The metabolism of chlorpromazine by microsomes in vitro has been examined with extracts from normal liver and small intestinal mucosa of man and guinea pigs. A GC-MS approach has been utilized to measure primary metabolites generated by these extracts, including the S-oxide, N-oxide, 7-hydroxyl, desmethyl, and didesmethyl species. In short term incubations (less than 30 min), the measured metabolites accounted for at least 90% of the substrate utilized. Chlorpromazine metabolism differed strikingly both between species and between hepatic and intestinal tissues of the same species. Guinea pig hepatic microsomes were the most active of the preparations studied, producing relatively large amounts of N-oxide. By contrast, human hepatic microsomes produced the 7-hydroxyl metabolite predominantly, with minimal formation of N-oxide. Extracts of guinea pig intestinal mucosa formed the desmethyl and S-oxide products; an extract of duodenal mucosa from a healthy accident victim exhibited minimal metabolism of chlorpromazine. The kinetics of metabolite formation and studies with inhibitors of cytochrome P-450 suggested the involvement of multiple microsomal enzymes in chlorpromazine metabolism.

Adult↗

PubMedDate not supplied

[Randomized study of the therapeutic effect of electroconvulsive therapy, uni- or bilateral, on certain cognitive functions in depression, with electroencephalography monitoring. Preliminary results].

Cognitive functions are known to be impaired by ECT. The aim of this study is to differentiate the effects of electroconvulsive therapy on some cognitive functions according to the mode of application of the electrodes. The brief-pulse Thymatron DG apparatus allows to control four electrical parameters and to assess electroencephalographic data. The preliminary sample comprises nine patients suffering of major depressive disorder; they are randomly assigned to the mode of application of the electrodes, bilateral or unilateral to the non dominant hemisphere. Clinical evolution is surveyed by the Montgomery and Asbert Depression Rating Scale. Non mnesic functions are assessed: arousal by CFF (Critical Fusion Frequency), and attentional, motor and decisional abilities by CRT (Choice Reaction Test). Different mnesic function are studied by selective reminding test, cued recall test, block tapping test and picture fragmentation test. After treatment by ECT, verbal mnesic functions assessed by selective reminding test are impaired with the bilateral application. Whereas they are not modified with the unilateral application. The variance of CFF regains a physiological value in the bilateral group, but remains altered in the unilateral.

Adult↗

PubMedDate not supplied

Expression of IL-2 receptors in human melanoma cells.

Melanoma cells can secrete several cytokines and express various cell surface molecules, such as the intercellular adhesion molecule ICAM-1, class II histocompatibility antigens, and the CALLA antigen, typically found in cells of the immune system. We have investigated the possible expression of interleukin-2 (IL-2) receptors in melanoma using monoclonal antibodies specific for the p55/alpha chain (TAC antigen) and the p75/beta subunit. Flow cytometric analysis of cultured melanoma cells showed the presence of low levels of the TAC antigen and of the beta chain on the surface of several cell lines. Similar results were obtained in vivo by immunohistochemistry on cryosections prepared from cutaneous and ocular melanoma explants. Positive staining was observed for the alpha chain of the IL-2 receptor in a high percentage of tumour cells. The beta chain could also be detected, although in a limited number of specimens. Analysis of RNA from melanoma cell lines by Northern blot showed the presence of typical 4 Kb transcripts for the p75 subunit, while low-abundance message for the p55 chain could be detected using combined reverse transcription/polymerase chain reaction analysis. Together, these results suggest that melanoma cells may express high affinity receptors for IL-2.

Antibodies, Monoclonal↗

PubMedDate not supplied

[Radiologic healing phenomena in chronic polyarthritis treated with methotrexate or sodium aurothiomalate].

PROBLEM: Do radiographs of hands and forefeet obtained from patients with rheumatoid arthritis present with healing phenomena? What is their importance relative to progressive changes? METHODS: Dorsopalmar/-plantar radiographs of hands and forefeet of 43 patients with early rheumatoid arthritis (median disease duration 1.7 years, anatomical Steinbrocker's age < or = 2, patients selected from a prospective study, treatment with methotrexate vs gold-sodiumthiomalate) were obtained at months 0, 6, 12, 24 and 36. Radiographs were evaluated without knowing the mode of treatment at 34 sites according to their time sequence for the following variables: a modified Larsen index, numbers of erosive and of radiologically active joints, and the numbers of joints being improved vs. deteriorated in relation to the preceding x-ray. RESULTS: The radiologic progression could be measured by both a score derived from the modified Larsen index as well as by the numbers of erosive joints with the result of an increasingly crescent, but flattening curve. The number of erosive joints was more sensitive to progression than the score derived from Larsen index. The number of joints deteriorating, compared with the preceding x-ray, decreased from month 6 to month 36 from 16.1% to 7.1% resp. At the same time, 90% of patients increasingly developed radiologic improvement in 2.9% zu 9.3% of joints, including diminution in size and recortication of erosions and particular cysts with a "filling in" by trabecular bone and recovery of a bony outline. There were no relevant differences between therapy groups. CONCLUSIONS: Progression in early rheumatoid arthritis is best measured by the number of joints with erosions. Reparative signs show up with increasing frequency during the course of the disease. After 3 years of treatment the numbers of joints exhibiting improvement predominate those with deterioration. The data support the concept of early aggressive therapy of rheumatoid arthritis and suggest the inclusion of reparative phenomena into the criteria for improvement of this disease.

Antirheumatic Agents↗

PubMedDate not supplied

Evaluation of ELISA to detect Chlamydia trachomatis antigen in urine samples from arthritis patients.

OBJECTIVE: To determine whether examination of urine samples using ELISA allows the detection of asymptomatic C. trachomatis infection in arthritis patients. METHODS: The in vitro sensitivity of IDEIA Chlamydia ELISA to detect C. trachomatis in urine samples was determined by the investigation of serial dilutions of chlamydial elementary bodies. In a clinical study, urine samples from 402 consecutive arthritis patients (182 men and 220 women) in a tertiary care rheumatology clinic were examined for asymptomatic chlamydial infection by ELISA and the results were compared to culture and direct immunofluorescence assay (DFA, MicroTrak) of urogenital swabs. RESULTS: The in vitro sensitivity of ELISA for detecting purified elementary bodies of C. trachomatis serovar K in urine was 60 infection forming units. Twenty-three of 402 arthritis patients (6%) had asymptomatic chlamydial infection as shown by DFA and culture from urogenital smears. The ELISA method identified only 3 of 17 swab-positive patients among 271 patients when urine specimens were collected during the clinical visit, while the assay detected all 6 swab-positive patients among 131 patients when first-voided early morning urine specimens were used (p < 0.001). CONCLUSION: It is mandatory to examine only first voided early morning urine samples if ELISA is used instead of DFA or culture from urogenital swabs to detect asymptomatic chlamydial infection in arthritis patients.

Adolescent↗