1,1,1,2-Tetrafluoroethane: Repeat Exposure Inhalation Toxicity in the Rat, Developmental Toxicity in the Rabbit, and Genoxicity in Vitro and in Vivo

Subchronic and chronic studies were carried out in the rat anda developmental toxicity study in the rabbit with exposuresto 1,1,1,2-tetrafluoroethane (HFC 134a) by inhalation. In therat repeated exposure to 50,000 ppm HFC 134a for 13,52, and104 weeks elicited no effect on clinical condition, growth,and survival, or on a variety of hematological, clinical chemistry,and urinary parameters. Treatment-related pathological changeswere seen only at study termination at 2 years and were confinedto increased incidence of Leydig cell hyperplasia and adenomain male rats exposed to 50,000 ppm. The tumors, which were alsoseen in control animals, were benign and not life-threatening.A battery of in vitro and in vivo tests gave no evidence ofgenotoxic activity. With exposure to pregnant rabbits, the onlytreatment-related effects were of minimal maternal toxicityat high exposure concentrations; there were no effects on fetaldevelopment. It is concluded that HFC 134a is of very low toxicityand should be an acceptable alternative to CFCs.     

Longitudinal Dissociation in the His Bundle: A Possible Mechanism of Two Distinct Cycle Lengths in Atrioventricular Reentrant Tachycardia

Two wide QRS tachycardias with identical morphology but different cycle lengths (CLs) developed in a 63-year-old man. Electrophysiological study demonstrated inducible atrioventricular reentrant tachycardia (AVRT) due to a concealed left posterior accessory pathway (AP), which was successfully ablated by radiofrequency application. Neither dual AV nodal pathways nor other APs were documented. Splitting of the His-bundle electrogram was shown, and programmed stimulation induced sudden prolongation of intra-hisian conduction time. These results suggest longitudinal dissociation in the His bundle may be responsible for two distinct CLs in AVRT without dualAV nodal physiology.     

Atrioventricular Nodal Physiology After Slow Pathway Ablation

The A V nodal physiology before and 1 week after “slow pathway potential” guided catheter ablation was examined in 32 patients with AV nodal reentrant tachycardia. A mean of 4.9 applications of radiofrequency energy eliminated AV nodal reentrant tachycardia in all patients. There were no significant differences in sinus cycle length (815 ± 159 msec vs 813 ± 162 msec;P = NS) and fast pathway conduction properties before and 1 week after ablation. Slow pathway conduction was completely eliminated in 10 (31%) (group I) of 32 patients after ablation. In the remaining 22 patients residual slow pathway conduction associated with one AV node echo was observed. In 15 patients (47%) (group II), the effective refractory period of the slow pathway showed a change of < 30 msec (265 ± 51 vs 266 ± 51 msec; P = NS), and in 7 patients (22%) (group III), a prolongation of more than 80 msec (247 ± 56 vs 340 ± 42 msec; P = 0.0001) before and 1 week after ablation. Minimal and maximal A₂-H₂ interval over the slow pathway in group II was not significantly changed (Min A₂-H₂:241 ± 37 vs 247 ± 40 msec; P = NS, Max A₂-H₂: 346 ± 79 vs 350 ± 60 msec; P = NS), while a significant prolongation was measured in group III (Min A₂-H₂: 261 ± 53 VS 373 ± 107 msec; P < 0.01. Max A₂-H₂: 359 ± 41 vs 427 ± 63 msec; P < 0.05) before and after ablation. Conclusion: In group II patients there was no evidence shown of impairment of the slow pathway. This suggests that disruption of the link between fast and slow pathways may be responsible for the elimination of AV nodal reentrant tachycardia, besides the elimination or impairment of the slow pathway itself, in “slow pathway potential” guided catheter ablation, and that the slow pathway potential may not necessarily represent activation of the slow pathway itself or of its atrial connection.     

Significance of plasma glutathione determination in patients with alcoholic and non-alcoholic liver disease

Plasma glutathione levels were determined in 79 patients with various types of liver disease and 18 healthy controls in order to study their significance in the course of liver disease. Plasma was taken at the time of needle liver biopsy. A positive linear correlation was found between plasma and hepatic glutathione concentrations, as has been suggested in experimental animals. In patients with acute viral hepatitis, chronic hepatitis, non-alcoholic liver cirrhosis and alcoholic liver disease, plasma glutathione levels were significantly decreased compared with those in controls. Of importance is the fact that the plasma levels increased after recovery in patients with acute viral hepatitis and after abstinence from alcohol intake in patients with alcoholic liver disease. Determination of plasma glutathione may be valuable in the evaluation of liver disease, particularly in acute viral hepatitis and alcoholic liver disease in which the hepatic content of glutathione is suggested to be decreased. Such patients may be susceptible to oxidative stress and radical-related hepatic injury.     

