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.     

Diagnosis of Small Pancreatic Carcinoma

A retrospective analysis was performed to evaluate the clinicalsymptoms and abnormal test findings in small pancreatic carcinoma.Five hundred and thirty-six cases of pancreatic carcinoma withthe histology of duct cell carcinoma were collected from 14medical centers in Japan. In 440 of the cases, tumor size wasmeasured at the time of laparotomy or from the resected specimen.Three hundred and seventy-seven patients (86%) had a carcinomalarger than 3.0 cm; only 30% of these were resectable. Sixty-threepatients (14%) had a carcinoma of 3.0 cm or less, with resectabilityof 97%. Detecting a tumor of "3 cm or less" with a high probabilityof resectability is the objective of early diagnosis with theresulting possibility of a cure. In most cases these small carcinomaswere found easily when obstructive jaundice was present (73%).However, the estimated occurrence of obstructive jaundice associatedwith carcinomas of 3 cm or less was only 10% among the totalcases of pancreatic carcinoma studied. Therefore, it is necessaryfor early diagnosis to detect carcinomas of 3 cm or less presentingwithout jaundice. The symptoms of small carcinoma without jaundiceare weight loss, anorexia, upper abdominal pain, back pain anda palpable abdominal mass. Among the various available examinations,endoscopic retrograde cholangiopancreatography, computerizedtomography and ultrasonography were valuable in diagnosing thesesmall carcinomas.     

Diastolic mitral annular motion in normal subjects and patients with coronary artery disease

The purpose of this study was to evaluate the characteristicsof mitral annular motion during diastole in 28 normal subjects,40 patients with prior myocardial infarction (MI), and 23 patientswith coronary artery disease but without prior MI. Mitral annularmotion during diastole was obtained from the apex by M-modeechocardiography at the posterior wall of the left ventricle.Determinants of mitral annular excursion during early (MAE-E)and late diastole (MAE-L) were investigated in all subjects.Differences in the MAE-E, MAE-L, and the MAE-L.MAE-E ratio werecompared among the three patient groups. The Doppler-derivedtransmitral flow velocity-time integral during early (El) andlate (AI) diastole and mitral annular excursions during diastolewere obtained in 55 other patients with a prior MI and in 29healthy volunteers. The relationships between the MAE-L: MAE-Eratio and AI: EI ratio in these two groups were studied. The MAE-E was determined mainly by heart rate and left ventricularejection fraction (LVEF). The MAE-L was determined only by age.The magnitude of MAE-E was significantly less in patients witha prior MI than in normal subjects (P<0.01). However, theMAE-L did not differ among the three groups. The MAE-L.MAE-Ewas higher in patients with a prior MI than in normal subjects(P<0.05), and was significantly correlated with AI: EI inhealthy volunteers (r=0.65, P<0.001) and in patients witha prior MI (r=0.50, P<0.001). The MAE-E in patients with a prior MI decreases in proportionto the deterioration in LVEF. The relative at rial contributionto left ventricular longitudinal distension is increased inpatients with a prior MI and diastolic mitral annular motionhas a significant relationship to the transmitral flow. Thesefindings suggest that mitral annular motion during late diastoleplays an important role in maintaining left ventricular fillingin patients whose left ventricular systolic function has deteriorated.     

Portal-hypertensive gastropathy

In the present article we describe updated information concerning the clinical feature of portal-hypertensive gastropathy (PHG), which is characterized by mucosal and submucosal vascular dilatation without inflammation. Although this lesion represents non-variceal bleeding, there is a wide variation of its prevalence. Portal pressure and some humoral factors may play important roles in its pathogenesis. Gastric acid secretory activity is reduced, whereas the gastric mucosal barrier is impaired. With regard to gastric mucosal haemodynamics, whether ‘overflow’ (i.e. active congestion) or ‘stasis’ (i.e. passive congestion) cause gastric mucosal hyperaemia is not known. A severe lesion is a potential source of bleeding, while mild lesions are of little clinical significance and endoscopic variceal obliteration aggravates PHG in some patients. In the treatment of PHG, pharmacological (e.g. propranolol), surgical (e.g. portosystemic shunt) and radiological (e.g. transjugular intrahepatic portosystemic shunt) procedures may be useful in preventing bleeding from PHG.     

''Metaplastic lesions'' in intrahepatic bile ducts in hepatolithiasis: A histochemical and immunohistochemical study

Pathology of the intrahepatic bile ducts bearing calculi was examined with an emphasis on metaplasia in 22 cases of hepatolithiasis and in seven cases of normal livers. Normal livers contained few glandular elements within the bile duct walls and no metaplastic lesions or endocrine cells. In hepatolithiasis, a number of mucous glands resembling pyloric glands (pseudopyloric gland metaplasia) were seen within duct walls in all cases. The epithelial cells of the glands were positive for class III mucin with paradoxical concanavalin A staining which is known to be specific for pyloric glands. These cells were also positive for neutral, sialo- and sulfomucin to a variable extent. Intestinal metaplasia, including goblet cell and Paneth cell metaplasia, was found within duct walls and in covering epithelia in five (23%) cases. Endocrine cells, including argyrophil, argentaffin and gut hormone-containing cells were present in these metaplastic lesions in 13 (59%) cases. The occurrence of endocrine cells was closely associated with intestinal metaplasia, although there were a few endocrine cells in metaplastic pseudopyloric glands. These findings suggest that metaplastic lesions similar to the well-known metaplastic lesions in the gallbladder occur in the intrahepatic bile duct walls in hepatolithiasis. The appearance of metaplastic lesions and endocrine cells may be causally related to chronic inflammatory processes associated with hepatolithiasis.     

Role of vagotony in sinus node dysfunction in children with symptomatic congenital long QT syndrome

The present study examined chronotropic dysfunction and the role of vagotony in congenital long QT syndrome, sinus node function and the effects of parasympathetic blockade. Six patients with congenital long QT syndrome were studied. The four males and two females, aged 1–15 years, had episodes of syncope and malignant ventricular arrhythmias. Congenital long QT syndrome was defined as a corrected QT interval greater than 0.45 s, T wave alternans and the age at diagnosis. The sinus heart rate measured from a 24 h electrocardiograph was abnormally low (< 50 min) in three patients (1, 4 and 5 years old) and did not increase sufficiently with the administration of atropine in five of the six patients with congenital long QT syndrome. From intracardiac electrophysiological studies, the corrected sinus node recovery time was prolonged in three patients and the total sinoatrial conduction time was prolonged in two patients. In most patients who had an abnormally long sinoatrial conduction time and corrected sinus node recovery time, these values returned to normal following atropine administration. In one patient, the corrected sinus node recovery time was prolonged paradoxically by atropine. Sinus node dysfunction in congenital long QT syndrome was affected by vagotony associated with a right sympathetic nerve system abnormality.