoperative coagulation data, blood requirements and other fluids administered were compared among the 3 groups. Results Before surgery, in addition to the three variables used to calculate MELD scores in other baseline laboratory values, including ratio of activated partial thromboplastin time (R-APTT), D-Dimer, hematocrit, platelet and blood urea nitrogen (BUN) were significantly different among the 3 groups. The blood loss increased with increasing MELD. The volume of RBC (allogeneinc, salvaged and total), FFP, platelet and the total volume of transfusion were also significantly different among the three groups (P＜0.01). The requirements for prothrombin complex and fibrinogen showed a similar pattern. During operation, the changing trends of each coagulation variable were different. Compared with baseline, during each intraoperative stage, INR and R-APPT increased in the low MELD group. While in the medium MELD and high MELD groups, INR did not changed significantly during the operation, and R-APPT significantly increased only after reperfusion. Conclusions This study provided some useful information for perioperative management of patients undergoing liver transplantation. Careful preoperative planning and resource preparation are crucial for patients with high MELD scores. Close communication between surgeon, anesthesiologist and the transfusion staff of blood bank before and during surgery should be stressed。

Abstract：Background The mechanisms underlying postoperative pain remain unclear. Neurotransmitters of excitatory and inhibitory amino acids play an important role in the transmission and modulation of pain in the spinal dorsal horn. This study aimed to investigate the changes of release of excitatory and inhibitory amino acids in the spinal cord during postoperative pain and to provide a novel theoretical basis for postoperative pain management.Methods Loop microdialysis catheters were implanted subarachnoidally via the atlanto-occipital membrane in 16 healthy Sprague-Dawley rats. All rats without neural deficits were divided into two groups, Group A and Group B,following 5 days of recovery. The tubes for microdialysis were connected and 25 μl microdialysate sample for baseline value was collected after one-hour washout in each rat. A plantar incision in the right hind paws of rats in Group A were performed under 1.2% isoflurane. All rats in Group B were only anesthetized by 1.2% isoflurane for the same duration.The microdialysate samples were collected at 3 hours, 1 day, 2 days and 3 days after the incision (or isoflurane anesthesia in Group B) in both groups. The cumulative pain scores were also assessed at the above time-points. The amino acids in the microdialysate samples were tested using high performance liquid chromatography.Results Within Group A, the release of aspartate and glutamate at 3 hours after the incision was significantly higher than the baseline values and the release of glycine at 1 day after the incision significantly increased compared with the baseline values (P＜0.01). Within Group B, the release of neurotransmitters at each time point had no significant difference compared with the baseline values (P＞0.05). The release of aspartate and glutamate at 3 hours after the incision in Group A was significantly higher than that in Group B (P＜0.01). The release of glycine at 1 day after the incision in Group A significantly increased compared with Group B (P＜0.01). The cumulative pain scores at 3 hours, 1day and 2 days after the incision in Group A were significantly higher than those in Group B (P＜0.01).Conclusions The release of the excitatory amino acids occurs in the early phase of postoperative pain and might not be involved in the maintenance of pain in a rat model of incision pain. The release of inhibitory glycine lagged behind the excitatory amino acids. The implication of inhibitory glycine release remained to be established further。

Abstract：Background Endogenous nitric oxide and adenosine increase simultaneously to keep the balance of energy demand and supply when the oxygen supply is insufficient, which suggests that nitric oxide and adenosine might exert a synergistic myoprotection during tissue hypoxia. In this study, we tested this hypothesis utilizing a canine model of prolonged global myocardial ischaemic reperfusion injury.Methods In this double blind, controlled study, the hearts of 24 anaesthetized mongrel dogs were arrested for 2 hours with aortic cross clamping and blood cardioplegia. The treatment groups were those supplemented with 2 mmol/L L-arginine (ARG), supplemented with 1 mmol/L adenosine (ADO), ARG + ADO supplemented with both, and no supplementation (control) (n=6 in each group). Haemodynamics, biochemical indices, adenosine triphosphate (ATP) content and myeloperoxidase activities of myocardium were determined to evaluate myocardial injury. Statistical comparison was performed by two way ANOVA.Results Although the requirements for inotropic supports were higher, the cardiac outputs were lower in control group than in ARG, ADO and the combination groups. Plasma cardiac troponin I levels were higher and the areas of hydropic changes were larger in control group than in ARG and ADO groups. Combination of arginine and adenosine provided further myoprotection with respect to better cardiac performance, lower release of cardiac troponin I, and smaller areas of hydropic changes compared with ARG and ADO groups. ATP content was higher, but myeloperoxidase activities of myocardium were significantly lower in the combination group than in control, ARG and ADO groups (P＜0.05).Conclusions Combination of L-arginine and adenosine provides synergistic myoprotection in a canine model of global myocardial ischaemia. Thus, the combination is recommended when the heart is exposed to a prolonged ischaemia during cardiac surgery。

