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H Löffler

Publications and source records attributed to H Löffler.

At least 55 records · Page 3Linked to original sources

[Surgical treatment of echinococcosis of the liver].

UNLABELLED: Echinococcosis is a parasitic disease which is most frequently located in the liver. The treatment of choice is surgery. METHODS: A total of 23 patients were hospitalised for liver echinococcosis during the period from January 1993 to September 1998. RESULTS: The diagnosis was in 20 cases (87%) cystic echinococcosis and in 3 patients (13%) alveolar echinococcosis. The regular intervention of cyst desinfection with cystectomy was carried out in 85% of the cases with cystic echinococcosis, whereas atypical or segmental liver resections were performed in 15%. Two patients with alveolar echinococcosis were operated upon by radical/extended liver resections, one was found intraoperatively inoperable. The mean hospital stay was 15.4 days with a mortality of 0% and a postoperative morbidity of 57%, including bile leaks in 30%. A perioperative antiparasitic chemotherapy with albendazole was prescribed in 91%. The apparent rate of recurrence was 7% for uncomplicated cystic echinococcosis. CONCLUSIONS: Cyst desinfection with cystectomy has been proved to be effective as the standard operative intervention for cystic echinococcosis. For alveolar echinococcosis, radical resections are required. Due to the risk of recurrence (especially in alveolar echinococcosis), the effectiveness of surgery should be improved by a perioperative chemotherapy with albendazole.

Adolescent↗

Definition of a standard-risk group in children with AML.

To define paediatric AML patients with a favourable outcome in order to design a risk-adapted therapy, we analysed 489 children under 17 years of age treated similarly in studies AML-BFM 83 and 87. 369 patients (75.4%) achieved remission. Estimated probabilities of survival, event-free survival (EFS) and disease-free survival (DFS) at 5 years were 50% (SE 2%), 43% (SE 2%) and 58% (SE 3%), respectively. Multivariate analysis revealed bone marrow blasts on day 15, morphologically defined risk groups and hyperleucocytosis to be of prognostic value. EFS at 5 years estimated for patients with < or = 5% and >5% blasts on day 15 were 56% (SE 3%) v 27% (SE 4%); for the favourable morphological subgroups (M1/M2 with Auer rods, M3 and M4eo) it was 60% (SE 4%) compared with other patients (33%, SE 3%), P (Kaplan-Meier) = 0.0001 each. Hyperleucocytosis proved to be an independent prognostic factor, indicating a high risk, especially for early failure. The specific karyotypes t(8;21), t(15;17) and inv16 were closely related to the favourable morphology and outcome was in the same range. We conclude that for the definition of a standard-risk group a combination of morphological and response criteria may be sufficient. The standard-risk group defined by favourable morphology and a blast cell reduction on day 15 (not required for M3) comprises 31% of all patients, P survival, pEFS and pDFS at 5 years were 73% (SE 4%), 68% (SE 5%) and 76% (SE 4%), respectively.

Acute Disease↗

[Depression after cerebrovascular injury. Review and differentiation from other psychiatric complications].

In spite of the high incidence and prevalence of psychiatric complications after cerebrovascular injury few results have remained uncontradicted so far. This article focuses on the variety of psychiatric disorders after stroke reviewing recent literature and concentrating in particular on Post-stroke Depression. The prevalence of depressive disorders following stroke is assessed between 20 and 50%. Serious consequences for post-stroke depressed subjects are their increased mortality, poor rehabilitation outcome and long-term affected quality of life. Nevertheless, depressive disorders following stroke usually remain untreated. To this date the effectiveness of only a few drugs has been studied in controlled clinical trials (Nortriptylin, Citalopram, Imipramin, Mianserin). Besides describing clinical presentation, epidemiology, pathogenesis and consequences of post-stroke depressive disorders for the patient different authors' statements are listed and critically commented. Finally recommendations concerning therapeutic intervention are mentioned.

Cerebrovascular Disorders↗

Skin susceptibility of atopic individuals.

