Microarray and allergenic activity assessment of milk allergens.

BACKGROUND: Cow's milk is one of the most common causes of food allergy affecting approximately 2.5% of infants in the first years of their life. However, only limited information regarding the allergenic activity of individual cow's milk allergens is available. OBJECTIVE: To analyse the frequency of IgE reactivity and to determine the allergenic activity of individual cow's milk allergens. METHODS: A nitrocellulose-based microarray, based on purified natural and recombinant cow's milk allergens was used to determine IgE reactivity profiles using sera from 78 cow's milk-sensitized individuals of varying ages. The allergenic activity of the individual allergens was tested using patients' sera for loading rat basophil leukaemia cells (RBL) expressing the α-chain of the human receptor FcεRI. RESULTS: Using the microarray and the RBL assay, cow's milk allergens were assessed for frequency of IgE recognition and allergenic activity. Moreover, the RBL assay allowed distinguishing individuals without or with mild clinical reactions from those with severe systemic or gastrointestinal symptoms as well as persons who grew out cow's milk allergy from those who did not. CONCLUSIONS: Component-resolved testing using milk allergen microarrays and RBL assays seems to provide useful additional diagnostic information and may represent a basis for future forms of prophylactic and therapeutic strategies for cow's milk allergy.

Current medicolegal and confidentiality issues in large, multicenter research programs.

The convenience of fast computers and the Internet have encouraged large collaborative research efforts by allowing transfers of data from multiple sites to a single data repository; however, standards for managing data security are needed to protect the confidentiality of participants. Through Dartmouth Medical School, in 1996-1998, the authors conducted a medicolegal analysis of federal laws, state statutes, and institutional policies in eight states and three different types of health care settings, which are part of a breast cancer surveillance consortium contributing data electronically to a centralized data repository. They learned that a variety of state and federal laws are available to protect confidentiality of professional and lay research participants. The strongest protection available is the Federal Certificate of Confidentiality, which supersedes state statutory protection, has been tested in court, and extends protection from forced disclosure (in litigation) to health care providers as well as patients. This paper describes the careful planning necessary to ensure adequate legal protection and data security, which must include a comprehensive understanding of state and federal protections applicable to medical research. Researchers must also develop rules or guidelines to ensure appropriate collection, use, and sharing of data. Finally, systems for the storage of both paper and electronic records must be as secure as possible.

Life expectancy estimation with breast cancer: bias of the declining exponential function and an alternative to its use.

BACKGROUND: Life expectancy gain (LEG) is an outcome measure commonly estimated with a declining exponential function in a Markov model. The accuracy of such estimates has not been objectively evaluated. PURPOSE: To compare LEGs from declining exponential function estimates with those calculated from population data, using published screening mammography studies as examples. METHOD: SEER-based population data are used to compare LEG calculation with declining exponential function estimation and empiric population data in a new model, the "nested" Markov. RESULTS: Analyses of the LEG of mammographic screening based on the declining exponential function significantly overestimate LEGs for younger women and underestimate them for older women. Because of offsetting errors, all-age analyses paradoxically appear accurate. CONCLUSION: Declining exponential function estimates of LEGs for chronic diseases with low mortality rates and long time horizons are liable to significant bias, especially with limited age cohorts.

Referral patterns for the evaluation of non-palpable breast abnormalities.

BACKGROUND: Non-palpable suspicious mammographic abnormalities require image-guided breast biopsies. In this study, we examined primary care physicians' knowledge of breast biopsy procedures for non-palpable lesions and referral patterns for breast biopsies; we also identified channels to disseminate information. METHODS: We mailed a baseline survey to all primary care physicians, surgeons, and radiologists in Vermont. RESULTS: Primary care physicians are more likely to refer for excisional rather than percutaneous biopsy. Unlike surgeons and radiologists who learned about these procedures through journals and professional meetings, primary care physicians' most common source of information was from radiologists. CONCLUSIONS: Information about indications for using percutaneous breast biopsy should be available in journals and at meetings to help primary care providers decide on the most appropriate algorithm of workup for patients with non-palpable suspicious breast abnormalities requiring biopsy.

Assessment of self-reward strategies for maintenance of breast self-examination.

This study examined the relative impact of different self-reward strategies on maintenance of breast self-examination (BSE) practice among 1649 women trained to do BSE. Training groups were randomized into four conditions: (a) self-reward instructions and materials delivered at the end of the BSE training session; (b) self-reward suggestions delivered through the mail each month, contingent upon the BSE performance; (c) external monetary rewards and self-reward suggestions delivered through the mail each month on an intermittent schedule, contingent upon BSE practice; and (d) a no-reward control condition. Follow-up assessments 12 months following training revealed a pattern of evidence in support of the benefits of external monetary rewards and self-reward prompts on BSE frequency and quality; however, it is likely that the value of that condition lies in the external reward component.

The future of pediatric psychopharmacology.

The future of pediatric psychopharmacology will be a collaborative effort among the public, the federal government, the pharmaceutical industry, and clinical scientists. Clinical scientists and the NIH have initiated the process. The federal regulatory guidelines are in place but may need to be amended further to truly facilitate needed research. The pharmaceutical industry is making efforts to study medications in childhood psychiatric disorders. More new drugs are being tested in humans. Many of the new agents offer the promise of more clinical benefit with milder side effects. The future is indeed promising.

Prepubertal and young adolescent bipolarity versus ADHD: assessment and validity using the WASH-U-KSADS, CBCL and TRF.

BACKGROUND: This addendum to 'Prepubertal and early adolescent bipolarity differentiate from ADHD by mania criteria; grandiose delusions; ultra-rapid or ultradian cycling' (in this volume) provides (1) a description of Washington University at St. Louis Kiddie Schedule for Affective Disorders and Schizophrenia (WASH-U-KSADS) with sample sections (hypersexuality, rapid cycling); (2) a comparison of WASH-U-KSADS to KSADS-P/L and KSADS-1986 and (3) a comparison of WASH-U-KSADS to Child Behavior Checklist (CBCL) and Teachers Report Form (TRF) data. METHODS: Data were from the first 60 bipolar (BP) and first 60 ADHD subjects of 270 consecutively ascertained cases (90 BP, 90 ADHD and 90 community controls) in the NIMH funded 'Phenomenology and Course of Pediatric Bipolarity' study. Comprehensive assessments included the WASH-U-KSADS (administered blindly to mothers and separately to children), CBCL and TRF. RESULTS: As reported elsewhere in this volume, WASH-U-KSADS data significantly differentiated BP and ADHD groups. Significant differences were also found with the parent-rated CBCL and the teacher-rated TRF, thereby providing cross-modality and cross-informant validation of the WASH-U-KSADS. Because of the close agreement with published CBCL data from another investigator, cross-site validation also occurred. LIMITATIONS: Venues for consecutive ascertainment from the lowest socioeconomic status classes were unavailable due to current health care policies. CLINICAL RELEVANCE: CBCL and TRF data separated BP from ADHD groups, largely by non-specific externalizing dimensions (e.g., hyperactivity, aggressivity). Clinically relevant differentiation by categorical mania-specific criteria (e.g., elated mood, grandiosity, racing thoughts) occurred with WASH-U-KSADS data. Both types of data are crucial for genetic and neurobiological studies.