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Journal Article 2005; 26(1): 71-74 PubMed PMID: 15726025 Citation  Keywords:  DNA:genetics, Female, Fragile X Mental Retardation Protein, Fragile X Syndrome:complications, Friedreich Ataxia:genetics, Gait Ataxia:etiology, Humans, Iron-Binding Proteins:genetics, Middle Aged, Mutation:physiology, Nerve Tissue Proteins:genetics, Pheno.   

: DNA testing broadens diagnostic tools available for hereditary ataxias. However, together with current knowledge of genes and their mutations crop up new phenotype figures of diseases already well known. Diagnostic problems in practice can consist in part due to the very similar symptoms of hereditary ataxias and acquaintance in or availability of new techniques such as DNA testing and result in misdiagnosis. We present a case study of a 57 year-old woman with both expansion of the triplet repetitive sequence of FRDA gene and a premutation in FMR1 gene. At present we diagnose her with Very Late Onset Friedreich s ataxia, but we advise of possible combinations or aggravations of her symptoms due to manifestation of Fragile X premutation tremor/ataxia syndrome. In nontypical phenotypes of DNA verifying hereditary ataxias we recommend searching of comorbidity, specifically from a range of hereditary ataxias with very similar spectra of symptoms....

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Clinical Trial 2004; 25(6): 438-442 PubMed PMID: 15665807 Citation  Keywords:  Adult, Estradiol:blood, Follicle Stimulating Hormone:blood, Humans, Hypothalamo-Hypophyseal System:drug effects, Klinefelter Syndrome:blood, Luteinizing Hormone:blood, Male, Naloxone:administration & dosage, Narcotic Antagonists:administration & dosage, P.   

UNLABELLED: AIM TO THE STUDY: The investigation of the influence of anti-opioid drug on hypophyseal and gonadal hormones secretion in case of Klinefelter syndrome.

MATERIAL AND METHODS: The naloxone test (0,4 mg iv) was performed in 14 patients with Klinefelter syndrome aged from 19 to 32 and in 12 age matched control subjects with azoospermia and normal spermatogenesis in testicular histology. The plasma levels of FSH, LH, prolactin, testosterone and estradiol were established before and after 30, 60, 60 and 120 minutes respectively, following the drug administration.

RESULTS: Basal FSH, prolactin and estradiol levels were significantly higher whereas basal testosterone was significantly lower in patients with Klinefelter syndrome than in the control group. After the naloxone administration the mean plasma prolactin level decreased significantly (p=0.01) in Klinefelter subjects. The respective diminution in control group was not significant. The levels of FSH and LH as well as testosterone and estradiol did not change during the naloxone test in both Klinefelter and control subjects.

CONCLUSIONS: The naloxone administration in Klinefelter syndrome caused the decrease in plasma prolactin levels but did not affect the plasma level of another hypophyseal and gonadal hormones. The opioid controlled gonadotropin secretion is altered in case of Klinefelter syndrome....

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Case Reports 2004; 25(4): 307-309 PubMed PMID: 15361823 Citation  Keywords:  Acromegaly:blood, Empty Sella Syndrome:blood, Female, Growth Hormone:blood, Humans, Magnetic Resonance Imaging, Middle Aged, Octreotide:therapeutic use, Treatment Outcome,.   

: The normal functions of the pituitary gland may be suppressed when the gland is compressed onto the sella floor by arachnoid tissue extending through an impaired sella diaphragm. Interestingly, pituitary hormone hypo- and hypersecretion, including acromegaly, have been observed in patients with an 'empty sella'(1-4). This 'empty sella syndrome' has been classified into a primary form, in which no inciting factor (pituitary irradiation or surgery for a pituitary tumor) is present, and a secondary form, in which the empty sella occurs after pituitary procedures. In this report we describe a patient who presented with clinical and biochemical features of acromegaly and who had an empty sella on pituitary magnetic resonance imaging (MRI)....

