Overview of the role of molecular methods in the diagnosis of malignant lymphomas

OBJECTIVE: To review the role of molecular genetics in the diagnosis of malignant lymphomas. DATA SOURCES AND STUDY SELECTION: Primary research studies and reviews published in the English literature that focus on molecular genetics and malignant lymphoma, in particular, clonality, chromosomal translocations, tumor suppressor genes, and Hodgkin disease. DATA EXTRACTION AND SYNTHESIS: Molecular genetics has an important role in the assessment of malignant lymphomas. Clonality, detected by Southern blot analysis or the polymerase chain reaction, is helpful for establishing the diagnosis of lymphoma in lesions with ambiguous morphologic and immunophenotypic findings. Southern blot analysis is the "gold standard" for clonality assessment, but the process is labor-intensive and time-consuming. Polymerase chain reaction analysis is more convenient, but a potentially significant false-negative rate exists in the analysis of some antigen receptor genes as a result of using consensus primers and the process of somatic hypermutation. Chromosomal translocations, which result in oncogene activation, occur in many types of B- and T-cell lymphomas, and their detection is helpful in classification as well as in establishing a diagnosis of malignancy. Gene rearrangements and chromosomal translocations also can be used to monitor minimal residual disease. Tumor suppressor genes, although their analysis is relatively less useful for diagnosis, are involved in both pathogenesis and tumor progression and will be more important diagnostically as this field continues to expand. Molecular genetic analysis has played a major role in improving our understanding of Hodgkin disease. CONCLUSIONS: Molecular genetic tests are currently important ancillary tools for the diagnosis and classification of malignant lymphomas, and their role is likely to increase in the future.     

A statistical approach to the evaluation of covariate effects on the receiver operating characteristic curves of diagnostic tests in glaucoma

PURPOSE: To describe an approach for the evaluation of covariate effects on receiver operating characteristic (ROC) curves and to apply this methodology to the investigation of the effects of disease severity and age on the diagnostic performance of frequency doubling technology (FDT) and standard automated perimetry (SAP) visual function tests for glaucoma detection. METHODS: The study included 370 eyes of 211 participants, with 174 eyes of 110 patients having glaucomatous optic neuropathy and 196 eyes of 101 subjects being normal. All patients underwent visual function testing with FDT 24-2 Humphrey Matrix and SAP SITA (Carl Zeiss Meditec, Inc., Dublin, CA). Disease severity was evaluated by the amount of neuroretinal rim loss assessed by confocal scanning laser ophthalmoscopy. An ROC regression model was fitted to evaluate the influence of disease severity and age on the diagnostic performance of the pattern SD (PSD) index from FDT 24-2 and SAP SITA. RESULTS: After adjustment for age, the areas under the ROC curves (AUCs) for SAP SITA PSD for 10%, 30%, 50%, and 70% loss of neuroretinal rim area were 0.638, 0.756, 0.852, and 0.920, respectively. Corresponding values for FDT 24-2 PSD were 0.766, 0.857, 0.922, and 0.962. For 10% and 30% rim loss, FDT 24-2 PSD had a significantly larger AUC than did SAP SITA PSD. CONCLUSIONS: A regression methodology to evaluate covariate effects on ROC curves can be useful for assessment of diagnostic tests in glaucoma. Using the proposed methodology, a significantly better performance of FDT 24-2 compared to SAP SITA for diagnosis of early glaucoma was demonstrated.     

Calcium channel blockade as a target for the cardiovascular effects induced by the 8 (17), 12E, 14-labdatrien-18-oic acid (labdane-302)

The cardiovascular effects induced by labdane-302, a diterpene isolated from the stems of Xylopia langsdorffianna St. Hill and Tull, were evaluated in male Wistar rats. In normotensive, conscious animals, labdane-302 produced dose-dependent hypotension and tachycardia. These effects were significantly attenuated after pre-treatment with L-NAME (20 mg/kg, i.v.). In isolated mesenteric artery rings, labdane-302 (10(-10)-10(-4)M) elicited concentration-dependent relaxation of phenylephrine-induced contractions (IC50 = 5.4 +/- 1.4 microM). Endothelium removal, and pre-treatment with L-NAME (100 microM) or indomethacin (10 microM) caused significant reductions in sensitivity. Labdane-302 also caused concentration-dependent relaxation in arterial rings pre-contracted with high extracellular KCl (80 mM). In Ca2+-free depolarized preparations, labdane-302 inhibited contractions produced by cumulative increases in extracellular Ca2+ concentration. In GH3 cells, labdane-302 (100 microM) inhibited whole-cell L-type Ca2+ currents by approximately 50%. These results demonstrate that labdane-302 causes hypotension through peripheral vasodilation, mediated in part by NO and PGI2 and by blockade of Ca2+ entry through L-type Ca2+ channels.     

Conjunctival hyperemia associated with bimatoprost use: a histopathologic study

PURPOSE: To evaluate histopathologic signs of conjunctival inflammation in patients with conjunctival hyperemia induced by bimatoprost treatment. DESIGN: Prospective interventional study. METHODS: The study included 15 eyes of 15 patients scheduled for cataract surgery. Patients in the treatment group (n = 9) exhibited trace to moderate conjunctival hyperemia when treated with bimatoprost 0.03% every day for 15 to 30 days before surgery. The control group (n = 6) included untreated patients with no ocular disease other than cataract. Conjunctival biopsies were obtained for histologic evaluation with light microscopy. RESULTS: Vascular congestion was observed in biopsies from 7 patients (78%) in the bimatoprost group and 5 patients (83%) in the control group. Signs of inflammation were found in biopsies from 2 patients (22%) in the bimatoprost group and 2 patients (33%) in the control group. CONCLUSIONS: Histopathologic signs of inflammation were no more frequent in conjunctival specimens from bimatoprost-treated patients with trace to moderate hyperemia than in those from untreated control subjects.