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1.
Gene Ther ; 24(3): 176-186, 2017 03.
Article in English | MEDLINE | ID: mdl-27996967

ABSTRACT

We evaluated late effects of AdhAQP1 administration in five subjects in a clinical trial for radiation-induced salivary hypofunction (http://www.clinicaltrials.gov/ct/show/NCT00372320?order=). All were identified as initially responding to human aquaporin-1 (hAQP1) gene transfer. They were followed for 3-4 years after AdhAQP1 delivery to one parotid gland. At intervals we examined salivary flow, xerostomic symptoms, saliva composition, vector presence and efficacy in the targeted gland, clinical laboratory data and adverse events. All displayed marked increases (71-500% above baseline) in parotid flow 3-4.7 years after treatment, with improved symptoms for ~2-3 years. There were some changes in [Na+] and [Cl-] consistent with elevated salivary flow, but no uniform changes in secretion of key parotid proteins. There were no clinically significant adverse events, nor consistent negative changes in laboratory parameters. One subject underwent a core needle biopsy of the targeted parotid gland 3.1 years post treatment and displayed evidence of hAQP1 protein in acinar, but not duct, cell membranes. All subjects responding to hAQP1 gene transfer initially had benefits for much longer times. First-generation adenoviral vectors typically yield transit effects, but these data show beneficial effects can continue years after parotid gland delivery.


Subject(s)
Aquaporin 1/genetics , Genetic Therapy/adverse effects , Xerostomia/therapy , Adenoviridae/genetics , Aquaporin 1/metabolism , Chlorides/metabolism , Genetic Vectors/genetics , Humans , Middle Aged , Radiotherapy/adverse effects , Salivary Glands/metabolism , Sodium/metabolism , Xerostomia/etiology
2.
Scand J Rheumatol ; 40(4): 299-303, 2011.
Article in English | MEDLINE | ID: mdl-21417550

ABSTRACT

OBJECTIVES: Thyroid dysfunction in the setting of systemic sclerosis (SSc) has been described previously. We aimed to determine the prevalence of anti-thyroid antibodies (ATA) in a large SSc cohort and to ascertain whether they are associated with distinct clinical phenotypes. METHODS: A total of 138 patients with SSc [46 with diffuse (dSSc) and 92 with limited scleroderma (lSSc)] and 100 healthy controls (HC) were tested for the presence of ATA [anti-thyroglobulin (anti-Tg) and anti-thyroid peroxidase (anti-TPO) antibodies] using a commercial enzyme-linked immunosorbent assay (ELISA). Clinical and serological data were recorded. RESULTS: An increased prevalence of anti-TPO but not anti-Tg antibodies was detected in patients with SSc compared to HC (27.5% vs. 14%, p = 0.016). Of note, a statistically significant increase of anti-TPO was detected only in patients with lSSc compared to HC (32.6% vs. 14%, p = 0.003). No correlations with other clinical features were detected. CONCLUSIONS: An increased prevalence of anti-TPO antibodies was identified in patients with lSSc. We propose that ATA testing should be offered to this subgroup of patients.


Subject(s)
Antibodies, Anti-Idiotypic/blood , Scleroderma, Diffuse/immunology , Scleroderma, Limited/immunology , Thyroid Gland/immunology , Adult , Aged , Autoantibodies/blood , Case-Control Studies , Cohort Studies , Female , Humans , Iodide Peroxidase/immunology , Male , Middle Aged , Phenotype , Scleroderma, Diffuse/blood , Scleroderma, Limited/blood
3.
Lupus ; 18(12): 1096-9, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19762385

ABSTRACT

Autoimmune thyroid disease has been associated with several systemic autoimmune disorders. However, limited data are available regarding the prevalence and clinical associations of thyroid autoimmunity in antiphospholipid syndrome (APS). Seventy-five patients with APS, 75 patients with systemic lupus erythematosus (SLE) and 75 healthy controls were tested for the presence of antithyroid antibodies (ATAs) (anti-thyroglobulin and anti-thyroid peroxidase [anti-TPO]) using commercial ELISA. Clinical data were also recorded. Although no significant differences in the prevalence of ATAs were detected among APS, SLE patient groups and healthy controls, a significant increase of anti-TPO antibodies in patients with APS-SLE was found. An increased prevalence of ATAs in APS population with ischemic central nervous system (CNS) clinical manifestations was also detected. We present novel associations between thyroid autoimmunity and ischemic CNS clinical manifestations in the setting of APS.


Subject(s)
Antiphospholipid Syndrome/immunology , Autoantibodies/immunology , Adult , Cross-Sectional Studies , Female , Humans , Lupus Erythematosus, Systemic/immunology , Male , Middle Aged
4.
Pediatr Hematol Oncol ; 21(6): 489-93, 2004 Sep.
Article in English | MEDLINE | ID: mdl-15552812

ABSTRACT

Hemangiopericytoma (HPC) is a rare soft tissue tumor The few published reports account for the little information available on its clinical management. Here the authors report the successful treatment of an adolescent girl with rare HPC of the tongue. After incomplete surgical excision of the tumor she was admitted to the Hematology-Oncology Department and was treated with a 3-drug combination regimen (ifosfamide, actinomycin D, vincristine) for 8 weeks. She achieved partial remission in week 9 based on the magnetic resonance imaging (MRI)findings. Conventional radiation therapy was initiated at week 9 and continued until week 16. At week 20, according to the MRI findings, she achieved complete remission and continuation therapy was initiated. The young girl has been alive without evidence of the disease for the last 3 years of follow-up. In conclusion, the current report indicates that in cases of incomplete surgical excision of the tumor, chemotherapy and radiotherapy seem to be effective.


Subject(s)
Hemangiopericytoma/therapy , Tongue Neoplasms/therapy , Adolescent , Combined Modality Therapy , Female , Hemangiopericytoma/pathology , Humans , Magnetic Resonance Imaging , Tongue Neoplasms/pathology
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