Pyritinol for post asphyxial encephalopathy in term babies-- a randomized double-blind controlled trial.

OBJECTIVE: To evaluate the efficacy of pyritinol in improving the neurodevelopmental outcome at one year of age among term babies with post-asphyxial encephalopathy. SETTING: Level II Neonatal Nursery and Child Development Centre, Medical College, Thiruvananthapuram. DESIGN: Randomised placebo controlled double blind trial. PARTICIPANTS: 108 term babies with post-asphyxial encephalopathy, stratified into three grades based on clinical criteria. INTERVENTION: The treatment group (n=54) received pyritinol and the control group (n=54) received placebo, in exactly the same increasing dosage schedule of 1 to 5 mL liquid drug (20-100 mg) from 8th postnatal day until the end of six months. OUTCOME VARIABLES: Mean Mental Development Index (MDI) and mean Psychomotor Development Index (PDI) measured on Bayley Scales of Infant Development at one year of age. RESULTS: No statistically significant difference was observed in MDI or PDI scores at one year between the treatment and control groups. The confidence interval for the differences ranged from -6.3 to 8.7 for MDI and from - 4.1 to 12.7 for PDI. On multiple regression analysis using one year MDI and PDI scores, even after controlling for birthweight, there was no statistically significant difference between the treatment and control groups. CONCLUSION: Pyritinol is not useful in improving the neurodevelopmental status of babies with post-asphyxial encephalopathy at one year of age.

Vasodilators in senile dementias: a review of the literature.

The rationale for the use of vasodilators in the aged has changed from the attempt to increase cerebral blood flow to the attempt to improve cerebral metabolism. Review of 102 studies of eight vasodilators showed that significantly more controlled studies claimed practical clinical benefit from drugs supposed to improve neuronal intermediary metabolism with secondary vasodilatation than from drugs supposed to have only vasodilator action (P less than .005). Studies of both classes of drugs often suffered from poor study design, inappropriate and inconsistent application of outcome measurements, as well as negative bias due to selection of severely demented subjects. Future studies should be placebo-controlled investigations of drugs with primarily metabolic action, address questions of dose and time response, consistently use appropriate outcome measurement, and concentrate on the elderly in whom cognitive improvement is possible.

Activation PET as an instrument to determine therapeutic efficacy in Alzheimer's disease.

Forty patients with probable Alzheimer's disease (AD) were selected from a pool of 80 patients and assigned to 4 groups. Each received either social support, cognitive training only, or cognitive training in combination with pyritinol or phosphatidylserine. Treatment duration was 6 months. Before and after treatment the patients underwent neuropsychological testing as well as measurement of the regional cerebral metabolic rate for glucose using positron emission tomography (PET) and 2[18F]-fluoro-2-deoxy-D-glucose (FDG). Before treatment, the groups were comparable in respect to resting and activated glucose pattern achieved by a visual recognition task. They did not differ in scores of a neuropsychological test battery. After the treatment period the group with cognitive training + phosphatidylserine showed a significant glucose enhancement during the stimulation tasks in various brain regions, and an improvement in cognitive functioning compared to the other groups. The group with cognitive training + pyritinol had better stimulation effect as that of the social support group indicating that a combination of cognitive training + pharmacological intervention was superior than that of cognitive training alone.

[Stellate ganglion block under EEG control in the treatment of complicated cervical migraine (author's transl)]. / Zur Anwendung der Stellatum-Blockade unter EEG-Kontrolle bei cervicogener Migraine accompagnée

Complicated migraine is regarded as a cerebrovascular syndrome of functional character. In the case of a young man with cervical migraine associated with paroxysmal neurological disorders and persisting EEG abnormalities, stellate ganglion blocks were performed under EEG control. A transient amelioration of the pathological EEG pattern was observed after each stellate ganglion block and after several treatments the EEG was normal and the migraine attacks disappeared. The pathophysiology of the effect of stellate ganglion block on cerebral blood flow is discussed.

Testing drug effects against hypoxic damage of cultured neurons during long-term recovery.

