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Biomedical subjects

P Lester

Publications and source records attributed to P Lester.

12 recordsLinked to original sources

Families living with HIV.

Given the historical emergence of the AIDS epidemic first among gay men in the developed world, HIV interventions have primarily focused on individuals rather than families. Typically not part of traditional family structures, HIV-positive gay men in Europe and the US lived primarily in societies providing essential infrastructure for survival needs that highly value individual justice and freedom. Interventions were thus designed to focus on at-risk individuals with programmes that were age and gender segregated. As the epidemic has unfolded, the early focus on individuals has become inadequate: families live with HIV, not just individuals. Families' structure, economy, migration patterns, and developmental life cycles are affected by HIV, and these changes radiate throughout the community creating parallel stresses. Family-based, intergenerational models of detection, prevention and treatment services offer enhanced opportunities for effective interventions and suggest very different intervention settings and strategies. However, these models also require addressing the family's basic needs for survival and security in order to be successfully implemented and sustained over time. As HIV was an opportunity for marginalized persons in the developed world to 'turn their life around', the strengths of families in the developing world may be mobilized to contribute to the community's long-term health, survival and security needs.

Community Health Services↗

Binding protein-3-selective insulin-like growth factor I variants: engineering, biodistributions, and clearance.

Insulin-like growth factor I (IGF-I) is a potent anabolic peptide that mediates most of its pleiotropic effects through association with the IGF type I receptor. Biological availability and plasma half-life of IGF-I are modulated by soluble binding proteins (IGFBPs), which sequester free IGF-I into high affinity complexes. Elevated levels of specific IGFBPs have been observed in several pathological conditions, resulting in inhibition of IGF-I activity. Administration of IGF-I variants that are unable to bind to the up-regulated IGFBP species could potentially counteract this effect. We engineered two IGFBP-selective variants that demonstrated 700- and 80,000-fold apparent reductions in affinity for IGFBP-1 while preserving low nanomolar affinity for IGFBP-3, the major carrier of IGF-I in plasma. Both variants displayed wild-type-like potency in cellular receptor kinase assays, stimulated human cartilage matrix synthesis, and retained their ability to associate with the acid-labile subunit in complex with IGFBP-3. Furthermore, pharmacokinetic parameters and tissue distribution of the IGF-I variants in rats differed from those of wild-type IGF-I as a function of their IGFBP affinities. These IGF-I variants may potentially be useful for treating disease conditions associated with up-regulated IGFBP-1 levels, such as chronic or acute renal and hepatic failure or uncontrolled diabetes. More generally, these results suggest that the complex biology of IGF-I may be clarified through in vivo studies of IGFBP-selective variants.

Aged↗

Management of cancer pain.

Pain secondary to cancer in animals should be promptly addressed to alleviate suffering, stress, and anxiety and to improve quality of life. Uncontrolled cancer pain can have a negative effect on the owners and caregivers of affected animals. The pathophysiology of cancer pain is discussed in this article, along with pain evaluation and monitoring. Treatment of cancer pain should be individualized, and a step-wise approach to the management of cancer pain is presented. The use of opioids, nonsteroidal anti-inflammatory drugs, and adjuvant medications are also reviewed.

Animals↗

The consequences of a positive prenatal HIV antibody test for women.

As more women of childbearing age are affected by the human immunodeficiency virus (HIV), many providers have demanded routine perinatal HIV screening, arguing that the medical benefits of testing outweigh the socioeconomic, medical, and psychological risks of a positive HIV test for women. In this primarily urban poor population, we used a semistructured interview to evaluate differences in health care discrimination, economic losses, risk behaviors, relationships changes, and psychological status in 20 HIV-positive and 20 HIV-negative mothers matched for HIV risk, race, income, and delivery date. Many (35%) seropositive and no seronegative women cited health care discrimination due to HIV status. Although seropositive women reported greater satisfaction with social support from friends (100%) and family (80%), many women had not disclosed their HIV status to any friends (65%) or family (25%), indicating fear of abandonment. Only 56% of HIV positive and 44% of seronegative women knew their partners' HIV status, and many HIV-positive and HIV-negative women reported having sex without condoms after the HIV test. Mean standardized anxiety (p < 0.05) and depression scores were higher in seropositive women. Despite added social support and medical treatments, HIV-positive women showed higher levels of health care discrimination, personal isolation, and psychological sequelae than their seronegative counterparts. As the medical benefits to prenatal HIV testing increase, we will need to develop focused medical, social, and mental health services addressing the needs of HIV-positive women.

Adult↗

Characterization of complex formation by humanized anti-IgE monoclonal antibody and monoclonal human IgE.

