RELATIONSHIP BETWEEN POST-TETANIC TWITCH AND SINGLE TWITCH RESPONSE AFTER ADMINISTRATION OF VECURONIUM

We have studied the relationship between posttetanic twitch(PTT) and single twitch response after administration of vecuronium0.2 mg kg^–1 in 100 patients during neuroleptanaesthesia(NLA) (droperidol and fentanyl) and during anaesthesia withhalo thane, isoflurane, enflurane or sevoflurane (1 MAC in nitrousoxide and oxygen). Intervals from PTT₁ to single twitch, andpost-tetanic-count (PTC) (number of PTT responses) at the onsetof single twitch were determined electromyographically. Theseintervals in the isoflurane, enflur ane and sevoflurane groupsdiffered from those in NLA and halothane groups. PTC in theisoflurane, enflurane and sevoflurane groups differed from thosein the NLA group, and PTC in the sevoflurane group significantlyfrom those in the NLA and halothane groups. These results areconsistent with the view that PTT reflects prejunctional block,whilst the single twitch response is indicative of postjunctionalblock. (Br. J. Anaesth. 1993; 71: 443–444)     

Prediction of Changes in the Clinical Pharmacokinetics of Basic Drugs on the Basis of Octanol-Water Partition Coefficients

A physiologically based pharmacokinetic model for basic drugs has been established on the basis of octanol-water partition coefficients of the non-ionized, unbound drugs (P_oct). The parameters for the physiological model in man were estimated from a regression equation obtained for the relationships between the P_oct and the tissue-plasma partition coefficient, the hepatic intrinsic clearance (CL_int,h) and the blood-to-plasma concentration ratio in rabbits. The plasma concentrations observed after intravenous administration of ten basic drugs (3.2 mg kg^?) to rabbits agreed with the levels predicted using the physiological model (r = 0.710–0.980). In man, the predicted plasma concentrations of basic drugs were in good agreement with reported values (r = 0.729–0.973), except for diazepam and pentazocine. Variations in plasma and brain-concentration profiles of clomipramine and nitrazepam in various disease states were simulated using the model. We assumed that the changes in unbound fraction of drug in serum (f_p), CL_int,h and the hepatic blood flow rate were from 0.25- to 4-fold that of the control and that fat volume changed by 0.2- to 5-fold. With regard to changes in f_p, we predicted that the brain-plasma concentration ratio of clomipramine was 1.5- to 25-fold that of the control 24 h after intravenous administration, although the variations in the plasma concentration-time profiles were less marked. Plasma concentrations predicted for several basic drugs were in good agreement with reported values and this physiological model could be useful for predicting drug-disposition kinetics in man.     

Degradation of Insulin and Calcitonin and Their Protection by Various Protease Inhibitors in Rat Caecal Contents: Implications in Peptide Delivery to the Colon

The objective of this study was to examine the metabolism of insulin and calcitonin, and their protection by various protease inhibitors, in the large intestine. Fresh caecal contents were prepared from non-fasted rats and the degradation of insulin and calcitonin was studied in a suspension of rat caecal contents, as a model of the content of the large intestine. Both insulin and calcitonin were metabolized in suspensions of rat caecal contents, but the degradation of calcitonin was much faster than that of insulin. The degradation of insulin was fastest at pH 6.8. Protease inhibitors such as camostat and aprotinin inhibited the degradation of insulin and calcitonin in rat caecal contents, which was consistent with the high chymotrypsin activity of these contents. These findings suggest that care should be taken when administering peptide drugs to the large intestine for colon-specific drug delivery because they can be degraded in rat caecal contents. Protease inhibitors might be useful for increasing the stability of these peptides in the large intestine, thereby improving their large-intestinal absorption to the systemic circulation.     

Expression of metastasis suppressor gene product, nm23 protein, is not inversely correlated with the tumour progression in human malignant melanomas

An inverse correlation between the nm23 RNA level and tumour progression of melanocytes has been reported. To elucidate whether the expression of nm23 gene product in malignant melanoma is also inversely correlated with metastatic potential, conventional prognostic parameters or the tumour suppressor protein p53, immunohistochemical studies using a monoclonal antibody against nm23-H1 protein were performed on 138 benign and malignant melanocytic tumours. The expression of nm23 protein was compared with that of p53 protein and conventional clinicopathological prognostic factors. The nm23 protein level in benign melanocytes and metastatic melanoma cells was also studied by Western blot analysis. No significant difference regarding the protein was observed between naevi and melanomas, either at histological or protein levels. The expression correlated with local recurrence within 1 year after surgery, level of invasion and tumour thickness, but no parallels were observed between the nm23 and p53 proteins, suggesting that gene is regulated by independent mechanisms, although located on the same chromosome. There was no inverse correlation between the nm23 protein and melanoma metastasis which suggested that the nm23 protein does not appear to be lost during melanoma metastasis.     

