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Biomedical subjects

Sunday O Akintoye

Publications and source records attributed to Sunday O Akintoye.

7 recordsLinked to original sources
PubMed2006

Pegvisomant for the treatment of gsp-mediated growth hormone excess in patients with McCune-Albright syndrome.

CONTEXT: GH excess affects approximately 20% of the patients with McCune-Albright syndrome (MAS). MAS is caused by sporadic, postzygotic, activating mutations in the GNAS gene, which codes for the cAMP-regulating protein, G(s)alpha (gsp oncogene). These same mutations are found in approximately one third of the sporadic cases of acromegaly. OBJECTIVE: We examined efficacy of the GH receptor antagonist, pegvisomant, in controlling gsp oncogene-mediated GH excess and skeletal disease (fibrous dysplasia of bone) associated with MAS. SETTING AND PATIENTS: Five MAS patients with GH excess were treated with 20 mg/d sc injection of pegvisomant for 12 wk in a randomized, double-blind, placebo-controlled crossover study at the National Institutes of Health. MAIN OUTCOME MEASURES: The primary measure of efficacy was normalization of IGF-I. Secondary outcome measures were reduction in serum IGF binding protein-3 (IGFBP-3), improvement of fatigue and sweating, and reduction in markers of bone metabolism and bone pain. RESULTS: Combined mean changes in serum IGF-I at 6 and 12 wk were -236.4 ng/ml (53%, P < 0.005) and -329.8 ng/ml (62%, P < 0.001), respectively. IGFBP-3 decreased by 0.8 mg/liter (24%, P < 0.01) and 2.9 mg/liter (37%, P < 0.005), respectively. There were no significant changes in signs and symptoms of acromegaly or markers of bone metabolism and bone pain, nor was there a significant change in pituitary size. Retrospective comparison of the degree of control achieved with pegvisomant vs. other medications (long-acting octreotide +/- dopamine agonist) in the same group showed that the two regimens were similarly effective. CONCLUSIONS: Pegvisomant effectively reduced IGF-I and IGFBP-3 levels in gsp-mediated GH excess but had no effect on fibrous dysplasia.

Bone and Bones↗
PubMed2006

Skeletal site-specific characterization of orofacial and iliac crest human bone marrow stromal cells in same individuals.

Autologous grafts from axial and appendicular bones commonly used to repair orofacial bone defects often result in unfavorable outcome. This clinical observation, along with the fact that many bone abnormalities are limited to craniofacial bones, suggests that there are significant differences in bone metabolism in orofacial, axial and appendicular bones. It is plausible that these differences are dictated by site-specificity of embryological progenitor cells and osteogenic properties of resident multipotent human bone marrow stromal cells (hBMSCs). This study investigated skeletal site-specific phenotypic and functional differences between orofacial (maxilla and mandible) and axial (iliac crest) hBMSCs in vitro and in vivo. Primary cultures of maxilla, mandible and iliac crest hBMSCs were established with and without osteogenic inducers. Site-specific characterization included colony forming efficiency, cell proliferation, life span before senescence, relative presence of surface markers, adipogenesis, osteogenesis and transplantation in immunocompromised mice to compare bone regenerative capacity. Compared with iliac crest cells, orofacial hBMSCs (OF-MSCs) proliferated more rapidly with delayed senescence, expressed higher levels of alkaline phosphatase and demonstrated more calcium accumulation in vitro. Cells isolated from the three skeletal sites were variably positive for STRO 1, a marker of hBMSCs. OF-MSCs formed more bone in vivo, while iliac crest hBMSCs formed more compacted bone that included hematopoietic tissue and were more responsive in vitro and in vivo to osteogenic and adipogenic inductions. These data demonstrate that hBMSCs from the same individuals differ in vitro and in vivo in a skeletal site-specific fashion and identified orofacial marrow stromal cells as unique cell populations. Further understanding of site-specific properties of hBMSCs and their impact on site-specific bone diseases and regeneration are needed.

Adolescent↗
PubMed2005

Recurrent aphthous stomatitis.

The cause of recurrent aphthous stomatitis (RAS) remains unknown despite considerable research. This article reviews the evidence for current theories regarding this disorder, including possible suspected relationships with microbial and immunologic factors, and presents medical diseases that mimic RAS lesions in certain patients. Topical management of the common form of minor RAS is described along with systemic therapy currently available to patients with severe forms of this disease.

Adolescent↗
PubMed2003

Dental characteristics of fibrous dysplasia and McCune-Albright syndrome.

