Role of alpha adrenoceptors in the nucleus accumbens in the control of accumbal noradrenaline efflux: a microdialysis study with freely moving rats.

Microdialysis technique was used to study the effects of the locally applied alpha adrenoceptor agonist phenylephrine and antagonist phentolamine on the basal noradrenaline efflux as well as on the noradrenaline uptake inhibitor desipramine-elicited noradrenaline efflux in the nucleus accumbens (NAc) of freely moving rats. Tetrodotoxin reduced basal noradrenaline efflux by 72%, whereas desipramine increased it by 204%. Phenylephrine reduced the basal noradrenaline efflux by 32% and phentolamine blocked this effect. Phentolamine elevated the basal noradrenaline efflux by 150% and phenylephrine counteracted this effect. The desipramine-elicited noradrenaline efflux was not affected by phenylephrine, but enhanced by phentolamine. Desipramine counteracted the effects of phenylephrine and potentiated those of phentolamine. These results indicate that the accumbal noradrenaline efflux is under inhibitory control of alpha adrenoceptors that are suggested to be presynaptically located on adrenergic nerve terminals in the NAc. Furthermore, this study suggests that the conformational state of alpha adrenoceptors varies across the available amount of noradrenaline. The clinical impact of these data is discussed.

Serologically defined genotypes of hepatitis C virus among Japanese patients with chronic hepatitis C.

Recently, Tsukiyama-Kohara et al. (1993) reported that most hepatitis C viruses (HCVs) in Japan can be classified into two types, type 1 and type 2, on the basis of the NS4 region nucleotide sequence. They developed a new assay in which antibodies against group-specific recombinant proteins of the NS4 region were measured by ELISA (serologically defined genotype, serotype). In the present study, we examined 306 patients with chronic liver disease due to HCV infection. The sensitivity of this assay was 98.7% (302/306). The serotype distribution of HCV was 230/306 (75.2%) for type 1, 65/306 (21.2%) for type 2, 7/306 (2.3%) for mixed, both being positive, and 4/306 (1.3%) indeterminate. The frequency of type 1 was significantly higher than that of type 2 (P < 0.01). There were no significant differences in clinical characteristics among the mixed and the indeterminate serotypes. Among the mixed-serotype patients, 4/7 (57.1%) showed seroconversion to a single serotype at 6 and 9 months later, although the serotypes of the indeterminate-serotype patients were also indeterminate at 6 and 9 months later. Using aliquots of the same serum samples, HCV genotyping was carried out by the reverse transcription polymerase chain reaction (RT-PCR) method using type-specific primers derived from the NS5 region of HCV to verify the specificity of this serotyping. The sensitivity of genotyping by RT-PCR was 167/183 (91.3%). The HCV genotypes determined by both methods were consistent in 161/183 (88.0%) of the cases, and there were no contradictory results for any sample between the two methods. These findings indicate that serological genotyping might be useful in determining the HCV genotype among Japanese patients with HCV infection.

Erythrocyte galactokinase assay with high performance liquid chromatography.

An assay for erythtocyte galactokinase based on high performance liquid chromatographic determination of galactose 1-phosphate (Gal-1-P) is described. The determination of Gal-1-P was applied to a post-column fluorometric detection of reducing sugars using arginine. This method is as sensitive and accurate as conventional radioisotopic methods, but needs no radioisotopic facilities. It requires only a small blood sample and is suitable as a follow-up test in neonatal screening.

Fetal diagnosis of galactosialidosis (protective protein/cathepsin A deficiency).

The fetal diagnosis of galactosialidosis is performed by measuring carboxypeptidase (cathepsin A) activity in cultured villous cells and by immunofluorescence analysis with an antibody against an oligopeptide corresponding to the N-terminal domain of the human mature protective protein. Neither carboxypeptidase activity nor immunofluorescence was detected in cultured villous cells derived from an at-risk fetus or in cultured fibroblasts derived from the sister with galactosialidosis. Neuraminidase and beta-galactosidase activities were also confirmed to be deficient or low. A direct assay system for protective protein/cathepsin A is useful for the accurate prenatal diagnosis of galactosialidosis.

Potential interaction between ritonavir and carbamazepine.

Ritonavir (RTV), a protease inhibitor, and carbamazepine (CBZ), an anticonvulsant, were administered concurrently to a patient who had human immunodeficiency virus infection and epilepsy. The combination resulted in elevated serum concentrations of CBZ, with accompanying vomiting, vertigo, and transient liver dysfunction. After discontinuing RTV and reducing the dosage of CBZ, the serum concentration of CBZ returned to the optimal range, symptoms subsided, and liver function returned to baseline. Carbamazepine is metabolized in the liver to a large extent by the cytochrome P450 (CYP) system, especially CYP3A4, 2C8, and 1A2, whereas RTV is metabolized primarily by CYP3A and is a potent inhibitor of this enzyme. Careful clinical monitoring may help prevent adverse drug interactions when these drugs are administered concurrently.