Frequency of abnormalities detected by abdominal ultrasound among Japanese adults

Abdominal ultrasound examination was given to 715 (566 male and 149 female) adult non-manual workers in Tokyo as part of their annually required medical check-up. Gross abnormalities were found in 44.5% of males and 34.2% of females. The most common finding was fatty liver (15.2%), seen four times as frequently in males as in females. There were 93 elevated lesions in the gall-bladder in 56 subjects (7.8%); some required follow-up examinations because malignancy could not be excluded. Small cystic lesions were frequently seen in the kidney (6.4%) and in the liver (4.8%). Gallstones were found in 3.4%. Mild splenomegaly occurred in 3.4%. Ten mass lesions, 8 hyperechoic and 2 hypo-echoic, were found in the liver, but subsequent imaging studies showed them to be benign haemangiomas. Other changes found included calcific lesions in the liver (2.1%) and in the spleen (0.4%), renal stones (2.0%), thickened wall of the gall-bladder (3.2%), intramural stones (0.8%) and debris/sludge (0.4%) in the gall-bladder, dilated pancreatic duct (0.7%) and common bile duct (0.3%), liver cirrhosis (0.4%), hydronephrosis (0.1%), enlarged pancreas (0.1%), small pancreas (0.1%), ovarian tumour (0.1%), uterine tumour (0.1%), abnormally shaped kidney (0.1%) and situs inversus (0.1%). It was concluded that abdominal ultrasound is an important examination for a mass screening or a physical check-up commonly practised as the 'human dock' for adults in Japan.     

Application of the relaxation technique in general hospital psychiatry

Abstract The present article demonstrates the clinical application and the efficacy of relaxation techniques in general hospital psychiatry in Japan. During April to December 1993, 20 patients were treated with progressive muscle relaxation and 'modified' autogenic training therapies. The targeted symptoms were anxiety attacks (or panic attacks), neurotic insomnia, hyperventilation syndrome, agoraphobia, chronic pain, and distress. Most patients (18/20) improved rapidly with the use of these techniques and their excellence encourages increased use in general hospital psychiatry for the following reasons. First, physically ill patients are likely to show unexpected reactions to psychotropic medications. Second, some patients prefer these treatment methods rather than medications because they feel that they are participating voluntarily in their own treatment and also because they are fearful of being addicted to tranquilizers. Third, these treatments have produced rapid improvement especially for patients with panic attacks and/or hyperventilation. This study strongly suggests that progressive muscle relaxation and 'modified' autogenic training are simple and useful methods which can be easily employed in the clinical practice of general hospital psychiatry.     

Improvement of peripheral blood lymphocyte subsets in primary biliary cirrhosis after ursodeoxycholic acid therapy

Immunological abnormalities frequently observed in patients with primary biliary cirrhosis are considered to be related to the pathogenesis of this disease. We performed a prospective trial to evaluate whether immune mechanisms play a role in the effectiveness of ursodeoxycholic acid (UDCA) therapy. Fifteen female patients with primary biliary cirrhosis were followed for 1 year and were then treated with UDCA (600 mg/day) for another year. Laboratory tests, including peripheral blood lymphocyte subsets assessed by dual colour fluorescence analysis using monoclonal antibodies against respective T cell markers, were evaluated at the beginning of the study, at the start of therapy and at the end of therapy. In primary biliary cirrhosis, the proportion of cytotoxic T cells, suppressor inducer T cells and αβ-receptor bearing T cells were significantly lower than in healthy controls. No significant changes were observed in the proportions during the year before the therapy. These reductions, however, recovered to normal ranges after 1 year of UDCA therapy. These changes were associated with an improvement in the serum levels of aspartate aminotransferase, alkaline phosphatase, γ-globulin and IgM. The close correlation between the improvement in the imbalance of lymphocyte subsets after the therapy and the clinical status suggests that an immunological process may play a role in the effectiveness of therapy in primary biliary cirrhosis.     

