Diagnostic capabilities of fractal dimension and mandibular cortical width to identify men and women with decreased bone mineral density.

UNLABELLED: Dental panoramic radiographs could be used to screen for osteopenia. We found the fractal dimension to be a good discriminator of osteopenia in both men and women but that the mandibular cortical width (MCW) did not perform as well in men. The fractal dimension may be a valid screening tool. INTRODUCTION: The aim of this study was to assess the diagnostic capability of the fractal dimension and MCW measured from dental panoramic radiographs in identifying men and women with decreased bone mineral density (BMD). METHODS: The MCW and fractal dimension were measured from dental panoramic radiographs as surrogates for BMD. These measures were then compared to the results from dual-energy X-ray absorptiometry (DXA) performed for clinical purposes. A total of 56 subjects with the panoramic radiograph taken within 6 months of the DXA exam were used in the analysis for this study. RESULTS: The area under the curve of the fractal dimension for identifying low BMD (T-score <-1.0) was 0.81 (0.67, 0.95) and 0.78 (0.49, 1.00) for men and women, respectively. For the MCW, the area under the curve was found to be 0.53 (0.34, 0.72) and 0.80 (0.58, 1.00) for men and women, respectively. CONCLUSIONS: In this largely male study population, the fractal dimension was found to be a good discriminator of low BMD in both men and women. The MCW did not perform as well in men.

Antiplatelet therapy in the elderly. Aspirin, ticlopidine-clopidogrel, and GPIIb/GPIIIa antagonists.

Antiplatelet agents including aspirin, dipyridamole, the thienopyridines, and the GPIIb/IIIa antagonists have collectively demonstrated their ability to have a significant impact on the incidence of recurrent MIs, strokes, and other vascular ischemic events in the geriatric population. Low-dose aspirin also seems to be effective and safe for the primary prevention of ischemic heart disease in men considered at high risk. There is no evidence that the recommendations from these studies had increased relevance to younger adults, and the studies considering age as a variable found antiplatelet agents had either similar or increased benefit in older patients. In view of the relatively reduced adverse effects of these agents when compared with their potential therapeutic benefit, it is important that they be considered in all older patients for secondary prevention and in certain high-risk groups for primary prevention of cardiovascular morbidity and mortality.

Mast cell disease associated with acute myeloid leukemia: detection of a new c-kit mutation Asp816His.

Mast cell disease (MCD), a proliferation of mast cells (MC), is occasionally associated with hematologic malignancies. Neoplastic MC have activating c-kit mutations. c-kit is a receptor tyrosine kinase required for the development, proliferation, and survival of MC. Interaction of c-kit with its ligand stem cell factor induces dimerization, receptor phosphorylation, and signal transduction. The most common c-kit mutation detected in neoplastic MCD is Asp816Val, which results in ligand-independent autophosphorylation of the receptor leading to MC proliferation. We describe the rare occurrence of MCD associated with acute myeloid leukemia, report a novel c-kit mutation Asp816 His, and discuss the pathogenesis of MCD associated with hematologic malignancies.

Human signaling protein 14-3-3zeta interacts with platelet glycoprotein Ib subunits Ibalpha and Ibbeta.

The initiation of primary hemostasis is mediated by interaction of the platelet glycoprotein Ib (GPIb) surface receptor and its arterial subendothelial von Willebrand factor (vWF) ligand. The intracellular signaling immediately following GPIb receptor occupancy connecting the adhesive event to platelet activation and aggregation has not been well characterized. The 14-3-3 proteins are a 27- to 30-kD ubiquitous protein family with diverse biologic roles, including functional modulation of several prominent signaling proteins. We used the yeast two-hybrid system and confocal microscopy to characterize the recently described interaction between GPIb and platelet 14-3-3zeta, and provide evidence for the potential signaling role of this protein. Two-hybrid interactions suggest that platelet 14-3-3zeta associates with the cytoplasmic domain of GPIb subunits Ibalpha and Ibbeta in transformed yeast cells. The 14-3-3 interaction with GPIbbeta may be partly mediated through the latter's phosphorylated serine 166 residue as its mutagenesis results in 20% to 40% reduced interaction. There was 51% to 59% reduced interaction between GPIb and three 14-3-3zeta deletion mutants compared with full-length 14-3-3zeta, suggesting that either the N-terminal dimerization or membrane-binding domains or more than one noncontiguous 14-3-3zeta element may be required for optimal GPIb interaction. Confocal studies of platelets and a megakaryocyte cell line provided additional evidence for interaction of 14-3-3zeta with GPIbalpha and GPIbbeta. We also found that, similar to the signaling mediators phosphatidylinositol 3-kinase and Src, platelet cytoskeletal 14-3-3zeta content is increased following vWF and ristocetin stimulation. We suggest that platelet 14-3-3zeta interacts with GPIbalpha and Ibbeta, that this interaction may be partly mediated through phosphoserine recognition, and that 14-3-3zeta cytoskeletal translocation may serve as a GPIb post-receptor occupancy signaling event.