Extracapsular cataract extraction with a sutureless incision for dense cataracts.

PURPOSE: To evaluate the use of extracapsular cataract extraction (ECCE) via a sutureless incision for dense cataracts. SETTING: Nagata Eye Clinic, Nara, Japan. METHODS: This retrospective study comprised 51 eyes of 45 consecutive patients with dense cataracts who had ECCE with a sutureless incision between January 1996 and April 1998. A scleral incision from 6.0 to 8.5 mm was made at 12 o'clock or between 9 and 12 o'clock (oblique incision). Measures of outcome included postoperative visual acuity, surgically induced astigmatism (polar value method and vector analysis), complications, and changes in corneal endothelial cell density and morphology. RESULTS: Self-sealing was achieved in 45 eyes (88.2%), but additional sutures were required in 6 (11.8%). Intraoperative complications included posterior capsule rupture in 3 eyes (5.9%) and iris prolapse in 2 (3.9%). Corneal flattening against the preoperative steep meridian was observed in the 12 o'clock incision group (0.24 diopter [D] +/- 1.23 [SD]) and in the oblique incision group (0.17 +/- 0.89 D). By vector analysis, the surgically induced vector was 1.41 +/- 0.72 D in the 12 o'clock incision group and 1.02 +/- 0.66 D in the oblique incision group. After surgery, the mean cell loss was 8.2% +/- 12.5%. There were no significant differences, however, between other preoperative and postoperative morphometric indexes. CONCLUSION: This fast, safe, and inexpensive technique may be a viable treatment for dense cataracts with large, hard nuclei.

Spontaneous disappearance of a middle cranial fossa arachnoid cyst after suppurative meningitis.

BACKGROUND: Spontaneous disappearance of an arachnoid cyst is very rare, particularly after suppurative meningitis. CASE REPORT: A 2-month-old boy with a high fever was diagnosed with suppurative meningitis by cerebrospinal fluid examination. Computed tomography disclosed a large arachnoid cyst in the left middle cranial fossa. Two months later, the meningitis was cured. The arachnoid cyst disappeared with long-term antibiotic therapy alone. CONCLUSION: Although an infected arachnoid cyst may disappear with antibiotic treatment alone, careful observation and individualized patient management are essential.

Primary intrathoracic extrapulmonary hemangiopericytoma. CT and MR findings.

We report the imaging features of a rare case of primary intrathoracic extrapulmonary hemangiopericytoma. Radiography, computed tomography, magnetic resonance imaging, and angiography, were used to evaluate this rapidly growing extrapleural tumor originating from the chest wall. The studies demonstrated smooth margins, hypervascularity, and intermediate signal on T1-weighted images and increased signal on T2-weighted images.

Scimitar syndrome associated with diaphragmatic herniation of the liver.

A rare case of scimitar syndrome associated with diaphragmatic herniation of the liver is reported. The upper lobe blood of this case drained abnormally to the inferior vena cava. Pulmonary angiography and radionuclide scintigraphy were useful in the diagnosis of the abnormal vessels and herniated liver.

[Significance of serological genotyping of hepatitis C virus in Japanese patients with chronic liver disease due to hepatitis C].

Recently, T-Kohara et al. reported that most hepatitis C virus (HCV) in Japan can be classified into two groups, group 1 (G-1) and group 2 (G-2), on the basis of the NS4 region nucleotide sequence. Using a genetic engineering method, they developed a new assay in which antibodies against group specific recombinant proteins of the NS4 region were measured by ELISA (Serological Genotype, Serotype). In the present study, we examined 100 patients with chronic liver disease due to hepatitis C. The sensitivity of this assay was 98.0% (98/100). The HCV serotype distribution was 74/100 (74.0%) for serotype G-1, 22/100 (22.0%) for serotype G-2, 2/100 (2.0%) for both being positive and 2/100 (2.0%) for indeterminate. The distribution of G-1 was significantly higher than that of G-2 (p < 0.05), however, we found no difference between the distribution of G-1 and that of G-2 in age, sex, history of blood transfusion or type of liver disease. In the same serum samples, we performed HCV genotyping by reverse transcription polymerase chain reaction (RT-PCR) using type specific primers derived from the NS5 region of HCV to verify the specificity of such serotyping. The sensitivity of genotyping by RT-PCR was 88.0% (88/100). The HCV genotypes determined by both methods were consistent in 86.0% (86/100) of cases, and were not contradictory in any sample. These data indicated that serological genotyping was more sensitive and was consistent with genotyping by RT-PCR. Therefore, we consider the method useful for epidemiologic studies of HCV in Japan.

