Immunological characterization of renal glycosuria patients.

We have evaluated the autoantibody pattern, the production of specific immunoglobulins against bacteria in the urinary tract and lymphocytes populations in peripheral blood of primary renal glycosuria patients. All the affected members present autoantibodies against various antigens. In nine patients immunofluorescence revealed antibody coated bacteria in urine specimens. Imbalances in lymphocytes subpopulations are also present, with a reduction of OKT8+ cells and an increase of B and natural killer cells. These results support previous observations about immunological abnormalities in these patients.

Close genetic linkage between HLA and renal glycosuria.

Renal glycosuria is an inherited disorder of renal tubule function in which significant amounts of glucose are excreted in the urine in the simultaneous presence of normal blood glucose levels. Renal glucose titration analyses and HLA genotypes were performed in 5 unrelated affected families with a total of 25 patients and 40 healthy relatives. In each family the gene responsible for renal glycosuria segregates with the HLA complex suggesting a close genetic linkage. 2 cases carry intra-HLA recombinant haplotypes; in these subjects our findings indicate that the abnormal gene is closer to the HLA-A locus than the HLA-B locus. No HLA-A, HLA-B or HLA-C specific antigen is selectively increased among the 5 unrelated families affected with renal glycosuria.

Is renal glycosuria a benign condition?

HLA typing and a range of autoantibodies were evaluated in five families affected with type A renal glycosuria. HLA typing demonstrates that this inherited disease is controlled by an autosomal dominant gene located on chromosome six in close genetic linkage with the HLA complex. All affected family members have significant titres of autoantibodies to nuclear antigens, native DNA, smooth muscle, mitochondria, liver antigens, thyroglobulin, thyroid microsomes and renal tubule brush border with variable association. This suggests that renal glycosuria is a complex HLA-linked disease with increased susceptibility to multiple autoantibody production and this urges caution with respect to its classical definition as a benign condition.

The utilization of hypnotics in chronic schizophrenics: some critical remarks.

Of 23 hospitalized chronic schizophrenic patients, all under neuroleptic medication, hypnotics taken previously for a long time could be totally withdrawn in 16 cases, and in 7 cases, the dosage was diminished by 30%, without any sleep impairment. The gradual reduction of hypnotics was accompanied by a shift of neuroleptic dosage to the evening and bedtime, with reduction of the morning and midday dose, without change of the total daily dose. A significant improvement in the psychic state was observed in 16 patients after withdrawal of the hypnotic; 7 patients showed a slight improvement after reduction of the hypnotic. Monthly or bimonthly reassessment of insomnia in the hospitalized population of chronic schizophrenics is indispensable to avoid the deleterious effects and abuse of hypnotic drugs.

Long term treatment of tardive dyskinesia.

A 4 year trial to treat tardive dyskinesia by a very slow progressive stepwise diminution of the neuroleptic dose and of antiparkinsonian agents as well as by administration of small, slowly increasing and then decreasing doses of reserpine or haloperidol was conducted on 62 chronic schizophrenic patients. This treatment program caused disappearance of tardive dyskinesia in 23, improvement in 26 patients and had no effect in 13 patients. The group of patients with disappearance of tardive dyskinesia had a mean age significantly lower than other groups. The rationale of this treatment was based on the concept of "desensitization" by a slow, progressive unblocking of dopaminergic receptor sites. Another tardive neuroleptic side effect, the "rabbit syndrome" was successfully treated in 7 other patients by antiparkinsonian drugs.

Pharmacokinetic interaction between amitriptyline and neuroleptics.

The influence of amitriptyline on the plasma level of various neuroleptics was studied in 25 chronic schizophrenic patients. The study lasted 20 weeks. Patients were kept first 4 weeks on their former neuroleptic medication, with amitriptyline added for 12 subsequent weeks, and withdrawn during the last 4 weeks when only the neuroleptic medication was continued unchanged. The plasma level of neuroleptics was assayed by gas-liquid chromatography, once weekly throughout the study. The amitriptyline plasma level was also evaluated once weekly during the 12 weeks of its administration. The mean neuroleptic plasma values for each 4-week period were pooled together in three groups: aliphatic, piperdine and piperazine phenothiazine derivatives. Amitriptyline provoked some increase of the plasma level of all phenothiazine derivatives. This augmentation was significant only transitorily, however. The putative mechanisms of this neuroleptic tricyclic antidepressant interaction are discussed.

