[Efficacy of cortexin in the treatment of memory disorders in children].

Children, aged from 7 to 12 years, with memory disorders were treated with cortexin (30 patients) and encephabol (30 patients). The comparative evaluation of efficacy and safety of these drugs was carried out. The higher cortexin efficacy (the improvement in 86.7% of cases) in comparison with encephabol (the improvement in 63.3% of cases) confirmed by the data of neuropsychological and neurophysiological research is established.

Comparison of pyritinol and auranofin in the treatment of rheumatoid arthritis. The European Multicentre Study Group.

The efficacy and tolerability of pyritinol (PY) and auranofin (AU) were compared in a multicentre double-blind study. Patients with RA received 600 mg/day PY or 6 mg/day AU for 1 year. Response was rated by a defined improvement in at least four of the following: Ritchie index, joint swelling index, rating scales for pain and general well-being, functional index, morning stiffness, ESR. Of the 139 fully evaluable PY patients 61 (44%) dropped out due to adverse events or response failure compared with 44 (31%) of the 142 AU patients. In patients treated for 1 year efficacy parameters improved more in the PY than in the AU group, with significant differences for the general well-being (P = 0.022), ESR (P = 0.029) and haemoglobin (P = 0.0042). The response rate for PY (61/78 patients, 78%) was significantly superior to AU (58/98 patients, 59% P = 0.009). An intention-to-treat analysis corroborated this result (P = 0.030). Adverse events (AE) occurred in 64% of PY patients and in 58% of AU patients: main AE were mucocutaneous symptoms (PY 36%, AU 23%) and gastrointestinal complaints (PY 30% AU 37%). Single cases of proteinuria, hepatic and haematological abnormalities were noted in both groups.

Erythema multiforme-like eruption in association with severe headache following pyritinol.

A 46-year-old woman presented with an unusual erythema multiforme-like eruption and severe headache 10 days after treatment with pyritinol for cerebral concussion. Histopathologic findings were consistent with erythema multiforme. Skin lesions and headache cleared after withdrawal of the drug. According to neurological examination and magnetic resonance imaging of the brain, the headache may have resulted from a slight, pyritinol-induced vasculitis. Previous reports on severe pyritinol-induced side effects and possible pathogenetic mechanisms are reviewed. Since pyritinol cannot be considered as an essential drug for cerebral concussion, adverse effects as described here raise doubts as to its general use in the given indication.

Therapeutic efficacy of pyritinol in patients with senile dementia of the Alzheimer type (SDAT) and multi-infarct dementia (MID).

This trial was performed to investigate the efficacy of pyritinol in the treatment of senile dementia. Initially, a total of 183 inpatients were screened for eligibility. Of 164 patients who met the inclusion criteria, 156 completed the trial. Allocation of the patients to the Senile Dementia of the Alzheimer Type group or the Multi-Infarct Dementia group was based on the Hachinski Ischemic Score, computed tomography scans and electroencephalographic (EEG) findings. In a 12-week double-blind treatment phase either 200 mg pyritinol dihydrochloride-monohydrate or placebo was given 3 times daily. Confirmatory statistics included item 2 of the Clinical Global Impression, the total score of the Short Cognitive Performance Test (Syndrom Kurz Test) and the factor 'cognitive disturbances' of the Sandoz Clinical Assessment Geriatric scale. In addition, data on tolerance, of EEG brain mapping and of a responder analysis were evaluated based on descriptive statistics. The therapeutic efficacy of pyritinol was clearly demonstrated by confirmatory analysis as the drug was statistically significantly superior to placebo in all 3 target variables. The clinical relevance of the outcome was underlined by the analysis of the descriptive variables and by the convergence found at the different observation levels. The EEG mapping demonstrated significant differences between placebo and pyritinol, with the latter decreasing slow and increasing fast alpha and beta activity, which reflects improvement of vigilance. Based on the results of this trial, it can be accepted that the therapeutic effect of pyritinol is superior to placebo in patients with mild to moderate dementia of both degenerative and vascular etiology.