Cultured neurons of chick cerebral embryo hemispheres were used to study drug effects against neuronal damage caused by hypoxia during long-term recovery. Sodium cyanide (NaCN, 1 mmol/l) induces hypoxia-like conditions by inhibiting oxydative phosphorylation. The sensitivity of the cultured neurons against this type of hypoxia was determined after 3, 4, 5 and 6 days of cultivation followed by 4, 3, 2 days and 1 day of recovery, respectively. The ATP level and the viability of cells as well as the total cell number and the protein content of the cultures were used to characterize the extent of posthypoxic neuronal damage. A hypoxic period of 30 min after 4 days of cultivation followed by 3 days of recovery seemed to be appropriate for determining protective drug effects. The drug effects obtained were comparable to those from in vivo models of cerebral ischemia or hypoxia. The results suggest that cultured neurons exposed to hypoxia and to long-term recovery could be suitable for studying post-hypoxic neuronal damage as well as neuroprotective drug effects.

Pyritinol treatment of SDAT patients: evaluation by psychiatric and neurological examination, psychometric testing and rCBF measurements.

A group of 26 patients with the diagnosis of Senile Dementia of Alzheimer type (SDAT) was included by random assignment in a double-blind, cross-over trial of pyritinol versus placebo. The patients had a mild to moderate degree of dementia. Psychiatric and neurological examination, psychometric testing, and measurement of the regional cerebral blood flow (rCBF) at rest and during mental activation were used to assess treatment effects. The results of the study showed that pyritinol was associated with a significant improvement in cognitive performance. RCBF data showed that treatment with pyritinol normalized the pattern of blood flow increase during activation and improved the score on the test used for activation.

The influence of the administration of pyritinol on the clinical course of traumatic coma.

(1) In a total of 100 patients with traumatic coma who were admitted to the intensive care unit of our Department of Neurosurgery we examined the effect of Encephabol after intravenous administration. (2) Compared to patients with the same clinico-neurological conditions who were, however, not treated with Encephabol, the cases treated by the preparation did not show any significant clinical improvement. Moreover, in the Encephabol group mortality rate in patients with an unfavourable prognosis sank to 35.3% (mortality rate in the comparative group: 54.2%). (3) Untoward effects on the clinico-neurological condition, cortical electrogenesis, vegetative functions and body fluid parameters were not observed after administration of the preparation.

Therapeutic effect of pyritinol on sequelae of head injuries.

Two hundred and seventy patients suffering from the sequelae of different forms of brain injury have been treated orally with pyritinol 200 mg three times a day for a period of 6 weeks. It has been shown that, compared with placebo therapy, pyritinol produces statistically significant improvement in the clinical and psychoneurological manifestations. It is concluded that pyritinol is a drug of therapeutic benefit in the treatment of the sequelae of cerebral trauma.

Clinical effect of Encephabol (pyritinol) in the treatment of cerebrovascular disorders.

The results of a series of multicentre, controlled, double-blind trials of the clinical efficacy of Encephabol compared with placebo in patients with a variety of cerebrovascular disorders are reported.

[Experience with detoxification and weaning of heroin addicts by means of acupuncture, gabergic drugs and psychopharmacologic agents in low doses]. / Esperienze di disintossicazione e disassuefazione in eroinomani attuate tramite agopuntura, farmaci gabergici e psicofarmaci a basso dosaggio.

UNLABELLED: Presents extensive reports of detoxification and habit loosing trials in 9 male heroine addicts, 19-26 yr. The therapeutic programs were centered on gabergic drugs, low doses tricyclic antidepressants and benzodiazepines, and acupuncture (main points: 8 GB; nasal GB; 1 GB; 3 L; 4 LI; 36 S; 7 H; auricular Shen men) and were continued weekly at the Mental Health Outpatients Service, after discharge from the hospital. RESULTS: 2 Ss, personally checked, abstinent 6 months after their discharge; 4 Ss heard as abstinent and 3 Ss relapsed. Technique, course and times of the therapeutic program seem to be one of the key factors for success.

[Two cases of superficial pemphigus induced by pyritinol (author's transl)]. / Deux cas de pemphigus superficiel induit par le pyritinol.

