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.

Combined therapy with external beam irradiation and hepatic arterial epirubicin infusion through an implanted port for advanced hepatocellular carcinoma.

Nineteen patients with advanced stage IV hepatocellular carcinoma for which transcatheter arterial embolization and percutaneous ethanol injection were not indicated have been treated by combined therapy with external beam irradiation and repeated hepatic arterial epirubicin infusion through an implanted port. The response rate was 47%, and the median survival was 11.6 months (range, 4.0 to 27.1 months). Eighteen of the 19 patients were able to undergo the infusion therapy on an outpatient basis 3 to 7 weeks after initiation of therapy. This combined therapy was effective in improving tumor-bearing survival and less stressful for the patients because of the minimal therapy-related toxicity and brief hospitalization.

Biometric confirmation of the Hirschberg ratio in strabismic children.

PURPOSE: In the Hirschberg eye position test, the ratio of strabismic angle to decentration of the corneal reflex is dependent on two biometric parameters of the eye: the radius of the corneal curvature and the depth of the anterior chamber. This study was designed to confirm whether the Hirschberg conversion ratio (HR) previously determined for adults can be used for children of various ages despite structural growth of the eye. METHODS: For 262 eyes of 131 children with strabismus (age range, 6 months to 11 years), the radius of the corneal curvature was measured with an auto-keratometer and the anterior chamber depth with an A-scan ultrasound unit under general anesthesia before the surgery. Using these measurements, the HR was computed on the basis of a geometric model. RESULTS: The calculated HR was constant across the age range, and the mean+/-SD was 19.9+/-1.9 prism diopters/mm (95% confidence interval, 16.1-23.6 prism diopters/mm). The ratios for the two eyes in each subject showed good correlation (R = 0.854, P = 0.0001). Neither of the biometric measurements was significantly correlated with age, although considerable scatter of the measurements was observed. CONCLUSIONS: These results indicate that the averaged HR can be applied in children regardless of the patient's age, although intersubject variance of the ratio should be taken into account.

Distribution of efferent neurons projecting to the tectum and cerebellum in the rat prepositus hypoglossi nucleus.

Distributions of efferent neurons projecting to the superior colliculus (SC), the pretectum, and the cerebellar cortex were studied in the rat prepositus hypoglossi nucleus (PRH) by retrograde labeling with wheat germ agglutinin-horseradish peroxidase (WGA-HRP). After injection of the tracer into the unilateral SC, small- and medium-sized neurons were labeled throughout the entire rostrocaudal extent of the PRH, with the highest proportion in the middle part of the nucleus. After application of WGA-HRP to the unilateral pretectal region, including the nucleus of the optic tract, numerous labeled neurons appeared in the bilateral PRH. The highest distribution was found in the most rostral part of this nucleus. Furthermore, small neurons of the supragenual nucleus of the facial nerve also were labeled. Injection of WGA-HRP into lobules VI-VII of the cerebellar vermis resulted in the labeling of mainly medium-sized neurons in the bilateral PRH, primarily in the caudal third. WGA-HRP-labeled neurons were less frequently observed in the PRH after unilateral injection into the flocculus and paraflocculus. Retrograde double labeling by fluorescent dyes showed that a few neurons in the middle part of the PRH sent divergent axons to vermal lobules VI-VII and the SC.

The reliability of a video-enhanced Hirschberg test under clinical conditions.