The relevance of the irritant skin reaction of individuals with an atopic history (atopic dermatitis, rhinoconjunctivitis or atopic asthma) to sodium lauryl sulfate (SLS), a widely used irritant, is still controversial. The aim of this study was to evaluate transepidermal water loss (TEWL) as an indicator of stratum corneum integrity, before and after SLS patch testing, in various groups of atopic individuals with and without atopic dermatitis. 95 volunteers were divided into 4 groups: (1) individuals with active atopic dermatitis; (2) individuals with a history of atopic dermatitis but without active skin lesions; (3) individuals with rhinoconjunctivitis or atopic asthma without any symptoms at the time of testing; (4) healthy individuals serving as controls. The volunteers were patch-tested at the unaffected volar side of the forearm with aqueous SLS 0.5% for 48 h. TEWL was measured before application and after removal of the patch. Individuals with active atopic dermatitis showed a significantly higher TEWL value after SLS and a tendency to a higher basal TEWL as compared to the 3 other groups. There were no significant differences in TEWL between individuals who were classified as atopic but without active dermatitis, individuals with rhinoconjunctivitis or atopic asthma and healthy controls, either at the basal or at the post-SLS measurement. Enhanced skin susceptibility is only present in individuals with active dermatitis. The skin susceptibility of atopic individuals might therefore be increased as soon as the skin becomes eczematous, suggesting a reduced epidermal integrity probably caused by the endogenous atopy and/or respiratory allergens. When interpreting the atopy score in relation to skin susceptibility, the actual condition of the skin should hence be taken into consideration.

Adolescent↗

Expression of the C-kit receptor (CD117) is a feature of almost all subtypes of de novo acute myeloblastic leukemia (AML), including cytogenetically good-risk AML, and lacks prognostic significance.

Because of conflicting reports on the prognosis of patients with c-kit receptor positive AML and lacking correlations with cytogenetic analyses, we prospectively evaluated the c-kit receptor expression in 917 AML patients (750 adult patients; 167 children) using flow cytometry and compared the results to the immunophenotype, morphological and cytogenetic findings as well as clinical outcome. Expression of the c-kit receptor was present in 63% of all AML investigated. Among these an immature immunophenotype was more frequent and 30% had a CD34+/CD15- and 37% a CD34+/CD14- phenotype, whereas only 9% and 10% showed these phenotypes in the c-kit receptor negative group, respectively. C-kit receptor expression ranged average in M0 and M1 subtypes (69% versus 70%) but was less pronounced among M5 subtypes (21%). Results of karyotyping were available in 280 patients. C-kit receptor expression occurred in 37 of 42 (88%) patients with favorable cytogenetic abnormalities such as t(8;21), t(15;17) or inv(16) which exceeded the expression rate in patients with intermediate risk, poor risk or other abnormalities. Information about the clinical outcome was available in 228 patients treated according to the protocols of two German multicenter trials (AML-BFM, AMLCG). We found no difference of CR-rate or event-free survival (EFS) in adults with or without c-kit receptor expression. Children with c-kit receptor negative AML had a lower CR-rate and EFS, but also a lower median age and a higher frequency of M5 subtype as compared to children with c-kit receptor expression. In conclusion, analysis of c-kit receptor expression may help to identify phenotypically immature AML but fails to identify myeloid differentiation of leukemic blasts in approximately one third of patients. We found no evidence of an adverse prognosis in AML patients with c-kit receptor expression. Analysis for c-kit receptor expression does not appear to add information to established prognostic parameters in AML.

Adolescent↗

Immunophenotypic and genotypic features, clinical characteristics, and treatment outcome of adult pro-B acute lymphoblastic leukemia: results of the German multicenter trials GMALL 03/87 and 04/89.

