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[CLINICAL STUDY OF CR 121 IN A HOSPITAL SERVICE].
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[APROPOS OF THE INCIDENCE OF ATHEROSCLEROSIS IN DIENCEPHALIC LESIONS].
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[OBJECTIVES OF THE EFFECT OF DRUGS ON CEREBROVASCULAR PROCESSES].
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[Psychiatric disorders of vascular genesis in women who committed crimes].
56 women having cerebral arteriosclerosis and arterial hypertension and committed crimes were observed. Serious psychic derangements such as chronic delirious psychoses, weak-mindedness, short-term mental conditions were regular features among aggressive women committing crimes. General medical practitioners are recommended to have such patients consulted by the psychiatrist.
[Changes of hearing threshold in the elderly].
A 10-year and 5-year longitudinal study of the hearing threshold of the aged was performed during 1977-1987 and 1982-1987. The results showed that the annual hearing loss was 1.0dB in the 10-year group, 1.03dB in the 5-year group for males and 0.7dB in the 5-year group for females. Annual hearing loss in the aged with hypertension, hyperlipidemia, cerebral arteriosclerosis and diabetes was much higher than that in the healthy ones (P less than 0.05). The rates of hearing loss between 60 and 70 years of age was not significantly different among the healthy males (P greater than 0.05). In the 5-year group the hearing loss at 4-8k Hz was much milder in the healthy females than in the healthy male s (P less than 0.05).
Maprotiline (Ludiomil) treatment of mental depression--a clinical report of 65 cases.
Sixty-five cases of mental depression were treated with maprotiline (Ludiomil), including 46 cases of endogenous depression, 18 cases of neurotic depression and 1 case of depression in association with hypertension and cerebral arteriosclerosis. Ludiomil of 50-200 mg/d was given for 4 weeks and clinical pictures evaluated weekly. Clinical results showed complete recovery in 33 cases (50%), improvement in 22 cases (34%), fair in 7 cases (11%) and poor in 3 cases (5%). Dry mouth, constipation and faintness were the commonest side effects. Seizure occurred in 1 case and skin rash in 3 cases. The authors suggest that Ludiomil at a maximal dosage of 150 mg/d can be considered a relatively safe and effective antidepressant.
[Changes in glucose metabolism before and after the onset of focal cerebral ischemia. I. The intravenous glucose tolerance test].
In a group of 22 patients with focal ischemia of the brain and in 11 patients with cerebral arteriosclerosis and vascular hypertension the tolerance to glucose administered by the i.v. route was investigated. The rate of glucose utilization was expressed by a utilization coefficient. The tolerance to i.v. glucose administration is reduced in the group of arteriosclerotic and hypertensive subjects. As a result of acute focal ischemia of the brain it declines even more, as compared with subjects in the control group. In the mean values of the coefficient of glucose utilization a significant difference was recorded between the group of patients with focal ischemia of the brain, as compared with the control group (p less than 0.001) and the group of arteriosclerotic and hypertonic patients, as compared with controls (p less than 0.005). The authors conclude from the results that the reduced glucose tolerance to orally administered glucose in patients with focal ischemia of the brain and their potential candidates in no causal relationship with the variability of intestinal absorption, as similar changes in glucose tolerance were recorded also after intravenous administration.
Alzheimer's disease: evolving clinical concepts and management strategies.
The prevalence of Alzheimer's disease is rising dramatically. This increase results from a "graying" of our population and a redefinition of the term Alzheimer's disease. Alzheimer's disease is recognized to be a progressive neurologic disorder of unknown cause but is not associated with any increased cerebral arteriosclerosis as compared to age-matched controls. The course of the illness on average is about ten years. A variety of inclusion and exclusion criteria, if used conservatively, can accurately predict the pathologic diagnosis of Alzheimer's disease. Whereas no specific cause or clearly effective treatment is currently available, care consists of pharmacologic therapy aimed at specific symptoms and measures designed to reduce patient confusion and care-giver burden. The physician can benefit the patient and care giver by providing an accurate diagnosis, providing therapy where available, counseling the family, and providing referrals to available community-support services.
