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Status of treatment of vascular dementia.

The therapeutic goal in treating vascular dementia has been based on its presumed association with cerebral arteriosclerosis. Therefore, it is necessary to control risk factors for arteriosclerosis. In this connection, application of platelet-aggregating substances has been used extensively. Promising results have also been observed by altering the hemorheologic profile because hemorheologically active substances may be able to ameliorate the course of vascular dementia. Further improvement could be achieved by application of the HELP system to enhance the effect of hemorheologically active drugs. Using the HELP system, LDL, cholesterol, triglycerides and fibrinogen can be lowered considerably and may result in clinical improvement or slowing of the progression of vascular dementia.

Anticoagulants↗

Medical therapy of cerebral ischemia. Vasoactive and eumetabolic therapy.

After briefly evaluating the contraindications and indications of vasoactive and eumetabolic therapy of cerebral ischemia, the paper considers the main drugs at present in use in therapy of the syndrome induced by diffused cerebral arteriosclerosis. Among the drugs with a mainly vasoactive effect, consideration is given in particular to nifedipine, cetiedil and nicergoline, which induced not only an improvement in the subjective symptoms, but also an increase--which was notable at times--in the sphygmic amplitude of the rheoencephalogram. Where drugs with a mainly eumetabolic action are concerned, xanthinol nicotinate, vincamine and (-)eburnamonine are discussed. The latter, in particular, proved effective in improving intellective recovery and mediate and deferred memory, accompanied by a fair increase in the sphygmic speed and amplitude on the rheoencephalogram.

Brain Ischemia↗

Familial young-adult-onset arteriosclerotic leukoencephalopathy with alopecia and lumbago without arterial hypertension.

Here we review a total of 17 patients, including 4 of our own, with young-adult-onset arteriosclerotic leukoencephalopathy, alopecia and lumbago without hypertension. All were Japanese and the illness seemed to be transmitted in an autosomal recessive fashion. The male to female ratio was 7.5:1. The age of onset usually ranged from 25 to 30 years. Acute lumbago, spondylosis deformans, diffuse baldness, and progressive motor and mental deterioration were common clinical features. Cerebral arteriosclerosis and white mater disease were demonstrated pathologically or radiologically. Although the pathogenesis has remained obscure, we think this is a new clinico-pathological entity distinct from the classic type of Binswanger's disease.

Adult↗

The physical and behavioural complex of dementia.

An inquiry was made into the physical and behavioural problems presented by patients admitted to hospital because of dementia. 81 patients were studied over a period of 3 years, and a comparison was made between the 38 with idiopathic (Alzheimer's) dementia, and the others, most of whom suffered from focal cerebral arteriosclerosis or Parkinson's disease with dementia. The average age was between 70 and 80 years, and the hospital stay averaged 18-28 months. Nursing difficulties ranged from immobility of the patients on the one hand to wandering on the other, especially in the Alzheimer's group. Behaviour disturbances, shouting, incontinence and degenerate habits were found in a high proportion and the incidence of fractures reached 15%. Vascular incidents as complications or causes of death were relatively uncommon; in those who died, the cause was usually infection. The mainstays of treatment were tranquillising drugs, used only when necessary, and in minimal quantities, simple occupational activity, and an awareness by the staff of the high morbidity to which these patients were prone.

Aged↗

Effect of smoking on regional cerebral blood flow in the normal aged volunteers.

The effects of long-term cigarette smoking on regional cerebral blood flow (rCBF) were studied in 67 normal male volunteers. All subjects were healthy volunteers without any past history of cerebral and pulmonary disease. rCBF decreased significantly with advancing age. Although there was no significant difference in rCBF between young smokers and nonsmokers, elderly smokers showed significantly lower rCBF than elderly nonsmokers. There was no difference in vital capacity and FEV 1.0% between smokers and nonsmokers in both young and elderly groups. The smokers, however, showed significantly lower V50 than the nonsmokers. PeCO2 in smokers was significantly lower than in nonsmokers. No significant differences were seen in hematocrit, antithrombin III, aggregating platelet, serum lipids and blood pressure between smokers and nonsmokers in both age groups. There was a significantly positive correlation between rCBF and PeCO2 in all groups. These results suggest that long-term smoking may reduce rCBF by means of hypocapnia, resulting from latent small airway disturbances, not by advancing cerebral arteriosclerosis.

Aged↗

Cerebrovascular CO2 reactivity in normotensive and hypertensive man.

