Pharmacological effects of concomitant administration of β-adrenoceptor blocker and agonist in normal subjects: characterization by heart rate response to exercise

The effects of a combination regimen of metoprolol and ₁-adrenoceptor agonist denopamine on resting and exercise heart rate have been studied in 10 normal volunteers. Maximal ramp upright bicycle exercise was performed three times at 1-week intervals. Two hours before each exercise test, 5 mg metoprolol plus 20 mg denopamine, 5 mg metoprolol plus a denopamine placebo, or two placebos were orally administered in a double-blind fashion.During exercise after placebo administration, heart rate increased in parallel with the exercise intensity. Compared to the placebo values, resting heart rate was significantly decreased by an average of 10 beats · min^–1 by 5 mg metoprolol, whereas it was not altered by the combination regimen. During exercise, however, both the combination regimen and metoprolol alone showed a significant negative chronotropic effect, decreasing peak exercise heart rate by an average of 14 and 21 beats · min^–1, respectively. Peak oxygen uptake was also significantly decreased by both regimens.We conclude that concomitant administration of 5 mg metoprolol and 20 mg denopamine exerts an effective -adrenoceptor blocking action during exercise but a minimal effect at rest in normal subjects. The combination regimen appears to have a favourable pharmacological profile for -adrenoceptor blocker therapy in patients with chronic heart failure.     

Poorer nutritional status of the older-generation in a Japanese farming village, as related to fewer types of food consumed

This study was carried out to determine whether the most recent nutritional improvements in Japanese farming villages were due to improvement in the diet of the young only or across all ages. Food duplicates for 24 h were collected. The number of food items and the adequacy of each nutrient level were compared between subgroups, by age of cooking and those eating meals. The older-generation used and ate fewer food items resulting in poorer nutrition. The most recent improvement in nutrition in the farming villages of Japan was found mainly to affect the younger-generation with the older-generations being more poorly nourished.     

The available period and kind of exercise for increasing osteo sono assessment index in women

PURPOSE: The purpose of this study is to determine the optimum period and kind of exercise which are more effective for increasing the calcaneus osteo sono assessment index (OSI) in adolescent women. METHODS: The subjects consisted of 600 female students aged from 19 to 21 studying at the Department of Food and Nutrition at Nakamura Gakuen University. The calcaneus OSI was measured by ultrasonic bone absorptiometry. The factors associated with an increased OSI were determined using piecewise linear regression analyses. RESULTS: Experience in performing impact-loading exercise either in junior high school or high school was found to be a significant predictive factor for increased calcaneus OSI after adjusting for age and weight. Regarding other exercise-related factors such as subjective intensity, frequency, hours at a time, and total duration of exercise, a piecewise liner regression analysis showed that a total duration of over 7 yr and a high subjective intensity of the impact-loading exercise during high school and junior high school periods caused a significant increase in the calcaneus OSI. However, the OSI decreased when the subjective intensity of the impact-loading exercise during the high school period was reported to be "very strenuous." CONCLUSIONS: Impact-loading exercise in junior high school and high school is important for increasing calcaneus OSI; however, impact-loading exercise in high school with a "very strenuous" subjective intensity was also found to possibly decrease the calcaneus OSI.     

Childhood multiple sclerosis and allied demyelinative diseases

We report five cases of multiple sclerosis (MS) and three cases of allied demyelinative diseases starting during childhood. Three of the MS patients presented with atypical initial symptoms, such as acute encephalitis or myelitis, making an early clinical diagnosis difficult. Ophthalmologic symptoms were noted in four of MS children, and in two with allied demyelinative diseases. Therefore, if a child shows ophthalmologic symptoms (i.e. optic neuritis, ophthalmoplegia), brain magnetic resonance imaging (MRI) should be conducted for the differential diagnosis of MS and other demyelinative diseases. Cerebrospinal fluid analysis is not useful for the initial diagnosis of MS, because pleocytosis and increase of oligoclonal IgG band in cerebrospinal fluid are seen in both MS and other demyelinative disorders. However, neuron specific enolase (NSE) is slightly higher in the latter than in the former. T2-weighted MRI of multiple sclerosis showed multiple high intensity areas in the white matter of the cerebrum and cerebellum, capsula interna, and crus cerebri etc. Most of these lesions were clinically silent, being characteristic of MS. In two MS cases, however, initial MRI revealed no abnormal findings. Thus, the diagnosis of MS can not be made by initial MRI only.     