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Comparative Study 2004; 25(1-2): 78-82 PubMed PMID: 15159688 Citation  Keywords:  Adenosine Triphosphatases:genetics, Animals, Cation Transport Proteins:genetics, Copper:deficiency, Disease Models, Animal, Female, Male, Median Eminence:diagnostic imaging, Menkes Kinky Hair Syndrome:genetics, Mice, Mice, Mutant Strains, Mutation, Recomb.   

OBJECTIVES: The mosaic mutation (Atp7a(mo-ms)) linked to X-chromosome is caused by changes in the Atp7a gene encoding CPx-type protein responsible for the ATP-dependent copper transport across cell membranes. Mosaic mutant males represent an animal model for Menkes disease in humans. Starting from the eighth day of life the mosaic males exhibit a progressive decrease in body weight with poor viability and progressive paresis of the hind limbs. In order to examine whether hypothalamic somatostatin metabolism may be different in normal and copper deficient mice, somatostatin accumulation at the level of median eminence in 14 days old normal and mosaic mutant males was compared.

METHODS: An electron microscopic immunocytochemical study on ultrathin brain slices was performed according to post-embedding immunogold procedure.

RESULTS: In non-mutant animals somatostatin has been detected in many synapses within median eminence. Gold particles moderately decorated synaptic vesicles and mitochondria. In mosaic mutant animals somatostatin expression within the median eminence was very low and only a few gold particles represented somatostatin. Particles were sporadically associated with synaptic vesicles, mitochondria or cytoskeleton elements. Moreover, pre- and post- synaptic parts of synapses were very often swollen.

CONCLUSION: Our data demonstrating that copper deficiency leads to the pathological changes within the median eminence ultrastructure and severe impairment of somatostatin expression suggest that this trace metal is an important element necessary for normal neurohormonal brain development....

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Journal Article 2004; 25(1-2): 31-39 PubMed PMID: 15159679 Citation  Keywords:  Arachidonic Acids:pharmacology, Cannabinoid Receptor Modulators:deficiency, Cannabinoids:therapeutic use, Endocannabinoids, Fibromyalgia:drug therapy, Humans, Irritable Bowel Syndrome:drug therapy, Migraine Disorders:drug therapy, Pain:drug therapy, Polyu.   

OBJECTIVES: This study examines the concept of clinical endocannabinoid deficiency (CECD), and the prospect that it could underlie the pathophysiology of migraine, fibromyalgia, irritable bowel syndrome, and other functional conditions alleviated by clinical cannabis.

METHODS: Available literature was reviewed, and literature searches pursued via the National Library of Medicine database and other resources.

RESULTS: Migraine has numerous relationships to endocannabinoid function. Anandamide (AEA) potentiates 5-HT1A and inhibits 5-HT2A receptors supporting therapeutic efficacy in acute and preventive migraine treatment. Cannabinoids also demonstrate dopamine-blocking and anti-inflammatory effects. AEA is tonically active in the periaqueductal gray matter, a migraine generator. THC modulates glutamatergic neurotransmission via NMDA receptors. Fibromyalgia is now conceived as a central sensitization state with secondary hyperalgesia. Cannabinoids have similarly demonstrated the ability to block spinal, peripheral and gastrointestinal mechanisms that promote pain in headache, fibromyalgia, IBS and related disorders. The past and potential clinical utility of cannabis-based medicines in their treatment is discussed, as are further suggestions for experimental investigation of CECD via CSF examination and neuro-imaging.

CONCLUSION: Migraine, fibromyalgia, IBS and related conditions display common clinical, biochemical and pathophysiological patterns that suggest an underlying clinical endocannabinoid deficiency that may be suitably treated with cannabinoid medicines....

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Journal Article 2003; 24(5): 321-324 PubMed PMID: 14647004 Citation  Keywords:  Adult, Coitus, Humans, Klinefelter Syndrome:blood, Male, Sexual Dysfunction, Physiological:blood, Testosterone:blood, Varicocele:blood,.   

OBJECTIVES: The aim of our study is to assess the relationship between serum testosterone levels and the coital activity in groups of married men with Klinefelter's syndrome and in men with a varicocele investigated for marital infertility. These are compared with a group of somatosexually well developed men with a normozoospermia and adequate sexual life.

