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Case Reports 2006; 27(6): 725-728 PubMed PMID: 17187011 Citation  Keywords:  Antineoplastic Agents:therapeutic use, Breast Neoplasms:drug therapy, Carcinoma, Medullary:drug therapy, Choroid Neoplasms:drug therapy, Female, Humans, Middle Aged, Palliative Care:methods, Photochemotherapy:methods, Photosensitizing Agents:therapeutic u.   

: A 55-year old woman with growing unilateral subfoveal choroidal metastasis of breast carcinoma was treated by photodynamic therapy (PDT) with verteporfin. Best corrected visual acuity remained stable during the whole follow-up of 6 months. Tumor flattened from 2.2 mm to 0 mm on ultrasound one month after the therapy. PDT with verteporfin appears to be the best tolerated method for palliative treatment of growing subfoveal choroidal metastasis of the breast carcinoma....

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Clinical Trial 2006; 27(6): 833-838 PubMed PMID: 17187010 Citation  Keywords:  Adolescent, Androgen Antagonists:therapeutic use, Autistic Disorder:drug therapy, Chelating Agents:therapeutic use, Child, Child Behavior:drug effects, Cognition:drug effects, Female, Humans, Leuprolide:therapeutic use, Male, Metals, Heavy:urine, Severity.   

BACKGROUND: A medical hypothesis has suggested that some autism spectrum disorders (ASDs) may result from interactions between the methionine cycle-transsulfuration and androgen pathways following exposure to mercury.

METHODS: The IRB of the Institute for Chronic Illnesses approved the present study. A novel treatment was utilized combining LUPRON (leuprolide acetate, TAP Pharmaceuticals, Inc.) and CHEMET (meso-2, 3-dimercaptosuccinic acid--DMSA, McNeil Consumer Products Company) on 11 consecutive children with ASDs.

RESULTS: A significant (p<0.01) overall improvement from the 70-79th percentile of severity (median baseline score=87) at baseline to the 40-49th percentile of severity (median end of study period score=63) at the end of the study was observed for patients treated for a median of approximately 4 months. Significant improvements in sociability, cognitive awareness, behavior, and clinical symptoms/behaviors of hyperandrogenemia were also observed. Significant decreases in blood androgens and increases in urinary heavy metal concentrations were observed. Minimal drug adverse effects were found.

CONCLUSION: This study provides the first clinical evidence for the benefit that combined anti-androgen and anti-heavy metal therapy may have on some children with ASDs. Additional studies should examine androgen and heavy metal mechanisms of action in ASDs, and future ASD treatment protocols should consider androgens and heavy metals....

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Journal Article 2006; 27(6): 799-802 PubMed PMID: 17187009 Citation  Keywords:  Adult, Catechol O-Methyltransferase:genetics, Czechoslovakia, Dopamine:metabolism, Exploratory Behavior:physiology, Female, Humans, Male, Methamphetamine, Polymorphism, Single Nucleotide, Substance-Related Disorders:enzymology,.   

OBJECTIVES: Measurable traits of human personality may mark the predisposition to psychopathology. Increased novelty seeking plays an important role in the pathogenesis of substance abuse. Novelty seeking, one of the fundamental traits of the human temperament, is related to dopamine. Catechol-O-methyltransferase (COMT) is essential for dopamine inactivation. The aim of our study was to assess whether the COMT gene Val158Met functional polymorphism in patients dependent on methamphetamine is related to their novelty seeking score.

METHODS: Patients dependent on methamphetamine who had been treated at the Addiction Treatment Unit in Nechanice in 2004 and 2005 agreed to participate in the investigation. We administered the Temperament and Character Inventory (TCI) questionnaire, assessed their novelty seeking score and analysed their DNA samples for COMT Val158Met genotype.

RESULTS: The subjects were thirty-seven Czech Caucasians (women N=10) dependent on methamphetamine with an average age of 23.6+/-3.8 years. We found a significantly higher mean novelty seeking score among the patients with the Met allele (Met/Met homozygotes+Val/Met heterozygotes; N=28) than in nine Val/Val homozygotes (27.4 vs 24.1; p=0.042, Two-Sample T-Test).

CONCLUSION: The Met allele of the COMT gene Val158Met polymorphism is associated with low COMT enzyme activity and high endogenous dopamine synaptic levels in the prefrontal cortex. This leads to a decrease in dopaminergic neurotransmission in nucleus accumbens and a need for an increased activity to stimulate it. Novelty seeking behavior corresponds with this need....