Multi-infarct dementia.
The participation of vascular disease in elderly dementia has been clarified to a significant degree in the past decade. The term multi-infarct dementia implies that severe mental impairment can result from thrombosis of large and medium arteries or from multifocal emboli of either cardiac or arterial origin. This is markedly different from the concept, which, unfortunately, is still the generally current view in the lay press, in some medical journals, and in advertisements of pharmaceutical companies, that gradual narrowing of cervical and cerebral arteries produces chronic hypoperfusion of the brain and is the basis of mental deterioration. This concept of generalized cerebral arteriosclerosis or arteriosclerotic dementia is no longer acceptable. Most patients with MID can be distinguished from those suffering from other types of dementia by employing a clinical ischemic score supplemented by electrophysiologic studies, CCT, and neuropsychological testing. Furthermore, the association of MID with severe hypertension and thromboembolism makes early diagnosis imperative, because appropriate treatment may arrest progression and even provide some improvement.
Clinical effects of oral cilostazol on suppression of platelet function in patients with cerebrovascular disease.
A new antithrombotic drug, cilostazol (6-[4-(1-cyclohexyl-1H-tetrazol-5-yl)butoxy]-3,4-dihydro-2(1H)-qui nolinone OPC-13013), was administered at daily oral doses of 75, 150 and 300 mg for 2 weeks in 15 patients with cerebrovascular disease including cerebral thrombosis, transient ischemic attacks and cerebral arteriosclerosis, and patient response was determined based on the degree of suppression of the platelet function. The antiplatelet-aggregating effect of the drug was determined by measuring the rate of inhibition of platelet aggregation induced by aggregation inducers such as adenosine diphosphate (ADP), collagen and epinephrine. The inhibition rates (percent difference between pre- and post-treatment rates/pre-treatment rate) obtained with the drug at 75 mg/day were 25.5, 36.5 (p less than 0.1) and 10.9% when platelet rich plasma (PRP) was added to ADP, collagen and epinephrine, respectively. The corresponding values at 150 mg/day were 34.2 (p less than 0.1), 50.7 (p less than 0.05) and 48.0% (p less than 0.1), and those at 300 mg/day were 62.1 (p less than 0.01), 71.7 (p less than 0.01) and 48.2% (p less than 0.1), respectively. The inhibitory effect of the drug thus appeared to be dose-related. Adhesiveness was also reduced by the drug, though a bleeding tendency was not indicated, and the reduction was found to be significant at 300 mg/day (p less than 0.05). The drug can, therefore, be considered to be a potent and safe antiplatelet-aggregating agent.
Antiaggregatory effect of oral cilostazol and recovery of platelet aggregability in patients with cerebrovascular disease.
A new antithrombotic drug, cilostazol (6-[4-(1-cyclohexyl-1H-tetrazol-5-yl)butoxy]-3,4-dihydro-2(1H)- qui nolinone, OPC-13013), was orally administered at 50, 100, 150 and 200 mg daily for four weeks to 24 patients with cerebrovascular diseases including cerebral thrombosis, cerebral embolism, transient ischemic attacks and cerebral arteriosclerosis. The drug effect on platelet aggregation induced by adenosine diphosphate (ADP), collagen, epinephrine and arachidonic acid and the recovery of platelet aggregation after drug withdrawal were monitored with time by determining the plasma concentrations of the drug. Prior to the repetitive administration study, the antiplatelet-aggregating effect of the drug was examined by single administration at 50 and 100 mg to six patients each. The dose of 50 mg was not sufficiently effective, but the dose of 100 mg significantly (p less than 0.05) reduced aggregation induced by collagen and arachidonic acid at 6 h suggesting the therapeutic value of the drug even by single administration. Following this study, the antiplatelet-aggregating effect of the drug was determined after four weeks of treatment. The pretreatment values for ADP-induced aggregation were 72.7, 72.1, 70.5 and 78.8% in the 50 mg/day (once daily), 100 mg/day (50 mg twice a day), 150 mg/day (50 mg three times a day) and 200 mg/day (100 mg twice a day) dosage groups, respectively. The aggregation rates determined after 4 weeks of treatment were 60.8, 56.8, 46.0 and 43.8%, respectively, and the values obtained at 100 mg/day or higher were significantly (p less than 0.05) low compared to the respective pretreatment values.(ABSTRACT TRUNCATED AT 250 WORDS)
Staining of minerals and solubility of iron in tissues.
