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The effects of gonadotropin treatment on the immunological features of male patients with idiopathic hypogonadotropic hypogonadism.

There is a significant line of evidence for a role of androgens in the modulation of the immune system. However, little is known about immunological features of male patients with idiopathic hypogonadotropic hypogonadism (IHH) and the potential effects of gonadotropin treatment. Thus, the objective of this study was to evaluate the levels of selected soluble immune parameters [IgA, IgG, IgM, C3c, C4, interleukin-2 (IL-2), and IL-4], the CD4+/CD8 ratio, and counts of total lymphocyte and some subpopulation of lymphocytes (CD3+, CD4+, CD8+, and CD19+ cells) before and after gonadotropin treatment in men with IHH. Twenty-nine IHH patients and 19 age-matched healthy controls were included in the study. The patients were treated with human menopausal gonadotropin/hCG for 6 months. The pretreatment levels of serum Igs, C3c, IL-2, and IL-4 in the patients were significantly higher than those in the controls (P<0.001 for all). After treatment, all Igs (P<0.001), C3c (P<0.01), and IL-2 and IL-4 levels (P<0.005) were decreased significantly compared to pretreatment levels. Pretreatment lymphocyte counts (P<0.05); the percentages of CD3+ cells (P<0.001), CD4+ cells (P< 0.001), and CD19+ cells (P<0.001); and the CD4/CD8+ ratio in the patient group were significantly higher (P<0.05) than those in the controls. After treatment, the lymphocyte count (P<0.001); CD3+ (P<0.01), CD4+ (P<0.001), and CD19+ (P<0.005) cells; and the CD4-/CD8+ ratio (P<0.001) were decreased, but CD8+ cells were increased significantly (P<0.001). In summary, lack of testosterone action results in the enhancement of cellular and humoral immunity. The results of this study allowed us to conclude that testosterone deficiency affects both cell-mediated and humoral immunity, and these may be modulated with gonadotropin therapy in male patients with IHH.

Adult↗

Effects of therapies of cervical cancer on the count and function of peripheral lymphocytes.

In 57 patients with stage I b cervical cancer, treated by three different methods, the total lymphocyte count, T- and B-cell counts and PHA-induced lymphocyte blast transformation were determined before and immediately after overall treatment as well as at 6-month intervals till 2.5 years after treatment. Exclusively applied radiotherapy caused, in stage I b cervical cancer patients a slight decrease in the total lymphocyte and T-cell counts, which disappeared at 3-6 months after treatment, as well as a very significant drop in the B-cell count, persisting even 2.5 years after treatment. The combined method comprising brachytherapy and surgery proved to least damage the non-specific cell-mediated immunity, whereas the method combining brachy- and teletherapy with surgery exerted the most harmful effect on this immunity. All three therapeutic methods compared led to a significant long-term decrease in the circulating B-cell count. It seems that whereas the operative procedure did not influence the cell-mediated immunity, it intensified the brachytherapy-caused decrease in the B-cell count.

Adult↗

Alterations in peripheral blood leucocyte distribution in response to local inflammatory stimuli in the rat.

Changes in peripheral blood leucocyte distribution were monitored following subcutaneous injections of turpentine and subcutaneous and intrapleural injections of dextran. The responses in all three groups were similar; marked increases in total counts occurred at 6 hr, due largely to significant increases in neutrophil counts. Increases in lymphocyte counts also occurred and were more marked in the dextran-treated animals. By 12 hr, total counts fell, due to drops in both neutrophil and lymphocyte counts. In both dextran groups, neutrophil counts rose again between 24 and 72 hr, but in the turpentine group the fall persisted until 96 hr before counts reached a second peak at 14 days. In all groups lymphocytes showed an increase again at 18-72 hr. The rise in neutrophil counts observed 6 hr after the injection of turpentine was shown to be due principally to premature release of neutrophils from the bone marrow maturation compartment. Depletion of this compartment resulted in a drop in numbers of circulating neutrophils between 6 and 12 hr, in spite of the continued release of progressively less mature cells. The recovery in neutrophil counts between 72 and 96 hr was thought to be the expression of an increase in the rate of stem cell division. The continued rise to a second peak at 7 days probably resulted from increased marrow cellularity. It is suggested that the fluctuations in peripheral blood leucocyte counts may influence the initial colonisation of the local inflammatory lesion. The increase in neutrophil counts at 6 hr corresponds with the time of maximum neutrophil emigration reported by other workers and the fall in counts at 12 hr corresponds with the time of decreased neutrophil emigration.

