COMPARISON OF THE RELAXANT EFFECTS OF DIAZEPAM, FLUNITRAZEPAM AND MIDAZOLAM ON AIRWAY SMOOTH MUSCLE

The mechanisms by which benzodiazepines produce muscle relaxationand respiratory depression are not know, but they may includeactions on peripheral benzodiazepine receptors or central GABAreceptors, or a direct action on airway smooth muscle may alsobe involved. We have compared, therefore, the effects of diazepam,fluni-trazepam and midazolam on airway tone by measuring isometrictension of guineapig trachealis muscle. Cumulative concentrationsof diazepam, flunitrazepam and midazolam caused concentration-dependentrelaxation of resting tone in the tracheal smooth muscle withno significant differences in pD₂ values (–log EC₅₀anindex of potency) or intrinsic activities (% of maximum response)for relaxations for the three compounds. Pretreatment with propranolol10^–6 mol litre^–1, flu-mazenil 1O^–7 and 1 C^–6mol litre^–1 or PK11195 10^–6 mol litre^–1 hadno effect on diazepam- or midazolam-induced relaxation. Diazepam3x Ky6 10^–6 mol litre^–1pretreatment shifted theconcentration-response curves for acetylcholine, histamine andserotonin (5-HT) to the right by a factor of approximately 2.Flunitrazepam 3 x 10^–6 mol litre^–1 pretreatmentalso shifted the curves for histamine and 5-HT similarly tothe right, whereas midazolam pretreatment did not inhibit anyagonist-induced contractions. These results suggest that benzodiazepinesrelax airway smooth muscle, not via neural pathways or centraland peripheral benzodiazepine receptors, but by a direct actionon airway smooth muscle.     

Kinetic analysis of propranolol-induced impairment of its own metabolism in rats

Abstract— The effect of repetitive oral administration of propranolol (100 mg kg^?1 day^?1, 5 days) on the kinetics of liver microsomal propranolol metabolism was investigated in the rat. V_max values of the high-affinity phase for biphasic kinetics of propranolol 4- and 5- hydroxylase activities were decreased by propranolol pretreatment, while those of the low-affinity phase were unchanged. The V_max value of monophasic 7-hydroxylase activity was also decreased. On the other hand, the V_max value of N-desisopropylase activity in the propranolol-treated rats was increased more than 2-fold compared with non-treated (control) rats, resulting in a change from monophasic in control rats to biphasic kinetics in propranolol-treated rats. These findings indicate that repetitive administration of propranolol selectively impairs a CYP2D isozyme that is involved in the high-affinity phases for propranolol ring-hydroxylations.     

Testicular metastasis from squamous cell carcinoma of the lung

We present a case of squamous cell carcinoma of the testis that metastasized from lung cancer. The patient, who had received left pneumonectomy 2 years earlier for squamous cell carcinoma (SCC) of the lung, developed pulmonary metastasis, which was treated with chemotherapy. Although the recurrence regressed after treatment, the testicular tumor progressed gradually. Left radical orchiectomy was performed. Pathological examination revealed metastatic SCC. Testicular metastasis from lung cancer is a very rare disease.     

Correlation between Dose and Tumor Response in the Radiotherapy of Lung Cancer of Various Histological Types

Correlation between dose and tumor response by cell types wasdetermined in 50 patients with lung cancer in order to predictthe possibility of further tumor regression. The TDF (time-dose-fractionation)concept was used as dose factor. The radiation source was a cobalt-60 -ray or linear accelerator10 MV X-ray. As a routine regime a fraction dose of 2 Gy fivetimes per week was given to 39 of the 50 patients, but a doseof 2 Gy three times per week or of 1.5 Gy five times per weekwas given to seven and four patients, respectively. Radiation response was the best in small cell carcinoma andbetter in adenocarcinoma than in squamous cell carcinoma, showinga tumor regression rate of 50% or more in 90%, 80% and 58% ofthe patients, respectively. The correlation between tumor regression rate and TDF valueswas good in squamous cell carcinoma (r=0.73) and small cellcarcinoma (r=- 0.72), but poor in adenocarcinoma (r=- 0.10).These results suggest that in squamous cell carcinoma improvementof tumor regression can be expected by increasing TDF values,and in adenocarcinoma and small cell carcinoma the optimal TDFvalues are about J00 and 60 to 80, respectively.     