Deanol, lithium and placebo in the treatment of tardive dyskinesia. A double-blind crossover study.

A double-blind crossover study on the effects of deanol and lithium carbonate was conducted on a sample of 29 chronic schizophrenic patients with tardive dyskinesia. In addition to his usual treatment with different neuroleptics, each patient received during an 8-week period either deanol, lithium carbonate or placebo. A 4-week wash-out period was inserted between each of the 8-week periods of experimental treatment of the tardive dyskinesia. The administration of either deanol, lithium carbonate or placebo added to the neuroleptic treatment did not produce a statistically significant improvement of tardive dyskinesia in our patient population as a whole. Favorable and unfavorable responses are discussed.

Influence of the antiparkinsonian drugs on the plasma level of neuroleptics.

The interaction between various neuroleptics and antiparkinsonian drugs was analyzed by measuring the neuroleptic plasma level before and after withdrawal of antiparkinsonian drugs. The population completing the study consisted of 32 chronic schizophrenics treated with chlorpromazine (8), levomepromazine (14), thioridazine (6), or haloperidol (4). Twenty-five were also receiving benztropine; 4, trihexyphenidyl; and 3, procyclidine. During the first 4 weeks patients remained on neuroleptics and antiparkinsonians, the latter being withdrawn during the 5th week, and the neuroleptics alone being administered during 16 following weeks. The plasma level of neuroleptics was assayed by gas liquid chromatography, once weekly in the morning at two different times. The analysis of variance showed a significant difference in neuroleptic plasma level when patients took neuroleptics only versus the period they had received neuroleptics and antiparkinsonians. The multiple comparison based on Studentized range Q0-05 revealed a significant progressive increase of neuroleptic plasma level during 12 weeks after withdrawal of antiparkinsonian drugs after which a plateau was reached. The hypothetical mechanisms of action of antiparkinsonians on neuroleptic plasma level are discussed.

Sleep analysis during drug-free weekends in chronic schizophrenic patients.

The authors made a polygraphic registration of the night sleep in a sample of 14 chronic schizophrenic patients who for several months (mean 8 months) have been on a stable, relatively low maintenance dosage of neuroleptics administered according to the drug-free weekend schedule (two consecutive drug-free days at the weekend). During this treatment none of them showed a relapse or deterioration (BPRS, CGI, and NOSIE rating scales were applied periodically). Their only complaint was of sleep deterioration during the drugfree weekend nights, especially during the second night. The polygraphic night-sleep pattern of each patient was studied during two consecutive weeks. No difference was found between the adaptation night on medication and the consecutive night on medication during the first week, and between the adaptation and readaptation nights on medication during two consecutive weeks. There was no difference in any sleep parameters between the nights on medication and the first drug-free nights. There was a signifcant difference in the total sleep time between the nights on medications and the second drug-free nights. No difference was found in any other sleep parameters in nights analysed as a blocks and in the distribution of NREM and REM stages in the first vs. the second half of the night when B3 was compared with A2. The practical implication is, that to avoid any change in nocturnal behavior it is preferable to withdraw the medication on two nonconsecutive days in the week. The evaluation of both daily and nocturnal behavior seems to be a useful tool in evaluating the first sign of the drug-withdrawal syndrome.

A long-term study of penfluridol in chronic schizophrenia.