Spatiotemporal profiles of transcallosal connections in rat insular cortex revealed by in vivo optical imaging.

The gustatory cortex (GC), a part of the insular cortex (IC), receives gustatory inputs from the parvicellular part of the ventroposteromedial thalamic nucleus (VPMpc). Transcallosal projections from the contralateral GC modulate neural responses to gustatory stimulation. However, the spatiotemporal dynamics of the amplitude and area of excitation induced by contralateral GC stimulation remain unclear. First, we demonstrated the distribution patterns of neurons projecting to the GC by injecting the anterograde tracer, biotinylated dextranamine (BDA), and retrograde tracer, Fluorogold (FG), into the unilateral putative GC throughout the layers in five male Sprague-Dawley and two vesicular GABA transporter-Venus rats. FG-labeled pyramidal neurons were found in the contralateral GC and ipsilateral VPMpc. The contralateral GC and ipsilateral VPMpc received BDA-positive fibers, suggesting that the GCs of both hemispheres are reciprocally connected. Second, the spatiotemporal profiles of neural responses evoked by five train pulses of electrical stimulation (50 Hz) were quantified by in vivo optical imaging with a voltage-sensitive dye in male Sprague-Dawley rats (n=56). Stimulation of the ipsilateral VPMpc evoked potent GC activation that was followed by propagation to the surrounding IC; this propagation was similar to that following ipsilateral GC stimulation. Contralateral stimulation of the somatosensory area I, dorsal IC, and ventral IC evoked excitation in the ipsilateral each corresponding area, suggesting that transcallosal fibers are symmetrically connected. Contralateral GC stimulation induced a similar spatial profile of excitation as ipsilateral GC stimulation; however, the latency was longer (~20 ms), and the excitation was frequently followed by a GABA(B) receptor antagonist-sensitive inhibitory signal. Excitation by ipsilateral GC stimulation was potentiated by simultaneous contralateral GC stimulation, especially in cases where the amplitude of the response to ipsilateral stimulation was small. These results suggest that the transcallosal projection may support the detection of gustatory inputs by potentiating weak gustatory signals in the GC.

Factors associated with nodal metastasis in nasopharyngeal cancer: an approach to reduce the radiation field in selected patients.

OBJECTIVES: The purpose of this study was to investigate factors associated with lymph node (LN) metastasis to identify which nasopharyngeal cancer (NPC) patients can undergo a reduction in the prophylactic radiation field. MRI of biopsy-proven NPC patients was evaluated to determine primary tumour extension and the existence of LN metastasis. METHODS: Sex, age, pathological type, T stage, primary tumour size, existence beyond the midline of the nasopharynx at the primary site and parapharyngeal extension of the primary tumour were assessed regarding their impact on the laterality of LN metastasis using the χ(2) test. RESULTS: Of the 167 patients, 149 (89%) showed nodal involvement. The existence beyond the midline of the nasopharynx was significantly associated with the laterality of LN metastasis (p<0.0001). Most patients (82%) with primary tumour presence within the midline showed only ipsilateral LN metastasis or no LN metastasis. In addition, contralateral LN metastases were seen only at Level II and the retropharyngeal LN among most of other patients. CONCLUSION: These results suggest that LN areas other than Level II and the retropharyngeal LN on the contralateral side could be omitted in patients with primary tumour presence within the midline and without the contralateral Level II or the retropharyngeal LN. Whether disease control is compromised by reducing the radiation field for subclinical diseases is a problem that should be solved in the future by prospective study.

A comparison of radiation treatment plans using IMRT with helical tomotherapy and 3D conformal radiotherapy for nasal natural killer/T-cell lymphoma.

The purpose of this study was to compare radiation treatment plans (RTPs) that used intensity-modulated radiation therapy (IMRT) with helical tomotherapy (HT) or three-dimensional conformal radiation therapy (3D-CRT) for nasal natural killer/T-cell lymphoma (NNKTL). We created RTPs that used IMRT with HT or 3D-CRT for eight NNKTL patients previously treated at our institution and conducted a pilot comparison between the two modalities using the parameters of the target coverage and homogeneity for the planning target volume (PTV) and the maximum and mean doses for organs at risk (OARs). The clinical target volume (CTV) included the gross tumour volume with an additional margin of 1.5 cm and the nasopharynx, palates and nasal cavity; the PTV with the CTV plus a 2 mm margin received a total dose of 50 Gy. IMRT achieved significantly better PTV coverage, with more than 99% of the PTV receiving 90% and 95% of the prescribed dose, whereas 3D-CRT could not provide adequate coverage of the PTV, with 89.1+/-2.6% and 84.5+/-2.7% of the PTV receiving 90% and 95% of the prescribed dose, respectively (both p <0.0001). The homogeneity index was 0.29+/-0.06 for IMRT and 0.046+/-0.022 for 3D-CRT, which was statistically significant (p <0.0001). IMRT tended to provide equivalent or slightly better OAR avoidance than 3D-CRT. In conclusion, 3D-CRT could not provide adequate coverage of the PTV because the PTV was close to many OARs. IMRT should be used for NNKTL because a lack of optimal RTPs could cause local failure.