Antiplatelet therapy. Aspirin, ticlopidine/clopidogrel, and anti-integrin agents.

Aspirin is the most widely employed antithrombotic agent in use today and has a proven role in the prevention and acute management of atherosclerosis-associated arterial thrombotic events. More recently developed antiplatelet agents have been found to have specific prophylactic roles associated with percutaneous coronary intervention and other clinical settings. This article outlines pharmacologic considerations and current clinical knowledge relevant to the use of aspirin, ticlopidine, clopidogrel, and the GPIIbIIIa antagonists in the management of thrombotic disorders.

Human platelet glycoprotein V: its role in enhancing expression of the glycoprotein Ib receptor.

Platelet adhesion to an injured blood vessel wall is a critical initiating step in hemostasis mediated by a four member receptor complex (glycoprotein Ib/V/IX) interacting with plasma von Willebrand factor (vWF). The function of the GPV subunit within this complex is presently undefined. To study the role of glycoprotein (GP) V within the GPIb receptor complex, we transfected the GPV subunit gene into a hematopoietic cell line that constitutively expresses the other three subunits (human erythroleukemia [HEL] cells). Using flow cytometry, we found transfected GPV was surface expressed in HEL cells; this, in turn, led to increased surface expression of the ligand-binding GPIb alpha and GPIX subunits. Radioligand binding assays showed that GPV-transfected HEL cells bound more vWF than their non- or mock-transfected counterparts. We employed confocal microscopy of GPV-transfected HEL cells to show that GPV colocalizes with GPIb alpha on the cell surface. These findings suggest that the GPV subunit plays a role within the GPIb receptor complex by enhancing Ib alpha surface expression.

The management of carcinoma of the anal canal by external beam radiotherapy, experience in Vancouver 1971-1988.

From 1971 to 1988 72 cases of carcinoma of the anal canal were treated by external beam radiotherapy, most commonly by 5000 cGy in 20 fractions given over 4 weeks. The actuarial survival at 5 years was 66% and the disease specific survival 78%. Nine patients had inguinal node metastases at diagnosis; their 5-year disease specific survival was 75%. 63 patients were inguinal node negative at presentation; their 5-year disease specific survival was 78%, by UICC 1987 staging: T1 71%, T2 88%, T3 41%, T4 42%. 17 patients developed local recurrence; 10 were suitable for abdominoperineal (AP) resection which was successful in 7. The probability of local control was related to T stage. 13 patients were left with a colostomy because of recurrence, 2 had a colostomy for radiation damage and 4 had their local recurrence managed palliatively, without a colostomy. As a result, 53 of the 72 patients (74%) were left with a functional anus. Severe late complications occurred in 6 (8%).

Splenic radiation for corticosteroid-resistant immune thrombocytopenia.

OBJECTIVE: To determine the role of splenic radiation as a treatment for immune thrombocytopenia. DESIGN: Retrospective analysis of an open, nonrandomized investigation. SETTING: A regional cancer center, referred care, and primary care settings. PATIENTS: Eleven older patients with idiopathic thrombocytopenic purpura (ITP) and 8 patients with secondary immune thrombocytopenia refractory to corticosteroid treatment for whom surgery would have posed a high risk. INTERVENTION: A short course (1 to 6 weeks) of radiation therapy to the spleen (total dose, 75 to 1370 cGy) with or without concurrent and postradiation corticosteroid administration. MEASUREMENTS: Efficacy was assessed by measuring any increase in the platelet count and by monitoring the duration of response and side effects. RESULTS: Of 11 patients with ITP, 8 patients responded. Three patients had a sustained (greater than 52 weeks) increase in the platelet count to safe levels after therapy was discontinued. An additional patient had a sustained response but required intermittent, low-dose corticosteroids. Four other patients had increases in their platelet counts that lasted from 8 to 25 weeks. Two of the eight patients without ITP had a positive response, whereas four did not respond, and two were not evaluable. Patients had no adverse reactions to the radiation treatment. CONCLUSION: Splenic radiation can be a safe and effective method to raise the platelet count in older patients with ITP that is refractory to corticosteroids and in whom the risks associated with splenectomy are high.