Predominantβ-adrenoceptor blocking effect of xamoterol averaged over the day in patients with mild to moderate heart failure: insight into the mechanism of its long-term clinical efficacy

Summary Xamoterol acts as a ₁-adrenoceptor agonist at low sympathetic activity and as an antagonist at high activity. Although its long-term efficacy has been proven in patients with mild to moderate heart failure, it remains unclear which effect, agonism or antagonism, accounts for its long-term activity.To clarify the effect of xamoterol on cardiac sympathetic activity in daily life, 24-h R-R interval histograms were obtained during administration of xamoterol 100 mg b. d. for 1 week to 10 patients with mild to moderate heart failure. Eight normal subjects were also studied as controls. To examine the relation between the effect of xamoterol and sympathetic activity, plasma noradrenaline (NA) levels were measured under 5 graded conditions simulating daily living.Xamoterol administration significantly decreased the standard deviation of the R-R interval, both in patients with heart failure and in normal subjects. The mean R-R interval, however, was increased in patients with heart failure, relative to normal subjects.In both groups, the R-R interval histograms had two peaks, i. e. a short daytime peak and a long night-time peak. Xamoterol decreased the median of the night-time peak without changing the daytime peak in normal subjects. In contrast, it increased the median of the daytime peak without producing a significant change in the nighttime peak in patients with heart failure. Levels of plasma NA were significantly higher in patients than in normal subjects under all conditions.Thus, in normal subjects xamoterol predominantly increased the slower heart rate at night with only a minor effect on the higher heart rate in the daytime, whereas it predominantly attenuated the daytime tachycardia induced by sympathetic stimulation in patients with heart failure.It is concluded that xamoterol tends overall to act as a-adrenoceptor antagonist during the day, especially in the daytime in patients with mild to moderate heart failure. Its antagonist rather than its agonist effect may account for the long-term efficacy of xamoterol in patients with mild to moderate heart failure.     

Peripheral nerve repair and grafting techniques: a review

In this review, various conventional nerve repair techniques including direct epineurial repair, grouped fascicular repair, fascicular repair, and nerve grafting are described. The indications for use, as well as the relative advantage and disadvantage, of each technique are discussed. The experimental and clinical evidence from a review of the pertinent literature does not demonstrate a significant difference in outcome of one method over the others. Surgical decisions should be made by a thorough evaluation of all aspects of the nerve injury and surgical methods. All nerve injuries cannot be repaired using only one type of nerve repair method. The surgeon should be familiar with all the techniques described and be prepared to use them under appropriate circumstances.     

Response of quiescent and total tumor cells in solid tumors to neutrons with various cadmium ratios

Purpose: Response of quiescent (Q) and total tumor cells in solid tumors to neutron irradiation with three different cadmium (Cd) ratios was examined. The role of Q cells in tumor control was also discussed.Methods and Materials: C3H/He mice bearing SCC VII tumors received continuous administration of 5-bromo-2′-deoxyuridine (BrdU) for 5 days using implanted mini-osmotic pumps to label all proliferating (P) cells. Thirty minutes after intraperitoneal injection of sodium borocaptate-¹⁰B (BSH), or 3 h after oral administration of dl-p-boronophenylalanine-¹⁰B (BPA), the tumors were irradiated with neutrons, or those without ¹⁰B-compounds were irradiated with gamma rays. This neutron irradiation was performed using neutrons with three different cadmium (Cd) ratios. The tumors were then excised, minced, and trypsinized. The tumor cell suspensions were incubated with cytochalasin-B (a cytokinesis-blocker), and the micronucleus (MN) frequency in cells without BrdU labeling (Q cells) was determined using immunofluorescence staining for BrdU. The MN frequency in total (P + Q) tumor cells was determined from tumors that were not pretreated with BrdU. The sensitivity to neutrons was evaluated in terms of the frequency of induced micronuclei in binuclear tumor cells (MN frequency).Results: Without ¹⁰B-compounds, the MN frequency in Q cells was lower than that in the total cell population. The sensitivity difference between total and Q cells was reduced by neutron irradiation. Relative biological effectiveness (RBE) of neutrons compared with gamma rays was larger in Q cells than in total cells, and the RBE values for low-Cd-ratio neutrons tended to be larger than those for high-Cd-ratio neutrons. With ¹⁰B-compounds, MN frequency for each cell population was increased, especially for total cells. This increase in MN frequency was marked when high-Cd-ratio neutrons were used. BPA increased the MN frequency for total tumor cells more than BSH. Nevertheless, the sensitivity of Q cells treated with BPA was lower than that in BSH-treated Q cells. This tendency was clearly observed in high-Cd-ratio neutrons.Conclusion: From the viewpoint of enhancing the Q-cell sensitivity, tumors should be irradiated with high-Cd-ratio neutrons after BSH administration. However, normal tissue reaction remains to be examined because of its low tumor-to-normal tissue and tumor-to-blood biodistribution ratios.     