Adult↗

Effect of hormone therapy on immune response in patients with prostatic cancer.

Thirty-one patients with adenocarcinoma of the prostate had laboratory studies done for total proteins, serum immunoglobulins, white blood cell counts, lymphocyte blastogenesis, skin tests, acid phosphatase, and CEA (carcinoembryonic antigen). The 16 patients receiving no hormones had depressed total proteins, lymphocyte and monocyte counts, skin tests, and CEA compared with the 15 patients receiving hromones who had depressed serum immunoglobulins, white blood cell counts, lymphocyte blastogenesis, and acid phosphatase.

Adenocarcinoma↗

Sequential evaluation of immunoreactivity in patients with melanoma undergoing surgery and adjuvant therapy.

The immunologic profile of 15 patients undergoing surgery and adjuvant chemoimmunotherapy for cutaneous melanoma was studied for a mean period of 18 months. In vivo cellular immunity was assayed by evaluation of delayed hypersensitivity response (DHR) to primary antigen and a panel of recall antigens. In vitro cellular immunity was evaluated to means of total and T-lymphocyte counts in peripheral blood and by the lymphocyte blastogenic response to phytohemagglutinin stimulation. Humoral immunity was assayed by determining the serum levels of IgG, IgA and IgM and of complement components C3c, C4 and Factor B. Phagocytic activity was studied by testing leukocyte chemotaxis, neutrophil phagocytosis and leukocyte random migration. The in vitro parameters were determined preoperatively at diagnosis, 6 times during the first 2 postoperative weeks, and then every month during adjuvant therapy. No correlation was found between DHR and clinico-pathologic stage of tumor, or with subsequent clinical course. Significant depression of total lymphocyte and T-lymphocyte count and blastogenic response of lymphocytes was found at diagnosis. The lymphocyte response to PHA decreased significantly in the early postoperative period but returned to preoperative levels one week after surgery. Periodic fluctuations of lymphocyte blastogenic response and progressive decrease of total lymphocyte counts and T-lymphocyte counts were observed during the 18-month follow-up. No significant alterations of immunoglobulin levels were recorded at diagnosis or during the postoperative period. Complement levels were within normal values preoperatively; in the early postoperative period a transient increase of C3c, C4 and Factor B was recorded, then complement levels progressively decreased. Parameters of phagocytic activity were normal at diagnosis and fluctuated within the normal range throughout the whole period of study.

Adult↗

Lymphocyte subsets in healthy children during the first 5 years of life.

OBJECTIVE: To assess whether relative and absolute values of CD4 and CD8 lymphocytes and CD4/CD8 ratio change in relation to age, and to estimate the fifth and 95th percentiles for these values in children of various ages. PATIENTS AND METHODS: Phenotypic analysis of lymphocyte subsets was performed on blood samples from 208 healthy children, aged 1 through 59 months, using standard flow cytometric techniques. RESULTS: Regression analysis demonstrated that CD4 and CD8 lymphocyte counts declined significantly with advancing age (P less than .000001 and P = .03, respectively). Since CD4 and CD8 counts depend on total lymphocyte count, the percentage of total lymphocytes of each phenotype was also analyzed and demonstrated that the CD4 percentage was highly age dependent (P less than .000001). The CD8 percentage increased with age (P = .0001) but not as much as the CD4 percentage decreased. Median CD4 counts (fifth and 95th percentiles) for children 2 through 3, 4 through 8, 12 through 23, and 24 through 59 months of age were 2.83 (1.46 to 5.11), 2.95 (1.69 to 4.61), 2.07 (1.02 to 3.60), and 1.80 (0.90 to 2.86) x 10(9)/L, respectively. CONCLUSION: Healthy children's CD4 lymphocyte counts are considerably higher than previously established adult values. These data demonstrate that age is an important consideration in interpretation of lymphocyte subsets in children. This may be especially relevant in children who are infected with the human immunodeficiency virus, where CD4 lymphocyte values play a central role in monitoring disease progression and determining thresholds for medical interventions.

CD4-CD8 Ratio↗

Absolute count and percentage of CD4+ lymphocytes are independent predictors of disease progression in HIV-infected persons initiating highly active antiretroviral therapy.