Pyritinol is presently prescribed in rhumatoid polyarthritis because of its structural analogy to D-penicillamin. Only benign cutaneous side effects had been mentioned up to now. We report two cases of pemphigus occurring during pyritinol therapy given in one case for rhumatoid polyarthritis, in the other case for memory deficiency. Clinical aspect was that of a superficial pemphigus. The histologic picture was in some instances that of a superficial acantholysis, and in other instances, that of an eosinophilic spongiosis. Definite proof of pemphigus was shown by presence of anti-intercellular substance antibodies in the serum and in the skin of both patients.

[Comparative evaluation of psychoactive drugs used in patients with subacute and chronic cerebrovascular disorders]. / Ocena porównawcza skutecznosci leków psychoenergizujacych u chorych z podostrymi i przewleklymi zaburzeniami krazenia mózgowego.

The report is based on 315 patients with subacute and chronic cerebral circulatory disturbances caused mostly by atherosclerosis aged 30 to 82 years, treated for 1-6 months. In 90 cases Piracetam (Nootropil) was given, 107 received Piritinol (Encephabol, Enerbol), 77 Piriditol, 41 Centrophenoxin. The patients were allocated randomly to these groups. In the treated patients improvement was achieved in a considerable proportion of cases (44-82%) treated with different drugs. This improvement manifested itself as regression or decreased intensity of neurotic complaints, labyrinthine-cerebellar signs, pyramidal signs, anxiety and fears, improvement of recent memory, attention, psychomotor activity. The best results were obtained with Nootropil, moderately good with Centrophenoxin, Encephabol, and poor with Piriditol. Drug tolerance was best with Encephabol, while that of other drugs was slightly worse. The only disquieting symptoms was activation of epileptic seizures in several patients treated with Nootropil or Centrophenoxin. The best way of administration was giving the drugs in two doses in the morning hours and at noon. The authors regard as useful the treatment of patients with subacute and chronic cerebral circulatory failure with psychoenergizing drugs.

[Comparative evaluation of the therapeutic effectiveness of drugs of different mechanisms of action in cerebral atherosclerosis]. / Porównawcza ocena skutecznosci terapeutycznej leków z róznymi mechanizmami dzialania w miazdzycy mózgu.

The author describes the results of treatment of 299 patients with clinical evidence of cerebral atherosclerosis receiving three groups of antiatherosclerotic agents: improving cerebral blood flow (naftidrofuryl, cinnarazine, pyridinol carbamate, low-molecular dextran), normalizing lipid metabolism (clofibrate, heparinoid, alpha-tocopherol, Procetophen) and improving the metabolism of nerve cells (piracetam, pyritinol). After a statistical analysis of the results of the author evaluated the effectiveness of these drugs in various groups and suggested practical conclusions and treatment schedules in various forms of cerebral atherosclerosis.

[Current strategies of pathogenetic therapy of Alzheimer's disease]. / Sovremennye strategii patogeneticheskoi terapii bolezni Al'tsgeimera.

This is a review of the data available in the literature and the authors' own findings on pathogenetical rationale for the use and clinical study of current treatments for Alzheimer's disease (AD) (synonym: Alzheimer-type dementia). In the past decade many attempts have been made at targeting different links of the pathogenesis of a neurodegenerative process that underlie AD. Several areas of pathogenetical therapy for AD have been developed on the basis of experimental studies and pilot clinical tests. The most developed areas are as follows: various compensatory (replacement) treatments aimed at overcoming neurotransmitter deficit in different neuronal systems that are damaged in AD to a greater or lesser extent; neuroprotective therapy promoting increased viability (survival) of neurons and their plasticity, and vasoactive therapy. Rather new directions of AD pathogenetic therapy, such as antiinflammatory and hormonal therapy along with antiamyloid therapeutic strategies are still under study.

[Correlations between biological and clinical indices in children with intellectual deficiencies]. / K voprosu o korreliatsiiakh biologicheskikh i klinicheskikh pokazatelei u detei s intellektual'noi nedostatochnost'iu.

Some biochemical and electrophysiological parameters were examined in 20 intellectually-defective children with a history of pre- and perinatal damages. Certain correlations between the character of EEG changes, the level of amino acids in the peripheral blood, and the efficacy of treatment with drugs acting upon metabolism were discovered. A marked slow-wave activity was observed on the EEG in the group of patients whose clinical course was the most unfavourable: this activity coincided with an elevated level of methionine (the source of the methyl groups in acetylcholine biosynthesis) in the peripheral blood. The therapeutic effect was the most marked in children with paroxysmal EEGs: this was accompanied in them with an increased content of functional amino acids. The data obtained are important for a more differentiated approach to the therapy of mentally retarded patients.

