High-performance Liquid Chromatographic Determination of Trazodone and 1-m-Chlorophenylpiperazine with Ultraviolet and Electrochemical Detector

A high-performance liquid chromatographic (HPLC) assay was developed for the determination of trazodone and its metabolite, 1-m-chlorophenylpiperazine (m-CPP), in plasma. The high level of trazodone in plasma was detected by ultraviolet absorbance at 254 nm and the low level of m-CPP in plasma was detected by coulometric electrochemical detection at 840 mV on the series arrangement of two detectors. Pilsicainide as an internal standard for both compounds was monitored by both detectors. Trazodone and m-CPP in plasma were extracted by a rapid and simple procedure based on CN bonded-phase extraction, and C₈ reversed-phase HPLC separation. Determination was possible for trazodone in the concentration range 100–2000 ng mL^?1 and for m-CPP in the concentration range 5–100 ng mL^?1. The recoveries of trazodone and m-CPP added to plasma were 81·0–84·2 and 68·0–73·2%, respectively, with coefficients of variation of less than 7·3 and 8·2%, respectively. The method is applicable to high level monitoring of trazodone and low level monitoring of m-CPP in plasma of healthy volunteers and patients treated with trazodone.     

A Case of Hamartomatous Adiposity--A Rare Type of Goiter

A rare case of hamartomatous adiposity of the thyroid occurringin a 4-year-old Japanese boy was studied by light and electronmicroscopy. This tumor-like disorder was composed of predominantlyadipose tissue and fibrous connective tissue with muscle fibersbut only a small amount of thyroid follicles at the periphery.The ultrastructural appearance showed corresponding featuresof mature fat cells, fibroblasts and other mesenhymal cellsin various grades of differentiation, and especially of striatedmuscle cells with myofilaments having electron-dense Z-lines.The findings suggest that this tumor is a hamartomatous or heterotopicdisorder caused by histogenetic malformation during embryonaldevelopment rather than a true neoplasm.     

Synthesis and central nervous system actions of thyrotropin-releasing hormone analogs containing a 1-substituted 2-oxoimadazolidine moiety*

A series of thyrotropin-releasing hormone (TRH) analogs in which the pyroglutamic acid residue was replaced by (S)-2-oxoimidazolidine-4-carboxylic acid (Oic-OH) and the related derivatives was prepared, and the central nervous system (CNS) actions were examined. Of these, 1-benzyl-Oic-His-Pro-NH₂ (2c) showed the most potent activities, which were 1.5-8 times greater than those of TRH. Moreover, the thyrotropin (TSH)-releasing activity of 2c was about 1/16 times weaker than that of TRH.     

Clinical and Electrophysiological Difference Between Idiopathic Right Ventricular Outflow Tract Arrhythmias and Pulmonary Artery Arrhythmias

Characteristics of Pulmonary Artery Arrhythmias. Introduction: The precise incidence and characteristics of ventricular arrhythmias originating from the pulmonary artery have not been fully described. The purpose of this prospective study was to clarify these points. Methods: Thirty‐three consecutive patients with an idiopathic left bundle branch block and inferior‐axis deviation type ventricular arrhythmia were included. All patients underwent detailed electroanatomical mapping (CARTO, Biosense‐Webster, Diamond Bar, CA, USA) during sinus rhythm prior to the catheter ablation. The precise location of the catheter tip at the successful ablation site was confirmed by both electroanatomical mapping and contrast radiography. The clinical and electrophysiological data were compared between the right ventricular outflow tract (RVOT) arrhythmia patients (RVOT group) and PA arrhythmia patients (PA group). Results: Eight patients (8/33 patients: 24.2%) had their ventricular arrhythmias successfully ablated within the PA. The local bipolar electrogram at the successful ablation sites in the PA group exhibited a significantly greater duration (P < 0.05) and lower amplitude (P < 0.05) than did those in the RVOT group (n = 19). In the PA group, all patients exhibited a multicomponent electrograms composed of a spiky potential and a dull potential, which might have consisted of near‐field PA activation and a far‐field ventricular activation, respectively, at the successful ablation site. Direct ablation to the spiky electrogram was able to eliminate the arrhythmias in all the PA group patients. Conclusions: PA arrhythmias may be more common than previously recognized. Careful mapping and interpretation of low amplitude and multicomponent electrograms are important for recognizing ventricular arrhythmias originating from the PA. (J Cardiovasc Electrophysiol, Vol. 21, pp. 163‐169, February 2010)     