In contrast to childhood acute lymphoblastic leukemia (ALL), the cell-biological features, clinical characteristics, and treatment outcome of CD10(-) pro-B ALL have not yet been determined in larger series of adult patients. Therefore, we studied 57 adult patients with newly diagnosed pro-B ALL (median age, 30 years) enrolled in two consecutive German multicenter ALL studies (03/87 and 04/89). Extensive immunophenotypic characterization of leukemic blasts could be performed on all patients, whereas adequate cytogenetic data were available in 33 cases and molecular studies in 18 cases, using reverse transcription-polymerase chain reaction to detect MLL-AF-4 transcripts. Twenty-two patients demonstrated a t(4;11)(q21;q23) and/or MLL-AF-4 rearrangements, and 6 patients had other structural abnormalities, including a t(9;22)(q34;q11) (N = 2). Nine patients had a normal karyotype. Patients with 11q23 abnormalities tended to be younger (median age, 29 years) and were characterized by male predominance (64%), hyperleukocytosis (median leukocyte count, 168 x 10(9)/L), and a frequent coexpression of CD65s (64%) as compared with patients with other cytogenetic abnormalities or a normal karyotype. Twelve of 16 (75%) pro-B ALL patients in study 03/87 and 30 of 41 (73%) in study 04/89 achieved a complete remission (CR). Sixteen of 30 patients in study 04/89 remain in continuous CR (CCR) in contrast to only 2 of 12 patients in study 03/87. Interestingly, all 7 patients treated with high-dose cytarabine and mitoxantrone as consolidation in study 04/89 remain alive and leukemia-free. One patient in study 03/87 and 8 in study 04/89 underwent autologous (N = 2) or allogeneic (N = 7) bone marrow transplantation (BMT). The median remission duration was 420 days for patients in study 03/87 and has not yet been reached in study 04/89. The median survival time of all pro-B ALL patients was 571 days in study 03/87 and 747 days in study 04/89. Among the 22 patients with a t(4;11) and/or MLL-AF-4 rearrangements, 17 achieved a CR and 8 are still in CCR, of whom 4 underwent an allogeneic BMT. Remission duration and overall survival did not differ significantly between pro-B ALL patients with 11q23 abnormalities and those with a normal karyotype or other structural abnormalities. These data indicate that intensification of postremission treatment may improve the prognosis of adult pro-B ALL, including patients with a t(4;11).

Adolescent↗

MLL and CALM are fused to AF10 in morphologically distinct subsets of acute leukemia with translocation t(10;11): both rearrangements are associated with a poor prognosis.

The translocation t(10;11)(p13;q14) has been observed in acute lymphoblastic leukemia (ALL) as well as acute myeloid leukemia (AML). A recent study showed a MLL/AF10 fusion in all cases of AML with t(10;11) and various breakpoints on chromosome 11 ranging from q13 to q23. We recently cloned CALM (Clathrin Assembly Lymphoid Myeloid leukemia gene), the fusion partner of AF10 at 11q14 in the monocytic cell line U937. To further define the role of these genes in acute leukemias, 10 cases (9 AML and 1 ALL) with cytogenetically proven t(10;11)(p12-14;q13-21) and well-characterized morphology, immunophenotype, and clinical course were analyzed. Interphase fluorescence in situ hybridization (FISH) was performed with 2 YACs flanking the CALM region, a YAC contig of the MLL region, and a YAC spanning the AF10 breakpoint. Rearrangement of at least one of these genes was detected in all cases with balanced t(10;11). In 4 cases, including 3 AML with immature morphology (1 AML-M0 and 2 AML-M1) and 1 ALL, the signals of the CALM YACS were separated in interphase cells, indicating a translocation breakpoint within the CALM region. MLL was rearranged in 3 AML with myelomonocytic differentiation (2 AML-M2 and 1 AML-M5), including 1 secondary AML. In all 3 cases, a characteristic immunophenotype was identified (CD4+, CD13-, CD33+, CD65s+). AF-10 was involved in 5 of 6 evaluable cases, including 1 case without detectable CALM or MLL rearrangement. In 2 complex translocations, none of the three genes was rearranged. All cases had a remarkably poor prognosis, with a mean survival of 9.6 +/- 6.6 months. For the 7 AML cases that were uniformly treated according to the AMLCG86/92 protocols, disease-free and overall survival was significantly worse than for the overall study group (P = .03 and P = .01, respectively). We conclude that the t(10;11)(p13;q14) indicates CALM and MLL rearrangements in morphologically distinct subsets of acute leukemia and may be associated with a poor prognosis.

Acute Disease↗

[Amantadine-induced livedo reticularis].

A 63-year old women developed livedo reticularis during treatment with amantadine. This reversible side effect of amantadine has been most often seen in women and is frequently associated with persistent ankle edema. We discuss the signs and symptoms, pathogenesis and treatment of amantadine-induced livedo reticularis.

Adult↗

[Corymbiform nevus cell nevus].

There is a wide morphological variety in the appearance of melanocytic nevi. We report a case of a 77-year-old woman with a pedunculated, lobulated intradermal nevus on her trunk. For this grape-like clinical variant, we propose the term "corymbiform nevus".