[Analysis of the effectiveness of treating children with different forms of intellectual deficiency with piriditol]. / Analiz éffektivnosti lecheniia piriditolom detei s razlichnymi formami intellektual'noi nedostatochnosti.

The clinical efficacy of piriditol treatment in children with intellectual insufficiency was studied by means of special techniques, determining the velocity of visual information processing (VVIP) and short-time visual memory (SVM), which reflects the functional state of the brain. Piriditol was administered to 50 children aged from 7 to 12 years. The clinical state was characterized as mental retardation, due to mild organic brain lesions or oligophrenia in the form of mild debility. The use of special techniques (VVIP and SVM) for the study of intellectual activity permitted to analyze more differentially the stimulating and sedative effect of piriditol, to detect the new property of the drug, i.e. to remove the processes of fatigue in the brain tissues. A positive effect of the treatment was most marked in children with mental retardation rather than in oligophrenic patients.

[Use of the new psychotropic preparation bemitil in treating asthenic disorders (clinico-pharmacological research)]. / Primenenie novogo psikhotropnogo preparata bemitila pri lechenii astenicheskikh narushenii (kliniko-farmakologicheskoe issledovanie).

In a series of 130 patients with asthenic conditions related to borderline forms of neuro-mental disturbances the authors compared clinico-pharmacological action of the actoprotector bemitil with that of nootropic drugs (piracetam and piridotol). The treatment with bemitil was either continuous or intermittent, being conducted according to the scheme elaborated in the course of the study. Bemitil proved to be more effective than piracetam and piriditol in relation to its influence on the manifestations of the asthenic symptom complex in general. Its application was characterized by a faster onset of the therapeutic effect and a peculiar mild psychostimulating action, primarily manifested in the impact on obligate manifestations of the asthenic disorders. The degree of the psychotropic action of the drug was found to be subject to changes depending on the scheme of its use.

[Certain principles for differential utilization of metabolic treatment preparations in the complex therapy of mental disorders]. / Nekotorye printsipy differentsirovannogo primeneniia preparatov metabolicheskoi terapii v kompleksnom lechenii psikhicheskikh zabolevanii.

A study of 246 patients (with schizophrenia, manic depressive psychoses and psychoorganic syndrome) treated by some drugs of a metabolic action (encephalotropic", "nootropic" drugs, piracetam, piriditol and pantogam) permitted one to determine the place of these preparations in a comprehensive treatment of mental disorders. On the basis of clinical studies of the above-mentioned preparations, the conclusion is made about desirability (and in some cases about necessity) of including them into pharmacotherapy. During such studies certain traits of the clinical effect in each of these drugs was examined, permitting the comparative spectra of the pharmacological activity of piracetam, piriditol and pantogam to be determined. The clinical studies of these patients indicate the necessity of a differentiated use of the mentioned drugs having in view the state of the patient and detected clinical profile of the drugs.

Pyrithioxine and thiopronine: new penicillamine-like drugs in rheumatoid arthritis.

Two new SH-CH3-containing drugs have been studied as penicillamine-like agents. Pyrithioxine--retrospectively compared to a D-penicillamine series--was associated with fewer side effect-related withdrawals (14 vs 39) but with more non-responses and withdrawals for relapse. A review of the literature shows that thiopronine and D-penicillamine have a similar "score" of side effects and good responses. More extensively-controlled trials are needed for a better assessment of these new drugs.

[Efficiency of encefabol use in patients with dyscirculatory encephalopathy]. / Effektivnost' lecheniia éntsefabolom bol'nykh distsirkuliatornoi éntsefalopatiei.

The article presents the findings of the Encefabol treatment of 50 patients aged 56-68 yy with vascular encephalopathy at the I-III stage, caused by atherosclerotic and high blood pressure pathological processes. The individual dose prescription of the medication to patients with vascular encephalopathy was substantiated in the article. The importance of psychodiagnostic tests in assessment of Encefabol treatment efficiency of the disease was shown in the article.