The postviral fatigue syndrome — an analysis of the findings in 50 cases

The clinical, pathological, electrophysiological, immunological and virological abnormalities in 50 patients with the postviral fatigue syndrome are recorded. These findings confirm the organic nature of the disease. A metabolic disorder, caused by persistent virus infection and associated with defective immunoregulation, is suggested as the pathogenetic mechanism.     

骨肉瘤CDKN2/P16基因外显因子2缺失率与病理分型、转移能力及性别的相关性

Osteosarcomaisacommontumorwhichoccupiesthefirstplaceinmalignantbonetumorwith44.8%.Itoftenoccursattheage10～20yearsoldwithyoungerage,highermalignancy,morerapidadvancing,earliermetastasismore,difficultfoundingandbadprog-nosisasitsmanifestation.Soithasanimportantsignificancetostudyongenesis,advancingandmetastasis.Thisresearchanalysisalternationofexon2whichwasoftenfounddeletionandmutationbyPCR-SSCPsilverstainingmethod.1Subjectsandmethods1.1Clinicdata25casesofosteosarcomawereinvestigatedinChang…     

P wave separation after atrial compartment operation for atrial fibrillation

Surgically induced abnormalities in atrial conduction could result in unusual P wave changes. A 31-year-old woman underwent concomitant mitral valve surgery and atrial compartment operation for mitral stenosis and atrial fibrillation (AF). After operation, the AF was successfully converted to sinus rhythm, whereas an unusual electrocardiogram (ECG) with a discrete negative deflection before the T wave in V1 was noted. Electrophysiological study showed a marked conduction delay from the high right atrium (HRA) to the right atrial appendage (RAA) compartment, which resulted in a separation of P waves. The P wave preceding the QRS complex represented the activation of sinus node and the left atrial compartments, and the P at the vicinity of T wave represented the activation of RAA compartment. The conduction from HRA to RAA was worsened on HRA pacing at a faster rate, and improved after isoproterenol infusion. This report demonstrated that conduction across a surgically created isthmus in the atrium could be severely impaired and result in unusual P wave separation.     

Adrenergic, cholinergic and peptidergic nerve fibres in dura mater involvement in headache?

Nerve fibres containing noradrenaline, acetylcholinesterase, vasoactive intestinal polypeptide and substance P were demonstrated in the dura mater of guinea-pigs using histochemical and immunohistochemical methods. These fibres accompanied blood vessels of all size, indicating a vasomotor role. In addition, some nerve fibres were observed without any obvious relation to the blood vessels. The rich supply of nerve fibres to the various parts of the dura mater may possibly be of importance in the pathogenesis of some types of headache.     

Vasoactive peptides in Bartter's syndrome

Abstract. Patients with Bartter's syndrome exhibit an increased vascular resistance to the pressor effects of angiotensin II and noradrenaline. Further, an increased production of vasodilating renal prosta-glandins, perhaps mediating the vascular unresponsi-veness, has been hypothesized in this syndrome based on high urinary prostaglandins. To determine whether different peptides might contribute to blood pressure control in this syndrome, the basal immunoreactive plasma levels of an array of vasoactive peptides and catecholamines were analysed in six patients with Bartter's syndrome. Among the vasoconstrictors analyzed, the mean plasma levels of noradrenaline (NA), adrenaline (A) and neuropeptide Y-like immunoreac-tivity (NPY-LI) were significantly increased as compared to healthy subjects ( P = 0.030, 0.046 and 0.001, respectively). The plasma level of the vasodilator substance P (SP-LI) was also higher in these patients ( P = 0.057 ).
These results indicate that in Bartter's syndrome the vasoconstrictive effect of catecholamines and angiotensin II may be enhanced by concomitant NPY release. Whether a release of the vasodilator substance P is an independent mechanism or represents a reflex response to the increased secretion of angiotensin II, catecholamines and/or NPY remains to be established. However, the significance of these biochemical findings for blood pressure maintenance in Bartter's syndrome remains to be settled.     

Arzneimittelwechselwirkungen mit Antiepileptika

Drug interactions with antiepileptic agents are based in large part on pharmacokinetic mechanisms. Most prominent are induction or inhibition of enzymes of the cytochrome P450 (CYP) system, which is of central importance for metabolic elimination of lipophilic xenobiotics. Potent inductors of CYP isoenzymes are carbamazepine, phenobarbital, phenytoin, and primidone, thereby decreasing not only their own plasma levels and efficacy but also that of other antiepileptics and other drugs. Felbamate, oxcarbazepine, and topiramate are weak inductors of the CYP isoenzyme 3A4, whereas they inhibit CYP2C19. Valproic acid is a potent inhibitor of several CYP isoenzymes and glucuronyltransferases, resulting in an increase in plasma concentrations and toxicity of antiepileptics and other drugs. Antiepileptics that are not involved in drug interactions include gabapentin, levetiracetam, and vigabatrine. The P-glycoprotein may mediate the exit of antiepileptics from the brain. This transport mechanism is inhibited by carbamazepine, which may explain the enhanced clinical efficacy of a combination of carbamazepin with other antiepileptics. Other possible pharmacokinetic interactions are precipitation of antiepileptics in the stomach by antacids or sucralfate and displacement from plasmaprotein binding of one antiepileptic agent by another. Therapeutic drug monitoring (TDM) may be helpful in assessing pharmacokinetic drug interactions. Pharmacodynamic interactions appear to be responsible for the enhanced efficacy of antiepileptic combination therapy. In prescribing drugs, their spectrum of interactions has to be known.     