OBJECTIVE: Fibrous dysplasia (FD) is a skeletal disorder often associated with McCune-Albright syndrome, a rare multisystem disorder caused by GNAS1 gene mutation. FD frequently affects the craniofacial bones, including the maxilla and the mandible; nevertheless, its effects on dental tissues and the implications for dental care remain unclear. The aim of this study was to characterize the dental features associated with FD and the reaction of affected bones to routine dental therapy. Study design Thirty-two patients with FD underwent dental evaluation and endocrine testing as part of the diagnosis of FD/McCune-Albright syndrome. Any dental anomalies were recorded, and the associations between endocrinopathies and dental anomalies were analyzed statistically by means of the paired t test. RESULTS: Eighty-four percent had FD in the maxilla and/or mandible; endocrine dysfunction; and/or renal phosphate wasting. The caries index scores were 2.9 (ages 4-17 years) and 9.6 (ages 18-50 years). Malocclusion (81%) and other prevalent dental anomalies (41%) included tooth rotation, oligodontia, and taurodontism. The expansion of the maxilla or mandible by FD did not distort the dental arch curvature, and routine dental therapies such as extractions, restorations, and orthodontic treatment did not exacerbate FD lesions. CONCLUSION: Maxillomandibular FD was associated with higher rates of caries and malocclusion than were present in healthy patients. Furthermore, patients with FD did not require special dental management and were able to undergo routine dental care without an exacerbation of FD lesions.

Adolescent↗
PubMed2002

A retrospective investigation of advanced periodontal disease as a risk factor for septicemia in hematopoietic stem cell and bone marrow transplant recipients.

OBJECTIVE: Septicemia is a cause of death in hematopoietic stem cell transplant (HSCT) recipients. Extraction of teeth with advanced periodontitis has been advocated before HSCT to prevent septicemia in myeloablated hosts. The primary aim of the present study was to determine impact of chronic periodontitis, as measured by radiographic alveolar bone loss, on septicemia and transplant mortality. STUDY DESIGN: A retrospective design was used to study 77 subjects who received pretransplant dental evaluation, panoramic radiography, and full myeloablative allogeneic HSCT to treat hematologic malignancies. Radiographic crestal alveolar bone loss was measured with a Schei ruler on all teeth. Microorganisms isolated from positive blood cultures within the first 100 days after transplant were categorized as of likely origin from periodontal, oral, or any body sites. Spearman correlation and logistic regression analysis assessed associations between positive blood cultures, mean subject whole-mouth percent radiographic crestal alveolar bone loss, and 100-day survival. RESULTS: Radiographic crestal alveolar bone loss per study subject averaged 13% +/- 7%, with 18.2% exhibiting bone loss of 20% or greater. During the initial 100 days after transplant, 63.6% subjects yielded septicemia-associated positive blood cultures, with Staphylococcus epidermidis, Streptococcus mitis, Enterococcus faecalis, Streptococcus sanguis, Staphylococcus aureus, and Escherichia coli as the most common isolates recovered. No statistically significant associations were found between mean subject radiographic alveolar bone loss and septicemia of likely periodontal or oral origin. CONCLUSION: In this preliminary study, no relationship was found between radiographic periodontal status and septicemia or mortality within the initial 100 days after transplant. A larger-sized, prospective study is warranted to further delineate the risk of septicemia from periodontal and other oral diseases in immunocompromised patients.

Adult↗
PubMed2002

Characterization of gsp-mediated growth hormone excess in the context of McCune-Albright syndrome.

McCune-Albright syndrome (MAS) is a disorder characterized by the triad of café-au-lait skin pigmentation, polyostotic fibrous dysplasia of bone, and hyperfunctioning endocrinopathies, including GH excess. The molecular etiology of the disease is postzygotic activating mutations of the GNAS1 gene product, G(s)alpha. The term gsp oncogene has been assigned to these mutations due to their association with certain neoplasms. The aim of this study was to estimate the prevalence of GH excess in MAS, characterize the clinical and endocrine manifestations, and describe the response to treatment. Fifty-eight patients with MAS were screened, and 22 with stigmata of acromegaly and/or elevated GH or IGF-I underwent oral glucose tolerance testing. Twelve patients (21%) had GH excess, based on failure to suppress serum GH on oral glucose tolerance test, and underwent a TRH test, serial GH sampling from 2000-0800 h, and magnetic resonance imaging of the sella. We found that vision and hearing deficits were more common in patients with GH excess (4 of 12, 33%) than those without (2 of 56, 4%). Of interest, patients with a history of precocious puberty and GH excess who had reached skeletal maturity achieved normal adult height despite a history of early epiphyseal fusion. All 9 patients tested had an increase in serum GH after TRH, 11 of 12 (92%) had hyperprolactinemia, and all 8 tested had detectable or elevated nighttime GH levels. Pituitary adenoma was detected in 4 of 12 (33%) patients. All patients with elevated IGF-I levels were treated with cabergoline (7 patients), long-acting octreotide (LAO; 8 patients), or a combination of cabergoline and LAO (4 patients). In six of the seven patients (86%) treated with cabergoline, serum IGF-I decreased, but not to the normal range. In the eight patients treated with LAO alone, IGF-I decreased, and, in four, returned to the normal range. The remaining 4 patients were treated with a combination of cabergoline and LAO. For them, symptoms of GH excess diminished, and IGF-I decreased further, but did not enter the normal range. GH excess is common in MAS and results in a distinct clinical phenotype characterized by inappropriately normal stature, TRH responsiveness, prolactin cosecretion, small or absent pituitary tumors, a consistent but inadequate response to treatment with cabergoline, and an intermediate response to LAO.

Adenoma↗