PURPOSE: To examine the reliability and usefulness of a video-based Hirschberg test under clinical conditions. METHODS: The authors estimated ocular deviation in 87 patients with strabismus through automated analysis of corneal reflex displacement using a video refractor. The reproducibility of measurement, the comparison with the prism and alternate cover test (PACT), and the distribution of the Hirschberg ratio were investigated. RESULTS: The 95% limits of agreement of the video-based Hirschberg test evaluated by repeated measurements were +/- 0.18 mm (equivalent to +/- 2.2 degrees or +/- 3.8 prism diopters [PD] of calculated strabismic deviation) for the horizontal deviation and +/- 0.28 mm (equivalent to +/- 3.4 degrees or +/- 5.9 PD) for the vertical deviation. The 95% limits of agreement between the Hirschberg measures and the PACT were within +/- 7.8 degrees or +/- 13.7 PD. The average (+/- SD) Hirschberg ratio was 12.3 +/- 1.2 degrees/mm or 21.8 +/- 2.1 PD/mm. CONCLUSIONS: The video-enhanced Hirschberg measurement shows good reproducibility and ease of application, even in the testing of infants. In quantitative analysis, however, systematic measurement error resulting from intersubject variance of the Hirschberg ratio should be taken into consideration.

Identification of the anti-adhesive site buried within the heparin-binding domain of fibronectin.

We recently found that heparin-binding domain 2 (Hep 2) of fibronectin (FN) exhibits cryptic anti-adhesive activity. In order to locate the anti-adhesive site, a number of synthetic peptides which represents the primary structure of the Hep 2 domain were characterized as to their ability to decrease the adhesion of A375SM melanoma cells to FN substrate. Only one peptide (T-E-A-T-I-T-G-L-E-P-G-T-E-Y-T-I-Y-V-I-A-L, residues 1835-1855) (peptide III14-2), which is situated between the previously identified adhesive sites, FN-C/H-I and II, decreased the cell adhesion to FN. Assaying of the anti-adhesive activities of sub-peptides showed that the hydrophobic moiety of peptide III14-2 (underlined sequence) seems to be indispensable for the anti-adhesive activity. These results suggest that anti-adhesive activity is closely associated with the sequence, Y-T-I-V-I-A-L, that is usually buried within the Hep 2 domain structure because of its hydrophobic nature.

Critical period for restoration of normal stereoacuity in acute-onset comitant esotropia.

We conducted a retrospective study of 25 patients with acute-onset comitant esotropia to evaluate whether the timing of the start of treatment is a critical factor in the development of normal stereopsis. The mean age at onset was 12 years 4 months, and mean age at the start of treatment was 17 years 9 months. Bifixation was defined as a stereoacuity threshold score that was numerically lower than 60 seconds of arc on stereotesting. An operation was performed on the nonfixating eye for the prism-adapted angle. At the final examination, bifixation was observed in four patients (16%) with the Randot test and in 15 patients (60%) with the Titmus test. No relationship was found between the time of the start of treatment and the postoperative development of stereopsis, nor was there a significant (P > .10) difference between the two groups with early and delayed start of treatment in the proportion of patients with bifixation.

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.

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.

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.

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.

Influence of the gas exchange function through the middle ear mucosa on the development of sniff-induced middle ear diseases.

To investigate the influence of gas exchange function through the middle ear mucosa on the development of sniff-induced middle ear diseases, the authors examined the mastoid pneumatization among patients with sniffing habit using computed tomography, and also examined the change of negative middle ear pressure induced by sniffing using tympanogram. In 20 ears with cholesteatoma or adhesive otitis media, the areas of mastoid cavity measured at the level of the lateral semicircular canal were significantly smaller than those in 26 ears with otitis media with effusion (OME) or attic retraction and in eight normal ears with sniffing habit (P < .01 and P < .0001, respectively). In 26 ears with OME or attic retraction, the areas of mastoid cavity were significantly smaller than those in eight normal ears with sniffing habit (P < .0001). By contrast, in the four ears with sniff-induced middle ear disease, the recovery of negative middle ear pressure in 5 minutes without swallowing was less than 10 mm H2O, whereas in all seven ears with normal eardrum, negative middle ear pressure recovered by more than 20 mm H2O in 5 minutes. These findings suggested that impairment of gas exchange function through the middle ear mucosa, as well as eustachian tube dysfunction, might be closely related to the development of sniff-induced middle ear diseases.

Gas exchange function through the mastoid mucosa in ears after surgery.

