Neurokinin 1 receptor antagonism requires norepinephrine to increase serotonin function.

The present studies examined the role of norepinephrine (NE) system in mediating the enhancement of 5-HT function produced by neurokinin (NK)1 receptor antagonism. Dorsal raphe 5-HT and locus coeruleus NE neurons were recorded in vivo in mice lacking NK1 receptors in wildtype mice pretreated with the NK1 antagonist RP67580 and its inactive enantiomer RP 68651. RP67580 and RP68651 were also tested on 5-HT neurons of mice lacking the 5-HT(1A) receptor. RP67580 increased the firing rate of 5-HT neurons in wildtype mice and in 5-HT(1A) null mutant mice to the same degree, thus indicating that the mechanism by which NK1 antagonists enhances 5-HT firing is independent of 5-HT(1A) receptors. NE neuronal burst activity was increased in NK1 null mutant and wildtype mice given RP67580, but not with RP68651. After NE depletion, RP67580 was ineffective in increasing 5-HT neuronal firing activity in NK1 wildtype mice, and the enhancement of 5-HT neuronal firing observed in NK1 null mutant mice was abolished. In conclusion, NE neurons are essential for the action of NK1 antagonists on 5-HT neurons. In addition, the desensitization of 5-HT(1A) autoreceptors produced by NK1 receptor antagonism is not critical for enhancing 5-HT neuronal firing.     

Anaesthetic management and outcome in right-lobe living liver-donor surgery

BACKGROUND AND OBJECTIVE: We reviewed retrospectively the anaesthetic management and perioperative course of eight right hepatectomies for living liver donation. METHODS: After preoperative psychiatric evaluation, eight ASA I-II individuals donated the right lobe of their liver to a family member. A graft-recipient body weight ratio of 0.8-1.0% was required for patient selection. Indications for liver transplantation were: hepatitis C viral-related cirrhosis in six patients; combined hepatitis C and B viral cirrhosis in one patient; multifocal hepatocellular carcinoma--four lesions, involving both liver lobes--of hepatitis C viral-related cirrhosis in another patient. Indication for adult-to-adult living-donor liver transplantation was retained in the latter because of rapid deterioration of liver disease, rare recipient's blood group and extended, unresectable hepatocellular carcinoma. Hepatitis C viral-related cirrhosis was casually the primary indication for adult-to-adult living-donor liver transplantation in this group. The condition of the donated hepatic lobe was optimized by appropriate drug and perfusion management. Preoperative investigations included: blood tests (full cell count and film, thyroid function tests, pregnancy tests, full virological tests and bacteriological cultures, and immunological typing), chest radiograph, electrocardiogram plus Doppler cardiac ultrasound, spirometry, aminopyrine breath test, liver Doppler examination, magnetic resonance imaging, angiography and cholangiography and a volumetric study of the whole liver and the right lobe. Haemoglobin and lactate concentrations, liver function tests and international normalized ratio were measured before and after operation. The volume and weight of the resected right lobe was calculated. Anaesthesia was induced with propofol 300 mL h(-1) and sufentanil 0.3 microg kg(-1) intravenously; cisatracurium, 0.15 mg kg(-1), was given to facilitate tracheal intubation. Anaesthesia was maintained during normocapnic ventilation of the lungs with oxygen 40% in air, isoflurane 1-1.5 MAC and sufentanil. Routine anaesthetic monitoring included electrocardiography, pulse oximetry, invasive blood pressure, central venous pressure, urine output, state of neuromuscular blockade and core temperature. Periods of hypotension (<80% of the preoperative blood pressure) or haemodynamic instability (requiring inotropic or vasoactive support) were registered. Total blood loss and transfusion (homologous, autologous or cell-saver blood) requirements were measured; volume replacements were derived. RESULTS: Data are presented as mean (range). There was no morbidity or mortality and no periods of intraoperative hypotension or haemodynamic instability. The operation time averaged 619 (525-780)min. Four donors were extubated in the operating room immediately after surgery; the others were extubated in the intensive care unit, where the mean extubation time was 16.3 (5-25)h after arrival. The estimated blood loss was 967 (550-1,600)mL. No homologous blood was administered; five donors received autologous blood, intraoperatively; three donors received a cell-saver blood transfusion. Intraoperative fluid replacement was with crystalloids, colloids and 4% albumin. Total urine output was 1,472 (700-3100)mL. Although intraoperative hypothermia occurred all subjects were normothermic at the end of operation. The pre- and immediately postoperative haemoglobin concentration averaged 13.6 (9.8-15.6) and 10.5 (6.9-13.0)gdL(-1), respectively. On the first postoperative day, the haemoglobin was 11.7 (8.4-15.1)gdL(-1). The donors' liver function tests were transiently elevated in the initial postoperative period. The intensive care unit discharge time was 2 (1-3) days. The hospital stay was 13 (7-17) days. There was no morbidity or mortality. CONCLUSIONS: The study demonstrates that right-lobe living-donor surgery was well tolerated, without intraoperative hypotension or haemodynamic instability, without perioperative anaesthetic or surgical complications, and with an excellent general outcome.     