High inducibility of Epstein-Barr virus replication in B lymphocytes in Vogt-Koyanagi-Harada disease]

PURPOSE: The role of Epstein-Barr virus (EBV) reactivation in the pathogenesis of Vogt-Koyanagi-Harada (VKH) disease was examined. MATERIAL AND METHODS: Using B lymphocytes obtained from 8 patients with VKH disease and 10 patients with other types of uveitis, immortarized lymphoblast lines were established and infected with EBV. The degree of EBV activation in each lymphoblast line, in the presence and absence of various stimuli, was assessed by measuring the expression of 3 different antigens involved in replication by immunofluorescent staining and western blot analysis. Quantification of EBV DNA in cell culture supernatants was done by polymerase chain reaction. RESULT: Cell lines established from VKH patients expressed more viral antigens that those established from patients with other types of uveitis. There were greater amounts of EBV DNA in the VKH cell lines. CONCLUSION: B lymphocytes from VKH patients may be more susceptible to EBV activation, and the reactivation of EBV may be involved in the pathogenesis of VKH.     

Plasminogen activator inhibitor 1 in central serous chorioretinopathy

PURPOSE: To describe the plasma level of plasminogen activator inhibitor 1, the major antifibrinolytic agent, in eyes with central serous chorioretinopathy, in which choroidal thrombosis is suspected as the underlying condition based on the findings of choroidal hyperpermeability in indocyanine green angiograms. METHODS: Plasminogen activator inhibitor 1 concentrations in the plasma of 17 patients with central serous chorioretinopathy were measured by enzyme-linked immunosorbent assay and compared with those in 12 age-matched normal volunteers. RESULTS: The plasma levels of plasminogen activator inhibitor 1 in patients with central serous chorioretinopathy (range, 25 to 439 ng/ml; median, 87 ng/ml) were significantly increased compared with those in normal volunteers (range, 7 to 84 ng/ml; median, 36 ng/ml) (P = .0013, Mann-Whitney U test). CONCLUSION: Increased plasminogen activator inhibitor 1 concentrations in patients with central serous chorioretinopathy support the hypothesis that the choroidal hyperpermeability disclosed by indocyanine green angiography is caused from impaired fibrinolysis and the resulting thrombotic occlusion in the choroidal veins.     

A mild transient decrease of peripheral red blood cell counts induced by a suprapharmacological dose of pegylated human megakaryocyte growth and development factor in rats.

Previous studies have shown that pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) at suprapharmacological dose induces a mild transient decrease of red blood cell counts according to thrombopoiesis in normal mice. To unravel the mechanism underlying this mild transient decrease of red blood cells, we have studied the effect of PEG-rHuMGDF on the circulating plasma and blood volume, and the serum biochemical parameters of anaemia and splenectomy. Also, we have performed histological studies of the bone marrow and the spleen of PEG-rHuMGDF-treated rats. PEG-rHuMGDF (300 microg kg(-1)]) or vehicle was subcutaneously administered to rats once a day for up to five days. From day 6 after the start of PEG-rHuMGDF administration, the platelet counts and plateletcrit levels were significantly increased, reaching peak values on day 10, and recovering to normal by day 20. The red blood cell counts and the haematocrit levels were significantly decreased on day 6 to 13. The decreases in red blood cell levels and haematocrit produced by PEG-rHuMGDF treatment were mild and had recovered by day 15. The plasma and blood volumes were significantly increased on day 10 in PEG-rHuMGDF-treated rats. No alteration of the serum biochemical parameters for anaemia, iron or total bilirubin, were observed on day 10. The histological examination on day 10 revealed a marked increase in megakaryocytes and a slight decrease in erythropoiesis in the bone marrow of rats that received PEG-rHuMGDF (300 microg kg(-1)). There was also a slight increase in splenic megakaryocytes and erythropoiesis. The decrease of red blood cells by PEG-rHuMGDF was not affected by splenectomy. These results suggest that the mild transient decrease of red blood cells induced by PEG-rHuMGDF treatment for up to five days is based mainly on the increases in the plasma and blood volume. These events are secondary changes due to the regulation of the excess production of megakaryocytes in the marrow and the peripheral platelets.     