Iron deposits in ethionine induced aortic siderosis of rats, in splenic deposits in sickle cell anemia and siderocalcific vessels in cerebral arteriosclerosis were completely removed by exposure to 20 percent hydrochloric acid for 30 min. This contrasted with idiopathic hemochromatosis and idiopathic pulmonary hemosiderosis in which the iron containing organs had to be exposed to 40 percent hydrochloric acid for two hours. The more soluble iron appeared colorless in unstained tissues, purplish blue with hematoxylin and eosin, turquoise blue with Perls' stain, violet blue with gallocyanin and dark-drown with sodium rhodizonate. The less soluble iron was golden yellow in unstained tissues. It appeared golden yellow with hematoxylin and eosin and sodium rhodizonate, but it stained greenish blue with Perls' method and dark brown with gallocyanin. Lead and copper were capable of deposition in some tissues in vitro in the presence of iron and/or calcium but not when these minerals were removed. This phenomenon may be of importance in certain pathological conditions, e.g. hemochromatosis, where on preexisting tissue-iron-complexes there is a secondary deposition of copper.
[Eutergin in the treatment of chronic cerebrovascular disturbance patterns (author's transl)].
After setting up a catalogue of complaints and signs for the most frequent disturbances of feeling tone of the patients suffering from cerebral arteriosclerosis, consisting of somatically subjective head pain and mental disturbances, treatment was given to 33 patients with cerebrovascular disturbances and 7 patients with similar, although non-vascular, disturbances (4 patients with presenile dementia, 3 patients with tinnitus in otosclerosis), the treatment consisting of eutergin 3 X 1 tablets to 3 X 2 tablets daily, the concomitant cardio-internistic medication remaining the same throughout the treatment course. The type and severity of the symptoms prevailing in each case were determined at the beginning, after 3 weeks and after 6 weeks of the medication with eutergin. It was found that improvement of the somatic-subjective head pain was more pronounced than that of the mental disturbances. Generally speaking, the disturbing somatic or mental signs were those which could be influenced better than the others. As far as the head pain was concerned, the feeling of giddiness, congestion in the head, rapid exhaustion, above all, tinnitus, responded best to the medication (the improvement amounting to approximately 40%), whereas of the mental complaints, a feeling of being "lost" or "abandoned" and a morose mood were most amenable to improvement (degree of improvement approximately 30%). The prevention of the delirogenic effect of antidepressives in senile depression was a remarkable effect; this means that effective antidepressive medication is made possible with the help of eutergin, EEG controls did not reveal any significant effects. There were no side effects. Elevated blood pressure levels showed a tendency to become normal without any dramatic drops. Hence, eutergin is recommended in all kinds of chronic cerebrovascular lesions, provided it is associated with concomitant cardiac and internistic treatment.
Cigarette smoking decreases cerebral blood flow suggesting increased risk for stroke.