Aged↗

Early stem cell transplantation for chronic lymphocytic leukaemia: a chance for cure?

B-cell chronic lymphocytic leukaemia (CLL) cannot be cured by conventional therapy. To improve the prognosis of patients with CLL, we have designed a sequential treatment strategy that comprises intensive chemotherapy for mobilization of peripheral blood progenitor cells (PBPCs) and induction of minimal disease, followed by high-dose radiochemotherapy with stem cell reinfusion and post-transplant molecular monitoring by polymerase chain reaction (PCR) amplification of the complementary determining region III (CDRIII) gene. In a prospective study, we have evaluated this protocol in 18 patients with CLL, also including early stages of the disease. The median age was 49 (29-61) years; Binet stages were A, six; B, nine; and C, three. Adverse prognostic factors [high lymphocyte count and/or diffuse bone marrow (BM) infiltration] were present in 16 out of 18 patients. All patients showed a clone-specific molecular marker as demonstrated by PCR amplification of CDRIII rearrangements. For stem cell mobilization and reduction of tumour load, one to two cycles of Dexa-BEAM chemotherapy were administered, resulting in minimal disease (circulating lymphoma cells <1 x 10(9) l(-1); BM infiltration <20%; lymphomas <2 cm) in 16 out of 18 patients, including four patients who already had minimal disease before Dexa-BEAM. Stem cell harvesting was successful in 14 patients. All grafts [three BM, 11 peripheral blood (PB)] were purged from leukaemic cells using immunomagnetic methods. Thirteen patients having achieved minimal disease were reinfused with purged autologous stem cells (ASC) after preparation with total body irradiation and cyclophosphamide. Engraftment was delayed in patients receiving BM (n = 3) but prompt [neutrophils >0.5 x 10(9) l(-1) after 10 (9-13) days, platelets >20 x 10(9) l(-1) after 11 (9-214) days] in patients restored with PBPCs (n = 10). Procedure-related deaths did not occur. Although the results of CDRIII PCR suggest persistence or recurrence of the leukaemic clone in at least three cases, to date only one patient has relapsed, whereas all others survive without clinical evidence of disease with a maximum follow-up of 48 months. We conclude that sequential high-dose therapy using Dexa-BEAM and autologous stem cell transplantation is a safe and highly effective treatment for patients with CLL. However, a longer follow-up is needed to assess whether definite cures can be achieved using this strategy.

Adult↗

High rate of chromosome abnormalities detected by fluorescence in situ hybridization using BCR and ABL probes in adult acute lymphoblastic leukemia.

The value of dual-color fluorescence in situ hybridization (FISH) with BCR and ABL probes for the detection of the Philadelphia (Ph) translocation and of other alterations involving ABL and/or BCR was evaluated in adult acute lymphoblastic leukemia (ALL). One hundred and four patients were studied prospectively using interphase nuclei FISH, chromosome analysis (CA), and PCR assays for the chimeric BRC/ABL transcript. FISH detected a Ph translocation in 24 cases (23.1%), as was confirmed by CA and/or PCR. FISH revealed a false positive diagnosis of a Ph translocation in four cases (5% false positive rate). Among 54 cases with combined FISH, CA and PCR assays, FISH failed to establish a correct diagnosis in 3.7%, PCR in 5.6%, and CA in 7.4%. The combination of two screening methods led to discrepant results in 9.3% (FISH + PCR), 11.1% (FISH + CA), or 13% (CA + PCR) of the cases. In seven of 80 (8.8%) Ph-negative patients, gain of BCR and/or ABL was identified. Overall, FISH detected alterations of the BCR and/or ABL genes with an incidence of 29.8% of the current study. Due to the possibility of false positive diagnosis of a Ph translocation using dual-color FISH the combination with chromosome and/or RT-PCR analyses is recommended in adult ALL patients.

Adolescent↗

Cell lineage specific involvement in acute promyelocytic leukaemia (APL) using a combination of May-Grünwald-Giemsa staining and fluorescence in situ hybridization techniques for the detection of the translocation t(15;17)(q22;q12).