Response of sympathetic nervous system activity to exercise in patients with congestive heart failure

To investigate the serial sympathetic nervous system response to exercise, plasma norepinephrine (NE) and epinephrine (E) concentrations were measured at rest, during each stage of treadmill exercise, and immediately and 5 minutes after exercise in 68 congestive heart failure (CHF) patients (NYHA functional class I 24, II 25, III 19) and 30 normal subjects. Circulatory responses of NYHA class II patients increased at early stages of exercise. Systolic blood pressure and double product at peak exercise were significantly lower in NYHA class III patients. Plasma NE response of NYHA class I patients was similar to that of normal subjects. However, plasma NE at rest, and during and after exercise were significantly higher in NYHA classes II and III patients than in normal subjects and NYHA class I patients (peak NE (pg ml-1); Normals: 547 +/- 37, I: 535 +/- 53, II: 867 +/- 87, III: 1033 +/- 157). There was no significant difference in plasma E levels among the four groups. NE response to exercise was augmented according to the severity of heart failure, which suggested compensatory activation of sympathetic nervous system activity. Circulatory responses were reduced in NYHA class III patients despite the exaggerated compensatory activation of the sympathetic nervous system. Blunted circulatory responses to increased NE concentration in NYHA class III patients might relate to a decreased cardiac responsiveness to sympathetic activity in severe CHF patients.     

Post-tetanic burst: a new monitoring method for intense neuromuscular block

A new stimulation pattern for evaluation of intense neuromuscularblock (post-tetanic burst (PTB)) was compared with post-tetanictwitch (PTT) during spontaneous recovery from vecuronium-inducedneuromuscular block. Thirty adult patients were allocated totwo equal groups and we measured times from administration ofvecuronium 0.1 mg kg^–1 to return of PTB and PTT responses,and evoked responses to PTB and PTT stimuli. For PTB stimulation,a 50-Hz tetanus was applied at 50 mA for 5 s, and after a pauseof 3 s, a 50-Hz burst stimulation was applied, consisting ofthree impulses at 50 mA. PTB stimuli were delivered every 5min. Similarly, PTT consisted of a tetanus, a 3-s pause andone single twitch stimulation repeated every 5 min. Time toreturn of the PTB response was significantly shorter than thatof PTT (mean 23.7 (SD 7.9) compared with 30.7 (7.0) min) (P= 0.0160), although evoked responses to PTB did not differ significantlyfrom those of PTT throughout recovery from vecuronium-inducedneuromuscular block. This study suggested that PTB was moresensitive in evaluating intense neuromuscular block than PTT.(Br. J. Anaesth. 1995; 74: 293–295)     

Methylmethacrylate bone cement does not release histamine in patients undergoing prosthetic replacement of the femoral head

This study was designed to see if methyl methacrylate monomerbone cement released his tamine in 13 patients undergoing totalhip replacement surgery with a cemented prosthesis, comparedwith seven control patients receiving a cementless porous-coatedprosthesis. Blood samples for plasma concentrations of histaminewere obtained before the start of anaesthesia, immediately beforeinsertion of methylmethacrylate bone cement into the shaft ofthe femur in the cemented fixation group or before insertionof the femoral component of the prosthesis in the cementlessfixation group, and 15, 30 and 60 min after the start of implantationof the prosthesis. In both groups, changes in plasma histaminedid not differ significantly from baseline before implantationof cement. There were no significant differences between groups.We conclude that methyl-methacrylate bone cement does not releasehis tamine during total hip replacement surgery.     

Relationship of angiographic finding with neovascular structure detected by immunohistochemical staining of α-smooth muscle actin in small hepatocellular carcinoma

To elucidate the relationship between angiographic features and histological findings, an immunohistological study of α-smooth muscle actin was performed in 106 patients with small hepatocellular carcinoma. Arterial dominance or portal blood paucity were found in 73 patients (68.9%) on digital subtraction angiography, 88 (83.0%) on computerized tomographic arterial portography and 87 (82.1%) on carbon dioxide-enhanced ultrasonography. Among 73 patients with hypervascularity on angiography, 57 (78.1%) had thick-walled, nuclei-rich and slender-shaped vessels (type II), eight (11, 0%) had thin-walled, nuclei-poor and oval-shaped vessels (type I) and the remaining eight had a mixed type of II and I. Conversely, among 33 patients without hypervascularity, five (15.2%) had a type II, 21 (63.6%) had a type I, five had a mixed type and two had no positive vessel. Tumour size, histological classification and amount of non-triadal vessels were also associated with the angiographic appearance of the tumours. Among varied aspects of the cancer including tumour size, tumour multiplicity, microscopic portal invasion, histological classification, amount of α-smooth muscle actin-positive vessels and shape of α-smooth muscle actin-positive vessels, multivariate logistic regression analysis demonstrated that the shape of α-smooth muscle actin-positive vessels was solely associated with angiographic hypervascularity independently (P < 0.0001). Although the existence of non-triadal vessels characterized hepatocellular carcinoma, angiographic hypervascularity was closely associated with the type II vessel. A morphological change of non-triadal vessel from type I to type II was considered to occur in an early stage of hepatocellular carcinoma.     

已领结婚证书性活跃夫妇对婚礼前妊娠的看法及影响因素

世界卫生组织近年来提出生殖健康的一项重要内容就是要减少非期望妊娠及人工流产。进入九十年代以来,上海青年发生性行为的年龄在逐渐提前,约2/3婚前人流的妇女均从未使用过避孕措施。年轻男女在领取结婚证书后从法定观念来看已是合法夫妇,如发生性关系或妊娠似乎都无可非议。然而,刚领证的年轻男女如因一时性冲动会发生过早的非期望妊娠及可能导致的人工流产。对婚后缺乏适应过程,过早