SUBJECT AND METHODS: The serum testosterone levels were assessed in 77 patients with Klinefelter's syndrome (mean age 31 years, SD 5.78), 58 men with a varicocele (mean age 30.5 years, SD 5.80) and 85 healthy men with normal spermiological values (mean age 32.7 years, SD 6.31). The frequency of sexual intercourse in their marriage was assessed by interview.

RESULTS: We found that, although their serum testosterone levels were significantly lower (p < 0.01), the coital activity in both groups with somatosexual disorders did not significantly differ from the group of men with normal semen parameters. The coital activity in the group of men with Klinefelter's syndrome decreased after 35 years of age, before any decrease in serum male sex hormone levels occurred.

CONCLUSION: Statistical analysis revealed that coital activity did not correlate with testosterone levels, but correlated significantly with age. A possible interpretation of the data is that Mother Nature ensues the survival of species by the production of not only a redundant amount of spermatozoids, but also of male sex hormones....

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Journal Article 2003; 24(3-4): 249-254 PubMed PMID: 14523365 Citation  Keywords:  17-alpha-Hydroxyprogesterone:blood, Adolescent, Adrenocorticotropic Hormone:blood, Adult, Female, Hirsutism:blood, Humans, Hydrocortisone:blood, Hyperandrogenism:genetics, Pituitary-Adrenal System:physiopathology, Polycystic Ovary Syndrome:genetics, Stero.   

OBJECTIVES: Impaired adrenal function is common in patients with polycystic ovary syndrome (PCOS). Abnormal regulation of cytochrome P450 17 alpha is believed to cause the exaggerated 17-hydroxyprogesterone (17OHP) response to ACTH stimulation. The aim of the study was to evaluate cortisol and 17OHP response to low dose (1 microg) ACTH test and to compare it with the standard ACTH (250 microg) test in hyperandrogenic women with PCOS.

DESIGN AND MEASUREMENTS: We studied 27 PCOS and 22 control women. All participants were examined for mutations of the CYP21 gene, Cortisol and 17OHP levels before, 30 and 60 minutes after the IV injection of 250 microg ACTH (SDT) and after 1 microg ACTH (LDT). Fasting serum levels of LH, FSH, testosterone, DHEAS were determined in all participants.

RESULTS: Basal and ACTH stimulated Cortisol during the SDT (470+/-138 nmol/L and 761+/-143, respectively) were significantly higher in PCOS vs. controls (232+/-124 and 670+/-130, respectively) (p<0.03, p<0.02, respectively). Basal 17OHP (6.1+/-2.1 nmol/L) and the peak response to SDT (14.2+/-3.6 nmol/L) were significantly higher in PCOS vs. controls (4.2+/-2.1, 10.9+/-3.0, respectively) (p<0.003, p<0.004, respectively). Abnormally elevated 17OHP response to SDT was detected in 6/27 PCOS women (22%). No statistically significant difference between the PCOS and control groups were noted during the LDT in both cortisol and 17OHP levels.

CONCLUSIONS: These data suggest that the exaggerated 17-hydroxyprogesterone (17OHP) response to ACTH stimulation in PCOS is revealed by stimulation at a pharmacological dose (250 microg) but not by a physiological dose (1 microg)....

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Journal Article 2002; 23(Suppl 1): 9-13 PubMed PMID: 12019344 Citation  Keywords:  Aged, Animals, Humans, Jet Lag Syndrome:drug therapy, Melatonin:pharmacology, Sleep:drug effects, Sleep Initiation and Maintenance Disorders:drug therapy,.   

: In elderly insomniacs, melatonin treatment decreased sleep latency and increased sleep efficiency. This is particularly marked in Alzheimer's disease (AD) patients. Melatonin is effective to reduce significantly benzodiazepine use. In addition, melatonin administration synchronizes the sleep-wake cycle in blind people and in individuals suffering from delayed sleep phase syndrome or jet lag. Urinary levels of 6-sulphatoxymelatonin decrease with age and in chronic diseases like AD or coronary heart disease. The effect of melatonin on sleep is probably the consequence of increasing sleep propensity (by inducing a fall in body temperature) and of a synchronizing effect on the circadian clock (chronobiotic effect)....

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