Acute health events in adult patients with genetic disorders: the Marshfield Epidemiologic Study Area.

PURPOSE: We ascertained and reviewed acute health events occurring in 2003 among patients age 18 and greater with well-defined single gene, chromosomal, and selected multifactorial conditions within the Marshfield Epidemiologic Study Area. METHODS: Of 47,077 adult Marshfield Epidemiologic Study Area Central cohort members, 1,831 (3.9%) had been given at least one of 71 ICD-9 codes appropriate for genetic diagnoses of interest. Physician review narrowed this to 591 (1.3%) validated patients for the study. Of the 591, 527 (89.2%) patients registered 6,849 visits, which were manually reviewed to delineate acute, relevant health events in the urgent care and primary care provider setting. RESULTS: A total of 244 acute relevant health events among 126 patients corresponding to 58 different genetic conditions were observed. Acute relevant health events corresponded to 3.4% of the total health events in patients identified with genetic problems. Categories of genetic conditions with the highest frequencies of acute relevant health events included chromosomal and microdeletion syndromes (21.3%), hematologic disorders (11.5%), muscular dystrophies (8.6%), and connective tissue disorders (10.2%). CONCLUSIONS: These data have multiple applications and implications in addressing the natural history, long-term medical needs and financial impact of adult patients with genetic conditions.     

Effects of silencing of HER2/neu gene in anti-BPDE-transformed cells

Anti-benzo[a]pyrene-7,8-diol-9,10-epoxide (anti-BPDE) is a metabolite of benzo[a]pyrene (B[a]P) and acts as a potent mutagen in mammalian systems. However, the molecular mechanisms related to anti-BPDE-induced carcinogenesis are poorly understood. We have used malignant human bronchial epithelial cells (16HBE-T) transformed by exposure to anti-BPDE to help characterize these possible molecular mechanisms. We have previously observed overexpression of HER2/neu in 16HBE-T. To further investigate the effects of HER2/neu on 16HBE-T cell biologic phenotype, we inhibited HER2/neu expression using RNA interference. Silencing of HER2/neu in 16HBE-T cells was performed in vitro using retrovirus-delivered short hairpin RNA (shRNA). Silencing of HER2/neu in 16HBE-T cells resulted in significant increases and decreases in the proportions of cells in G₀/G₁ phase (67.1 ± 2.1%) and in S phase (17.3 ± 4.1%), respectively, and significantly reduced cell viability and colony formation rate. These results may help to explain epithelial cell transformation following exposure to anti-BPDE, and suggest an oncogenic role for HER2/neu in anti-BPDE-induced carcinogenesis.     

Individual differences in phonological development: ages one and three years

This paper reports the results of a study of the persistence of individual differences in the phonological development of 10 normally developing children observed at age 1 year and again at age 3 years. Data were based on 1/2-hr audio and video recordings of weekly spontaneous mother-child interaction sessions in the home between 9 and 17 months and at 36 months. In addition, phonological and cognitive probes were administered at age 3. At age 1 the children were compared at four times selected on the basis of the number of different word types used in a session. Preferences for particular phonological categories (fricatives, liquids, final consonants) were found not to correspond to relative mastery of those categories at age 3. Based on both babble and words, high use of vocalizations containing true consonants was found to be predictive of greater phonological advance at age 3. Phonological errors of two kinds were distinguished for age 3: those resulting from difficulty with specific segments and those more typical of younger children, involving the rearrangement, assimilation, or deletion of segments or syllables (prosodic errors). The children differed in intelligibility and in specific segment substitutions and cluster reductions. They also differed in the proportion of prosodic errors made and in consistency in segmental errors. Lastly, aspects of cognitive or learning style as expressed in phonological organization were found to be recognizable at both age 1 and age 3.     

Ocular MR imaging and spectroscopy: an ex vivo study

Six eyes, freshly enucleated because of choroidal melanoma, were imaged on a 1.4-T superconducting magnetic resonance (MR) imaging system, and relaxation times were calculated for various parts of the eye. Unfixed fresh tissue samples were obtained for nuclear magnetic resonance spectroscopy (NMRS) on a variable-field (0.19-1.4 T) resistive unit. Detailed ocular anatomy was demonstrated. The NMRS relaxation times correlated with the MR imaging intensity patterns. The sensitivity of MR imaging to states of hydration provides an excellent window for appreciation of ocular anatomy.     

