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Journal Article 2001; 22(1): 53-73 PubMed PMID: 11393163 Citation  Keywords:  Adrenal Glands:physiology, Animals, Biological Clocks, Blood Pressure:physiology, Chronobiology Disorders:physiopathology, Chronobiology Phenomena, Chronotherapy, Circadian Rhythm:physiology, Drug Administration Schedule, Genomics, Homeostasis, Humans, Pi.   

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Journal Article 2006; 27(Suppl 1): 7-16 PubMed PMID: 17261999 Citation  Keywords:  Biomarkers:blood, Dental Amalgam:toxicity, Environmental Pollutants:toxicity, Humans, Hypersensitivity:diagnosis, Inflammation, Lymphocyte Activation, Metals:toxicity, T-Lymphocytes:immunology, Titanium:toxicity,.   

: Environmental factors are recognized as a cause of the increasing frequency of allergic and autoimmune diseases. In addition to external pollutants, metal ions released from dental restorations or from other body implants might trigger inflammation in susceptible subjects. In humans, genes governing metal-induced inflammation and autoimmunity are not yet known. In clinical praxis, metal-sensitive patients will present various symptoms ranging from oral mucosal changes and skin disease to excessive fatigue and autoimmune diseases. Since genetic markers of genetic susceptibility in man are not known, one has to rely on the phenototypic markers. Such biomarkers might be certain detoxification enzymes but also the presence of metal-specific memory cells in the blood. With the increasing use of metal implants in medicine and dentistry, it is important to have a proper tool for the diagnosis of metal allergy in susceptible subjects. After nickel, gold is now the second most common sensitizer. In addition to patch test, an in vitro blood test, an optimized commercially available lymphocyte transformation test (MELISA) is discussed. Both tests were used for the diagnosis of metal allergy in a selected group of 15 patients who suffered from clinical metal sensitivity in addition to other health problems. The concordance of the two tests was good but MELISA detected more metal allergies than patch test. The removal of incompatible dental material (RID) resulted in long-term health improvement in the majority of patients. We postulate that in vivo, metal ions activate T-cells, initiating systemic inflammation, which, through cytokines, affects the brain and hypothalamus-pituitary-adrenal axis. We postulate that in vivo metal ions will activate T-cells starting systemic inflammation which, through cytokines affect the brain and hypothalamus-pituitary-adrenal (HPA) axis. The treatment and rehabilitation of metal sensitive patients is based on a firm understanding and recognition of individual susceptibility. RID has to be done done with extreme caution and according to standard working protocol. If performed properly, this treatment can result in decreased systemic inflammation and improved health in sensitized patients....

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Case Reports 2006; 27(Suppl 1): 17-24 PubMed PMID: 17261998 Citation  Keywords:  Adult, Aged, Dental Amalgam:toxicity, Environmental Exposure, Female, Humans, Hypersensitivity:diagnosis, Immunoassay:methods, Lymphocyte Activation, Metals:toxicity, Middle Aged, Occupational Exposure, Reproducibility of Results, Sensitivity and Specific.   

OBJECTIVES: Chronic low-level metal exposure may result in metal sensitization and undesirable side-effects. The main sources of metal exposure are from the environment or from corrosion of dental metal alloys. Affected patients are routinely diagnosed with the epicutaneous (patch) test. However, such testing may induce false-positive (irritative) reactions and may in itself sensitize or exacerbate symptoms. Alternatively, MELISA (Memory Lymphocyte ImmunoStimulation Assay), an optimized lymphocyte transformation test (LTT), can be used. In this study we analyzed the overall frequency and distribution of metal sensitization among symptomatic, metal-exposed patients. In addition, we determined the reproducibility of the assay and assessed its clinical relevance for detecting and monitoring hypersensitivity to metals.

METHODS: To analyze the frequency and distribution of metal sensitization, blood from 700 consecutive patients was tested against a total of 26 metals in the validated LTT-MELISA. For reproducibility testing, 391 single metal tests from 63 patients were performed in parallel. Finally, to assess clinical relevance, 14 patients with known metal exposure showing local (dry mouth, Oral Lichen Planus, Burning Mouth Syndrome, eczema) and/or systemic (chronic infections, fatigue, autoimmune disorders, central nervous system disturbances, depression) effects were tested in LTT-MELISA. In 7 cases testing was repeated following removal of the allergy-causing metals or, in 2 additional cases, without therapeutic intervention.

RESULTS: Of the 700 patients tested, 74.6% responded to >/= 1 metal in LTT-MELISA, with a subgroup of 17.9% responding to >/= 3 metals. Reactivity was most frequent to nickel (68.2%), followed by cadmium (23.7%), gold (17.8%), palladium (12.7%), inorganic mercury (11.4%), molybdenum (10.8%), beryllium (9.7%), titanium dioxide (4.2%), lead (3.7%), and platinum (3.4%). Reproducibility was 94.9%, with most discordant results in a low-positive range. Removal of the alloys or prostheses containing allergenic metals resulted in remarkable clinical improvement correlating with a significant reduction or complete normalization of specific lymphocyte reactivity. In contrast, both LTT-MELISA reactivity and clinical symptoms remained unchanged in follow-up samples from the 2 patients who did not remove the source of metal exposure.

CONCLUSION: The optimized LTT-MELISA test is a clinically useful and reliable tool for identifying and monitoring metal sensitization in symptomatic metal-exposed individuals....