Effects of chronic cigarette smoking on cerebral blood flow were investigated by measuring gray matter blood flow (Fg) using xenon 133 inhalation among 192 volunteers without cerebrovascular symptoms. There were 108 normal, healthy volunteers; 84 had risk factors for stroke (hypertension, hyperlipidemia, diabetes mellitus, and/or heart disease). Of both risk and nonrisk groups, 75 were habitual smokers (0.5 to 3.5 packs per day for 25 years). Comparisons of mean Fg values for both hemispheres showed significant reductions related to tobacco consumption and risk factors for stroke. Multiple-regression equations using smoking, age, risk, and alcohol consumption indicated a combined R2 value of 0.22. Smoking seems to be a potent risk factor decreasing cerebral blood flow probably by enhancing cerebral arteriosclerosis. Chronic cigarette smoking in persons with other risk factors further reduced Fg values in an additive manner when compared with subjects who had corresponding risk factors who did not smoke.
Clinical evaluation of GABA in the treatment of cerebrovascular disorders. Multi-center double-blind study in comparison with pyrithioxine and placebo.
The therapeutic efficacy of GABA was compared with pyrithioxine and placebo in 432 patients with cerebrovascular disorders by a multi-center (50 hospitals) double-blind clinical trial. 12 tablets (3 g) of GABA and 3 tablets (600 mg) of pyrithioxine were given daily for 8 weeks. Subjective complaints, neurological and psychiatric findings, activity of daily living were checked at the 4th and 8th weeks after medication. The global improvement rates in GABA-treated groups were 59% and 70% each after 4 and 8 weeks of medication, and were significantly superior to the other two groups. Especially on cerebral arteriosclerosis GABA was more effective than the other two drugs, with statistical significance. As for improvement rates of symptoms there were significant differences between GABA and the other two drugs in subjective complaints and in psychiatric findings. The incidence of side effects was 5%, 20% and 8% in GABA, pyrithioxine and placebo, respectively. The incidence of abnormal laboratory data was 2% (3 cases), 8% (11 cases) and 4% (6 cases), respectively. Those in GABA group were transient and restored to normal values after the trial. It is concluded from these results that GABA is safe and effective in the treatment of cerebrovascular disorders.
Clinical trials of plafibride in geriatric patients.
During a period of 15 days, 90 geriatric patients with various disturbances in blood lipids and manifestations of cerebral arteriosclerosis ingested 1200 mg/d of N-2-(p-chlorophenoxy)-isobutryl-N'-morpholinomethylurea (plafibride, ITA 104). Its significant activity in decreasing the pre-beta-lipoproteins and increasing alpha-lipoproteins was demonstrated. At the same time plafibride inhibited platelet aggregation by 50%. The activity of plafibride was compared to those of clofibrate and the inactive placebo. A similar experiment was carried out with 44 geriatric patients comparing the clinico-therapeutic and biochemical benefits of plafibride in relation to clofibrate and acetylsalicylic acid (ASA). Apart from the biochemical results, the symptomatologic and eletroencephalographical results of the patients treated with plafibride was more significant and positive than with the other drugs. Plafibride also showed better gastric tolerance and a lower incidence of collateral effects than did clofibrate and ASA.
[Hypertensive crisis and its treatment].
Sudden and large increase of the blood pressure may be life-threatening, particularly when they are accompanied by encephalopathy, left-ventricular insufficiency or other complications. The crisis of hypertension shall be treated possibly without loss of time and with energy. If there is the possibility for a permanent control of the patient, the infusion by drops of nitroprusside sodium is the therapy of choice. It at once decreases the blood pressure and is free of side-effects. Diazoxide has the advantage compared with nitroprusside sodium that an intravenous injection decreases the blood pressure for several hours. But the rapid and drastic decrease of blood pressure may occasionally be dangerous in patients with coronary insufficiency and cerebral arteriosclerosis. In certain indications also other medicaments, such as reserpine, alpha-methyldopa, phentolamine, saralasin or nifedipine can be applied. The crisis of hypertension is always to be regarded as an emergency situation, since always irreversible lesions may be appear on the different organs as a sequel of the permanent vasoconstriction and ischaemia.