Gas exchange function through the mastoid mucosa was investigated in ears after surgery using nitrous oxide. Increase in the mastoid pressure was assessed by a micropressure sensor placed in the mastoid cavity during the second-stage revision operation performed under general anesthesia using 67% nitrous oxide, 33% oxygen, and sevoflurane on 14 ears with chronic adhesive otitis media or cholesteatoma as well as on seven ears without inflammation as controls. All seven control ears showed pressure increase in the mastoid in various degrees. In the 14 postoperative ears, nine of the 10 ears on which the mastoid mucosa had previously been able to be preserved in various degrees showed pressure increase in the mastoid, but none of the remaining four ears, which had previously had mastoidectomy, showed any pressure increase. The presence or absence of the mastoid pressure increase of those ears was also found to be correlated well with the presence or absence of mastoid aeration on computed tomography examined just before the second-stage operation. These results appear to indicate that, in ears after surgery, recovery of both the gas exchange function and aeration in the mastoid is expected only when the mastoid mucosa can be preserved even partially.

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.

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.

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.

Using Ga-67 scintigraphy in prostatic abscess.

The use of Ga-67 scintigraphy (Ga) in prostate inflammatory diseases may be restricted by the difficulty in distinguishing between the accumulation of Ga-67-citrate (Ga-citrate) in the lesion and feces. The diagnosis of prostatic abscess has been mainly made by other radiologic methods without scintigraphic studies and no finding of Ga has been reported. This patient demonstrated that coordinating the findings of Ga-citrate accumulation can be helpful in making a prompt diagnosis of a possibly fatal prostatic abscess, especially in those patients with poorly defined clinical symptoms and high risk factors.

Precision of the gallbladder ejection fraction obtained with Tc-99m-pyridoxyl-5-methyl-tryptophan (99mTc-PMT) hepatobiliary scintigraphy as compared with the contraction ratio in three-dimensional computed tomography.

UNLABELLED: The gallbladder ejection fraction (GBEF) obtained with Tc-99m-pyridoxyl-5-methyl-tryptophan (99mTc-PMT) hepatobiliary scintigraphy has been used as a parameter of gallbladder function. To determine the accuracy of GBEF, the relationship with the contraction ratio of the gallbladder (GBCR) obtained with three-dimensional helical computed tomography (3D-CT) was studied. PATIENTS AND METHODS: A normal volunteer, 8 patients suffering from cholecystolithiasis and a patient with gallbladder dyskinesia were examined. The percent initial dose (%ID) for the gallbladder and GBEF with hepatobiliary scintigraphy were used to compare the volume of the gallbladder and GBCR which was measured by 3D-CT. RESULTS: The %ID of the gallbladder was correlated with the volume of the gallbladder by 3D-CT (Y = 1.000X - 1.818, r = 0.928). GBEF was correlated well with GBCR by 3D-CT (Y = 0.916X + 6.296, r = 0.975). CONCLUSIONS: The %ID of the gallbladder obtained with hepatobiliary scintigraphy may be a good indicator of the volume of the gallbladder. The accuracy of GBEF was confirmed by comparison with 3D-CT examination. GBEF is considered a useful parameter of pathophysiological gallbladder function.

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.

Influence of the upper respiratory tract infection on tubal compliance in children with otitis media with effusion.

To clarify the influence of inflammation on tubal compliance in children with otitis media with effusion (OME), we investigated the change of compliance of the ET by upper respiratory tract infection (URTI) in 18 children (23 ears) with OME using the forced response test. The tubal compliance index (TCI), the ratio of passive tubal resistances at two different airflow rates, significantly increased during URTI represented by acute rhinitis or paranasal sinusitis in comparison with non-URTI periods (paired t-test: t = 4.14, p < 0.001). In nine ears, the TCI could be followed for some months after that, during which the children had had URTI several times. A clear reproducible correlation was found between the presence or absence of URTI and the TCI values; the TCI values increased again during URTI and decreased after the URTI periods. These results seemed to support our hypothesis that compliance of the ET may depend not only on the property of the cartilaginous framework of the ET but also upon the mucosal condition.