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Comparative Study 2005; 26(6): 675-679 PubMed PMID: 16380708 Citation  Keywords:  Adolescent, Adrenergic Uptake Inhibitors:therapeutic use, Adult, Analysis of Variance, Appetite Depressants:therapeutic use, Appetite Regulation:drug effects, Cyclobutanes:therapeutic use, Female, Humans, Insulin:blood, Leptin:blood, Neuropeptide Y:blood,.   

OBJECTIVE: Some neuropeptides and monoaminergic neurotransmitters may affect hypothalamic feeding centres, sympathetic activity and thermogenesis. Sibutramine (BTS54524; N-[1-[1(4-chloro phenyl) cyclobutyl]-3methyl N,N-dimethylamine hydrochloride monohydrate) is a new 5-HT serotonin and noradrenaline reuptake inhibitor (SNRI), antiobesity drug. The aim of this study was to evaluate the effects of the sibutramine therapy on plasma neuropeptide Y (NPY), insulin, leptin and beta-endorphin concentrations in obese patients.

METHODS: Sibutramine, serotonin and noradrenaline reuptake antiobesity drug was administered for 6 months in a dose of 10 mg daily in 60 obese women (BMI 30-40 kg/m2) (mean 34 kg/m2). Plasma NPY, leptin, beta-endorphin and insulin concentrations were measured with RIA methods using commercial kits (Peninsula Lab, Linco, Peninsula Lab, Swierk respectively). The above neuropeptides levels were evaluated before and after the 6 month sibutramine therapy in 60 obese women as well as in 30 obese women on low caloric diet and in 30 of the control group.

RESULTS: In 85% obese patients a decrease of body weight was found after 6 month therapy with sibutramine. A decrease in total cholesterol, LDL and triglycerides and an increase in HDL were observed after the sibutramine treatment. We have demonstrated that the sibutramine therapy leads to the decrease of plasma NPY, beta-endorphin, insulin and leptin concentrations in obese patients. After low diet therapy we have observed a decrease in plasma leptin levels, however we did not find significant changes in plasma leptin, NPY, beta-endorphin and insulin concentrations.

CONCLUSIONS: We suggest that the effects on the disturbed activity of NPY, beta-endorphin, insulin and leptin may be involved in the mechanism of sibutramine action....

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Controlled Clinical Trial 2005; 26(6): 713-718 PubMed PMID: 16380702 Citation  Keywords:  Adult, Anthropometry, Anxiety:physiopathology, Autonomic Nervous System:physiology, Combined Modality Therapy, Electrocardiography, Exercise:physiology, Exercise Therapy, Female, Heart Rate:physiology, Humans, Male, Psychiatric Status Rating Scales, Psych.   

OBJECTIVES: The aim of the study was to determine the status of the autonomic nervous system (ANS) in anxiety disorder patients and to evaluate possible exercise intervention in order to improve the ANS and overall psychiatric status of patients.

PATIENTS AND METHODS: The ANS function was monitored via means of heart rate variability (HRV) changes during a 6-week hospitalization at the Psychiatric Clinic of University Hospital in Olomouc. The status of ANS was monitored by the new evaluation method of spectral analysis (SA) of HRV. The research involved 43 anxiety patients (29 women and 14 men) who underwent six weeks of intensive psychotherapy; part of the test group also participated in regular aerobic exercise.

RESULTS: In the sense of autonomic dysfunction we can not give clear-cut answers to the question whether the autonomic dysfunction could be one of the predictors of anxiety disorder, although our results suggest lower vagal representation in the spectra. Unlike in the healthy population the exercise had a positive impact only on a limited number of patients. Regular endurance exercise on a stationary bicycle had a positive impact on the ANS efficiency only in patients with primary ANS activity reduction. In patients with normal ANS efficiency the exercise intervention had no effect; in some cases we even found activity reduction during the hospitalization period. However, the exercise had a positive effect on the course and outcome of the applied therapy in all patients.