Adenosine-Sensitive Atrial Reentrant Tachycardia Originating from the Atrioventricular Nodal Transitional Area

Adenosine-Sensitive AT from AVN Area. Introduction : Atrial tachycardia shows wide variations in its electrophysiologic properties and sites of origin. We report an atrial tachycardia with ECG manifestations and electrophysiologic characteristics similar to an atypical form of AV nodal reentrant tachycardia (AVNRT).
Methods and Results : This supraventricular tachycardia was observed in 11 patients. It was initiated by atrial extrastimulation with an inverse relationship between the coupling interval of an extrastimulus and the postextrastimulus interval. Its induction was not related to a jump in the AH interval, and its perpetuation was independent of conduction block in the AV node. Ventricular pacing during tachycardia demonstrated AV dissociation without affecting the atrial cycle length. A very small dose of adenosine triphosphate (mean 3.9 ± 1.2 mg) could terminate the tachycardia. The earliest atrial activation during tachycardia was recorded at the low anteroseptal right atrium with a different intra-atrial activation sequence from that recorded during ventricular pacing, where the tachycardia was successfully ablated in 9 of 10 attempted patients. Bidirectional AV nodal conduction remained unatttched after successful ablation.
Conclusion : There may he an entity of adenosine-sensitive atrial tachycardia probably due to focal reentry within the AV node or its transitional tissues without involvement of the AV nodal pathways. This tachycardia can he ablated without disturbing AV nodal conduction from the right atrial septum.     

Complications of percutaneous transhepatic catheterization of the portal venous system in patients with portal hypertension

We report here complications of percutaneous transhepatic catheterization of the portal venous system in 170 Japanese patients with portal hypertension. All patients underwent percutaneous transhepatic portography and percutaneous transhepatic obliteration of oesophagogastric varices was also performed in 29 patients. After retraction of the catheter, the puncture canal was plugged with gelatin sponge in 150 subjects and with one steel coil in 20 others. The overall complication rate was 16.5%. Intraperitoneal bleeding occurred in 10.6% of patients and 2.9% required blood transfusion. In these patients with intraperitoneal bleeding, the gelatin sponge was used for plugging after retraction of the catheter, while in the 20 patients with a steel coil plug, haemoperitoneum never occurred. Right pleural effusion was recognized in 3.5% of patients, intraperitoneal bile leakage in 1.8% and deterioration of liver function due to arteriovenous fistula in 0.6%. By univariate and multivariate analyses, female gender was the only risk factor for intraperitoneal bleeding among 150 patients investigated by percutaneous transhepatic catheterization of the portal venous system with gelatin sponge plugging. Intraperitoneal bleeding is the most important complication in patients with portal hypertension; it is difficult to predict intraperitoneal bleeding before retraction of the catheter in patients for whom gelatin sponge is used. Thus, for patients undergoing percutaneous transhepatic catheterization of the portal venous system, close follow up is recommended.     

High Energy Radiofrequency Catheter Ablation for Common Atrial Flutter Targeting the Isthmus between the Inferior Vena Cava and Tricuspid Valve Annulus Using a Super Long Tip Electrode

There have been controversies concerning the optimal target sites and approaches in radiofre-quency catheter ablation of common atrial flutter. We attempted high energy radiofrequencv catheter ab-lation targeting the isthmus between the inferior vena cava and tricuspid valve annulus (IVC-TV isthmus) with a super long (8 mm) tip electrode, and compared the efficacy of this anatomical approach with the electrophysiological approach targeting the posteroseptal right atrium posterior to the coronary sinus us-ing a standard 4-mm tip electrode. Atrial flutter was successfully ablated in 12 of 12 patients (100%) with-out recurrence with the anatomical approach, while, in 7 of 9 patients (64%) with 2 recurrences with the electrophysiological approach. In comparison of ablation data between the anatomical and electrophysi-ological approaches, there were significant differences in the mean number of application pulses (anatomical vs electrophysiological: 2.3 ± 0.8 vs 9.9 ± 6.4, P < 0.01), applied wattage (39 ± 12Wvs24 ± 6W.P < 0.01), applied energy per application (1.986 ± 426 / vs 659 ± 323 J. P < O.O1), fluoroscopic time (26 ± 11 min vs 74 ± 30 minutes, P < 0.01), and procedure time (59 ± 8 min vs 181 ± 53 min. P < 0.01). In conclusion, the anatomical approach is superior to the electrophysiological one with respect to proce-dure and radiation time, and linear ablation at the IVC-TV isthmus with an 8-wm tip electrode and high energy application is highly effective and safe.