Anti-anhedonic effect of selective serotonin reuptake inhibitors with affinity for sigma-1 receptors in picrotoxin-treated mice.

BACKGROUND AND PURPOSE: Prefrontal dopamine release by the combined activation of 5-HT1A and sigma-1 (σ1 ) receptors is enhanced by the GABAA receptor antagonist picrotoxin in mice. Here, we examined whether this neurochemical event was accompanied by behavioural changes. EXPERIMENTAL APPROACH: Male mice were treated with picrotoxin to decrease GABAA receptor function. Their anhedonic behaviour was measured using the female encounter test. The expression of c-Fos was determined immunohistochemically. KEY RESULTS: Picrotoxin caused an anxiogenic effect on three behavioural tests, but it did not affect the immobility time in the forced swim test. Picrotoxin decreased female preference in the female encounter test and attenuated the female encounter-induced increase in c-Fos expression in the nucleus accumbens. Picrotoxin-induced anhedonia was ameliorated by fluvoxamine and S-(+)-fluoxetine, selective serotonin reuptake inhibitors with high affinity for the σ1 receptor. The effect of fluvoxamine was blocked by a 5-HT1A or a σ1 receptor antagonist, and co-administration of the σ1 receptor agonist (+)-SKF-10047 and the 5-HT1A receptor agonist osemozotan mimicked the effect of fluvoxamine. By contrast, desipramine, duloxetine and paroxetine, which have little affinity for the σ1 receptor, did not affect picrotoxin-induced anhedonia. The effect of fluvoxamine was blocked by a dopamine D2/3 receptor antagonist. Methylphenidate, an activator of the prefrontal dopamine system, ameliorated picrotoxin-induced anhedonia. CONCLUSION AND IMPLICATIONS: Picrotoxin-treated mice show anhedonic behaviour that is ameliorated by simultaneous activation of 5-HT1A and σ1 receptors. These findings suggest that the increased prefrontal dopamine release is associated with the anti-anhedonic effect observed in picrotoxin-treated mice.

Observation of magnetic multilayers by electron holography.

Magnetic structures of Co/Cu multilayers in cross section are observed by two kinds of electron holography: a Fourier method and a phase-shifting method, which is introduced briefly. The Fourier method can easily reconstruct wave functions and is applied to many specimens, whereas the phase-shifting method requires longer time for processing, but has a higher spatial resolution that permits us to discuss fine structures. Magnetization vectors in Co layers aligning parallel and separating into two blocks with antiparallel alignment are observed. Magnetic blurring on the boundary between Co and Cu in the reconstructed phase images is larger than the estimated atomic roughness.

ARIX gene polymorphisms in patients with congenital superior oblique muscle palsy.

AIM: To identify ARIX gene polymorphisms in patients with congenital superior oblique muscle palsy and to find the relation between the ARIX gene and congenital superior oblique muscle palsy. METHODS: The three exons of the ARIX gene were sequenced by genomic DNA amplification with polymerase chain reaction (PCR) and direct sequencing in 15 patients with superior oblique muscle palsy (13 with congenital and two with acquired palsy) and 54 normal individuals. PCR products cloned into plasmids were also sequenced. A family with father and a daughter each having congenital superior oblique muscle palsy was also involved in this study. RESULTS: Four patients with congenital superior oblique muscle palsy carried heterozygous nucleotide changes in the ARIX gene. One patient with the absence of the superior oblique muscle had T7C in the 5'-UTR of the exon 1 and C-44A in the promoter region, both of which were located on the same strand. Another unrelated patient with congenital superior oblique muscle palsy had C76G in the 5'-UTR of the exon 1 and C-9A in the promoter region on the same strand. G153A in the 5'-UTR of exon 1 was found in common in two affected members of a family with congenital superior oblique muscle palsy. This G153A in the 5'-UTR of exon 1 was also present in four unrelated normal individuals. No other heterozygous nucleotide changes were found in normal individuals. CONCLUSIONS: The nucleotide change (G153A) in the 5'-UTR of exon 1 co-segregated with congenital superior oblique muscle palsy in one family. Four other nucleotide changes in the exon 1 or the promoter region were found only in patients with congenital superior oblique muscle palsy. These nucleotide polymorphisms may be one of the risk factors for the development of congenital superior oblique muscle palsy.