CONCLUSIONS: ANS disturbances have not been exhibited in some patients suffering from anxiety disorder. Due to the positive impact of regular physical activity on cardiovascular, metabolic, neural, and psychological changes in organism, monitored exercise should be implemented into therapeutic programs for patients with anxiety disorders....

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Clinical Trial 2005; 26(6): 709-712 PubMed PMID: 16380696 Citation  Keywords:  Adrenocorticotropic Hormone:blood, Adult, Dexamethasone:therapeutic use, Down-Regulation, Female, Humans, Hydrocortisone:blood, Middle Aged, Nelson Syndrome:blood, Somatostatin:therapeutic use, Treatment Outcome, Valproic Acid:therapeutic use,.   

OBJECTIVE: Pituitary tumours occurring in patients bilaterally adrenalectomized because of Cushing's disease (Nelson's syndrome) are frequently invasive and a complete their resection is not possible in most of them. Administration of the drugs decreasing ACTH secretion could be helpful in such unresectable tumours. We tried to evaluate the influence of somatostatin and valproic acid, compared to dexamethasone, in short-term studies, on plasma ACTH levels in Nelson's syndrome (NS).

MATERIAL AND METHODS: Basal ACTH levels were determined within 18 h after last dose of hydrocortisone and next, 1 and 2 hours following oral administration of 20 mg of hydrocortisone. Somatostatin was injected s.c. in two patients with NS while sodium valproate and dexamethasone were administered orally for three days in three patients with NS (two with an invasive pituitary tumour and one with a localized, intrasellar adenoma). The blood for ACTH and cortisol determination was drawn before the tests (two hours after 20 mg of hydrocortisone ingestion) as well as 1 and 2 hours following somatostatin injection and after 3 days of valproic acid or dexamethasone administration.

RESULTS: High plasma ACTH levels were found before the tests. Somatostatin lowered ACTH levels in both patients, more effectively in the patient with non-invasive pituitary adenoma. Valproic acid decreased moderately ACTH concentration in two patients, while following dexamethasone administration a fall in ACTH levels was observed in all three patients, the most evident in the patient with a non-invasive Nelson's adenoma.

CONCLUSION: Somatostatin seemed to be more effective in its inhibitory action on ACTH secretion than valproic acid, thus its administration in invasive cases of NS could be tried as a supplementary method to neurosurgery. The response to dexamethasone administration indicates that a feed-back regulation, although impaired, exists in these cases....

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Clinical Trial, Phase I 2005; 26(6): 685-689 PubMed PMID: 16380684 Citation  Keywords:  Adult, Antipsychotic Agents:therapeutic use, Benzodiazepines:therapeutic use, Brain Mapping, Cerebrovascular Circulation:drug effects, Cysteine:analogs & derivatives, Frontal Lobe:blood supply, Humans, Male, Middle Aged, Organotechnetium Compounds, Psychi.   

OBJECTIVES: Altered regional cerebral blood flow (r-CBF) is mentioned as one of possible etiological factors or as a consequence of schizophrenia. Perfusion scintigraphic brain studies with SPECT (Single Photon Emission Computed Tomography) and PET (Positron Emission Tomography) can detect areas of the brain with altered perfusion during the disease. Conflicting data exist on follow-up after treatment. The aim of our study was to evaluate r-CBF in acute first-episode schizophrenia and early effect of antipsychotic drugs on r-CBF.

DESIGN AND SETTING: Clinical criteria for schizophrenia were met according to International Classification of Diseases-10th Edition (ICD-10). Psychic status and severity of the disease in each patient were evaluated with psychiatric interview, Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression (CGI) on the same day as the scintigraphic study. Brain perfusion SPECT was performed 20 minutes after 99mTc-ECD application. R-CBF was measured in 9 first-episode schizophrenic male patients 2-7 (median 6) days after the beginning of antipsychotic treatment and 8-15 (median 9) weeks later. Semiquantitative analysis of r-CBF was performed with cerebellum as the reference region. R-CBF was evaluated for 12 regions in each study.