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Comparative Study 2006; 27(6): 779-785 PubMed PMID: 17187008 Citation  Keywords:  Antigens, Neoplasm:immunology, Apoptosis:immunology, Decidua:immunology, Endometriosis:immunology, Female, Humans, Immune Tolerance:immunology, Immunity, Cellular:physiology, Lymphatic Metastasis:immunology, Menstrual Cycle:immunology, Metallothionein:imm.   

: Acquiring the immune-mediated apoptosis and the ability to regulate the cytotoxic immune response are the main phenomena playing fundamental roles in such situations as neoplasm survival and creation of immune tolerance during pregnancy. The aim of this study was to investigate these phenomena through the evaluation of metallothionein and RCAS1 proteins in neoplasm and its healthy environment (clear surgical margin), physiological conditions in placenta and its environment (decidua) and the comparison to non-neoplasmatic lesions originating from the environment (nasal polyps, endometriosis). We have shown that the growth of RCAS1 expression was simultaneous to the infiltration of activated immunological cells of tumor environment as well as decidua. The activity of immunological cells was in our study selectively suppressed. Metallothionein expression growth was also observed in healthy tumors stroma and in decidua probably in response to the growing cytotoxic activity and tumor spread. Alterations in RCAS1 and Metallothionein expression seem to be associated with local immune dysfunction in nasal polyps and endometriosis. In conclusion, the ability to compensate the growing cytotoxic immune response is physiologically observed in decidua, the lost of this ability in tumor environment might participate in the development of tumor spread....

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Comparative Study 2006; 27(6): 786-794 PubMed PMID: 17187007 Citation  Keywords:  Analysis of Variance, Antigens, CD:immunology, Antigens, Neoplasm:immunology, Apoptosis:immunology, Breast Neoplasms:immunology, Carcinoma, Ductal, Breast:immunology, Female, Gene Expression Regulation, Neoplastic, Humans, Immune Tolerance:immunology, Imm.   

INTRODUCTION: The generation of proper immune response in the tumor environment seems to be essential in antitumor defense. RCAS1 expression has been shown to participate in the regulation of immune cytotoxic activity, metallothionein participates in the protection of cells against immune mediated apoptosis. Since MT and RCAS1 expression is observed within healthy tumor environment we aimed to focus on the proteins expression in tumor and its healthy adjacent tissue in invasive ductal breast cancer regarding the immune cells presence and activity.

MATERIAL AND METHODS: RCAS1, metallothionein, CD3, CD56, CD4, CD25, CD69, CD68 and CD16 antigens expression was assessed by immunohistochemistry in invasive ductal breast cancer. Tissue samples were obtained from 45 patients and were grouped according to the presence of lymph nodes metastases. Two groups were obtained: with and without lymph nodes metastases.

RESULTS: Significant differences were observed in RCAS1 and metallothionein expression in tumor and significant differences in metallothionein expression in healthy stroma regarding the presence of lymph nodes metastases. The significantly higher RCAS1 expression was noticed in tumor in comparison to stroma in patients with the presence of lymph nodes metastases. No such difference was observed in patients without the metastases. Significantly higher metallothionein expression was identified in tumor than in stroma in both groups of patients, with and without lymph nodes metastases. These changes in RCAS1 and metallothionein expression were significantly related with the changes in the number and activity of immune cells.

CONCLUSION: RCAS1 and metallothionein expression in breast cancer healthy stroma seems to be essential for the coexistence of cytotoxic immune cells and normal epithelial cells. The loss of the ability to compensate the growing cytotoxic immune response in the environment might participate in the development of tumor spread....

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Clinical Trial 2006; 27(6): 803-806 PubMed PMID: 17187006 Citation  Keywords:  Adult, Anti-Anxiety Agents:administration & dosage, Antidepressive Agents:administration & dosage, Antipsychotic Agents:administration & dosage, Anxiety:blood, Benzodiazepines:administration & dosage, Depressive Disorder:blood, Dose-Response Relationship,.   

OBJECTIVE: Risperidone in antipsychotic doses induces hyperprolactinemia. The aim of this study was to verify whether the same is true for low doses of risperidone (0.5-2 mg per day) added to antidepressants or anxiolytics.

