Antiviral immunity in chronic lymphocytic leukemia measured by anti-rubella antibody.

BACKGROUND: Chronic lymphocytic leukemia (CLL), the most common form of adult leukemia in Caucasian populations, is characterized by a decrease in anti-infective immunity. Clinical evidence of antiviral immunity decrease is the reactivation of herpes virus in the form of skin lesions. In Europe, rubella infection is common and creates lifelong persistence of IgG antibodies. OBJECTIVES: The aim of our study was to determine whether hemagglutination inhibition (HAI) rubella test can be used to determine antiviral immunity in CLL patients. MATERIAL AND METHODS: The titers of the HAI test against rubella were examined in a group of 26 healthy subjects, 7 subjects with herpes labialis infection and 56 patients with CLL, among which 9 patients were co-infected with herpes virus. RESULTS: Statistical tests have shown differences between groups and a significant decrease of the titers of the test in patients with CLL, compared with healthy persons and the herpes group compared with other persons. CONCLUSIONS: Our results indicate a significant decrease of antiviral immunity in patients with CLL and persons with herpes-type skin lesions. Simultaneously, relying on our previous studies, we also suggest that the result of this test may be an important indicator of antiviral immunity in patients with CLL.

[Acute dyskinetic syndrome during chloropromazine treatment of a female patient with CYP2D6 poor metabolism phenotype]. / Ostry zespól dyskinetyczny w trakcie leczenia chloropromazyna u pacjentki z fenotypem wolnej oksydacji w obecnosci CYP2D6.

The authors describe the case of a female patient with the diagnosis of schizophrenia and the CYP2D6 poor metaboliser phenotype (PM phenotype), who experienced severe extrapyramidal side effects, including acute dystonia, while being treated with chloropromazine at 100 mg per day (in the third day of therapy). The CYP2D6 phenotype was determined using the sparteine test before and after 3 days of treatment. Metabolic ratio increased 12 times during treatment, from initial 30 to 355. The authors conclude that CYP2D6 poor phenotype leading to slow chloropromazine metabolism, which was further inhibited by chloropromazine during treatment (as chlorpromazine is a strong CYP2D6 enzyme inhibitor) had significant importance on the occurrence of acute extrapyramidal side effects. Most likely the antidopaminergic influence of the drug on the CNS was much more marked due to an inhibition of chlorpromazine metabolism leading probably to an increase of the chlorpromazine blood level.

[Phenotypes of oxidation and acetylation in Alzheimer's disease--preliminary report]. / Fenotyp oksydacji i fenotyp acetylacji w chorobie Alzheimera--doniesienie wstepne.

AIM: The relationship between genetically determined polymorphic oxidation and acetylation and susceptibility to some disease has aroused much interest. The aim of our study was to evaluate whether patients with Alzheimer's disease differ from healthy persons in their ability to oxidize sparteine and acetylate sulphadimidine as model substance. METHOD: Oxidation and acetylation phenotype were estimated in 20 patients with Alzheimer's disease. The control group consisted of 160 healthy volunteers for comparison of oxidation phenotype and 45 healthy subjects for comparison of acetylation phenotype. RESULTS: The phenotyping of oxidation revealed two distinct populations among 20 patients with Alzheimer's disease: 19 persons (95%) were extensive metabolizers (EMs) of sparteine and 1 person (5%) was a poor metabolizer (PMs). In 160 healthy persons, 146 persons (91.2%) were extensive metabolizers of sparteine and 14 persons (8.8%) were poor metabolizers. The difference between the frequency distribution of PMs and EMs in healthy persons and in patients with Alzheimer's disease was not statistically significant. The phenotyping of acetylation showed that among 20 patients with Alzheimer's disease 10 persons (50%) were rapid acetylators and 10 persons (50%) were slow acetylators. In 45 healthy subjects the phenotype of rapid acetylation was observed in 23 persons (5 1%) and slow acetylation in 22 persons (49%). Our study showed a lack of statistically significant differences between the percentage of rapid acetylators (51%) and of slow acetylators (49%) in the control group of healthy volunteers and in the group ofAlzheimer's disease. CONCLUSION: The results of our study may suggest that phenotypes of oxidation and acetylation are not associated with risk of the development of Alzheimer's disease.

[The influence of clomipramine on CYP2D6 activity]. / Wplyw klomipraminy na aktywnosc CYP2D6--doniesienie wstepne.

