Effect of the putative cognitive enhancer, linopirdine (DuP 996), on quantal parameters of acetylcholine release at the frog neuromuscular junction.

1. The subcellular mechanism and site of action of linopirdine or DuP 996 (3,3-bis(4-pyridinylmethyl)-1-phenylindolin-2-one) was investigated at the frog neuromuscular junction, using miniature endplate potential (m.e.p.p.) counts and a new method for obtaining unbiased estimates of n (number of functional release sites), p (probability of release), and varsp (spatial variance in p). 2. DuP 996 produced an increase in m (no. of quanta released), which was due to an increase in n and p. The increase in m was concentration-dependent over a range of 0.1-100 microM and completely reversible with 15 min of wash. There was a saturation in the increase in p, but not in the increase in m and n, for [DuP 996] > 10 microM. By contrast, there was no major change in varsp. 3. Block of presynaptic Na(+)- and Ca(2+)-channels with 3 microM tetrodoxin and 1.8 mM Co2+ prevented the m.e.p.p. frequency increase to DuP996, and this effect was completely reversed by washing. 4. Application of the neuronal Ca(2+)-channel blocker, omega-conotoxin GVIA (1 microM) brought about a rapid and profound decrease in the m.e.p.p. frequency increased produced by DuP996. The effect of the toxin was not reversed by prolonged washing. 5. Block of voltage-gated K(+)-channels with 100 microM 4-aminopyridine (4-AP) resulted in only a small (28%) increase in m. The combination of 4-AP (100 microM) and DuP996 (10 microM) produced an increase in m (189%) which was much greater than the sum of the responses to each agent alone.(ABSTRACT TRUNCATED AT 250 WORDS)     

Utilization of autologous vein graft for replacement of the inferior vena cava in living-donor liver transplantation for obliterative hepatocavopathy

Obliterative hepatocavopathy (OHC) is a subtype of Budd-Chiari syndrome in which stenosis or obstruction of the retrohepatic inferior vena cava (IVC) is observed. Although IVC replacement is necessary in OHC patients, there are hardly any graft vessels available for IVC reconstruction during living-donor liver transplantation (LDLT). Here, we describe a novel technique of IVC reconstruction using only the autologous blood vessels in an OHC patient during LDLT. In this case, sufficient drainage of the hepatic outflow and reconstruction of the venous return from the lower half of the body were simultaneously required. Therefore, we substituted the retrohepatic IVC with the suprarenal IVC of the recipient, and we reconstructed the IVC continuity by using the autologous internal jugular vein and external iliac vein. The operation was safe, and the postoperative venous drainage from the hepatic tributaries was in good condition. This procedure might be an option for IVC replacement during LDLT.     

Development of a digital imaging system for objective measurement of hyperpigmented spots on the face

Background/aims: There are few available methods that can be used to quantify hyperpigmented spots on a wide area of the face. The objective of this study was to develop such a method through the use of specialized image analysis technologies. Methods: This imaging system was composed of a source of illumination whose light intensity was controlled with a dimmer, a 3-CCD video camera connected to a computer, and a positioning device used to correctly align the subject's face. This system was calibrated by adjusting the light intensity, the camera position, and white balance of the camera in order to acquire reproducible images. Using a specific algorithm for the image analysis, this system enabled us to measure both the total area of hyperpigmented spots (mm²) and the averaged skin colour tone (quasi L*a*b*) excluding the area of those hyperpigmented spots in a wide area of the face. The accuracy and reproducibility of the system was validated using a mannequin head with six standard colour chips obtained from the GretagMacbeth ColorChecker^®, and brown-coloured patches that simulated hyperpigmented spots whose colour and area were both known. The correlation between CIE L*a*b* and quasi L*a*b* values was examined by conducting simultaneous measurements of the facial skin colour of 187 subjects with a tristimulus colourimeter (Minolta Chromameter) and our imaging system. Results: The measurement errors in quasi L*a*b* values of colour chips and the area of brown patches were less than 2 and 5%, respectively, unless these chips or patches were located in the peripheral zone of the mannequin head. The variation in quasi L*a*b* values and the area of hyperpigmented spots (mm²) in five repeated measurements performed once every hour was less than 2%. There was an excellent correlation between the CIE L*a*b* and quasi L*a*b* values, and the Pearson's correlation coefficient between CIE L* and quasi L* value, for instance, was 0.908. Conclusions: As long as the region to be evaluated is limited to the cheek and periorbital areas, this system enables automatic detection of hyperpigmented spots in a wide area of the face, as well as the correct measurement of those areas and determination of skin colours.     