Acute promyelocytic leukaemia (APL) is strongly associated with the translocation t(15;17) which therefore provides a reliable marker to assess the potential involvement of different cell lineages. Six cases with morphologically, cytogenetically and molecularly proven APL were analysed at diagnosis or relapse by combining fluorescence in situ hybridization (FISH) with standard May-Grünwald-Giemsa (MGG) staining at the single cell level on bone marrow and blood smears. With the FICTION technique, combining immunophenotyping with FISH, haemopoietic precursor cells were identified using monoclonal antibodies against CD34, B- and T-lymphocytes could be identified with CD19 and CD3. In addition, HLA-DR-positive cells were studied for the presence of t(15;17). Morphologically identified myeloblasts were relocated on the smear after FISH and were found to be PML/RARA positive in 91%, abnormal promyelocytes in 97%. In contrast, a positive signal was obtained in only 18% of PMN. Erythroblasts, lymphocytes and plasma cells did not show a PML/RARA rearrangement. Accordingly, all cells expressing CD3 or CD19 were PML/RARA negative. CD34 positive precursor cells identified by FICTION were PML/RARA positive in 97%. HLA-DR-positive cells contained a PML/RARA rearrangement in 24% of cells in one case and were negative in the two other cases investigated. These data indicate that APL appears to originate from a level of haemopoietic precursor cells but is restricted to the myeloid lineage. The low proportion of PML/RARA-positive PMN points to the impairment of blast cell differentiation beyond the promyelocyte stage but also emphasizes the existence of normal residual haemopoietic stem cells from which PML/RARA-negative PMN must be derived.

Adult↗

Molecular and cellular basis of radiation fibrosis.

PURPOSE: Recent data from the literature and the experimental work of the authors clearly indicate that TGF-beta1 is a key modulator of cellular events, for example, induction of terminal differentiation, resulting in radiation-induced fibrosis. Therefore, the present study analysed which cellular processes induced by exogenously added TGF-beta could be responsible for the induction, development and manifestation of the fibrotic phenotype in culture. MATERIALS AND METHODS: Rat lung fibroblast cultures (passage 1) were used. As a function of treatment with TGF-beta and/or anti-TGF-beta-antibody, the clonogenic activity and differentiation pattern were analysed by colony-formation assays. RESULTS: It could be demonstrated that treatment of rat lung progenitor fibroblasts with TGF-beta1 resulted in a pronounced shift in the differentiation pattern, i.e. induction of post-mitotic fibrocytes. This TGF-beta1-dependent terminal differentiation could be abolished by simultaneous treatment with a neutralizing antibody directed against TGF-beta1. CONCLUSIONS: The data presented indicate that TGF-beta1 is one major candidate mediating the accelerated terminal differentiation of progenitor fibroblasts to post-mitotic functional fibrocytes, which results in the fibrotic phenotype of this cell system.

Animals↗

Abrogation of graft-vs.-leukemia activity after depletion of CD3+ T cells in a murine model of MHC-matched peripheral blood progenitor cell transplantation (PBPCT).

Using a murine transplantation model, we simulated a clinical situation in which major histocompatibility complex (MHC)-identical allogeneic peripheral blood progenitor cells (PBPCs) are transplanted for the treatment of a malignant disease that is resistant to resting natural killer (NK) cells but sensitive to cytokine-activated NK cells and T cell-mediated antitumor activity. We determined the influence of selective T cell depletion of allogeneic PBPC grafts on graft-vs.-leukemia (GVL) activity and investigated the effectiveness of ex vivo treatment with NK cell-activating cytokines to compensate for the putative loss of T cell-derived factors stimulating natural cytotoxicity. After pretreatment of Balb/c (H-2d) recipients with 7.5 Gy of total body irradiation, 2x10(7) rhG-CSF-mobilized PBPCs of splenectomized syngeneic or MHC-identical DBA (H-2d) mice were transferred. Selective T cell depletion (TCD) was performed by immunomagnetic purging with a mononoclonal antibody directed against CD3. In some experimental groups, T cell-depleted PBPCs were incubated with 200 U/mL interleukin (IL)-2 and 100 U/mL IL-12 for 24 hours. To investigate antileukemic activity in vivo, recipient mice were inoculated with 1x10(5) A20 cells (a B-lymphoblastic leukemia of Balb/c origin) 2 days before PBPC transplantation (PBPCT). After transplantation of unmanipulated allogeneic cells, 25% of the animals died with signs of graft-vs.-host disease (GVHD) but 71% were free from relapse 100 days after PBPCT. After TCD of allogeneic grafts with anti-CD3, the incidence of GVH-related mortality was below 5% but the leukemia-free survival rate was significantly (p < 0.05) decreased to 25% and thus was similar to that observed after syngeneic PBPCT (17%). When CD3-depleted grafts were incubated with IL-2 and IL-12, 45% of the animals remained free from leukemia; however, the difference was not statistically significant. Our results suggest that ex vivo activation of residual NK cells with IL-2 and IL-12 does not fully compensate for the abrogation of GVL activity after depletion of CD3+ T cells from MHC-matched PBPCT.