AIM: Genetically determined activity ofCYP2D6 may be modified by some drugs through inhibition processes. Inhibition properties of TCA's were confirmed mainly in in vitro studies. The aim of the study was to assess the influence of clomipramine on CYP2D6 activity in vivo. METHOD: 11 patients diagnosed with depression according to ICD-10 and DSM-IV (major depression) criteria were included in the study. In all the cases clomipramine therapy was indicated. CYP2D6 activity was assessed by the phenotyping method. All patients were treated simultaneously. Each of the patients ingested one tablet containing 100 mg of sparteine sulfate. Urine excreted during the following 6 h was collected. Based on sparteine metabolic ratio (MR) the phenotype status was estimated twice: after the wash-out period, before clomipramine treatment, sparteine metabolic ratio (MRI), and after 2-weeks of clomipramine treatment (MR2). RESULTS: During clomipramine treatment MR2 values were statistically significantly higher than MRI. In 3 patients (27.3%) treated with clomipramine the changes of phenotype status were observed. CONCLUSIONS: Clomipramine is a CYP2D6 inhibitor and may change the CYP2D6 phenotype status (EM into PM).

[Clinical significance of oxidation and acetylation genetic polymorphism in patients with hyperthyreosis]. / Kliniczne znaczenie fenotypu oksydacji i fenotypu acetylacji u chorych na nadczynnosc tarczycy.

INTRODUCTION: The relationship between genetically determined polymorphic oxidation and acetylation and susceptibility to some disease was aroused much interest. The aim of our study was to evaluate whether patients with hyperthyreosis differ from healthy persons in their ability to oxidize sparteine and acetylate sulphadimidine as model drugs. Oxidation and acetylation were estimated in 48 patients with hiperthyreosis. MATERIAL AND METHODS: The control group consisted of 160 healthy volunteers for comparison of oxidation phenotype and 60 healthy volunteers for comparison of acetylation phenotype. The phenotyping of oxidation revealed two distinct populations among 40 patients with hyperthyreosis: 38 persons (95%) were extensive metabolizers (EM) of sparteine and 2 persons (5%) was poor metabolizers (PM). In 160 healthy persons (91.2%) were EM and 14 persons (8.8%) were PM. The difference between frequency distribution of PM and EM in healthy persons and in patients with hyperthyreosis was not statistically significant. RESULTS: The phenotyping of acetylation showed among 48 patients with hyperthyreosis 8 persons (13%) were rapid acetylators (RA) and 40 persons (87%) were slow acetylators (SA). In 60 healthy volunteers the phenotype of rapid acetylation was observed in 31 persons (51%) and slow acetylation in 29 persons (49%). Relative risk (odds ratio) of development of thyroid diseases was 5.34 times higher for SA in comparison to RA. The prevalence of SA among patients with hyperthyreosis in comparison to healthy volunteers was statistically significant (p < 0.0002). CONCLUSIONS: The results of our study may suggest that slow acetylation phenotype is associated with increased risk of the development of hyperthyreosis.

Doxepin inhibits CYP2D6 activity in vivo.

OBJECTIVE: Doxepin is a tricyclic antidepressant formulated as a mixture of E-(trans) and Z-(cis) stereoisomers. Cytochrome P450 2D6 (CYP2D6) catalyzes the hydroxylation of E-doxepin and E-N-desmethyldoxepin stereospecically. There is evidence that tricyclic antidepressants might inhibit CYP2D6 activity but there is no data about the influence of doxepin on CYP2D6. MATERIALS AND METHODS: Eleven patients diagnosed with depression according to ICD-10 criteria were included in the study. After wash-out period, before doxepin treatment, sparteine metabolic ratio (MR1) was assessed. After 2-weeks of doxepin treatment, MR2 was estimated. Sparteine and its metabolites were determined in urine by gas chromatographic method of Eichelbaum et al. RESULTS: Based on MR1 values, 10 patients were classified as EM (extensive metabolizers) and 1 patient as PM (poor metabolizer). During the study, after doxepin treatment, none of patients has changed phenotype status. However, MR2 values were statistically significantly higher than MR1. CONCLUSION: These results show the inhibitory effect of doxepin on CYP2D6 activity and may be of clinical value, especially in polymedicated patients treated with other CYP2D6 substrates or inhibitors.