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.     

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.     

Cerebral energy metabolism in insulin induced hypoglycemia in newborn piglets: in vivo31P-nuclear magnetic resonance spectroscopy

The effect of insulin induced hypoglycemia on cerebral energy metabolism was examined in four newborn piglets. Cerebral energy metabolism was assessed using in vivo ³¹P-nuclear magnetic resonance spectroscopy. It was demonstrated that the normal level of phosphocreatine/inorganic phosphate (PCr/Pi), an indicator of phosphorylation potential, was maintained at a blood glucose level of 40 mg/dL or above, whereas when blood glucose was reduced to less than 40 mg/dL, PCr/Pi rapidly decreased in parallel with this. Below the critical blood glucose level of 40 mg/dL, a positive correlation (y = 0.02x + 0.632; r = 0.668; P < 0.001) existed between blood glucose and PCr/Pi. In the present investigation, a reduction of blood glucose level to 20 mg/dL or lower resulted in a PCr/Pi of less than 1, indicating a state of cerebral energy failure. The intracellular pH (pHi) was 7.08 ± 0.05 at the onset and 7.15 ± 0.07 in the hypoglycemic state, indicating no significant difference between the two groups. The present study has clarified that cerebral energy failure occurs when the blood glucose level is about 20 mg/dL or lower. The critical point of blood glucose exists to maintain brain energy metabolism.     

Adrenoleukodystrophy indicated by abnormal electroencephalography

An 8 year old boy with adrenoleukodystrophy and his asymptomatic brother, both with abnormal electro-encephalography as the initial sign of adrenoleukodystrophy, are reported. After suffering from aseptic meningitis caused by Echo virus 30, the first case was suspected of having a complication of meningitis because of persistent abnormal electro-encephalography (i.e. slow wave bursts in the occipital region). This patient was finally diagnosed as having adrenoleukodystrophy because of the increased level of very long chain saturated fatty acids, and typical occipital lesions demonstrated by magnetic resonance imaging and computed tomography. Dietary therapy was tried, but the course was progressive. The brother's electroencephalography was also abnormal and so was diagnosed as having asymptomatic adrenoleukodystrophy because of an increased level of very long chain saturated fatty acids, although brain magnetic resonance imaging was normal. Abnormal electro-encephalography can therefore be an initial sign of adrenoleukodystrophy even if magnetic resonance imaging shows no abnormality in the brain.