Animals↗

Allogeneic peripheral blood progenitor cell transplantation in a murine model: evidence for an improved graft-versus-leukemia effect.

Peripheral blood progenitor cells (PBPCs) are increasingly being used to replace bone marrow cells (BMCs) as a source of hematopoietic stem cells also in the field of allogeneic transplantation. Whereas it is well known that PBPC grafts and BM differ significantly in progenitor cell content and lymphocyte dose, the clinical consequences of these differences with respect to engraftment, graft-versus-host disease (GVHD), and the graft-versus-leukemia (GVL) effect are more difficult to assess. We present a murine model that allows us to evaluate engraftment, GVHD, and GVL effect of allogeneic PBPC transplantation (PBPCT). Balb/c mice (H-2d) served as recipients. Donors were major histocompatibility complex-matched DBA/2 mice or syngeneic Balb/c mice, respectively. Experiments with increasing numbers of BMCs or Filgastrim-mobilized PBPCs showed that the number of progenitor cells in the graft was correlated with the probability to engraft, irrespective of the graft type. With identically high cell numbers transferred (1 x 10(9) nucleated cells/kg body weight [BW]), the mortality rates due to GVHD (25%) were about the same after allogeneic BM transplantation (BMT) and allogeneic PBPCT, although PBPC grafts contained four times more CD3+ T cells as compared with BM grafts (6.2 x 10(8) v 1.4 x 10(8)/kg BW). For investigation of GVL activity, Balb/c recipients were injected with syngeneic cells of the B-lymphocytic leukemia cell line A20 2 days before transplantation. After total body irradiation to a dose of 7.5 Gy, 1 x 10(9)/kg BW Balb/c PBPCs, DBA BMCs, or DBA PBPCs were infused. The relapse rates observed were 80% after syngeneic PBPCT (n = 22), 60% after allogeneic BMT (n = 23), and 34% after allogeneic PBPCT (n = 26) (allogeneic BMT v PBPCT, P = .032). We conclude that transplantation of allogeneic PBPCs instead of BM may enhance the GVL effect without an increase of GVHD.

Animals↗

[Clinical aspects of sleep disorders--experiences with 817 patients of an ambulatory sleep clinic; comment].

Between 1992, the year in which the Sleep Out-Patient Clinic at the Department of Psychiatry, University of Vienna, Allgemeines Krankenhaus (General Hospital) Vienna, was established, and 1996, 817 patients (58% females, average age 52 years; 42% males, average age 48 years) were treated for sleep disorder. According to the International Statistical Classification of Diseases and Related Health Problems (ICD-10) of the World Health Organization (WHO), 70% of the patients presented with a non-organic sleep disorder and 30% with an organic sleep disorder as main diagnosis. Non-organic insomnia was by far the most frequently diagnosed sleep disorder (48%), while within the organic sleep disorders sleep apnea was dominant (12%). In regard to the additional non-organic (mental disorder) diagnoses rounding off the clinical picture, neurotic, stress related, and somatoform disorders were the most common (41%), followed by affective disorders (31%) and mental and behavioural disorders due to intake of psychoactive substances, e.g. alcohol, drugs (15%). Additional organic diagnoses related to sleep disorders involved primarily endocrine disorders such as adipositas (23%), followed by cardiovascular disorders (19%), and primary snoring (17%). The sleep out-patient clinic has at its disposal a supportive diagnostic armamentarium such as all-night sleep polysomnography, 24-hour polysomnography, the Multiple Sleep Latency Test, EEG and EEG-mapping in the affiliated sleep laboratory, the evaluation of event-related potentials (P300) and actometry in the psychophysiological laboratory, as well as psychological and psychophysiological tests in the clinical psychodiagnostic laboratory, in order to determine the right treatment or preventive measures for the individual patients.

Adult↗