BACKGROUND: Highly active antiretroviral therapy (HAART) is recommended when the absolute CD4(+) T lymphocyte count is <200 cells/mm(3), and it should be considered when that count is > or =200, although the optimal timing when it is > or =200 is unclear. Because preliminary data had suggested that a low CD4(+) T lymphocyte percentage (%CD4) is associated with disease progression in persons initiating HAART who have a higher absolute CD4, we sought to further characterize the predictive utility of %CD4. METHODS: We conducted an observational study of persons in Collaborations in HIV Outcomes Research/US cohort who initiated their first HAART regimen between 1997 and 2004, received > or =30 days of therapy, and had baseline values of absolute CD4, %CD4, and HIV-1 RNA. Cox proportional-hazards models determined associations between %CD4 and disease progression (to either a new AIDS-defining event [ADE] or death). RESULTS: Of 1891 persons, 11% were female and 18% were African American; the median age was 38 years. Median follow-up was 55 months (interquartile range, 23-83 months), and 468 (25%) had disease progression. Multivariable analysis including age, race, sex, HIV-1 RNA, prior antiretroviral therapy, probable route of infection, prior ADE, absolute CD4, and %CD4 was performed; prior ART (P<.0001), injection-drug use (P=.04), lower absolute CD4 (P=.002), and lower %CD4 (P=.002) predicted disease progression. CONCLUSIONS: %CD4 at initiation of the first HAART regimen predicted disease progression independent of absolute CD4; %CD4 may be used to determine the timing of HAART.

Adolescent↗

Impact of suppression of viral replication by highly active antiretroviral therapy on immune function and phenotype in chronic HIV-1 infection.

We compared immune phenotypes, lymphocyte proliferation (LP), and delayed type hypersensitivity (DTH) responses in 28 male antiretroviral treatment-naive and experienced HIV-1-infected patients, matched pair-wise according to age and CD4+ T-lymphocyte count. Median CD4+ T-lymphocyte counts were 441 cells/microL and 483 cells/microL and median CD4+ T-lymphocyte nadirs were 435 cells/microL and 150 cells/microL in both groups, respectively. Absolute numbers of circulating T-lymphocyte subpopulations and proportions of naive and memory T-lymphocytes were comparable in the two groups. Untreated patients had greater proportions of activated CD4+ (p <.05) and CD8+ (p <.01) T-cells expressing human leukocyte antigen (HLA)DR and CD38 and fewer CD8+ cells expressing CD28 (p <.05). DTH and LP responses were comparable in both groups except for HIVp24, LP responses, and mumps DTH responses, which were of greater magnitude in the group treated with highly active antiretroviral therapy (HAART) (p <.05). Thus, HIV-1-infected patients who experienced substantial increases in CD4+ T-lymphocyte counts after suppression of viral replication on HAART had fewer activated lymphocytes and similar immune function when compared with findings in untreated patients with similar CD4+ T-cell counts. HIV replication has minimal real-time effect on CD4+ T-cell function in response to non-HIV antigens but helper T-cell responses to HIV-gag antigen are impaired during ongoing viral replication and may be restored by antiretroviral therapy.

ADP-ribosyl Cyclase↗

Cortisol response to exercise and post-exercise suppression of blood lymphocyte subset counts.

This study examined a temporal relationship between exercise-induced changes in blood cortisol levels and circulating leukocyte and lymphocyte subset counts during and after exercise. Twenty-one young male, sedentary subjects [mean age, 20.8 +/- 2.4 (SD) yr; mean VO2max, 48.0 +/- 7.9 (SD) ml/kg/min] underwent a cycle ergometer exercise for 60 min at 60% VO2max. Peripheral blood samples, collected every 30 min during exercise and at 30, 60 min, 2.5 and 6 h of recovery, were used for the determination of serum cortisol and plasma catecholamines; lymphocyte subsets were analyzed by flow-cytometry. Based on the analysis of serum cortisol levels in response to exercise, the subjects can be identified as two groups: cortisol-responder (n = 13) and non-responder (n = 8) groups. Other than the cortisol response, the two groups showed no significant differences in terms of age, physical build, aerobic fitness, maximal heart rate, and pre-exercise blood leukocyte and lymphocyte subset counts. The two groups also did not differ significantly in their relative work rate and catecholamine response to the exercise. Both cortisol responder and non-responder groups displayed a granulocytosis, lymphocytosis and monocytosis during exercise, and a further granulocytosis after exercise. Changes in lymphocyte count and distribution during recovery, however, differed significantly between the two groups. In the circulation of the cortisol non-responder group, total lymphocyte counts returned to the baseline level shortly after exercise, whereas a significant lymphopenia occurred at 2.5 h of recovery in the cortisol responder group: the CD4+ cells showed the greatest decrease in cell count, followed by the CD8+ cells. In both groups, the CD16+ cell-counts tended to decline below the pre-exercise values at 30 and 60 min of recovery and returned to the baseline values by 2.5 h of recovery. The CD19+ cell-count was not suppressed in both groups after exercise. These results suggest that exercise-induced secretion of blood cortisol may contribute to post-exercise suppression of the helper- and cytotoxic-T cell counts, but does not seem to be involved in post-exercise changes in the NK-cell and B-cell counts as well as in post-exercise granulocytosis.