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Journal Article 2006; 27(Suppl 1): 31-35 PubMed PMID: 17261997 Citation  Keywords:  Adolescent, Adult, Aged, Aged, 80 and over, Dental Implants:adverse effects, Humans, Hypersensitivity:diagnosis, Immunoassay, Lymphocyte Activation, Middle Aged, Prostheses and Implants:adverse effects, Titanium:adverse effects,.   

OBJECTIVES: This study was carried out to investigate the potential of titanium to induce hypersensitivity in patients chronically exposed to titanium-based dental or endoprosthetic implants.

METHODS: Fifty-six patients who had developed clinical symptoms after receiving titanium-based implants were tested in the optimized lymphocyte transformation test MELISA against 10 metals including titanium. Out of 56 patients, 54 were patch-tested with titanium as well as with other metals. The implants were removed in 54 patients (2 declined explantation), and 15 patients were retested in MELISA.

RESULTS: Of the 56 patients tested in MELISA, 21 (37.5%) were positive, 16 (28.6%) ambiguous, and 19 (33.9%) negative to titanium. In the latter group, 11 (57.9%) showed lymphocyte reactivity to other metals, including nickel. All 54 patch-tested patients were negative to titanium. Following removal of the implants, all 54 patients showed remarkable clinical improvement. In the 15 retested patients, this clinical improvement correlated with normalization in MELISA reactivity.

CONCLUSION: These data clearly demonstrate that titanium can induce clinically-relevant hypersensitivity in a subgroup of patients chronically exposed via dental or endoprosthetic implants....

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Introductory Journal Article 2006; 27(Suppl 1): 3-4 PubMed PMID: 17261996 Citation  Keywords:  Autoimmune Diseases:etiology, Dental Amalgam:adverse effects, Environmental Exposure, Humans, Hypersensitivity, Metals:adverse effects,.   

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Introductory Journal Article 2006; 27(Suppl 1): 5-6 PubMed PMID: 17261995 Citation  Keywords:  Dental Amalgam:adverse effects, Humans, Hypersensitivity, Immune System:drug effects, Inflammation, Metals:adverse effects, Neurosecretory Systems:drug effects,.   

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Journal Article 2006; 27(6): 828-832 PubMed PMID: 17187024 Citation  Keywords:  Acromegaly:blood, Adenoma:blood, Adult, Aged, Aged, 80 and over, Bromocriptine:therapeutic use, Female, Follow-Up Studies, Hormone Antagonists:therapeutic use, Human Growth Hormone:blood, Humans, Insulin-Like Growth Factor I:analysis, Male, Middle Aged, P.   

OBJECTIVES: Acromegaly is a rare disease with increased mortality rate. The aim was to present our centre experience in the diagnosis and treatment of a series of patients suffering from acromegaly.

METHODS: 130 patients (55 men, 75 women) aged 19-84 years presenting with clinical and hormonal features of acromegaly, attending Department of Endocrinology and Out-patient Clinic between 1990 and 2004 were studied. They were analyzed their GH and IGF-1 levels, CT and MRI scans, and they were administered medical therapy, neurosurgery and radiotherapy.

RESULTS: We have observed 106 macro-, 16 microadenomas and 1 case of ectopic GHRH. 115 patients were operated, as cured were recognized 74 of them. Pituitary irradiation was applied to 11 patients, in 4 of them it did not cure the disease. Medical therapy was efficacious in 12% patients treated with bromocriptine, 73% with long-acting lanreotide and 58% with long-acting octreotide. In 7 patients other malignant neoplasm were detected. 11 patients died during the follow-up.

CONCLUSIONS: There is possible underdiagnosis of acromegaly in our region, especially in males. We have observed better diagnostic opportunities in recent years when MRI was available. It was accompanied by better outcome of surgical and pharmacological treatment and better control of the complications of the disease....

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Case Reports 2006; 27(6): 691-694 PubMed PMID: 17187023 Citation  Keywords:  Age of Onset, Gene Deletion, Humans, Male, Membrane Proteins:genetics, Mental Disorders:complications, Pedigree, Severity of Illness Index, Suicide, Urologic Diseases:complications, Wolfram Syndrome:complications,.   

OBJECTIVE: Wolfram syndrome (WS) is an autosomal recessive disorder characterized by the association of juvenile-onset diabetes mellitus and optic atrophy. It is also known by the acronym DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness).

PATIENTS, METHODS AND RESULTS: We diagnosed Wolfram syndrome in 2 male siblings and determined a new mutation (c. 1522-1523delTA, Y508fsX421). Both affected siblings were homozygous, other family members were heterozygous. Dilated renal outflow tracts in the third decade, and neuropsychiatric disorders including bipolar disorder and neurosensorial deafness appear in the fourth decade in ordinary WS, whereas these features appeared in second decade in our patients. This mutation may be responsible for early appearance of dilated renal outflow tracts and multiple neurological abnormalities. Psychiatric disturbances such as suicide were reported at increased frequency in Wolfram patients and in heterozygous carriers. Suicidal behaviour occurred in our patients when they were yet 11 and 13 years old. Therefore, our findings may indicate that there may be a relationship between this WFS1 mutation and mood disorder such as suicidal behaviour.

CONCLUSIONS: We determined a new mutation (c. 1522-1523delTA, Y508fsX421) in WS1 gene in 2 siblings with Wolfram syndrome. This mutation may be responsible for early appearance of clinical features of Wolfram syndrome, and there may be a relationship between this mutation and suicidal behaviour....

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