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 protease inhibitor attenuates gastric erosions and microcirculatory disturbance in the early period after thermal injury in rats

The effects of camostat mesilate, a synthetic serine protease inhibitor on gastric microcirculation and active oxygen species generated by leucocytes from the gastric and jugular veins in the early period after thermal injury were assessed. Male Wistar rats were anaesthetized and a 30% full skin-thickness dorsal burn was inflicted. Camostat mesilate (100 mg/kg) was dissolved in distilled water and administered orally to rats 40 min before thermal injury (the camostat group). The control animals (the vehicle group) were administered distilled water orally. Rolling leucocytes as well as Monastral blue B deposits in venules were observed using in vivo microscopy. Active oxygen species were measured by chemiluminescence. Camostat mesilate decreased the total length of gastric erosion, venular deposits of Monastral blue B, and rolling of leucocytes in venules, and relatively increased luminol-dependent chemiluminescence activity generated by zymosan-stimulated leucocytes 15 min after thermal injury. These results suggest that serine proteases are involved in the formation of gastric erosions and gastric microcirculatory disturbance in the early period after thermal injury.     

Frequency and Output-Dependent Change in Conduction Over Slow Pathways in a Patient with Sustained Ventricular Tachycardia Unrelated to Coronary Artery Disease

In a patient with sustained ventricular tachycardia, we obtained two different paced QRS morphologies from a single pacing site. In one QRS morphology the stimulus to the QRS complex was long, 150 msec, and in the other it was 100 msec. At the paced cycle length of 600 msec and the stimulus output of 4 V, one QRS morphology with the stimulus to the onset of QRS activation (St-QRS) interval of 150 msec was observed. At the paced cycle length of 400 msec, the other QRS morphology with a St-QRS interval of 100 msec was observed alternatively with the former. At the paced cycle length of 353 msec or 316 msec, the latter with a shorter St-QRS interval was exclusively observed. When the stimulus output was increased from 4 to 10 V, keeping with the paced cycle length at 400 msec, the St-QRS interval was shortened from 100 to 80 msec. For the two QRS morphologies with two St-QRS intervals, two slowly conducting pathways would be responsible. The site of the block in the faster pathway must be located at the proximity of the pacing site and the conduction at a shorter paced cycle length would be explained by "supernormal conduction."     

THE IMPACT OF DIABETES MELLITUS ON THE PROGNOSIS OF ALCOHOLICS

In this study, the mortality of clinically treated Japanesealcoholics with diabetes mellitus was analysed. Fifty-one diabeticalcoholics without liver cirrhosis (DM), 23 diabetic and cirrhoticalcoholics (DM LC), 44 cirrhotic alcoholics without diabetes(LC), and 354 alcoholics without either complication (AL) admittedto the National Institute on Alcoholism in 1985 were studied.Thirty-seven diabetics required insulin treatment, and 12 oralhypoglycemic agents. The 4.4-year survival and drinking statusafter discharge were studied in 1990. Stepwise logistic regressionanalysis showed that the estimated odds for death increased8.10, 4.38, 3.70, and 3.27 times for the subjects with the alcoholmisuse after discharge, DM, DM LC, and LC, respectively. The4.4-year survival rate of alcoholics who continued misusingalcohol was much lower in DM (26%, P < 0.0005) and LC (35%,P < 0.0001) than in AL (73%). The survival rate of thosewho stopped misusing alcohol was significantly higher in DM(90%, P < 0.0001), LC (88%, P < 0.0001) and AL (94%, P< 0.0005) than those who continued misusing alcohol. Therewas no significant difference in the survival rate between thealcoholics with DM LC who continued misusing alcohol (50%) andthose who stopped misusing alcohol (73%). In the dead patients,56% of DM died unexpectedly or suddenly, whereas 71% of LC diedof liver failure after hospitalization. These results suggestthat diabetic alcoholics should be intensively educated forabstinence.     