Significance of erb B-2 Gene Product as a Target Molecule for Cancer Therapy

The new monoclonal antibodies (MoAbs) E401, E811, E907 and E919 were prepared and characterized. These recognized an extracellular domain (amino acids No. 292–370) on the human c-erbB-2 gene product. Utilizing MoAb E811 and MoAb E919, a double determinant immunoassay (DDIA) was established to detect the soluble and the shed forms of the c-erbB-2 molecule. The levels of circulating erbB-2 antigen in the sera of patients with benign diseases and healthy controls were very low. The incidence of positivity for shed c-erbB-2 antigen in gastric cancer, eolonic cancer, gall-bladder caneer, pancreatic eancer and other cancers were 7.4%, 4.2%, 0%, 6.7% and 0%, respectively. Four of 54 patients with gastric carcinoma showed high levels of serum c-erbB-2 antigen. They belonged to clinical stage IV and their histological types were all well differentiated adenoeareinomas (two papillary and two tubular adenoeareinomas). Furthermore, the incidence of positive staining in gastric cancer was 34.6%; higher than that for shedding erbB-2 antigen. Most of the cases v-hich showed erbB-2 expression on cells were well-differentiated adenoeareinomas. Meanwhile, the distribution of erbB-2 antigen was limited in normal tissues. The results suggest that the expression of erbB-2 antigen is largely restricted to adenocarcinoma cells. It may not shed easily from these cells, and therefore It may be a very useful target molecule for passive immunotherapy.     

Endoscopic Mucosal Resection (EMR) of Early Gastric Cancer

Abstract: We conducted this study to clarify the effectiveness of aspiration endoscopic mucosal resection (EMR) using a cap-fitted scope for early gastric cancer in the C and M regions of the stomach. EMR was performed in 111 early gastric cancer patients with 123 lesions in the C and M regions. The patients were divided into three groups. The EMR-1CS group consisted of patients who had undergone EMR with a one-channeled scope, the EMR-2CS group those who had received EMR in which a two-channeled scope was utilized. The EMRC group consisted of patients who had undergone aspiration EMR with a cap-fitted scope. The rate of complete resection improved to a statistically significant degree in the EMRC group in comparison with that in the EMR-1CS group. In type lie, a statistically significant improvement was achieved in the EMRC group in comparison with the EMR-2CS group. In the M region or in lesions 10 mm or less in diameter, the rate of complete resection improved in the EMRC group as compared with that in the EMR-2CS group. Our results suggest that EMRC is useful for lesions of early gastric cancer in the C and M regions.     

A new antimicrobial quinolone (AM-1155) analysed in hair as an index of drug exposure and as a time-marker

Abstract— Scalp hair samples were obtained at one-month intervals for up to four months after the administration from each of twelve healthy male volunteers participating in a phase I study of a new antimicrobial quinolone, AM-1155, (±)-1-cyclopropyl-6-fluoro-1, 4-dihydro-8-methoxy-7-(cis-3,5-dimethyl-1-piperazinyl)-4-oxo-3-quinoline carboxylic acid. After hair was sectioned into 1 cm lengths from the scalp end, corresponding portions from five pieces of hair were dissolved in 1 m NaOH and assessed for AM-1155 by HPLC. In all subjects who had taken a single dose (600 mg, n = 6) or repeated doses (300 mg twice daily for 6·5 days, n = 6), the drug was detected in hair. The hair portions containing the drug were shown in most subjects to move outwards month by month at the rate of about 1 cm month^?1. A single hair, which was obtained from each subject of the repeated-dose study 3 months after the completion of administration, was cut into 2·5-mm lengths from the scalp side and analysed for AM-1155. The drug was shown to be contained in 4 to 6 consecutive 2·5-mm lengths, showing that there was no large axial diffusion of the drug along the hair shaft even after 3 months. These findings indicate the utility of measuring this quinolone derivative in hair as an index of drug exposure and, furthermore, as a time marker for analysing other drugs in hair.