Adult↗

Oral manifestations of human immunodeficiency virus-infected patients in Taiwan.

To understand the characteristic clinical features of human immunodeficiency virus (HIV)-related oral lesions and determine the prevalence of various oral lesions in HIV-infected patients in Taiwan, we conducted a cross-sectional study of 207 HIV-infected patients at the Taipei Municipal Institute for Venereal Disease Control. Overall, 108 (52.2%) patients had at least one oral lesion. The most common oral manifestation of HIV infection among these 207 patients was oral hairy leukoplakia (OHL, 29.5%), followed by candidiasis (12.1%), xerostomia (10.6%), aphthous ulcers (8.7%), and linear gingival erythema (5.8%). Less frequently encountered oral lesions included leukoplakia (1.9%), papilloma (1.4%), necrotizing ulcerative periodontitis (1.0%), Kaposi's sarcoma (1.0%), herpes simplex (0.5%), Burkitt's lymphoma (0.5%), and parotid gland enlargement (0.5%). Thirty-one (15%) patients had multiple oral lesions. Patients with oral candidiasis or multiple oral lesions had significantly lower mean CD4 lymphocyte counts and CD4/CD8 lymphocyte ratios than those without any oral lesions (p < 0.05). Chi-square analysis revealed that patients with CD4 lymphocyte counts below 200 cells/mm3 were more prone to have OHL (p < 0.002), oral candidiasis (p < 0.001) and multiple oral lesions (p < 0.001). Those with CD4/CD8 lymphocyte ratios below 0.4 were more likely to have OHL (p < 0.02), oral candidiasis (p < 0.01) and multiple oral lesions (p < 0.02) than those with higher counts. In conclusion, the occurrence of oral lesions, especially OHL and oral candidiasis, is fairly common in Taiwanese HIV-infected patients.

Adolescent↗

The role of non-viral load surrogate markers in HIV-positive patient monitoring during antiviral treatment.

Monitoring the efficacy of highly active antiretroviral treatment (HAART) is crucial if disease progression and the emergence of viral mutants are to be avoided. Classical viral load monitoring is too expensive for large-scale use in resource-limited settings. Three alternative measures, CD4 count, total lymphocyte count (TLC) and haemoglobin, were evaluated as surrogate markers of treatment success (viral load below detection level) among 710 HIV-positive patients who started HAART in an HIV treatment centre in Belgium. TLC correlated well with changes in CD4 counts during HAART, but an increase in TLC alone was a poor predictor of treatment success. A combination of increases in both haemoglobin levels and TLC proved a reliable predictor of successful treatment outcome comparable to the increase in CD4 count, but its specificity and sensitivity were low.

Adult↗

Prognostic factors in Hodgkin's disease. II. Role of the lymphocyte defect.

Purified blood lymphocytes from 81 consecutive and previously untreated patients with Hodgkin's disease were studied in vitro. The patients were evaluated 23 to 52 months after institution of therapy and were divided into two prognostic groups: 1. Complete remission with or without previous relapse/relapses. 2. Uncontrolled relapse or decreased from Hodgkin's disease. Lymphocyte activation by concanavalin A, pokeweed mitogen or phytohaemagglutinin was impaired and spontaneous DNA synthesis was high in patients with poor prognosis as compared to the good prognosis group. The prognostic information increased if the four lymphocyte tests were combined in a score (range 0-8). All 8 patients with pronounced lymphocyte defects (score 7-8), died, while all patients with score 0 and 1 were in complete remission. In contrast, total lymphocyte and T-lymphocyte counts and lymphocyte stimulation by PPD were of no prognostic value. The ability of certain lymphocyte functions to predict prognosis was equal or better than that of age and better than clinical staging, histopathology and symptoms.