Penfluridol, a member of the novel diphenylbutylpiperidine class of antipsychotic drugs, is the first long-acting oral neuroleptic. The population of the present study consisted of 24 chronic schizophrenic patients (14 males, ten females) whose treatment with penfluridol was initiated in our previous open/double-blind trial lasting 32 weeks 1; mean age was 42.2 years and mean duration of illness, 15.4 years. During one additional year in an uncontrolled clinical study, penfluridol in the form of 20-mg capsuent procedures included BPRS, CGI, NOSIE, vital signs, and laboratory measurements. During this long-term treatment with penfluridol, the scores of a cluster of BPRS items that included emotional withdrawal, conceptual disorganization, motor retardation, uncooperativeness, and blunted affect showed a progressively significant improvement. This indicated that the Bleulerian primary symptoms in chronic schizophrenics can be improved by the long-term administration of this long-acting neuropleptic with concomitant betterment of social adaptation and activity. The percentage of failure was very low (four patients) and was marked by instability of psychopathology with periods of excitation. The incidence of extrapyramidal reactions necessitating the administration of an antiparkinsonian drug during the length of trial was 35 per cent. No serious effects nor significant laboratory test changes were observed.

Epidemiology of tardive dyskinesia. Part II.

In the part II of an epidemiological study on tardive dyskinesia performed on the same sample of 332 chronic schizophrenic patients (142 males and 190 females), the authors come to the conclusion that the prevalence of tardive dyskinesia is significantly higher if the mean age was higher at the beginning of treatment with sedative or incisive neuroleptics, their combinations (cocktails) and added antiparkinsonian drugs. Age seems to be the most important factor in the prevalence of tardive dyskinesia. The mean longer duration of "incisive" free intervals significantly decreases the prevalence of tardive dyskinesia. Other factors analysed in our sample, especially the total amount of neuroleptics administered, the type of neuroleptics and the mean duration of neuroleptic treatment, do not play a significant role in the prevalence of tardive dyskinesia.

Influence of reserpine on all-night sleep pattern in nonlobotomized and lobotomized chronic schizophrenic patients.

This study was performed on two groups of schizophrenic patients. One group consisted on nine nonlobotomized patients and the other of nine lobotomized ones. The groups were matched for age, sex, duration of illness, clinical symptoms, type and dose of psychopharmacological treatment. The patients of both groups were administered 1 mg of reserpine half an hour before bedtime, for three successive days. Before reserpine administration the mean percentage time of the NREM stage 4 was significantly higher in the lobotomized group. There was no significant difference in the REM parameters. After three days of reserpine administration in the nonlobotomized group, there was no significant difference in the mean percentage of the NREM stage 4, whereas the mean REM percentage significantly increased and REM latency decreased. In the lobotomized group the same procedure, i.e., three days of reserpine administration, provoked a significant decrease in the mean percentage of the NREM stage 4 and no significant changes in the REM parameters. This difference in reserpine action on sleep in the lobotomized group is discussed.

Polygraphic night sleep pattern during chronic single and multiple neuroleptic dose administration.

A comparison was made between the polygraphic night-sleep pattern of chronic schizophrenic patients who were receiving a single dose of neuroleptics at bedtime and between the night-sleep pattern of the same patients receiving the same amount of the same neuroleptic divided into 3-4 doses during daytime. It was shown that the single bedtime dose provoked a significant increase in the mean percentage of the NREM stage 4 and of the mean percentage of the REM state whereas the mean percentage of the NREM stage 2 was significantly decreased.

Release phenomena and iterative activities in psychiatric geriatric patients.

This survey was undertaken to assess the frequency of some of the so-called release phenomena and iterative activities in an aged psychiatric population. Three groups of geriatric psychiatric patients with diagnoses of (I) organic brain syndrome, including senile dementia (56), (II) functional psychoses, predominantly schizophrenia (51) and (III) chronic schizophrenia never treated by neuroleptics or other biologic agents (16), were compared with (IV) a control group of 32 elderly people in good physical and mental health.In general, for the manifestations studied, the geriatric psychiatric patients suffering from an organic brain syndrome and treated with neuroleptics differed notably from the control group. This latter group, although older, had few neurological signs of senescence and the spontaneous oral movements usually associated with the use of neuroleptics were absent. Release phenomena such as the grasp and pouting reflexes, as well as the stereotyped activities, were encountered significantly more frequently in patients with an organic brain syndrome than in the two other groups of patients. Our survey has yielded limited results with regard to the possible influence of type of illness and neuroleptic treatment on the incidence of release phenomena and iterative activities.