Comparison of brain metabolic activity patterns induced by ketamine, MK-801 and amphetamine in rats: support for NMDA receptor involvement in responses to subanesthetic dose of ketamine

Subanesthetic doses of NMDA receptor antagonists induce positive, negative and cognitive schizophrenia-like symptoms in healthy humans and precipitate psychotic reactions in stabilized schizophrenic patients. These findings suggest that defining neurobiologic effects induced by NMDA antagonists could guide the formulation of experimental models relevant to the pathophysiology of schizophrenia and antipsychotic drug action. Accordingly, the effects of subanesthetic doses of the non-competitive NMDA antagonists ketamine and MK-801 were examined on regional brain [¹⁴C]-2-deoxyglucose (2-DG) uptake in rats. The effects of these drugs were compared to those of amphetamine, in order to assess the potential role of generalized behavioral arousal, motor activity and dopamine release in brain metabolic responses to the NMDA antagonists. Subanesthetic doses of MK-801 and ketamine induced identical alterations in patterns of 2-DG uptake. The most pronounced increases in 2-DG for both NMDA antagonists were in the hippocampal formation and limbic cortical regions. By contrast, amphetamine treatment did not increase 2-DG uptake in these regions. In isocortical regions, ketamine and MK-801 reduced uptake in layers 3 and 4, creating a striking shift in the laminar pattern of 2-DG uptake in comparison to control conditions. After amphetamine, the fundamental laminar pattern of isocortical labeling was similar to saline-treated rats. Administration of ketamine and MK-801 decreased 2-DG uptake in the medial geniculate and inferior colliculus, whereas amphetamine tended to increase uptake in these regions. Since ketamine induced similar effects on regional 2-DG uptake as observed for the selective antagonists MK-801, the effects of ketamine are likely related to NMDA antagonistic properties of the drug. The distinct differences in brain 2-DG uptake induced by amphetamine and NMDA antagonists indicate that generalized behavioral arousal, and increased locomotor activity mediated by dopamine release, are not sufficient to account for the alterations in brain metabolic patterns induced by ketamine and MK-801. Thus, the dramatic alteration in regional 2-DG uptake induced by ketamine and MK-801 reflects a state selectively induced by reduced NMDA receptor function.     

Thermal effect of illumination on microsurgical transfer of free flaps: experimental study and clinical implications

The light source of a modern operating microscope gives a clear operative field, but the possibility of thermal impairment by the strong light is substantial. We aimed to elucidate the potential risk of such strong light on transfer of free flaps and the optimal application of light. First, the thermal effect of clinically used microsurgical illumination was examined by direct irradiation of a thermometer. Secondly, the thermal influence on living tissue of microsurgical light was evaluated using a model of vascularised and non-vascularised pedicled groin flaps in rats. Thirdly, the influence of strong light on the transfer of free flaps was investigated using a model of a free groin flap in rats. Fourthly, histological alteration was investigated by a light microscopy and scanning electron microscopy. With direct irradiation of a thermometer, temperatures reached values in excess of 80 degrees C with maximal xenon light illumination from 20 cm. The mode of illumination significantly influenced the results of free flaps. Prolonged irradiation of the vascular pedicle in particular resulted in an increase in the number of failures, supposedly caused by venous occlusion. Bright illumination contributed to efficient microvascular procedures, but we confirmed its potential risk. Our findings may benefit all surgeons engaged in transfer of free flaps, as potential impairment caused by excessive operative irradiation is prevented simply by recognition of its harm.     

Postnatal development of choline uptake by cholinergic terminals in rat brain

‘Our data on the rat include one case, number 2, with a lesion restricted to the extreme temporal retina, entirely on the temporal side of the fixation point. In this case the great majority of the degenerated fibers are uncrossed. None of the crossed fibers can be seen to terminate in the lateral geniculate nucleus and certainly most of them pass over the nucleus and terminate in the lateral margin of the superior colliculus. The uncrossed fibers, on the other hand, all enter the lateral geniculate nucleus and terminate within its caudal third.’ K. S. Lashley, 1934 (ref. 7).     

Anatomy of the choledochopancreatic duct junction in primary sclerosing cholangitis

Primary sclerosing cholangitis (PSC) is a rare disease for which the etiology is unknown. Because abnormalities of the choledochopancreatic duct junction (CDPDJ) have been implicated in the pathogenesis of other rare biliary problems such as choledochal cysts and biliary atresia, we reviewed the cholangiographic anatomy of the CDPDJ in our patients with PSC. From 1955 through July 1983, 46 patients with PSC were seen at the University of California at Los Angeles Medical Center. In 20 of these 46 patients anatomy of the CDPDJ could be evaluated by review of endoscopic retrograde cholangiopancreatography (11 patients) or by reflux into the pancreatic duct during transhepatic, operative, or postoperative tube cholangiography (nine patients). Roentgenograms were evaluated for the length of common channel of the biliary and pancreatic ducts and the degree of reflux into and anatomic abnormalities of the pancreatic duct. All bile ducts were abnormal, and pancreatic duct reflux occurred in 14 of 42 patients (33%) who underwent transhepatic or tube cholangiography. An abnormally long (greater than 15 mm) common channel was present in two of 20 patients (10%), pancreatic duct reflux of more than 100 mm occurred in six of 14 patients (43%), and pancreatic duct abnormalities were seen in nine of 18 patients (50%). These data suggest that in patients with PSC abnormal pancreatic duct reflux and anatomy are common but variations in the anatomy of the CDPDJ are rare. However, altered function of the CDPDJ may contribute to excessive reflux into and anatomic changes of the pancreatic ducts and the moderate incidence of pancreatitis observed in patients with PSC.