Mastoid condition and clinical course of cholesteatoma.

This study was carried out to establish which type of cholesteatoma is controllable by conservative treatment from the viewpoint of mastoid ventilation. We examined the area of the air cell system and airspace (aeration) in the mastoid cavity by computed tomography and eustachian tube (ET) function by inflation-deflation test in 20 ears (20 patients) with severe attic retraction for over 12 months (retraction pocket group), 16 ears (16 patients) with cholesteatoma which could be controlled only by conservative treatment for over 12 months (nonsurgical group) and 43 ears (43 patients) which required surgery within a year in spite of similar conservative treatment (surgical group). The size of the mastoid air cell system in the retraction pocket group, nonsurgical group and surgical group was 2.9 +/- 1.3, 1.9 +/- 0.7 and 1.5 +/- 0.9 cm(2) on average, respectively, with no significant difference between both cholesteatoma groups (nonsurgical and surgical group). While aeration was observed in the mastoid in 17 of 20 ears (85.%) in the retraction pocket group and in 12 of 16 ears (75.0%) in the nonsurgical group, aeration was present only in 9 of 43 ears (26.5%) in the surgical group, being significantly less in the surgical group than in the nonsurgical group and the retraction pocket group. In all ears in the retraction pocket and nonsurgical groups, and 19 of 30 ears in the surgical group, ET function was poor, there being no significant difference among the three groups. The present clinical observations suggest that progressiveness of cholesteatoma could be related to the ventilatory conditions in the mastoid rather than ET function, and that conservative treatment may be effective when ears with cholesteatoma have aeration in the mastoid.

Unusual early bile excretion from the liver in patients with fulminant hepatic failure as detected by Tc-99m-PMT hepatobiliary scintigraphy; comparison with Tc-99m-GSA scintigraphy.

In two females (58 and 14 years old) with fulminant hepatic failure, Tc-99m-PMT hepatobiliary scintigraphy was used to evaluate intrahepatic bile stagnation, and Tc-99m-GSA scintigraphy to evaluate hepatic functional reserve. In both patients, Tc-99m-PMT hepatobiliary scintigraphy showed unusual early bile excretion into the extrahepatic bile duct and small intestine within the first 30 min of imaging. These findings contradicted typical findings of intrahepatic bile stagnation of fulminant hepatic failure. The receptor index and blood clearance index determined from dynamic acquisition data on Tc-99m-GSA scintigraphy suggested a markedly decreased hepatic functional reserve. These findings were compatible with fulminant hepatic failure. A discrepancy was observed between the findings of hepatobiliary scintigraphy and those of Tc-99m-GSA scintigraphy. The pathological state of early bile excretion from the liver into the bile duct should be considered in fulminant hepatic failure.

Fatigue reduces tonic accommodation.

Ocular accommodation adopts a mean baseline response level of approximately 1.0 D in the absence of blur feedback (open-loop state). This baseline or tonic accommodation (TA) can be elevated following a sustained monocular accommodative response to a dioptric stimulus (lens adaptation) that exceeds the baseline open-loop level of TA. The accommodative response to the lens persists in the open-loop state (accommodative hysteresis), and eventually decays to a stable end-point. Interestingly, if the baseline TA is high, the monocularly adapted accommodative state can decay to an end-point that is below the initial pre-adapted baseline level of the TA (counter-adaptive response) (McBrien, N.A. and Millodot, M., (1988). Differences in adaptation of TA with refractive state. Invest. Ophthalmol. Vis. Sci., 29, 460-469). We have investigated the possible contribution of accommodation fatigue to the counter-adaptive change in baseline TA following sustained accommodation. Two fatigue procedures were used while viewing a target at 66 or 33 cm. In a monocular condition, accommodation was stimulated for 3 min with lens values alternating from -1.5 to +1.5 D at a rate of 0.25 Hz. In the binocular condition, convergence was stimulated with alternating prism values from 9 prism diopters (PD) base-out to 9 PD base-in. Both monocular and binocular tasks resulted in a significant reduction of TA. These results suggest that previously reported reductions of baseline TA following sustained monocular accommodation or binocular convergence could have resulted from fatigue of the accommodative system. Accommodative fatigue could be responsible for the lower values of TA observed in counter-adaptive responses to sustained accommodative or convergence effort.