Superior labrum anterior-posterior lesions: diagnosis with MR arthrography of the shoulder

PURPOSE: To determine the accuracy of magnetic resonance (MR) arthrography in the diagnosis of superior labrum anterior-posterior (SLAP) lesions of the shoulder. MATERIALS AND METHODS: From January 1995 to June 1998, MR arthrography of the shoulder was performed in 159 patients with a history of chronic shoulder pain or instability. Fifty-two patients underwent arthroscopy or open surgery 12 days to 5 months after MR arthrography. Diagnostic criteria for SLAP lesion included marked fraying of the articular aspect of the labrum, biceps anchor avulsion, inferiorly displaced bucket handle fragment, and extension of the tear into the biceps tendon fibers. Surgical findings were correlated with those from MR arthrography. RESULTS: SLAP injuries were diagnosed at surgery in 19 of the 52 patients (37%). Six of the 19 lesions (32%) were classified as type I, nine (47%) as type II, one (5%) as type III, and three (16%) as type IV. MR arthrography had a sensitivity of 89% (17 of 19 patients), a specificity of 91% (30 of 33 patients), and an accuracy of 90% (47 of 52 patients). The MR arthrographic classification showed correlation with the arthroscopic or surgical classification in 13 of 17 patients (76%) in whom SLAP lesions were diagnosed at MR arthrography. CONCLUSION: MR arthrography is a useful and accurate technique in the diagnosis of SLAP lesions of the shoulder. MR arthrography provides pertinent preoperative information with regard to the exact location of tears and grade of involvement of the biceps tendon.     

Antigen processing and presentation by EBV-carrying cell lines: Cell-phenotype dependence and influence of the EBV-encoded LMP1

Burkitt's-lymphoma (BL) lines which have maintained in vitro the tumor-cell phenotype (group-1 BLs) are poor antigen- presenting cells (APC), in spite of a relatively high surface expression of MHC class II. In order to investigate the mechanism of this deficiency, we have compared group-1 BL lines, their sub-lines which have progressed in vitro towards an LCL-like phenotype (group-III BL), and EBV-transformed lymphoblastoid cell lines (LCLs), for their ability to bind and process tetanus toxoid (TT). The uptake and internalization of ¹²⁵I-labelled TT was equivalent in the 3 cell types. Only LCLs and group-III BL lines were able to process the IT,as shown by the identification of discrete proteolytic products after separation of whole-cell extracts in tricine-SDS-polyacrylamide gels, and by the recovery of TCA-soluble radioactivity in the culture supernatant. Processing of TT was induced by expression of the EBV- encoded membrane protein LMPI in transfected group-I BLs. The present findings suggest that the inability of group-I BLs to act as APC is due to their failure to process exogenous antigens. This function appears to be related to phenotypic properties that can be modulated by the expression of LMPI.     

Prenatal exposure model simulating CO inhalation in human cigarette smokers: sphingomyelin alterations in the rat sciatic nerve

Prenatal exposure to low concentrations of carbon monoxide (CO, 150 ppm) causes long-term alterations in sphingomyelin (SM) homeostasis in peripheral nervous system, but not brain of male rat offspring. In particular, unlike sphinganine (intermediate of complex sphingolipid biosynthesis de novo), the concentrations of sphingosine (intermediate of complex sphingolipid turnover) were increased by 2.35-fold in the sciatic nerve of CO-exposed offspring with respect to controls (P<0.05, overall one-way ANOVA). These subtle alterations were not accompanied by changes in motor activity (F=0.25, df=1/10, n.s., overall one-way-ANOVA). The results suggest that the SM homeostasis in the sciatic nerve is particularly susceptible to prenatal CO exposure resulting in maternal carboxyhaemoglobin (HbCO) levels equivalent to those found in human cigarette smokers.     

ATP and ADP content of human ejaculated spermatozoa

ATP and ADP were measured by a bioluminescent method in human ejaculated spermatozoa from 31 normal donors and oligozoospermic patients. ATP and ADP expressed for the sperm total number were significantly correlated ( P < 0.001). ATP and ADP levels were found significantly correlated with the total motile spermatozoa and with the total viable cells (respectively P < 0.001 and P < 0.001 for ATP and P < 0.001 and P < 0.001 for ADP). ATP/ADP ratio was found significantly lower in subjects with sperm motility less than 50% ( P = 0.024) and total viable cells less than 80% ( P = 0.026).