Abstract：Background Transmyocardial laser revascularization (TMLR) has been used in the treatment of patients with end-stage coronary artery disease (CAD) since 1990. The aim of this study was to evaluate the long-term effectiveness of TMLR in patients with diffuse CAD.Methods Ninety-four consecutive patients underwent TMLR in one center from July 1997 to December 2000. The follow-up data of these patients were obtained through face-to-face, mail questionnaires, or telephone interviews in July 2004 and December 2004. Four cases failed to respond. Mean follow-up time was (5.5±1.0) years.Results Mean Canadian Cardiovascular Society (CCS) angina scores of TMLR patients were 3.1±0.8 at baseline,1.7±0.9 at 1 year (P＜0.05), 1.7±0.9 at 3 years (P＜0.05), and 1.9±0.9 at 5 years (P＜0.05). At an average of 5 years, 69%of the patients had ≥ 1 angina class reduction, mean NYHA class level (1.9±0.9) ameliorated compared to the baseline (2.5±0.7, P＜0.001), the rate of re-hospitalization was 2.7 times/person. Kaplan-Meier survival rate was 87% at 1 year,69% at 3 years and 64% at 5 years. The causes of death were attributed more to heart failure (58.9%) and myocardial infraction (14.7%) after TMLR. The patients with no angina relief, or who died after TMLR, had a higher percentage of preoperative unstable anginas or prior myocardial infraction compared to the survivors. The assorted shapes of myocardial laser channels were detected in some patients by the color Doppler velocity technique.Conclusions TMLR provided a long-term improvement in the quality of life, including CCS angina class or NYHA heart functional class for about 70% of Chinese patients with severely disabling angina pectoris. The various myocardial laser channels would always be visible after TMLR. 5-years after TMLR as a sole therapy, the survival rate of the patients was 64%。

Abstract：Background Early local platelet activation after coronary intervention identifies patients at increased risk of acute stent thrombosis (AST). However, early changes in platelet activation in coronary circulation following drug-eluting stent (DES) implantation have never been reported.Methods In a prospective study of 26 consecutive elective stable angina patients, platelet activation was analyzed by measuring soluble glycoprotein V (sGPV) and P-selectin (CD62P) before and after implantation of either DES or bare metal stent (BMS). All patients were pretreated with clopidogrel (300 mg loading dose) and aspirin (75 mg orally) the day before the procedure. Blood samples were drawn from the coronary ostium and 10 - 20 mm distal to the lesion site.Results Consistent with the lower baseline clinical risk, the levels of CD62P and sGPV were within normal reference range, both in the coronary ostium and distal to the lesion before percutaneous coronary intervention (PCl) procedure.The levels of CD62P and sGPV did not change significantly (CD62P: (31.1 ± 9.86) ng/ml vs (29.5 ± 9.02) ng/ml, P=0.319and sGPV: (52.4 ± 13.5) ng/ml vs (51.8 ± 11.7) ng/ml, P=0.674, respectively) after stent implantation when compared with baseline. Changes in these platelet activation markers did not differ between stent types.Conclusions Intracoronary local platelet activation does not occur in stable angina patients before and immediately following DES implantation when dual anti-platelet is administered。