No evidence of frequent human immunodeficiency virus type 1 infection in seronegative at-risk individuals

The possible existence of human immunodeficiency virus type 1 (HIV-1) infection in asymptomatic seronegative at-risk individuals was investigated in a prospective study of 55 seronegative high-risk individuals (42 homosexual men and 13 heterosexual individuals) and 32 seronegative hemophiliacs treated with factor VIII or IX concentrates before viral inactivation by heat treatment and systematic screening of blood donations. Tests used include the polymerase chain reaction assay with three primer pairs (one in the gag region and two in the pol region) and tests for serum p24 antigen, anti-nef serology (Western blot), and five biologic markers frequently altered by HIV infection (CD4 lymphocyte count, serum beta 2-microglobulin and neopterin concentration, and serum IgG and IgA concentration). Although 91 of 92 HIV-1-seropositive persons were positive in testing with at least one primer pair, no positive result was observed in seronegative at-risk individuals or in 117 seronegative low-risk controls. No nef antibody was found in seronegative at-risk individuals or seronegative controls, but 44 (47%) of 92 HIV-1-seropositive persons had nef antibodies. These findings do not support the existence of frequent HIV-1 infection in seronegative at-risk individuals.     

MM6 Decision Analysis: What is its Utility for Pharmacoeconomic Analysis?

This session is intended for sharing and comparing computer software applications for research, management, and practice. Software applications will be demonstrated for decision analysis, cost effectiveness analysis, multiattribute utility computation, and assessing patient utilities. Desktop applications, will be discussed. Laptop and handheld computer software will be demonstrated. Pharmacoeconomic software allows data to be analyzed from different perspectives: patient, provider, hospital, managed care, and society. Software models also allow assessment of health care products or services from different quantitative perspectives: cost of illness, cost minimization, cost-benefit, cost-effectiveness, and cost-utility. The integration of decision analysis and spreadsheets will also be discussed. Software is utilized to collect information, analyze data, present findings, or educate managers, providers and patients. Pros and cons of each analytical and software approach will be discussed. Participants are encouraged to bring their own laptops to demonstrate their own software or related Internet offerings in an informal roundtable fashion. Software beta versions allowed; "viruses" discouraged.     

A double‐blind,randomized trial of 0.05% betamethasone vs. topical catalase/dismutase superoxide in vitiligo

Background Among all the topical immunomodulators, vitiligo's mainstay therapy includes topical corticosteroids. Many other non‐immune theories have also been suggested for vitiligo's pathogenesis, but the role of oxidative stress has gained more importance in recent years. Objective To compare the effect of topical 0.05% betamethasone vs. catalase/dismutase superoxide (C/DSO). Study design Randomized, matched‐paired, double‐blind trial. Setting Dermatology Section, University of Antioquia, Medellín, Colombia. Subjects Patients (aged > 18 years or between 12 and 18 years) with parent's informed consent, with stable or active bilateral vitiligo. Intervention Topical 0.05% betamethasone or C/DSO. Methods Two lesions similar to each other in size were chosen. All assessments were made by two blinded investigators, and photographs were subjected to morphometry analysis. Main outcome Skin repigmentation by digital morphometry. Results Twenty‐five patients were enrolled in the study (21 women and 4 men). Mean age of participants was 40 years (range: 12–74 years). One patient on C/DSO experienced a mild local erythematous papular rash that self‐resolved. At 4 months of therapy, there was no statistical difference on the percentage of repigmentation between betamethasone and C/DSO (5.63% ± 27.9 vs. 3.22% ± 25.8, respectively, P = 0.758). After 10 months of therapy, the percentage of skin repigmentation increased to 18.5 ± 93.14% with betamethasone and to 12.4 ± 59% with C/DSO, but again, we found no statistical differences (P = 0.79). Discussion and conclusions Few studies have described objective methods to evaluate repigmentation among vitiligo patients. Digital morphometry provides an objective assessment of repigmentation in vitiligo. Objective vitiligo repigmentation with topical C/DSO at 10 months is similar to topical 0.05% betamethasone. Although a mild adverse effect was related to the use of C/DSO, such finding was not severe enough to discontinue treatment.     

Meniscus tears of the knee: prospective evaluation with CT

A total of 209 patients underwent prospective axial computed tomography (CT) examinations of the knee to evaluate the ability of this technique to identify and characterize knee menisci in patients believed to have meniscus tears. Of the 359 knees examined, 105 subsequently underwent arthrography, arthroscopy, or arthrography and arthroscopic surgery. In this group, the sensitivity of CT was 88.5%, specificity was 95.5%, and accuracy was 91.5%. Although axial CT is a sensitive and effective method for the detection and characterization of tears involving the medial and lateral menisci, purely horizontal or nondisplaced peripheral tears may be difficult to demonstrate.