Correction of cyclovertical strabismus induced by limited macular translocation in a case of age-related macular degeneration.

PURPOSE: To report a case of strabismus surgery performed to treat cyclovertical strabismus induced by limited macular translocation. METHODS: Case report. RESULTS: A 62-year-old man suffering with age-related macular degeneration and subfoveal choroidal neovascularization, RE, underwent limited macular translocation surgery. The fovea was rotated downward, and his visual acuity improved from 20/100 to 20/25 postoperatively. Cyclovertical diplopia persisted for 6 months after the operation. A Hess screen test revealed a pattern that simulated an underaction of the superior oblique muscle and inferior rectus muscle with an overaction of the ipsilateral inferior oblique muscle. To treat the diplopia, advancement of the superior oblique muscle tendon and resection of the ipsilateral inferior rectus muscle were performed. Binocular single vision with 140 seconds of arc for stereopsis was obtained. CONCLUSION: Cyclovertical strabismus after limited macular translocation is corrective with conventional surgery on the treated eye.

Prism adaptation response is useful for predicting surgical outcome in selected types of intermittent exotropia.

PURPOSE: To evaluate the prevalence of prism adaptation response in Japanese patients with intermittent exotropia (X [T]) using the prism adaptation test and to assess whether patients with selected types of X [T] benefit from surgical outcome to which prism adaptation response may contribute. METHODS: In a prospective study, 128 consecutive patients with X [T] between 1990 and 1995 were enrolled. The prism adaptation test was conducted by neutralizing the angle of deviation for 2 to 3 hours. Patients who showed an increase in exodeviation by 10triangle up or more with the prism adaptation test were defined as having a prism adaptation response. For classification of the pattern of X [T], we chose a value of 15triangle up as the difference between the distance and near measurements. RESULTS: The percentage of patients in whom the prism adaptation response was observed at near fixation was significantly larger than those at distance fixation [35 (27%) patients versus 10 (8%) patients, P <.05]. Of 35 patients shown to have a prism adaptation response at near fixation, 21 patients (83%) had the basic type of exotropia. Fourteen patients (17%) with the basic type were changed to convergence insufficiency type because of an increase in near deviation and were defined as pseudo basic type. Patients with pseudo basic type had a significantly better surgical outcome compared with that of true basic type, whereas in the convergence insufficiency type, no definite tendency was found between the two subtypes, true and pseudo types. CONCLUSION: Patients with the pseudo basic type of X [T] in whom a prism adaptation response was demonstrated had a more favorable surgical outcome.

Large Bielschowsky head-tilt phenomenon and inconspicuous vertical deviation in the diagnostic positions in congenital superior oblique palsy.

PURPOSE: To report a case of congenital superior oblique palsy with an unusually large Bielschowsky head-tilt phenomenon (BHP) and disproportional inconspicuous vertical deviation. METHODS: Case report. RESULTS: An 18-year-old woman presented with slight compensatory head tilting and a Bielschowsky head-tilt phenomenon of 50 Delta on left tilting. Magnetic resonance imaging revealed atrophy of the left superior oblique muscle. A Hess screen test showed a slight underaction of the left superior oblique muscle, but neither an obvious overaction of the ipsilateral inferior oblique muscle nor inhibitory palsy of the contralateral superior rectus muscle was found. With a 3-mm recession of the ipsilateral superior rectus muscle, Bielschowsky head-tilt phenomenon decreased to 25 Delta. CONCLUSION: A large Bielschowsky head-tilt phenomenon was possibly caused by an increased gain of the otolith-ocular reflex affecting the vertical rectus muscle.

Organic change of effusion in the mastoid in otitis media with effusion and its relation to attic retraction.

To try to solve the pathogenesis of severe attic retraction viewed from mastoid condition, we examined the residual soft tissue density (RSTD) in the mastoid by computed tomography (CT) in 85 patients (107 ears) with otitis media with effusion (OME) 3 months after tympanostomy tube insertion or later. The incidence of RSTD in the mastoid was significantly higher in OME of adults (52.6%) than in children (24.1%). Ears with severe attic retraction had RSTD significantly more frequently (80%) than those with no or mild attic retraction, and many of the mastoids with severe attic retraction were occupied totally by RSTD. The area of the mastoid (mastoid pneumatization) was significantly smaller, and CT density of the mastoid (sclerotic tendency) was significantly higher in ears with RSTD than in those without. RSTD after tympanostomy tube insertion in the mastoid indicating organic change of effusion was considered one of the important factors relating to the pathogenesis of severe attic retraction.