[Drug-induced pemphigus diseases]. / Durch Medikamente induzierte Pemphigus-Erkrankungen.

An overview is given on pemphigus diseases induced by certain drugs. Well known inducers are D-penicillamine, and pyritinol-chlorhydrate. Besides that in some rather rare cases other drugs were connected to pemphigus induction: rifampicin, INH, etambutol, practolol, propranolol, phenylbutazone, aurothiomalate, ibuprofen, heroin, penicillin, ampicillin, captopril, thiopromine, alpha-mercaptopropionylglycine and piroxicam.

[Autoimmune hypoglycemia: the fault of pyritinol?]. / Hypoglycémie autoimmune: responsabilité du pyritinol?

Initially reported in Japan, autoimmune hypoglycemia is related to the presence of insulin-binding antibodies, even in patients who have never been treated with insulin. The authors report a case of spontaneous autoimmune hypoglycemia in a French woman receiving pyritinol. The difference between insulin and C peptide radioimmunoassay levels prompted a search for insulin antibodies. In vitro studies confirmed their presence and showed that they were immunoglobulins G with two binding sites without species specificity. The outcome of autoimmune hypoglycemia is usually favourable, with a rapid decrease of insulin antibodies but steroid therapy is needed when serious clinical manifestations are present. The differential diagnosis with factitious hypoglycemia may be difficult. The reasons for the appearance of the insulin antibodies and the exact mechanisms of hypoglycemia remain hypothetical. However, drugs with a sulfhydril group, such as pyritinol, could play a causative role in this syndrome.

[Auto-immune hypoglycemic syndrome induced by pyritinol]. / Syndrome hypoglycémique auto-immun induit par le pyritinol.

The auto-immune hypoglycemic syndrome is characterized by the association of hypoglycemia (clinical and/or biological) and anti-insulin antibodies in patients who have never received exogenous insulin. Initially this syndrome was most often described in Japanese patients some of whom were treated with drugs containing a sulfydril group. We now recall the case of a female caucasian patient treated with Pyritinol for rhumatoid polyarthritis and who presented severe spontaneous hypoglycemia linked with the presence of anti-insulin antibodies in her serum. The level of her antibodies decreased abruptly on suspension of the drug. The recent and more developed characterization techniques of the different forms of circulating insulin and of their antibodies may help to differenciate an auto-immune hypoglycemia from hypoglycemia due to the secret auto-administration of bovine and porcine insuline, and permit us to suggest that an abnormality in the structure of the molecule of insulin might be a cause of this syndrome. However, the exact mechanism of hypoglycemia linked with the presence of anti-insulin auto-antibodies is not yet clear as is the predisposition of a drug with a sulfydril group to induce such an auto-immune phenomenon.

On the effects of pyritinol on functional deficits of patients with organic mental disorders.

In 120 geriatric patients suffering from cerebral functional disorders with a moderate to rather severe degree of chronic brain syndrome, the effects of pyritinol were investigated in a placebo-controlled, randomized double-blind study. Furthermore, we attempted to find some evidence for the validity of a neurophysiological vigilance model which had already been used earlier. In the previous study it had been possible to show a rise in the vigilance level in patients under pyritinol treatment. The investigation began with a two-week single-blind placebo wash-out phase and continued over a 12-week treatment period, with six weeks' treatment in a hospital ward and six weeks' outpatient treatment (or in a geriatric home within a hospital setting). Pyritinol was administered three times daily in coated tablets each containing 200 mg. The course of the trial was controlled using two rating scales (SCAG, BGP), a physician's Global Impression (GI) and two performance tests (SKT, ZVT-G). There were 13 drop-outs, four because of intercurrent diseases, nine because they did not fulfill the inclusion criteria. The data of 107 patients were included in the statistical analysis, 54 on pyritinol and 53 on placebo. No notable adverse drug reactions were observed that were not similarly reported in the placebo group (Table 1). Statistically significant results were found in favor of pyritinol compared with placebo in both the level of clinical symptomatology (Fig. 1) and the performance level (Fig. 4). Particularly impressive was the superiority of pyritinol in the factor "social behavior" of the SCAG. Considering the clinical relevance of the changes it can be concluded that in both groups improvements occurred.(ABSTRACT TRUNCATED AT 250 WORDS)

Contact dermatitis caused by airborne agents. A review and case reports.