Cerebrovascular reactivity to CO2 inhalation and voluntary hyperventilation was studied in seven normotensive subjects and nine hypertensive patients without clinical or angiographical signs of arteriosclerosis. Cerebral blood flow (CBF) was measured by the intracarotid 133Xe clearance method and calculated as the initial slope index. Three to five CBF measurements were made in each patient in the PaCO2 range of 20 to 55 mm Hg. No difference was observed in reactivity between hypertensive and normotensive patients, either during CO2 inhalation or during hyperventilation. The shape of the CBF:PaCO2 curve suggested a decrease in reactivity below a PaCO2 of 30 to 35 mm Hg in both groups. Above a PaCO2 of 35 mm Hg, exponential regression analysis yielded a mean reactivity of 6 +/- 2%, whereas below a PaCO2 of 30 mm Hg it was about 2%. The rise in CBF during CO2 inhalation was not influenced by the intravenous infusion of a small dose of trimethaphan which blocked the concomitant rise in blood pressure.

Adolescent↗

The treatment of depressed geriatric patients.

Biological changes more frequently associated with late onset depressions, such as cerebral arteriosclerosis, increased urinary MHPG concentrations, decreased gonadal functions, and increased MAO activity were reviewed and the therapeutic implications of these biological changes considered. The rationale for the use of Hydergine, amitriptyline, Gerovitol H3, fluoxymesterone, doxepin, and trazodone in geropsychiatric patients was discussed.

Age Factors↗

Spindle activity in the waking EEG in older adults.

Sleep spindles are an EEG sign of light sleep under physiological conditions. We reported the simultaneous occurrence of sleep spindles and alpha activity in the waking EEG in 12 patients with a mean age of 59.0 years. Most of the patients were diagnosed as cerebrovascular disorders such as cerebral arteriosclerosis, transient ischemic attack and vascular dementia. The mean alpha frequency in the presence of WSA significantly decreased by 1.5 Hz. The frequency and spatial distribution of waking spindle activity were similar to those of sleep spindles. In our cases, at least the two factors of cerebrovascular involvement and older adults were considered to be primarily responsible for the intrusion of sleep spindles into wakefulness (presumably a state close to very light drowsiness) due possibly to the instability of sleep-waking cycle regulation.

Adolescent↗

A syndrome of misinterpreting role changes as changes of person.

A syndrome is described in three elderly women who all suffered from cerebral arteriosclerosis, and who in their dependent condition were looked after by their daughters. These women accepted their daughters as their daughters when carrying out directly caring tasks related to them, but spoke of them and addressed them as different women, with the same forenames as their daughters, when their daughters were engaged in other duties. This syndrome is compared with the syndromes of Capgras and similar conditions. It is likely to be detected with increasing frequency as psychiatrists become involved in the community aspects of the speciality.

Aged↗

Development of natural products as drugs acting on central nervous system.

We have recently studied several natural product constituents which have effects on the CNS. (1) Tetrahydropalmatine (THP) and its analogues were isolated from Corydalis ambigua and various species of Stephania. (+)-THP and (-)-THP possess not only analgesic activity, but also exert sedative-tranquilizing and hypnotic actions. Results of receptor binding assay and their pre- and post-synaptic effects on dopaminergic system indicate that (-)-THP and (-)-stepholidine are dopamine receptor antagonists while (+)-THP is a selective dopamine depletor. (2) 3-Acetylaconitine (AAC) is an alkaloid isolated from Aconitum flavum. The relative potency of analgesic action of AAC was 5.1-35.6 and 1250-3912 times that of morphine and aspirin, respectively. The analgesic effect of AAC was not antagonized by naloxone, but was eliminated by reserpine. In monkeys, after AAC was injected for 92 days, no abstinence syndrome was seen after sudden AAC withdrawal or when challenged with nalorphine. (3) Huperzine A (Hup-A) is an alkaloid isolated from Huperzia serrata which was found to be a selective ChE inhibitor and could improve learning and retrieval processes. Preliminary clinical studies showed that Hup-A improve short- and long-term memory in patients of cerebral arteriosclerosis with memory impairment. (4) Ranamargarin is a new tetradecapeptide isolated from the skin of the Chinese frog Rana margaratae. This peptide may mainly act on NK-1 receptor.

Amino Acid Sequence↗

Clinical features and management of adverse effects of quinolone antibacterials.