Adolescent↗

Effect of protein synthesis inhibition by cycloheximide on lymphocyte circulation.

BACKGROUND: Lymphocyte recirculation is directed by glycoprotein adhesion molecules on lymphocytes and endothelial cells of lymphoid tissues. Lymphocyte circulation in different lymphoid tissues is dependent on the type of glycoprotein adhesion molecules present. In the present study, the effects of inhibiting new protein synthesis on the ability of lymphocytes to circulate and home to different lymphoid tissues was investigated. EXPERIMENTAL DESIGN: New Zealand White rabbits and Lewis white rats were treated with cycloheximide or buffer. Total circulating lymphocyte counts and lymphocyte subsets were measured. Rabbits were given autologous, 111indium-labeled lymphocytes to determine if there were changes in the organ distribution of lymphocytes after cycloheximide treatment. RESULTS: After cycloheximide treatment, the number of circulating lymphocytes but not neutrophils increased significantly by 2 hours in both rabbits and rats. T cells, B cells, and L-selectin-positive lymphocytes showed similar increases. Measurements of the distribution of the radiolabeled, autologous lymphocytes in cycloheximide-treated animals showed significantly greater numbers circulating in the peripheral blood and decreased numbers in Peyer's patches, mesenteric lymph nodes, and spleens compared with controls. In contrast, the number of radiolabeled lymphocytes in the lung was not decreased after cycloheximide administration. CONCLUSIONS: These results indicate that protein synthesis inhibition causes lymphocytosis due to decreased lymphocyte homing to mesenteric nodes, Peyer's patches, and spleen, but not lung. This effect was not specific for distinct lymphocyte subsets, including T cells, B cells, or lymphocytes expressing L-selectin. These data show that molecules modulating lymphocyte homing in some organs have rapid turnover rates and suggest that changes in homing during the inflammatory process can be rapidly regulated by changes in protein translation.

Animals↗

[Changes in lymphocyte cytochemical markers in radiation-exposed patients under mountain conditions].

It is shown that 24-day rehabilitation in the mountains reduced general sensitization in subjects exposed to radiation after the Chernobyl accident. The assessment of lymphocyte population and functional activity (lysosomal, mitochondrial, mitotic) by their markers (acid phosphatase, succinate dehydrogenase, DNA) indicated lowering of B-lymphocyte count, T-killers, increased count of o-lymphocytes, DNA in all lymphocyte populations, a rise in the activity of SDG and acid phosphatase. Subjects from the Chernobyl rescue teams living in high altitudes for 3-15 years after the accident had low T-lymphocyte but high o-lymphocyte counts, stable SDG, enhanced activity of acid phosphates in T-killers. The fact of lymphocyte populations increase, stimulation of their activity observed in the end of the radiation-exposed subjects, rehabilitation gives grounds for further investigations of beneficial effect of mountain climate on irradiated body, of relevant indications and contraindications.

Acid Phosphatase↗

Melatonin prevents testosterone-induced suppression of immune parameters and splenocyte proliferation in Indian tropical jungle bush quail, Perdicula asiatica.

During reproductive inactive phase (winter months) peripheral high melatonin and low testosterone was noted in male Indian tropical bird, Perdicula asiatica. During this phase exogenous testosterone (1 mg/100 g Bwt./day) suppressed the immune parameters [spleen weight, total leukocyte count (TLC), lymphocyte count (LC), and percent stimulation ratio (% SR)] and depleted splenic cellular density, while melatonin (25 microg/100g Bwt./day) restored the immune parameters and splenic cellular density to the level of control birds. In vitro suppression of splenocyte proliferation by testosterone (3 ng/ml) was also reversed by melatonin (500 pg/ml) supplementation. Therefore, high melatonin in circulation during the reproductive inactive phase acts as immunostimulator and is of high adaptive significance to this bird for survival during the adverse conditions of season and reproductive phase.

Animals↗

Beta 2-microglobulin in chronic lymphocytic leukaemia.