Signet-ring cell carcinoma of the prostate effectively treated with maximal androgen blockade

Primary signet-ring cell carcinoma (SRCC) of the prostate is very rare and has a poor prognosis, even when treated with aggressive therapy. We report herein a case of a 72-year-old man with prostatic SRCC. The patient had a tumor that extended directly to the rectum. Maximal androgen blockade was started and 20 months later, the patient was alive without evidence of recurrence. The present case of prostatic SRCC responded well to medical therapy, however, tumors can recur after a long period of time. Therefore, adjuvant therapy is recommended.     

Electrophysiologic Evaluation of Asymptomatic Patients with the Wolff-Parkinson-White Pattern

In the past 4 years, 34 asymptomatic patients with the Wolff-Parkinson-White (WPW) pattern underwent electrophysiologic study. The effective refractory period (ERP) of antegrade conduction over the accessory pathway was 288 +/- 29 msec. In three asymptomatic patients (9%), the antegrade ERP of the accessory pathway was shorter than 250 msec. The antegrade ERP of the accessory pathway became shorter than 250 msec in an additional 12 of 22 (55%) patients after isoproterenol administration. Nineteen (56%) of the asymptomatic patients showed the absence of retrograde conduction over the accessory pathway even after isoproterenol administration. The rate of induction of orthodromic reciprocating tachycardia in the asymptomatic WPW patients was 15% (5/34), which was significantly lower than that in the symptomatic patients. These data suggest that in the asymptomatic patients, the absence of retrograde conduction over the accessory pathway is the reason they remained asymptomatic, free of reciprocating tachycardia. However, even in the asymptomatic patients, some had the accessory pathway in which antegrade ERP was shorter than 250 msec. They may result in rapid ventricular conduction over the accessory pathway when atrial fibrillation develops.     

Prognosis of the middle-aged and aged patients with obstructive sleep apnea syndrome

Abstract The long-term natural course of obstructive sleep apnea syndrome (OSAS) is studied in order to determine whether severity of nocturnal oxygen desaturation associated with apnea/hypopnea, body mass index (BMI), and hypertension influence survival in young (<40 years), middle-aged (40–64 years), and aged (65 years) using a questionnaire survey. One hundred and forty-eight patients with OSAS aged 17–78 years (136 men, 12 women, mean 52.0±12.3 yean), who were diagnosed by standard polysomnography (PSG) between 1983 and 1993, participated in the study. The survey revealed 15 deaths and 101 survivors; 32 subjects could not be located. The survival rate was 71.4% (95% confidence interval:55.6–87.2%). The survival rate in patients with OSAS was significantly lower than that in the age and sex-adjusted control Japanese population (87.6%). In the young group, only one death (a 19–year-old woman) occurred unexpectedly during sleep. The patient showed an apnea/hypopnea index (AHI) of 33 per h and the length of time that the nocturnal oxygen saturation (SaO₂) fell below 90% (time of SaO₂ < 90%) of 205 min. The survival rate in middle-aged patients with OSAS was significantly lower than that in the age and sex-adjusted control Japanese population (79.2 vs 91.0%), but this pattern was not seen among the aged. Time of SaO₂ <90% was significantly longer in the middle-aged patients than in the aged patients, but AHI did not differ between the two groups. Moreover, it was significantly correlated with AHI in middle-aged patients, but not in the aged patients. The survival rate was significantly lower in patients with hypertension than in the patients without such complications in the middle-aged group (57.9 vs 90.4%). Cox proportional-hazard regression model including age, hypertension, BMI, AHI, lowest SaO₂, and time of SaO₂ <90% showed that hypertension was only significantly associated with lower survival rate in total group and middle-aged patients, but not in the young or aged patients. The prognosis in patients with OSAS may differ among the generations. The prognosis in the middle-aged population may depend on the role of OSAS on the complications of hypertension or severity of oxygen desaturation, but not on AHI only.