Abstract：Background Melilotus suaveolens Ledeb (M. suaveolens Ledeb) has long been used as a folk medicine in inflammation-related therapy. This study was undertaken to determine the anti-inflammatory effect of the plant.Methods Petroleum ether fraction, ethyl acetate fraction, n-butanol fraction, aqueous fraction were obtained from ethanol extract of M. suaveolens Ledeb and evaluated by high performance liquid chromatography (HPLC). While dexamethasone (DM) was used as a positive control, the effects of different solution fractions of ethanol extract on tumor necrosis factor α (TNF-α) mRNA, cyclooxygenase 2 (COX-2) mRNA, COX-2 and nuclear factor κB (NF-κB) of LPS-stimulated RAW 264.7cells were studied by real-time PCR, Western blot analysis and immunocytochemical assay, respectively.Results Coumarin was one of the main ingredients in different solution fractions of ethanol extract except the aqueous fraction with no inflammatory effect. The petroleum ether fraction, ethyl acetate fraction and n-butanol fraction of ethanol extract could inhibit the production of TNF-α mRNA, COX-2 mRNA and NF-κB to some extent.Conclusions Different solution fractions of ethanol extract from M. suaveolens Ledeb had similar anti-inflammatory effect as did dexamethasone except the aqueous fraction. Coumarin was likely to be essential to the anti-inflammatory effect, and other ingredients might attribute to their different anti-inflammatory effects from the HPLC fingerprint。

Abstract：Background Previous studies have shown that oncosis in malignant tumors might be related to cellular energy supply.The aim of this study was to detect oncosis in human esophageal squamous cell carcinoma (ESCC), and to investigate its relationship with apoptosis and microvessel density (MVD).Methods ESCC specimens were obtained from 30 patients with ESCC after surgery. Transmission electron microscopy,TUNEL, and immunohistochemistry were used to detect oncosis, apoptosis, and MVD. The relation of oncosis to apoptosis and MVD was analyzed by ANOVA, t test, and q test using SPSS 10.0.Results Transmission electron microscopy revealed both oncosis and apoptosis in the ECSS tissues. About 10% of the TUNEL-positive cells, which were considered apoptotic cells, showed the characteristics of oncosis. In the areas, where oncotic cells accumulated, apoptotic cells were rare; contrarily, where apoptotic cells gathered, oncotic cells were sparse.Compared with the tissues with a high MVD, the number of oncotic cells was increased and that of apoptotic cells was decreased in the tissues with a low MVD.Conclusions Cellular oncosis can be detected in human ESCC tissues. The distribution of oncotic cells presents a close relationship with cellular apoptosis and MVD. Oncosis might be induced by poor blood supply。

Abstract：Background There has been continuous debate as to whether Y chromosome loss is an age related phenomenon or a cytogenetic marker indicating a malignant change. This study aimed to investigate the frequency of Y chromosome loss in the specific patients in order to determine whether it is an age related phenomena or a cytogenetic marker indicating a malignant change.Methods Five hundred and ninety-two male patients with a median age of 59 years old (22-95 years) were included in this study. These patients were divided into two groups: the study group, including 237 patients who had hematological disorders included myeloproliferative disorder (MPD), myelodysplastic syndrome (MDS), acute myeloid leukemia (AML),chronic myeloid leukemia (CML), multiple myeloma (MM), and lymphoma and the control group including 355 patients with no evidence of hematological disease. Both conventional cytogenetics and fluorescence in situ hybridization using DNA probes specific for the centromere of chromosomes X or Y were performed according to our standard laboratory protocols.Results Twenty-four out of 237 patients with hematological disorders (10.1%) had Y chromosome loss. Of these 24patients, 2 patients had AML (5.0% of all AML patients), 2 patients had CML (5.7% of all CML patients), 2 patients had MPD (8.0% of all MPD patients), 3 patients had MM (10.0% of all MM patients), 5 patients had lymphoma (10.6% of all lymphoma patients) and 10 patients had MDS (16.7% of all MDS patients). Twenty-one out of these 24 patients had a loss of Y chromosome as the sole anomaly and the remaining three had a loss of Y chromosome accompanied with otherstructural changes detected by conventional cytogenetic analysis. Fluorescence in situ hybridization (FISH) analysis confirmed the routine cytogenetic results. All 24 patients had a loss of Y chromosome with a range of 17.5%-98.5% of cells. Two of the patients, one with AML and another with CML, had karyotype and FISH testing done both at the initial diagnosis and during remission. The results showed a loss of Y chromosome at initial diagnosis but a normal 46,XY karyotype during remission. Only 9 out of 355 patients (2.5%) without evidence of hematological disease had Y chromosome loss, among them 7 patients had cardiovascular diseases and 2 patients had kidney diseases. Comparison of the incidence of Y chromosome loss in patients with hematological disorders or without evidence of hematological disease using statistical analysis showed a statistically significance difference (P＜0.05).Conclusions The present study demonstrated that the frequency of Y chromosome loss is significantly higher in patients with hematological disorders than in patients without hematological disorders, which indicates that the loss of Y chromosome is associated with a neoplastic change。