Comparison of Survival of Patients With Lung Cancer Between Elderly (greater double equals70) and Younger (70>) Age Groups

Results of radiotherapy for lung cancer in the elderly werecompared with those in younger patients. A total of 129 patientswere treated by radiation therapy with or without chemotherapy.Fifty-six patients (43.4%) were 70 years old or more (elderlygroup) at the time of treatment, and the remaining 73 patientswere below age 70 (younger group). Treatment results in the elderly group were nearly the sameas those in the younger group in all stages of the disease.Survival time was longer for patients with performance status(PS) of 0 to 2 than for those with PS 3 or 4 regardless of age(p < 0.05). The survival time of the elderly group was nearlythe same as that of the younger group for squamous cell carcinoma,but somewhat shorter for adenocarcinoma although the differencewas not statistically significant. There was no difference insurvival between the two groups when they were treated by combinedradiation therapy and chemotherapy. Our results suggest thatelderly patients can be treated as safely as younger patientsby radiotherapy alone or combined radiation therapy and chemotherapy.     

Difference in Prognosis between T- and B-Cell Lymphomas: Clinical Study at Shikoku Cancer Center Hospital

In order to determine whether the surface marker phenotypesof non-Hodgkin's lymphomas affect the prognosis, we have studiedthe differences in response rate and duration of survival betweenT- and B-cell lymphomas. Sixty-four patients who underwent first-linetherapy, including combination chemotherapy and/or radiotherapy,from February 1979 to August 1985 were evaluated. With the aidof standard immunological methods and monoclonal antibodiesrelated to T-cells and B-cells. 21 T-cell lymphomas and 21 B-celllyrnphomas were identified. In the other 22 cases phenotypeswere not determined mainly because of the inability to obtainfresh samples. The complete remission rate was 100% for B-celllymphomas and 52.3% for T-cell lymphomas. The median survivaltime for patients with lymphomas of Stage III and IV. excludingthose with low-grade histology, was nine months for T-cell lymphomasand 17 months for B-cell lymphomas. T-cell lymphomas were foundto have significantly poorer prognosis than B-cell lymphomas.One patient with B-cell lymphoma and six patients in an undeterminedphenotype group, who were treated with combination chemotherapy,have been alive more than three years without relapse and thesepatients are considered potentially cured. Our results suggestthat the surface marker phenotype study of lymphoma cells aswell as histological subtying is important in prognosis andthat more effective therapy is needed to improve the prognosisof T-cell lymphomas.     

Correlation Between Disappearance of the Intrahepatic Bile Ducts and Histologic Changes in the Liver in Primary Biliary Cirrhosis

Statistical investigations indicate that disappearance of bile ducts, estimated by a histometric method, was more extensive in symptomatic than in asymptomatic patients with primary biliary cirrhosis. The extent and degree of intrahepatic bile duct disappearance in PBC is related to the degree of copper granule deposition in the hepatocytes, the degree of atypical ductular proliferations and the fibrous septa formation. Bile plug formation and chemically determined copper content are not so well related to the bile duct disappearance, while periportal lymphoid cell infiltration is not related to the degree or extent of bile duct disappearance at all.     

Suppressive effect of perinatal testes on the differentiation of fetal ovaries transplanted into adult males in the rat

A 14 d ovarian primordium was transplanted with a fetal testis (13–18 d and 21 d of gestation) or a neonatal testis (15, 20, 30 and 45 d after birth) into the renal subcapsular position of an adult male rat. Two weeks after transplantation, transplants were examined as to the degree of ovarian and testicular differentiation. In the combination of a 14 d ovary and a 13 d testis, there were 3 types of result: either the ovary or the testis alone developed or both gonads developed well. Ovaries transplanted in union with 15–18 d testes did not develop, although the testes developed normally. Some ovaries in union with 21 d testes developed normally. In combination with infantile testes, the incidence of developed ovaries increased as the age of testes advanced. These results suggest that the 13 d fetal testes begin to suppress the development of cotransplanted 14 d ovaries, that 14–18 d fetal testes maintain such suppressive effects and that this effect gradually diminishes in infantile testes as they progress toward 45 d after birth.     

Ageing reduces sympatho-suppressive response to head-out water immersion in humans

Muscle sympathetic nerve activity (MSNA) is suppressed during thermoneutral head-out water immersion (HOI) in humans. In this study, the effects of ageing on the suppressive response of MSNA to HOI were determined. MSNA was recorded microneurographically from the tibial nerve in 16 healthy men, 10 of whom were aged 19–30 years (young group) and six aged 45–67 years (older group). MSNA was suppressed in all the subjects during HOI. The suppressive response was significantly less prominent in the older group than in the young group. A significant negative correlation between age and the suppressive response of MSNA induced by HOI (r=-0.53, P<0.05) was found. We conclude that suppressive response of sympathetic nerve activity to HOI is reduced with age.