Factors associated with social contacts in four communities during the 2007-2008 influenza season.

Mathematical models of influenza pandemics are sensitive to changes in contact rates between individuals. We conducted population-based telephone surveys in four North Carolina counties to determine the number of social interactions between individuals during the 2007-2008 influenza season. Influenza activity was monitored through sentinel medical practices. Among 3845 adults, the number of social contacts varied with age, was lower on weekends than on weekdays, and further decreased during school holiday periods. Adults with influenza-like illnesses had fewer social contacts. Adults' contacts in the community setting increased during periods of peak influenza activity. Among 290 children, potential contacts (i.e. other people in the same location) were lowest among preschool-age children and decreased on weekends and during school holidays. In adjusted analyses, children's potential social contacts did not change during periods of peak influenza activity. These results should be useful for modelling influenza epidemics and pandemics and in planning mitigation and response strategies.

Providing information to help Medicare beneficiaries choose a health plan.

Many Medicare beneficiaries have limited knowledge of the Medicare program and related health insurance options. This is due in part to the complexity of the Medicare program and supplemental health insurance market. A recent congressional mandate through the Balanced Budget Act of 1997 called for broad dissemination of information to educate beneficiaries about their health plan options and to encourage informed health plan decision-making. In response, the Health Care Financing Administration (HCFA) launched the National Medicare Education Program (NMEP) to support the educational objectives of the BBA. This paper provides an overview of the components of the NMEP information campaign. We also review lessons learned from our experience in designing and testing a prototype consumer handbook that explains the different health plan options to Medicare beneficiaries. Through our discussion of the handbook, we highlight several ways to communicate information effectively about a complex publicly funded program to an older adult population.

Maximizing participation by black Americans in population-based diabetes research: the Project DIRECT pilot experience.

Diabetes and its associated complications and risk factors have a higher prevalence among blacks than whites. To reduce the burden of diabetes within the black community, research is needed to assess the behavioral, social, and environmental correlates associated with this disproportionate burden. Because of some well known instances of historical exploitation and abuse from medical and public health research conducted in black communities, this population has little enthusiasm for additional research, despite pressing health needs. This paper describes the process used to eliminate barriers and enhance trust between the target community and the researchers conducting a population survey of diabetes in Wake County, North Carolina. A community advisory board was organized to (1) review the survey instruments and methodologies, (2) identify persons from the community to serve as interviewers, and (3) promote the survey using the major local communication channels. The response rate to both the household survey and the comprehensive medical exam was 77%. Eighty-one percent of eligible black respondents completed the household exam and 80% completed the comprehensive medical exam. Advantages of building collaborative relationships between the community and research team are discussed.

Consumer perspectives on information needs for health plan choice.

The premise that competition will improve health care assumes that consumers will choose plans that best fit their needs and resources. However, many consumers are frustrated with currently available plan comparison information. We describe results from 22 focus groups in which Medicare beneficiaries, Medicaid enrollees, and privately insured consumers assessed the usefulness of indicators based on consumer survey data and Health Employer Data Information Set (HEDIS)-type measures of quality of care. Considerable education would be required before consumers could interpret report card data to inform plan choices. Policy implications for design and provision of plan information for Medicare beneficiaries and Medicaid enrollees are discussed.

In vivo administration to rhesus monkeys of a CD4-specific monoclonal antibody capable of blocking AIDS virus replication.

Monoclonal antibodies (mAbs) specific for CD4 are potent inhibitors of HIV replication in vitro. These agents may be useful prophylactically or in chronic HIV infection if they can be administered without inducing immunosuppression. In the present study, we explored the safety of a CD4-specific murine mAb in rhesus monkeys. The mAb 5A8, which binds to domain 2 of the CD4 molecule, inhibits AIDS virus replication noncompetitively at a postvirus binding step. This antibody, which had a similar affinity for rhesus monkey and human CD4 cells, efficiently inhibited in vitro replication of both HIV-1 and the simian immunodeficiency virus of macaques. A single 3-mg/kg injection of mAb 5A8 into normal rhesus monkeys coated all circulating and lymph node CD4 cells for 4-6 days. CD4 cells were not cleared from circulation nor was the CD4 molecule modulated from the lymphocyte surface. In fact, administration of mAb 5A8 resulted in an approximately one-to twofold increase in absolute number of circulating CD4 cells. Repeated administration in normal rhesus monkeys resulted in CD4 lymphocyte coating with mAbs for > 9 days without CD4 cell clearance or modulation. While coated with mAbs, PBLs of these monkeys retained normal in vitro proliferative responses to mitogens and these animals generated normal humoral responses in vivo to tetanus toxoid. Loss of cell coating with mAbs in normal monkeys corresponded to the appearance of anti-mouse immunoglobulin antibodies. Thus, administration of certain anti-CD4 mAbs capable of blocking HIV replication can achieve coating of the entire CD4 cell pool in rhesus monkeys without inducing significant cell loss or immunosuppression.

CD4-Pseudomonas exotoxin hybrid proteins: modulation of potency and therapeutic window through structural design and characterization of cell internalization.

Replacing the Pseudomonas exotoxin A (PE) cell binding domain with the human immunodeficiency virus (HIV) gp120 binding domain from CD4 yields a hybrid toxin (CD4-PE) with potential therapeutic use in treating acquired immunodeficiency syndrome (AIDS). To find the most therapeutically potent combination of CD4 and PE four different hybrid toxins composed of one [CD4(122)] or two [CD4(181)] Ig-like CD4 domains and sequences of PE where the binding domain was partially [PE(392)] or completely [PE(364)] removed were constructed and expressed in Escherichia coli. The number of CD4 domains determined the binding affinity to gp120 and in cell viability assays the window between specific and nonspecific cytotoxicity. The length of PE determined the potency of the drug. The optimal hybrid toxin was composed of two Ig-like domains of CD4 and PE(392). Investigation of the internalization mechanism of CD4-PE revealed that the hybrid toxin binds to target cells and is endocytosed within one hour. However, more than 6 hours are required for maximum translation inhibition. In contrast to PE which is inhibited by ammonium chloride treatment, cell toxicity of CD4-PE is not affected by ammonium chloride. Further investigations showed that the acid-induced hydrophobicity change which is required for membrane translocation is also observed with CD4-PE but at significantly higher pH than with PE.

Human recombinant interleukin 1 stimulates collagenase and prostaglandin E2 production by human synovial cells.

The pathogenesis and progression of rheumatoid arthritis involves the production of biologically active lymphokines and monokines. Of these, interleukin 1 (IL-1) has been somewhat of a controversial molecule because it seems to evoke various biological responses in several different tissues. In these studies we demonstrate that three biological properties of human monocyte-derived IL-1 (T-lymphocyte activation and human synovial cell prostaglandin E2 and collagenase production) co-purify. The complementary DNA for the prominent pI 7 form of human IL-1 was expressed, purified, and tested. Any controversy now appears resolved since homogeneous recombinant human IL-1 stimulates prostaglandin E2 and collagenase from human synovial cells as well as activates T cells in vitro.