RESULTS: Decrease in perfusion in comparison to cerebellum was detected in left (90%) and right (93%) frontal lobes. Increase in perfusion between the first (t1) and the second (t2) investigation was significant (p<0.05) for both frontal regions (left 94%, right 97%). Significant decrease in PANSS (p<0.05) and CGI (p<0.001) scores was noted and correlated well with the increase of r-CBF.

CONCLUSIONS: Our findings implicate that patients with first-episode schizophrenia have significant left hypoperfusion relative to the right in dorsolateral frontal lobes. Increased blood flow was observed bilaterally in dorsolateral frontal lobes after 10 weeks of antipsychotic medication. Significant amelioration of r-CBF correlated with clinical improvement....

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Clinical Trial 2005; 26(6): 667-674 PubMed PMID: 16380683 Citation  Keywords:  Adult, Agoraphobia:complications, Alprazolam:therapeutic use, Anti-Anxiety Agents:therapeutic use, Cognitive Therapy, Combined Modality Therapy, Female, Follow-Up Studies, Humans, Male, Middle Aged, Panic Disorder:complications, Paroxetine:therapeutic use.   

UNLABELLED: Most clinicians tend to believe that the occurrence of the anxiety disorder in comorbidity with a personality disorder often leads to longer treatment, worsens the prognosis, and thus increasing treatment costs. The study is designed to compare the short-term effectiveness of combination of cognitive behavioral therapy and pharmacotherapy in patient suffering with panic disorder with and without personality disorder.

METHOD: We compare the efficacy of 6th week therapeutic program and 6th week follow up in patients suffering with panic disorder and/or agoraphobia and comorbid personality disorder (29 patients) and panic disorder and/or agoraphobia without comorbid personality disorder (31 patients). Diagnosis was done according to the ICD-10 research diagnostic criteria confirmed with MINI and support with psychological methods: IPDE, MCMI-III and TCI. Patients were treated with CBT and psychopharmacs. They were regularly assessed in week 0, 2, 4, 6 and 12 by an independent reviewer on the CGI (Clinical Global Improvement) for severity and change, PDSS (Panic Disorder Severity Scale), HAMA (Hamilton Anxiety Rating Scale), SDS (Sheehan Disability Scale), HDRS (Hamilton Depression Rating Scale), and in self-assessments BAI (Beck Anxiety Inventory) and BDI (Beck Depression Inventory).

RESULTS: A combination of CBT and pharmacotherapy proved to be the effective treatment of patients suffering with panic disorder and/or agoraphobia with or without comorbid personality disorder. The 12th week treatment efficacy in the patients with panic disorder without personality disorder had been showed significantly better compared with the group with panic disorder comorbid with personality disorder in CGI and specific inventory for panic disorder--PDSS. Also the scores in depression inventories HDRS and BDI showed significantly higher decrease during the treatment comparing with group without personality disorder. But the treatment effect between groups did not differ in objective anxiety scale HAMA, and subjective anxiety scale BAI....

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Case Reports 2005; 26(6): 757-758 PubMed PMID: 16380671 Citation  Keywords:  Aged, Atrophy, Diagnosis, Differential, Empty Sella Syndrome:complications, Fatigue:diagnosis, Female, Hormones:therapeutic use, Humans, Hydrocortisone:therapeutic use, Hypopituitarism:complications, Inflammation:complications, Magnetic Resonance Imaging,.   