The quinolone antibacterials are proving very useful in the management of infection, notably for the treatment of Gram-negative bacteria. With the increasing use of these drugs, adverse effects are being recognised more often and careful documentation is still required. In general, the quinolones are of low toxicity. Gastrointestinal adverse effects are the most common, and are usually mild; indeed, all adverse events are generally mild and resolve on withdrawal of the offending drug. Certain precautions and contraindications are apparent. Because drug-induced arthropathies occur in juvenile animals, quinolones should not be administered to pregnant or lactating women or to growing children, unless the clinical benefit outweighs the risk. Caution should also be observed in patients with previous epilepsy or severe cerebral arteriosclerosis. Neurological effects may require the use of appropriate neuro- and psychoactive drugs, as well as the withdrawal of the precipitating agent. Hypersensitivity reactions to a fluoroquinolone may require the use of antihistamines, and in some cases topical or systemic steroids, and may well preclude future use of a fluoroquinolone. Dose adjustments may be necessary in patients with reduced renal function, when the measurement of serum concentrations may be desirable. Interstitial nephritis, haematuria and acute renal failure are rare effects of quinolone therapy which will require appropriate management including withdrawal of the precipitating drug. Interactions with theophylline and warfarin are of clinical significance, and may require plasma concentration monitoring and adjustment of dosage.

4-Quinolones↗

Indications for shunting in patients with idiopathic normal pressure hydrocephalus presenting with dementia and brain atrophy (atypical idiopathic normal pressure hydrocephalus).

The indications for shunt operation in patients with idiopathic normal pressure hydrocephalus accompanied by brain atrophy (atypical idiopathic normal pressure hydrocephalus: AINPH) were investigated in 25 patients who satisfied the diagnostic criteria and underwent ventriculoperitoneal (VP) shunting. All patients had no apparent history of intra- or extracranial disease; dementia and gait disturbance as the main complaints; moderate to severe cerebral atrophy and ventricular dilatation and at least periventricular low density around the anterior horn on computed tomography; normal cerebrospinal fluid (CSF) pressure and filling of ventricles or cortical surface space with contrast medium at 24 hours on cisternography. The 15 male and 10 female patients were aged 47-83 years (mean 60.4 years). VP shunting was effective in 12 improved patients and not effective in 13 unimproved patients according to NPH grading. Pathological pressure wave on epidural pressure monitoring was observed in eight of 12 improved patients, but none of 13 unimproved patients. CSF outflow resistance was 35.33 +/- 11.16 mmHg/ml/min in improved patients and 9.12 +/- 3.51 mmHg/ml/min in unimproved patients. Preoperative serum alpha-1-antichymotrypsin value (alpha-1-ACT) was 42.02 +/- 8.64 mg/dl in improved patients and 61.72 +/- 11.03 mg/dl in unimproved patients. Alpha-1-ACT over 55 mg/dl occurred only in unimproved patients. Cerebral arteriovenous difference of oxygen content value (c-AVDO2) before and after surgery was 6.34 +/- 0.9 ml% and 5.91 +/- 0.78 ml% in improved patients and 4.75 +/- 1.85 ml% and 4.81 +/- 1.73 ml% in unimproved patients, respectively. The two cases with preoperative c-AVDO2 value over 8.5 ml% were both unimproved. Mean cerebral blood flow value before and after surgery was 23.51 +/- 4.20 ml/100 g/min and 45.22 +/- 8.11 ml/100 g/min in improved patients and 21.77 +/- 5.12 ml/100 g/min and 24.82 +/- 4.97 ml/100 g/min in unimproved patients, respectively. Cerebral atrophy in improved patients is caused by a cerebral circulation disturbance defined as a cerebral blood flow of penumbra or more due to cerebral arteriosclerosis, etc. A flow-chart of indications of shunt surgery for AINPH was prepared based on the results of the present study.

Aged↗

Effect of pentoxifylline on red cell flexibility in arterio-sclerotic patients and in patients with heart valve prosthesis.

Red cell flexibility (RCF) was studied in 40 patients with severe occlusive arterio-sclerotic disease of the lower extremities (Group I) and in 17 patients with aortic or mitral valve prosthesis (Group II). RCF was studied in terms of rigidity and fragility using a filtration method. Pentoxifylline, which according to our previous observations increases the flexibility of red cells in healthy subjects, also markedly improved RCF in Group I, particularly in terms of fragility. The pentoxifylline-induced increase in RCF was less marked in Group II; only the rigidity parameter was significantly decreased. Reid et al [11] reported decreased deformability of red cells in patients with intermittent claudication. Since then a few other studies have been published, in which decreased red cell flexibility (RCF) was observed in patients with diabetic vascular disease [1, 4, 9, 12] and cerebral arteriosclerosis [10]. The objective of this study was to compare RCF in patients with widespread arteriosclerosis and heart valve prosthesis, the latter condition inducing a 'pure' mechanical red cell injury. Both patient groups were also studied after the administration of pentoxifylline, a drug known to improve the flexibility of normal red cells--see [6].