The serum level of beta 2-microglobulin (S-beta 2 m), a cell membrane protein associated with HLA-antigens, was quantitated in a series of 23 consecutive patients with chronic lymphocytic leukaemia (CLL). Markedly elevated values of S-beta 2 m (greater than 4.5 mg/1) were found in 10 patients, while only 3 patients had normal values (less than 3.0 mg/1). High serum values correlated with a large tumour mass, as estimated by Rai's clinical staging and by the total peripheral lymphocyte count. Blood lymphocyte proliferative activity, which has been suggested as reflecting disease activity in CLL, was measured by 3H-thymidine uptake in cells in vitro. The 3H-thymidine uptake was high in 3 patients all of whom were among the 5 patients with the highest S-beta 2m-values. S-beta 2m-determinations seem to be of definite interest in the study of patients with CLL although long term studies will be necessary for evaluation of the practical clinical value.

Aged↗

Toxicity evaluation of petroleum blending streams: inhalation subchronic toxicity/neurotoxicity study of a light catalytic reformed naphtha distillate in rats.

A 13-wk whole-body inhalation study was conducted with Sprague-Dawley CD rats (16/sex/group) exposed to a light catalytic reformed naphtha distillate (LCRN-D, CAS number 64741-63-5) at target concentrations of 0, 750, 2500, and 7500 ppm for 6 h/d, 5 d/wk. Sixteen rats per sex in the control and high-dose groups were maintained after final exposure for a 4-wk recovery period. The highest exposure concentration was 75% of the lower explosive limit. Standard parameters of subchronic toxicity were measured throughout the study; at necropsy, organs were weighed and tissues processed for microscopic evaluation. Neurotoxicity evaluations consisted of motor activity (MA) and a functional operational battery (FOB) measured pretest, throughout exposure and after the recovery period. Neuropathology was evaluated at termination. No test-related mortality or effects on physical signs, body weight, food consumption, or clinical chemistry were observed. In males exposed to 7500-ppm LCRN-D, a statistically significant decrease in white blood cell counts and lymphocyte counts was observed at the termination of exposure that was not present in animals after the 4-wk recovery period. However, mean corpuscular volume was slightly decreased in high-dose males after the recovery period. Statistically significant increases in kidney weights relative to body weights in 7500-ppm male rats correlated with microscopically observed hyaline droplet formation and renal tubule dilation, indicative of light hydrocarbon nephropathy, a condition in male rats that is not toxicologically significant for humans. Statistically significant decrease in absolute and relative spleen weights in 7500-ppm male rats correlated with decreases in hematologic parameters but had no microscopic correlate and was not observed in animals after 4 wk of recovery. This mild, reversible effect in white blood cell populations may relate to the presence of aromatics in the distillate. The only effect of LCRN-D on neurobehavioral parameters was significantly higher motor activity counts among high-dose (7500 ppm) males after the 4-wk recovery period, suggesting a possible delayed effect of LCRN-D. However, there was no evidence of hyperactivity or abnormal behavior from the functional observational battery evaluations, and there were no microscopic changes in neural tissue to support this observation. The no-observed-adverse-effects level (NOAEL) for LCRN-D was 2500 ppm for both subchronic toxicity and neurotoxicity. The no-observed-effects level (NOEL) was 750 ppm.

Administration, Inhalation↗

[Non-specific immunologic reactivity in epilepsy].

Humoral and cell-mediated immunity was determined in 28 epileptics, in 22 patients observed and investigated because of an only one seizure, and 26 healthy controls. Anticonvulsants had not been used in the treatment of these cases up to that time. The total lymphocyte count and the count of lymphocytes forming spontaneously rosettes with sheep erythrocytes were found to be significantly lower in the group of patients with epilepsy of unknown aetiology in relation to controls. The quantitative changes in the composition of the lymphocyte population were not significant and caused, probably, no immunological deficit, but were only a reaction to organic damage to the nervous system. Slight disturbances in the functions of the immune system cannot be, however, ruled out since this group showed also a significantly higher IgG level which suggests long-standing antigenic stimulation. No defect in IgA synthesis and disorders of the cell-mediated immunity (blastic transformation test, leucocyte migration inhibition test, skin test) were demonstrated in this study, although they had been reported by some authors in cases of epilepsy, mainly, however, in patients treated with anticonvulsants. In the patients having started anticonvulsive treatment these investigations will be repeated for establishing the effect of drugs on the immune reactions.

Adult↗