The local spread of lower bile duct cancer: evaluation by thin-section helical CT

This study illustrates the local spread of lower bile duct cancer with thin-section helical CT in correlation with the surgical and pathological findings. Pathologically, 16 patients had pancreatic invasion, 4 had small bowel mesentery invasion, 7 had extrapancreatic nerve plexus invasion, and 3 patients had vascular invasion. On thin-section helical CT, pancreatic invasion was correlated to the clarity or non-clarity of the bile duct mass-pancreas border and the presence of an intrapancreatic mass. Cases with small bowel mesentery and extrapancreatic nerve plexus invasion showed mass or stranding around the superior mesenteric artery and/or inferior pancreatoduodenal artery. Vascular invasion was seen as tumor contiguity to these vessels. Received: 28 September 1998; Revised: 30 December 1998; Accepted: 2 April 1999     

Stress coping strategy in Japanese patients with eating disorders: relationship with bulimic and impulsive behaviors

Although maladaptive coping strategies in eating disorder patients have been reported, the relationship between impulsivity and coping strategy has not previously been studied. Subjects consisted of 43 patients with anorexia nervosa restricting type (AN-R), 42 patients with anorexia nervosa binge eating/purging type (AN-BP), 71 patients with bulimia nervosa purging type (BN), and 97 controls. The Coping Inventory for Stressful Situations was used to evaluate coping strategies. Only AN-BP patients had a significantly lower task oriented-coping score than controls, and AN-R and BN patient groups used significantly less social diversion-avoidance coping strategies than controls. Emotion-oriented coping scores of AN-BP and BN patients were significantly higher than those of controls. In addition, impulsive BN patients had significantly higher emotional coping scores than less impulsive BN patients. These results suggest that maladaptive coping strategies may be a perpetuating factor even for impulsive patients and emphasizing a change in maladaptive coping strategies may be a useful treatment strategy even for highly impulsive patients.     

Long-term effect of polystan monocusp ventricular outflow patch after right ventricular outflow tract reconstruction

Forty-eight patients who underwent right ventricular outflow tract reconstruction with Monocusp Ventricular Outflow Patch (MVOP) fifty-five times and survived surgery, were reviewed in this study. Mean age at surgery was 6.4 years-old and mean follow-up interval was 75.2 months. There was no late death, however reoperation was performed 7 times. Freedom from reoperation rate was 97.2% and 80.7% after 5 and 10 years after surgery, respectively. The main cause for reoperation were right ventricular outflow obstruction RVOTO (5 cases). All of the RVOTO occurred at the distal end of the anastomosis. However, there was no RVOTO in patients who underwent RVOTR with MVOP during the past ten years. So, we considered the cause of RVOTO a technical problem. Pulmonary regurgitation was one to two degree early after surgery, and had worsened by almost two or three degrees more than 5 years after surgery. Moreover, five of six patients who underwent cardiac catheterization more than 10 years after surgery had three degrees of pulmonary regurgitation as well as a large CTR. In conclusion, according to long-term results, especially more than 10 years post operatively, pulmonary regurgitation was the most important problem.