Adult↗

[A clinicopathological study of senile dementia of Alzheimer's type (SDAT) and white matter lesions of Binswanger's type].

A clinicopathological study of senile dementia of Alzheimer's type (SDAT) accompanied by the white matter lesions of Binswanger's type was carried out. Fifty-seven patients, who were diagnosed as suffering from SDAT based on clinical and pathological criteria, were classified into two groups based on the white matter lesions of Binswanger's type. Namely, group 1 consisted of the SDAT patients without any subcortical or white matter lesions (30 cases); group 2 consisted of those with white matter lesions of Binswanger's type (11 cases). The other 9 cases included those with vascular lesions and 4 with some of the same pathological changes found in Parkinson's disease. Clinically, group 2 patients showed subcortical symptoms such as urinary incontinence, Parkinsonian gait, being accompanied by hypertension and arrhythmias. Periventricular lucency (CT) were common in group 2. Macroscopically, both groups showed moderately to severe atrophy, and the width of the corpus callosum of group 2 was narrower than that of group 1. There was no difference in cerebral arteriosclerosis between the groups. In microscopic findings, patients in group 2 showed diffuse distribution of cortical changes such as senile plaques as well as Alzheimer's senile plaques as well as Alzheimer's neurofibrillary tangles while those in group 1 showed various types of diffuse or local distribution. Arteriolosclerosis of the white matter were found in both groups. There was no difference in aortic atherosclerosis and/or heart disease. The complication of white matter lesions of Binswanger's type was not a rare finding in SDAT.

Aged↗

Essential (hereditary or senile) tremor.

Sixteen cases (eight in males and eight in females) of essential (hereditary or senile) tremor were collected over a two-year period. Ten patients had near relatives with a similar disorder. All but one patient had a tremor of the upper limbs which was absent when the arms were at rest, but which appeared on movement, and was made worse by emotion. The severity of the tremor varied considerably from patient to patient, and often was temporarily lessened by alcohol. The tremor involved the head and neck in six subjects and the legs in two. One subject has associated neurological abnormalities probably due to cerebral arteriosclerosis. Otherwise no neurological abnormality except tremor was present in any patient. No patient showed evidences of Parkinsonism. To the time of collection of the series the tremor had been present for periods of between one and 62 years. Many patients with essential tremor are not severely enough affected to warrant therapy. Propranolol, a beta-adrenergic blocking agent, appears to reduce the tremor in at least some patients who need treatment.

Adolescent↗

[The occurence of multiple diseases in high-aged patients (author's transl)].

Analysis of 1385 autopsies of 80-102 year-old patients was performed to investigate the frequency of simultaneous occurence of the following functionally pertinent diseases in one organism (polypathia): Severe aortic, coronary and cerebral arteriosclerosis, chronic pulmonary emphysema, contracted kidneys, fractures of the femur and malignant tumors. 80% of all patients of both sexes suffered from 2-4 of the above diseases. Even in the highest age group, however, 5 and more of the above diseases were very rarely developed. Patients with none of the above diagnoses were almost never encountered. The "polypathia" was stated also in patients who died by suicide or accident.

Aged↗

Ethyl apovincaminate therapy in neurovascular diseases.

Of a series of 100 patients 46 were given combined (i.m. and oral) treatment with ethyl apovincaminate (RGH-4405, Cavinton) in daily doses of 10-30 mg; 54 were put on oral Cavinton (30-45 mg daily). Significant and relatively quick improvement was obtained in reversible vascular diseases, such as hypertensive encephalopathy, intermittent vascular cerebral insufficiency, in the early stage or light cases of cerebral endarteriitis and cerebral arteriosclerosis. On Cavinton effect hypoxic character of the EEG improved, and so did performance in psychodiagnostic tests, alertness and memory in the first place, furthermore changes of the eyeground. The doses administered did not damage parenchymal organs, they did not cumulate and when used in combination incompatibility could not be observed.

Cerebrovascular Disorders↗