: A 75-year-old woman complained about progressing fatigue. She appeared somnolent, but fully oriented and in no acute distress. Her face was pale and puffy. She did not show any signs of focal neurological disease, and the remainder of the physical examination was unrevealing. Routine laboratory tests were unremarkable except for hyponatremia and mildly decreased levels of free T3 and free T4, with TSH in the normal range. Pituitary function tests demonstrated secondary adrenal insufficiency and hypothyroidism. Magnetic resonance imaging (MRI) unmasked hypophysitis with the characteristic findings of homogeneous gadolinium uptake of the pituitary and a prominent pituitary stalk ('dural tail sign', arrows in Fig. 1 A and B, sagittal and coronal views). Substitution of hydrocortisone and levothyroxine resulted in rapid and sustained improvement of all symptoms and normalisation of laboratory findings. MRI abnormalities normalized within the following six months. At follow-up three years later, MRI signs had further regressed and demonstrated an empty sella (Fig. 2 A and B)....

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Clinical Trial 2005; 26(5): 447-452 PubMed PMID: 16264418 Citation  Keywords:  Adolescent, Aging:physiology, Body Height:drug effects, Child, Female, Growth Hormone:therapeutic use, Hormones:blood, Human Growth Hormone:deficiency, Humans, Magnetic Resonance Imaging, Male, Pituitary Gland:anatomy & histology, Predictive Value of Test.   

INTRODUCTION: Certain relationships between pituitary size and growth hormone (GH) secretion have previously been observed, however they are still a matter of controversy. Organic abnormalities of the hypothalamic-hypophyseal region are important for predicting growth response to GH therapy.

AIM: Evaluation of relations between GH secretion and the pituitary size in short children and estimation of the efficacy of GH therapy in children with GH deficiency (GHD).

PATIENTS AND METHODS: The analysis comprised 216 short children (159 boys). Two GH stimulation tests, as well as magnetic resonance image (MRI) examination, were performed in each patient. All the patients with GHD were treated with GH for, at least, one year.

RESULTS: Significant correlations were found between pituitary height and GH secretion (p < 0.05). Patients were classified into three (3) groups: 1) pituitary hypoplasia (HP) for height age; 2) HP for the chronological age but not for the height age; 3) normal pituitary size. Significant differences in GH secretion were observed among the groups (6.1+/-5.3 vs. 8.1+/-4.4 vs. 12.3+/-9.1 ng/mL, respectively). There was a negative correlation between GH peak and height gain during GH therapy (r = -0.34). The highest growth improvement was noticed in patients with HP for the height age.

CONCLUSIONS: Pituitary hypoplasia for the height age is related to more severe GH deficiency and the best response to GH therapy....

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Journal Article 2005; 26(5): 439-446 PubMed PMID: 16264412 Citation  Keywords:  Autistic Disorder:chemically induced, Autoimmune Diseases:chemically induced, Chelating Agents:therapeutic use, Child, Humans, Inflammation:chemically induced, Mercury:analysis, Mercury Poisoning:epidemiology,.   

: The causes of autism and neurodevelopmental disorders are unknown. Genetic and environmental risk factors seem to be involved. Because of an observed increase in autism in the last decades, which parallels cumulative mercury exposure, it was proposed that autism may be in part caused by mercury. We review the evidence for this proposal. Several epidemiological studies failed to find a correlation between mercury exposure through thimerosal, a preservative used in vaccines, and the risk of autism. Recently, it was found that autistic children had a higher mercury exposure during pregnancy due to maternal dental amalgam and thimerosal-containing immunoglobulin shots. It was hypothesized that children with autism have a decreased detoxification capacity due to genetic polymorphism. In vitro, mercury and thimerosal in levels found several days after vaccination inhibit methionine synthetase (MS) by 50%. Normal function of MS is crucial in biochemical steps necessary for brain development, attention and production of glutathione, an important antioxidative and detoxifying agent. Repetitive doses of thimerosal leads to neurobehavioral deteriorations in autoimmune susceptible mice, increased oxidative stress and decreased intracellular levels of glutathione in vitro. Subsequently, autistic children have significantly decreased level of reduced glutathione. Promising treatments of autism involve detoxification of mercury, and supplementation of deficient metabolites....

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