Comparative study of brain lesions detected by magnetic resonance imaging between strabismus and nonstrabismus in infancy.

PURPOSE: To elucidate the causative factors in infantile esotropia, we evaluated morphological abnormalities in brain structures of esotropia patients showing any abnormal neurological signs in comparison to those of normal controls. METHODS: Sixty-five developmentally normal children participated in this study. Of these 65, 38 demonstrated infantile esotropia and 27 were normal controls. All underwent magnetic resonance imaging (MRI) of the brain between 2 and 30 months. RESULTS: Abnormal brain findings were noted in 3 (7. 9%) children in the strabismus group, whereas none of the children in the normal control group showed brain lesions. In these 3 cases, brain lesions involved periventricular leukomalacia, enlargement of the lateral ventricles with hypoplasia of the corpus callosum and myelination delay at the anterior horn adjacent to the lateral ventricles. CONCLUSIONS: Brain lesions that may disturb normal maturation of the visuomotor system and eventually lead to strabismus could be found in some patients without any episode that would cause birth injury.

Soft-wall reconstruction for cholesteatoma surgery: reappraisal.

OBJECTIVE: To reevaluate the validity of the soft-wall reconstruction method of the posterior meatal wall in surgeries for cholesteatomas. STUDY DESIGN: Retrospective case review. PATIENTS: Subjects consisted of 52 patients (54 ears) with fresh cholesteatoma (excluding residual or recurrent cholesteatomas) who were operated by the soft-wall reconstruction method in our clinic and observed for more than 2 years after surgery, and 29 patients (29 ears) who were operated by canal-wall-down and open method. MAIN OUTCOME MEASURES: Postoperative period required for complete epithelization (dry ear), hearing, and incidence of the residual and recurrent cholesteatomas were compared with those operated by canal-wall-down and open method. The postoperative conditions of the soft posterior meatal wall was also investigated. RESULTS: Postoperative period to be a dry ear was significantly shorter in the soft-wall reconstruction group than in the canal-wall-down and open group (Student's t-test, t = 2.99, p < 0.01). There was no significant difference in the postoperative hearing or incidence of residual and recurrent cholesteatomas between the two groups. CONCLUSIONS: These results indicate that the soft-wall reconstruction method seems more versatile than the canal-wall-down and open method for cholesteatoma surgery.

Prognostic factors for successful surgical outcome with preoperative prism adaptation test in patients with superior oblique palsy.

PURPOSE: This study evaluated the surgical outcome of patients managed with preoperative prism adaptation test (PAT) and investigated prognostic factors for successful motor alignment in adult patients with superior oblique palsy. METHODS: Prospective study of preoperative PAT was performed. Fifty-seven patients with superior oblique palsy, aged 16 to 81 years, participated in this study. Patients were assigned to surgery with the target angle based on either the original angle or the prism compensated angle. When the amount of neutralizing prism exceeded 4delta or more compared to the original angle of deviation, the patient was defined as having prism compensation, and the target angle for surgery was based on the amount of neutralizing prism. The motor success rate was compared between the 2 groups at the 3-month postoperative follow-up. RESULTS: The prism responders group showed a superior outcome compared to that of the prism non-responders group (77% successful outcome compared with 46%, p = 0.0397). The presence of prism compensation and the amount of vertical deviation were significant prognostic factors for successful motor alignment. CONCLUSION: Preoperative PAT is a useful prognostic indicator of successful surgical outcome in patients with superior oblique palsy.

Predicting survival and post-operative complications with Tc-GSA liver scintigraphy in hepatocellular carcinoma.