Betaine and homocysteine concentrations in infant formulae and breast milk.

BACKGROUND: Early diagnosis and treatment of homocystinuria with methionine-free or low methionine formulae significantly improve prognosis in children found by newborn screening and treated soon after birth. Betaine (Bet) supplementation is also an effective strategy for dietary treatment of homocystinuria. However, previous reports on diet therapy have only examined methionine and cysteine concentrations but not those of Bet and homocysteine (Hcy) in infant diets. METHODS: We measured Bet and Hcy concentrations in three methionine-free formulae, five infant starter formulae, and 33 samples of human breast milk from 10 mothers. RESULTS: In methionine-free formulae, Hcy but not Bet was isolated. However, in human breast milk and infant starter formulae, both Bet and Hcy were detected. However, the Bet concentration was not sufficient for the treatment. CONCLUSIONS: Our study suggests that methionine-free formulae should have Hcy eliminated and be fortified with Bet to the concentration of 150 mg/dL for the treatment of homocystinuria.

Galactose metabolites in blood from neonates with and without hypergalactosaemia detected by mass screening.

UNLABELLED: Concentrations of galactose (Gal) in plasma and galactose metabolites in red blood cells (RBC) were determined in 18 normal neonates and 249 others with hypergalactosaemia according to the Paigen method. Normal neonatal values for plasma Gal, RBC galactose-1-phosphate (Gal-1-P), RBC uridine diphosphate glucose (UDP-Glc), and RBC uridine diphosphate galactose (UDP-Gal) were 0.96 +/- 0.71 mg/dl, 1.69 +/- 1.45 mg/dl of packed RBC, 1.00 +/- 0.45 mg/dl of packed RBC, and 1.44 +/- 0.45 mg/dl of packed RBC, respectively. The UDP-Gal concentration was higher and the UDP-Glc concentration lower than previously reported in normal children. Of the 249 cases with excessive Gal in whole blood, 23 showed high Gal concentrations in plasma; among these, four portacaval shunts and one case of congenital biliary atresia were diagnosed. In subjects homozygous or heterozygous for UDP-Gal-4 epimerase deficiency, concentrations of UDP-Gal and Gal-1-P were elevated only in RBC, corresponding to restriction of the metabolic abnormality to these cells. Most cases of hypergalactosaemia detected by the Paigen method have large excesses of Gal-1-P in RBC. Although a specific diagnosis based solely on blood Gal metabolites is difficult, individual concentrations reflect underlying conditions to some extent. CONCLUSION: In neonates, uridine diphosphate galactose concentrations were higher and uridine diphosphate glucose concentrations were lower than previously reported paediatric values. Patients with high plasma galactose concentrations should be investigated by hepatic imaging.

Manganese elevations in blood of children with congenital portosystemic shunts.

UNLABELLED: Magnetic response imaging has demonstrated increased signal intensities within the basal ganglia in patients with hepatic encephalopathy; the densities are considered to represent manganese deposition. We measured whole blood manganese concentrations in nine children with congenital portosystemic venous shunts detected by screening tests for galactosaemia. Beyond 1 year of age, these patients showed significantly higher manganese concentrations than controls (2.40 +/- 0.43 versus 1.48 +/- 0.38 micrograms/dl; P = 0.0001). Four of the nine patients were studied by magnetic response imaging. T1-weighted images showed increased signal intensities in the basal ganglia of those four patients, suggesting manganese accumulation. CONCLUSION: Children with congenital portosystemic venous shunts showed manganese elevations in blood and magnetic response imaging changes in the basal ganglia. These children should avoid excessive manganese intake.

Determination of cystathionine in rat tissues using isotachophoresis.

A method for measurement of cystathionine in biological samples has been developed by using an isotachophoretic analyzer. The determination of the amount of cystathionine was carried out by measuring a zone length of cystathionine in isotachophoresis. The amount of cystathionine in brains of normal rats determined by using this method was 0.084 +/- 0.023 mumol/g. This value agreed well with earlier reports. The amount of cystathionine in rats with experimental cystathioninuria was determined in several tissues. The results determined by using this method for the determination of cystathionine in the rat tissues agreed well with the results obtained by using an amino acid analyzer.