METHODS: Prolactin levels were measured in 4 men (mean age 49.5+/-19.1 years) and 8 women (mean age 31.3+/-8.2 years) inpatients with depressive and anxiety disorders who were treated with risperidone (median doses per day 1.25 mg) for median 15.5 days as an augmentation treatment to antidepressants (n=8), anxiolytics (n=6) and mood stabilizers (n=2).

RESULTS: 11 of 12 patients had hyperprolactinemia. Median plasma prolactin level was 1598 mIU/ml, 95% CI 1 040-2 661 mIU/ml. Significant correlation between risperidone daily dose and plasma prolactin level (Spearman's R=0.655, p=0.02) was detected. Two women suffered from galactorrhea and one from amenorrhea.

CONCLUSIONS: Even low doses of risperidone used as an augmentation to antidepressants or benzodiazepines are associated with hyperprolactinemia and can induce endocrinological side effects. The co-medication of antidepressants and benzodiazepines can potentially increase intensity of prolactinemia....

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Comparative Study 2006; 27(6): 763-767 PubMed PMID: 17187005 Citation  Keywords:  Adult, Androgen Antagonists:therapeutic use, Androgens:blood, Androstenedione:blood, Cyproterone Acetate:therapeutic use, Dehydroepiandrosterone:blood, Drug Combinations, Ethinyl Estradiol:therapeutic use, Female, Ghrelin, Humans, Peptide Hormones:blood, .   

OBJECTIVE: Ghrelin is a natural ligand of the growth hormone secretagogue receptor and has been shown to be a potent stimulant of GH secretion. It has also orexigenic effects and regulates energy homeostasis. Recent studies claim that ghrelin influences the androgen level and probably takes part in PCOS pathomechanism. The aim of the study was an assessment of ghrelin level in plasma in women with PCOS before and after the treatment and ghrelin's influence on androgen level change.

MATERIAL AND METHODS: The study included 25 women with the diagnosed PCOS (mean age 25.3+/-4.05 yr). The tests were done twice: before the treatment and after 6-month therapy with Diane 35 (cyproterone acetate 2 mg with ethinylestradiol 35 mug). Following hormones were measured: ghrelin, free testosterone, androstendione, dehydroepiandrosterone sulfate, 17-OH-progesterone and estradiol.

RESULTS: The received results in both groups were compared with the control group (11 healthy women, mean age 26.0+/-2.6 yr). No statistically significant differences in ghrelin levels before (187.8+/-8.1 fmol/ml) and after the therapy (185.6+/-9.5 fmol/ml) were found. Similar results were received when two groups of women compared with the control (186.5+/-8.7 fmol/ml). No correlations between ghrelin and androgen levels were confirmed.

CONCLUSIONS: Final conclusion is that there is no direct impact of ghrelin level on PCOS pathogenesis, however, its role in development of obesity, hyperinsulinemia and insulin resistance co-occurring with metabolic disorders syndrome cannot be excluded....

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Journal Article 2006; 27(6): 795-798 PubMed PMID: 17187004 Citation  Keywords:  Adult, Female, Glycoprotein Hormones, alpha Subunit:metabolism, Humans, Male, Middle Aged, Prolactin:metabolism, Reference Values, Stimulation, Chemical, Thyroid Function Tests, Thyrotropin:metabolism, Thyrotropin-Releasing Hormone:physiology,.   

OBJECTIVE: The alpha-subunit (Alpha-SU) response to TRH was studied to examine the response of alpha-SU under TRH stimulation in normal situation.

METHODS: Thirty seven healthy individuals were included in the study. They were divided into two groups according to the data taken: A with TSH equal or more than seven fold the basal values (0: 3.14+/-1.2 microU/ml., 30 after TRH: 20.22+/-4.6 microU/ml) and B with TSH 2 to 6 fold the basal values (0: 0.5+/-0.1 microU/ml., 30 after TRH: 2.9+/-0.5 microU/ml). Both groups exhibited similar FT3 and FT4 levels.

RESULTS: In group A, prolactin displayed a 3 fold increase from the basal values, whereas alpha-SU increased 4 fold with a difference being statistically significant (p<0.001). In contrast, in group B individuals neither prolactin nor alpha-SU exhibited any significant difference from the basal values.

CONCLUSION: The expression of alpha-SU upon TRH stimulation is dependent on the TSH basal values....

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