Catheter ablation of atrial fibrillation (AF) has been increased dramatically recently.1 However, it is an unpleasant procedure with intolerable pain without sedation. Propofol and fentanyl/midazolam have been widely used in painful clinical examination and cardiovascular procedures with established safety and efficacy.2,3 Propofol, alfentanyl and midazolam were administrated for catheter ablation in some electrophysiological labs for a less painful procedure.4However, there is few published work on the sedation regimen for catheter ablation of AF。

The action potential of pacemaker cells in the sino-atrial node forms the automatic rhythm of the heart. The automatic depolarization in phase 4 is the basis of the automaticity in pacemaker cells. Many currents are included in phase 4, such as calcium current,1TTX-sensitive sodium current,2 sustained inward current (Isi),3 decay of delayed rectifier potassium current,4 etc.Funny current (If) has long been recognized as important in this phase and is activated at hyperpolarized potentials during cell diastole and in turn activates other currents to form automatic depolarization.5 It is controlled by voltage and cAMP, an intracellular messenger, so the auto no-mic nerve can modulate this current by increasing or decreasing intracellular cAMP。

Atrial fibrillation (AF) is the most common cardiac arrhythmia in man, and epidemiological study has shown the close relationship between the incidence of AF and aging.1 Although the effects of aging on atrial electrophysiology have been investigated in humans and animal models,2-9 the electrophysiological changes that make the atria of aged individuals more susceptible to AF than those of adults remain poorly understood。

Diffuse panbronchiolitis (DPB) is a relatively recently recognized, idiopathic progressive disease, originally described in Japan in 1969.1 It has distinctive clinicopathological features characterized by chronic pulmonary inflammation in the respiratory bronchioles of the lung and paranasal sinuses.2 It has been reported more extensively among Japanese than other ethnic populations.The first case of DPB in China was reported in 1996.3Since then, an increasing number of cases have been described, which suggest that this disease may not be rare in China. However, clinicians are not familiar with this disease and it may be 4actually under-recognized and under-reported in China.4 Therefore we summarize the cases reported in the mainland of China since 1996,hoping that this would help to increase the awareness of this disease。

Von Hippel-Lindau (VHL) disease is a rare autosomal dominant disorder caused by germ line mutations of the VHL tumour suppressor gene. It predisposes affected individuals to develop a variety of neoplasms, including haemangioblastomas of the central nervous system,retinal angiomas, renal cell carcinomas (RCCs),pheochromocytomas and cysts of the kidneys and epididymis。

Pulmonary vein varix, congenital or acquired dilation of the pulmonary vein, is a rare vascular abnormality.This disease often presents as a pulmonary mass on chest roentgenography, and pulmonary angiography, computed tomography (CT), or magnetic resonance imaging (MRI)is considered necessary for diagnosis.1 The diagnosis of the disease by thoracic exploration is rare because the present case was diagnosed as a pulmonary arteriovenous fistula before operation。

Paroxysmal nocturnal hemoglobinuria (PNH) is a consequence of nonmalignant clonal expansion of one or several hematopoietic stem cells that have acquired a somatic mutation of phosphatedalinositol glycae-class A (PIGA) gene leading to deficient glycosyl phosphatidylinositol (GPI) synthesis。

Holmes' tremor has been postulated as a syndrome attributed to those lesions that interrupt the dentatethalamic and the nigrostriatal tracts thus causing both an action and a rest tremor.1 It may arise from various underlying structural disorders including multiple sclerosis, stroke, or tumors. So far, to our knowledge, few studies on Holmes' tremor secondary to cavernoma have been reported.2 Here we report a case of disabling tremor,who harbored a cavernoma in the midbrain。

Spontaneous regression of pituitary macroadenomas is rare. It is generally thought that absorption of the necrotic tissue after pituitary apoplexy may cause the spontaneous healing of the tumor. However, such cases are often accompanied by hypopituitarism, which sould be treated with hormone replacement therapy. Here we report two cases of spontaneous remission of pituitary macroadenomas in women, who had complete tumor disappearance with preserved pituitary function。