A general review is given of airborne-induced contact dermatoses, particularly of the irritant and allergenic types. Because the reports in the literature often omit the term airborne, 12 volumes of Contact Dermatitis (January 1975-July 1985) were screened, and the cases cited were classified in function of the anamnesis, lesion locations, causative irritants and allergens, and other factors. The present article also discusses differential diagnoses, in particular with regard to contact dermatitis of the face, ears, and neck. Finally, seven case reports of occupational and nonoccupational contact dermatitis problems caused by airborne agents are presented. In some of the cases the allergens have not been mentioned in published literature previously.

[Drug-induced pemphigus]. / Arzneimittelbedingter Pemphigus.

A review of the literature on previous cases of drug-induced pemphigus as well as two case reports of pyritinole-induced pemphigus show a few characteristics: D-penicillamine was responsible in 42 cases, pyritinole in 4 cases, the two case reports included. Superficial pemphigus was seen in about 75% of the cases, most times associated with preexistent autoimmunological disorders. Immunological findings were identical with normal, non-drug-induced pemphigus, while the prognosis was better under mostly necessary immunosuppressive therapy at relatively low doses.

Adverse effects profile of sulfhydryl compounds in man.

Many of the adverse reactions produced by penicillamine and other compounds with an active sulfhydryl group form a distinctive pattern when viewed as a class. Alterations in taste perception, mucocutaneous lesions, proteinuria due to immune-complex membranous glomerulopathy, and pemphigus are adverse reactions that have been encountered with all of the compounds discussed herein. Hematologic reactions such as neutropenia and thrombocytopenia occur rarely and with variable frequency. The angiotension converting enzyme inhibitor captopril has an active sulfhydryl group. When it was first given in high doses to patients with severe hypertension, adverse effects similar in pattern to those just outlined were reported. With reduced doses and more careful patient selection, the more serious reactions are no longer found, but disturbances of taste perception, rash, and oral mucosal ulcers are still encountered.

Contribution to the search for vigilance-indicative EEG variables. Results of a controlled, double-blind study with pyritinol in elderly patients with symptoms of mental dysfunction.

We used a clinical pharmacological model to test pyritinol versus placebo in patients with mental deficiency and a clinical diagnosis of beginning chronic brain syndrome. Following a two weeks' washout phase, 50 patients were randomly allocated to two treatment groups of 25 patients each, receiving either 200 mg pyritinol three times daily, or placebo under double-blind conditions. The treatment period lasted 8 weeks. To be included in the study, patients had to have at least 50% subvigil phases in the 15-min EEG resting recording. We define such behaviour as a neurophysiological disturbance of vigilance. Scores in the Benton test were to be 2 points below the expected value, and/or the NAF score was to be above a standard value attained in an old peoples' home (greater than or equal to 14). We used this clinical pharmacological model for an internal validation of our Vigilance Index (VI). According to our definition, the Vigilance Index should express vigilance in the sense of an optimalization of the neuronal system to enable this system to perform better. The delta F power and the alpha slow-wave index have been considered as vigilance-indicative variables in the EEG. We believe that vigilance can be better expressed by a multidimensional approach, which takes into account all EEG elements that express vigilance, such as the replacement of the occipital basic rhythm (e.g. alpha or beta rhythm) into slow waves, the lowering of the dominant occipital frequency (be it an alpha or beta frequency), the anteriorization of the basic rhythm in the occipital field to the frontal region.(ABSTRACT TRUNCATED AT 250 WORDS)