The studies of hemodynamic changes and liver uptake in a combination of ATP stress test and low workload exercise test on myocardial scintigraphy

A pharmacological adenosine-tri-phosphoric acid (ATP) stress test has been used in patients who can not perform an enough exercise stress test. However, falling blood pressure during the stress test and increased liver uptake of the tracer are often found in patients undergoing the ATP test. To prevent these phenomena, a combination of ATP stress test and low workload exercise test (ATP & EX) is proposed. The usefulness of this newly developed stress test was elucidated from two viewpoints. Firstly, the changes of hemodynamic parameters were measured in 34 patients: 17 undergoing ATP alone and 17 undergoing ATP & EX. Systolic blood pressure fell from 150 +/- 20 mmHg to 126 +/- 16 mmHg (p < 0.05) for ATP alone. However, it changed from 141 +/- 19 mmHg to 149 +/- 31 mmHg (ns) for ATP & EX. There was a significant fall in systolic blood pressure (> 30 mmHg) in 58.8% for ATP alone and 5.9% for ATP & EX (p < 0.01). Secondly, the ROI count in the liver and heart on an anterior projection image were measured in 38 patients: 11 undergoing ATP alone, 13 undergoing ATP & EX, and 14 undergoing an ergometer exercise test (EX). The ROI count in the liver at 60 minutes after tracer injection were 29.0 +/- 10.7 count/pixel, 21.4 +/- 5.2 count/pixel, 18.3 +/- 4.5 count/pixel for ATP alone, ATP & EX and EX, respectively. The activities for ATP & EX and EX were lower than that for ATP alone (p < 0.05 and p < 0.01). Thus, ATP & EX decreased the rates of the fall of systolic blood pressure and decreased liver uptake of the tracer compared with ATP alone. In conclusion, ATP & EX is a useful stress method for myocardial perfusion scintigraphy in patients who can not perform the enough exercise stress test.     

A residual cystic lesion in acute disseminated encephalomyelitis

We report a case of acute disseminated encephalomyelitis (ADEM) with a residual cystic lesion on MRI. This seemed to be induced by Japanese encephalitis vaccination. Despite complete clinical improvement with high-dose steroid therapy, the cystic lesion has persisted for 3 years on MRI. There have been no previous reports of residual cystic lesions in ADEM. Received: 20 August 1999/Accepted: 11 November 1999     

Histopathological grading and clinical features of patients with mucoepidermoid carcinoma of the salivary glands]

In the 22 years between March 1979 and February 2001, we treated 16 patients--10 men and 6 women aged 10-80 years (mean: 44 years)--with mucoepidermoid carcinoma (MEC) of the salivary gland, evaluating them clinically and histopathologically. Tumor sites included 12 at the parotid gland, 3 at the submandibular gland, and 1 at the minor salivary gland. All tumors were graded histopathologically based on the criteria of Goode et al. as follows: low grade (n = 10), intermediate grade (n = 1), and high grade (n = 5). Female gender was associated with low grade MEC and male gender with high grade MEC (P < 0.05). The age at onset in high grade MEC was older than that in low grade MEC (P < 0.005). Lymph-node metastasis was detected in 7 out of the 16 patients (44%) associated significantly with high grade MEC (P < 0.05). Distant metastasis was detected in 4 of 16 patients (25%). Distant metastasis was significantly associated with high grade MEC (P < 0.05). Local recurrence was detected in 3 of 15 patients undergoing surgery (20%). No difference was seen in local recurrence frequency between low and high grade MEC. Survival was calculated with Kaplan-Meier's method. In all 16, 5-year survival was 86% and 10-year survival 75%. Five-year survival in low grade MEC was 100%, whereas that in high grade MEC was 67% (P < 0.05). In MEC of the salivary gland, it was suggested that the histopathological MEC grade evaluated by Goode's criteria significantly correlated with gender, age, lymph-node metastasis, distant metastasis, and 5-year survival.