The interaction of human IgE with high-affinity IgE Fc receptors on cells of the immune system plays an essential role in the type I hypersensitivity reaction. A proposed therapy is to use an anti-IgE monoclonal antibody to block the binding of IgE to its high-affinity receptor on mast cells and basophils, thus preventing subsequent release of the inflammatory agents after exposure to allergen. We report here the solution characteristics of immune complexes formed by a humanized anti-IgE monoclonal antibody (rhuMAb E25) and IgE using sedimentation analysis and size exclusion chromatography. We demonstrate that the rhuMAb E25 is able to form a variety of complexes with IgE at different molar ratios. The largest complex was identified by sedimentation equilibrium analysis as a heterohexamer with very high stability. The intermediate complex formed when one of the interacting components is in large molar excess appears to have a trimeric structure. The high-affinity interaction of rhuMAb E25 and IgE has also been confirmed. Furthermore, by using hydrodynamic modeling, we show that the largest complex may be represented by a cyclic structure.

Antibodies, Anti-Idiotypic↗

Postnatal human immunodeficiency virus antibody testing. The effects of current policy on infant care and maternal informed consent.

Routine human immunodeficiency virus (HIV) antibody screening of umbilical cord blood identifies neonates at risk for HIV infection but may hold risks as well as benefits for infants and mothers. We describe the effect of testing on infant placement and care and report the women's understanding of pretest counseling and consent. In a case-control analysis of 327 tested infants, seropositive infants (13) had a higher rate of discharge to home (62%) than did controls (31%). More case infants (100%) received follow-up care and vaccinations than control infants (46%). Of 32 women interviewed after HIV antibody test informed consent, only 31% understood that a positive cord blood test result was inconclusive for the infant, and most (78%) did not identify any associated socioeconomic risks. Most (88%) stated an interest in learning their serostatus, but only 22% returned for test results. Despite the benefits of HIV antibody testing of at-risk infants, current testing and counseling procedures inadequately inform women, limiting the testing benefits to them.

AIDS Serodiagnosis↗

Cancer prevention and detection centers: an overview and critique.

Cancer screening is ideally carried out in free standing centers that are located near shopping centers, are quite visible, and have a warm, friendly appearance. This chapter describes the basic elements of such a center, including the use of a mobile mammogram van based at the center. While the precise size, location, and design of a center will vary depending on the specific demographics of an area, these data should facilitate such planning. Programs that can be carried out in this center are described utilizing information from preceding chapters. This chapter enlarges upon their application and then outlines criteria and services. Furthermore, a large section on general or whole-body screening is included. As in other programs, those at risk and the benefits are discussed. While not a high volume, income producer, this program is a requisite component offering great service to the customer.

Community Health Centers↗

Intensive combination drug therapy of familial hypercholesterolemia with lovastatin, probucol, and colestipol hydrochloride.

Patients with familial hypercholesterolemia (FH) have had a life-long sustained elevation of low-density lipoprotein (LDL) cholesterol levels. Consequently, there is a need to maximally lower their elevated levels, and this usually requires lowering LDL levels more than 50%. Because no single hypolipidemic drug will consistently produce such degrees of lowering, combination drug therapy with two or even three agents is required to produce the desired degree of cholesterol lowering. A prospective trial was designed to determine if combination therapy using three hypolipidemic agents could effectively lower LDL levels in 17 severely affected FH subjects. Colestipol hydrochloride (10 g b.i.d.), probucol (500 mg b.i.d.), and lovastatin (20 or 40 mg b.i.d.) were given to each patient, in varying combinations, over a 25-month period. Lovastatin (40 mg/day) uniformly lowered LDL levels 36%. Probucol lowered LDL only 14% and in a variable manner. The combination of lovastatin and probucol lowered LDL no better than lovastatin alone. Lovastatin plus colestipol lowered LDL 52%; probucol added as a third agent produced no further lowering. Lovastatin (80 mg/day) plus colestipol lowered LDL 56%. Lovastatin increased high-density lipoprotein (HDL) cholesterol levels 6%, whereas probucol decreased HDL 29%. In all patients there was an effective lowering of LDL levels, ranging from 40% to 70%. Thus, lovastatin plus colestipol is an effective hypolipidemic regimen for producing marked decreases in LDL levels in FH subjects. The addition of probucol as a third hypolipidemic agent adds little to the therapeutic regimen as measured by lowering of LDL levels.

Cholesterol↗

Factors affecting the displacement of human chromosomes from the metaphase plate.

In order to elucidate some of the factors influencing the attachment of chromosomes to spindles, an analysis was made of the displacement of chromosomes from the metaphase plate in preparations that received no colchicine or hypotonic treatment. Displaced chromosomes were identified by Giemsa banding. Three hypotheses were tested and led to the following conclusions: (1) Chromosomal displacement is a function of size--smaller chromosomes are displaced more often than larger ones. (2) The position of the centromere does not influence chromosome displacement. (3) The amount of centromeric heterochromatin in the chromosome has a highly significant effect on displacement--chromosomes with more heterochromatin are displaced more often than those with less.

Centromere↗