BACKGROUND/AIMS: Technetium-99m galactosyl human serum albumin is a novel liver scintigraphic agent. The aim of the present study was to examine whether liver scintigraphy with this agent could predict changes in hepatic function affecting survival in patients with inoperable hepatocellular carcinoma and liver cirrhosis. We also investigated whether the risk of major complications after hepatectomy for hepatocellular carcinoma could be assessed. METHODOLOGY: Liver scintigraphy was performed in 42 patients with inoperable hepatocellular carcinoma and cirrhosis and 40 patients undergoing hepatectomy. The ratio of liver to heart plus liver radioactivity 15 min after injection (LHL15) was calculated. RESULTS: The 1-year survival rates were higher in patients with higher LHL15: 100%, LHL15 > or = 0.91; 77.8%, 0.81 < or = LHL15 < or = 0.90; and 28.6%, LHL15 < or = 0.80. On multifactorial analysis, LHL15 significantly predicted the 1-year mortality rate in the 42 patients (p<0.001). Pre-operative LHL15 was significantly lower in 9 patients with major post-operative complications (0.88+/-0.02) than in 31 patients with uneventful courses or minor post-operative complications (0.93+/-0.01, p<0.001). CONCLUSIONS: Our results suggest that technetium-99m galactosyl human serum albumin liver scintigraphy is effective for predicting short-term survival in patients with inoperable HCC and cirrhosis and for assessing the risk of major complications after hepatectomy.

Factors affecting recovery of mastoid aeration after ear surgery.

Fifty-six patients after tympanomastoid surgery were examined to determine recovery of mastoid aeration and various pre- and intraoperative factors such as eustachian tube (ET) function, how the mastoid mucosa had been treated during surgery and whether or not a large silastic sheet had been placed in the middle ear or a ventilation tube used. Mastoid aeration recovery was confirmed by computed tomography in 27 of the 57 cases (47%) within 12 months of surgery. Among the factors examined, preservation of the epitympanic mucosa was found to be most important in mastoid aeration recovery. Use of a large silastic sheet to cover the area from the bony ET and tympanic cavity to epitympanum, aditus ad antrum or antrum was found to be of some help in recovery mastoid aeration after complete resection of the mucosa and mastoid air cells. Preoperative ET function, anterior tympanotomy and use of a ventilation tube did not influence recovery.

The diagnostic and prognostic value of eardrum mobility in otitis media with effusion.

Diagnostic and prognostic values of eardrum mobility were determined by pneumatic otoscopy in 37 patients (56 ears) having otitis media with effusion (OME). Eardrum mobility was impaired or lost in less than half of the ears (46.4%), while a tympanogram detected 77.8% of OME. In 27 of the 37 patients (42 of the 56 ears), aeration of the middle ear space was examined by CT and demonstrated that the presence or absence of aeration was significantly correlated with the presence or absence of eardrum mobility. In another 38 children (62 ears with OME), effect of antibiotics was correlated with eardrum mobility before treatment, and the improvement rate was found to be significantly higher in ears with positive mobility of eardrum (34.3%) than in ears without eardrum mobility (10.0%). These results indicate that eardrum mobility is a good prognostic indicator of OME rather than its diagnostic indicator alone.

Perioperative hepatic functional risk assessed with technetium-99m diethylenetriamine pentaacetic acid-galactosyl human serum albumin liver scintigraphy in patients undergoing pancreaticoduodenectomy complicated by obstructive jaundice.

CONCLUSION: Liver scintigraphy with technetium-99m diethylenetriamine pentaacetic acid-galactosyl human serum albumin (Tc-GSA) can be used to predict outcome of biliary drainage and hepatic function after pancreaticoduodenectomy in patients with pancreatic, biliary, and ampullary carcinomas complicated by obstructive jaundice. BACKGROUND: Preoperative obstructive jaundice has been reported as a crucial risk factor for serious postoperative complications in patients undergoing pancreaticoduodenectomy. The aim of the present study was to investigate whether Tc-GSA liver scintigraphy can assess hepatic functional risk in patients with pancreatic, biliary, and ampullary carcinomas complicated by obstructive jaundice. METHODS: Liver scintigraphy was performed before biliary drainage in 18 patients with obstructive jaundice. The maximum removal rate of Tc-GSA (GSA-Rmax; standard normal value > or = 0.60) was calculated. These patients underwent pancreaticoduodenectomy with wide lymphadenectomy. The efficacy of preoperative biliary drainage was assessed with the decrease in serum bilirubin concentration in the first week after biliary drainage. Postoperative liver function was assessed with the increase in serum bilirubin concentration, which was the difference between the immediate preoperative and maximal postoperative bilirubin concentrations. RESULTS: Serum bilirubin decreased more in the first week after biliary drainage in patients with GSA-Rmax > or = 0.60 (7.64 +/- 1.09 mg/Dl/wk) than in patients with GSA-Rmax < 0.60 (3.56 +/- 1.25 mg/DL/wk, p = 0.042). Postoperative bilirubin increased less in patients with GSA-Rmax > or = 0.60 (0.81 +/- 0.30 mg/dL) than in patients with GSA-Rmax < 0.60 (4.00 +/- 0.69 mg/DL, p = 0.0012). Multivariate analysis showed that GSA-Rmax significantly predicted the postoperative bilirubin increase (p = 0.020).