唾液腺癌中P16、CyelinD1和Cdk4的表达及临床意义

目的探讨正常唾液腺组织唾液腺癌中P16、CyclinD1和Cdk4的表达及临床意义。方法应用免疫组化S—P法分别检测10例正常唾液腺，30例黏液表皮样癌，30例腺样囊性癌组织P16、CyclinD1和Cdk4蛋白表达。结果P16蛋白阳性表达率在正常唾液腺和唾液腺癌中分别为90％和38％，有显著差异（P〈0．01）。CyclinD1蛋白阳性表达率在正常唾液腺和唾液腺癌中分别为20％和80％，有显著差异（P〈0．01）。Cdk4蛋白阳性表达率在正常唾液腺和唾液腺癌组段中分别为30％和88％，有显著差异（P〈0．01）。在唾液腺癌组织中P16、CyclinD1和Cdk4蛋白表达正相关（P〈0．01）。P16、CyclinD1和Cdk4蛋白表达正相关（P〈0．05）。P16、CyclinD1和Cdk4与患者年龄。癌细胞恶性程度无关（P〉0．05）。结论P1。蛋白表达减少与唾液腺癌的发生有关。P16、CyclinD1和Cdk4蛋白表达的增加与唾液腺癌的发生有关。     

Metabolic drug interactions with new psychotropic agents

New psychotropic drugs introduced in clinical practice in recent years include new antidepressants, such as selective serotonin reuptake inhibitors (SSRI) and 'third generation' antidepressants, and atypical antipsychotics, i.e. clozapine, risperidone, olanzapine, quetiapine, ziprasidone and amisulpride. These agents are extensively metabolized in the liver by cytochrome P450 (CYP) enzymes and are therefore susceptible to metabolically based drug interactions with other psychotropic medications or with compounds used for the treatment of concomitant somatic illnesses. New antidepressants differ in their potential for metabolic drug interactions. Fluoxetine and paroxetine are potent inhibitors of CYP2D6, fluvoxamine markedly inhibits CYP1A2 and CYP2C19, while nefazodone is a potent inhibitor of CYP3A4. These antidepressants may be involved in clinically significant interactions when coadministered with substrates of these isoforms, especially those with a narrow therapeutic index. Other new antidepressants including sertraline, citalopram, venlafaxine, mirtazapine and reboxetine are weak in vitro inhibitors of the different CYP isoforms and appear to have less propensity for important metabolic interactions. The new atypical antipsychotics do not affect significantly the activity of CYP isoenzymes and are not expected to impair the elimination of other medications. Conversely, coadministration of inhibitors or inducers of the CYP isoenzymes involved in metabolism of the various antipsychotic compounds may alter their plasma concentrations, possibly leading to clinically significant effects. The potential for metabolically based drug interactions of any new psychotropic agent may be anticipated on the basis of knowledge about the CYP enzymes responsible for its metabolism and about its effect on the activity of these enzymes. This information is essential for rational prescribing and may guide selection of an appropriate compound which is less likely to interact with already taken medication(s).     

Purinergic transmission and transglial signaling between neuron somata in the dorsal root ganglion

Most dorsal root ganglion neuronal somata (NS) are isolated from their neighbours by a satellite glial cell (SGC) sheath. However, some NS are associated in pairs, separated solely by the membrane septum of a common SGC to form a neuron–glial cell–neuron (NGlN) trimer. We reported that stimulation of one NS evokes a delayed, noisy and long‐duration inward current in both itself and its passive partner that was blocked by suramin, a general purinergic antagonist. Here we test the hypothesis that NGlN transmission involves purinergic activation of the SGC. Stimulation of the NS triggered a sustained current noise in the SGC. Block of transmission through the NGlN by reactive blue 2 or thapsigargin, a Ca²⁺ store‐depletion agent, implicated a Ca²⁺ store discharge‐linked P2Y receptor. P2Y2 was identified by simulation of the NGlN‐like transmission by puffing UTP onto the SGC and by immunocytochemical localization to the SGC membrane septum. Block of the UTP effect by BAPTA, an intracellular Ca²⁺ scavenger, supported the involvement of SGC Ca²⁺ stores in the signaling pathway. We infer that transmission through the NGlN trimer involves secretion of ATP from the NS and triggering of SGC Ca²⁺ store discharge via P2Y2 receptors. Presumably, cytoplasmic Ca²⁺ elevation leads to the release of an as‐yet unidentified second transmitter from the glial cell to complete transmission. Thus, the two NS of the NGlN trimer communicate via a ‘sandwich synapse’ transglial pathway, a novel signaling mechanism that may contribute to information transfer in other regions of the nervous system.