Soft-wall reconstruction of posterior canal wall for surgery of noninflamed ears: a preliminary report.

OBJECTIVE: To test whether the posterior external auditory canal (EAC) wall reconstructed only by soft tissues retracts after surgery in the noninflamed ear. STUDY DESIGN: The condition of the posterior EAC wall was observed for more than 1 year after surgery in 20 noninflamed ears in which only the posterior EAC wall skin was preserved or in which the wall was reconstructed only by soft tissue during surgery. PATIENTS: Eighteen patients (20 ears) underwent ear surgery for conditions other than otitis media, including ossiculoplasty in 12 ears, cochlear implant in 3, resection of congenital cholesteatoma in 4, and resection of glomus tympanicum tumor in 1. RESULTS: Retraction of the soft posterior EAC wall was observed in only 1 of the 20 ears. In this ear, the posterior EAC wall showed only a slight retraction without any serious problems. Computed tomography revealed that mastoid aeration recovered in all 20 ears. CONCLUSIONS: In noninflamed ears, surgeons can remove the bony posterior EAC wall if necessary, and may not need to reinforce or reconstruct the wall with hard tissue. This enables surgeons to spare time and energy and obtain the same advantages as in the intact-canal-wall technique or canal wall reconstruction by a hard material.

Productivity of concentrated hyaluronic acid using a Maxblend fermentor.

Application of the Maxblend impeller to the fermentative production of hyaluronic acid (HA) was investigated. A 2-m3-scale fermentor fitted with this impeller (MBF) was used and the main fermentation was started with 85% of the nominal volume containing the pre-culture broth and medium. The kinetic characteristics of the MBF were compared with those of a conventional-type fermentor fitted with a turbine blade (TBN). The HA production yield in the MBF was over 20% higher than that in the TBN under the operating conditions of a high aeration rate and low vessel pressure since the broth viscosity increased. The apparent viscosity of the broth at the end of the cultivation rose to about 70 Pa.s. The molecular weight of the HA produced was independent of the agitation speed within the investigated range, and no significant difference was observed between the viscosity-average molecular weights of the HA obtained in the two types of fermentor, each having an estimated value of 4.3 x 10(6) under the same agitation power.

[Combined scatter and attenuation correction for 201Tl myocardial perfusion SPECT using OS-EM algorithm].

There are two possible ways to obtain scatter-corrected images with the ML-EM (maximum likelihood expectation maximization) algorithm: one is the subtraction of scatter estimate si from projection data pi, and then (pi-si) is used for scatter-corrected projection data (denoted as SC(T)); the other method is the addition of scatter estimate si to the projections calculated from the reconstructed image without performing data subtraction (SC(E)). This paper investigated these two ML-EM algorithms of combined scatter and attenuation correction on 201Tl myocardial perfusion SPECT imaging. Scatter windows were placed one full width at half maximum (FWHM) below and above the photopeak centerline. The scatter fraction in the primary peak was estimated using trapezoidal approximation by the triple energy window method. Phantom and clinical images were reconstructed using 6 iterations of ordered subsets EM algorithm (OS-EM). A cylindrical phantom with a cold-rod insert and a heart/thorax phantom with liver insert were used to evaluate scatter and the attenuation compensation technique. A cylindrical phantom filled with uniform 201Tl solution was used to evaluate statistical noise. The percent root-mean-square uncertainty (%RMSU) was used as a quantitative measure of noise amplification. %RMSU showed that the SC(E) method amplified noise less in comparison with the SC(T) method, however, no significant difference in image quality was observed between the two methods. In conclusion, both the SC(T) and SC(E) methods provided significant and similar improvement in the removal of scatter in 201Tl myocardial perfusion SPECT imaging.