Search PubMed⌕ Search

Biomedical subjects

R Wallace

Publications and source records attributed to R Wallace.

At least 55 records · Page 3Linked to original sources

Serum IL-6 level and the development of disability in older persons.

BACKGROUND: The serum concentration of interleukin 6 (IL-6), a cytokine that plays a central role in inflammation, increases with age. Because inflammation is a component of many age-associated chronic diseases, which often cause disability, high circulating levels of IL-6 may contribute to functional decline in old age. We tested the hypothesis that high levels of IL-6 predict future disability in older persons who are not disabled. METHODS: Participants at the sixth annual follow-up of the Iowa site of the Established Populations for Epidemiologic Studies of the Elderly aged 71 years or older were considered eligible for this study if they had no disability in regard to mobility or in selected activities of daily living (ADL), and they were re-interviewed 4 years later. Incident cases of mobility-disability and of ADL-disability were identified based on responses at the follow-up interview. Measures of IL-6 were obtained from specimens collected at baseline from the 283 participants who developed any disability and from 350 participants selected randomly (46.9%) from those who continued to be non-disabled. FINDINGS: Participants in the highest IL-6 tertile were 1.76 (95% CI, 1.17-2.64) times more likely to develop at least mobility-disability and 1.62 (95% CI, 1.02-2.60) times more likely to develop mobility plus ADL-disability compared with to the lowest IL-6 tertile. The strength of this association was almost unchanged after adjusting for multiple confounders. The increased risk of mobility-disability over the full spectrum of IL-6 concentration was nonlinear, with the risk rising rapidly beyond plasma levels of 2.5 pg/mL. INTERPRETATION: Higher circulating levels of IL-6 predict disability onset in older persons. This may be attributable to a direct effect of IL-6 on muscle atrophy and/or to the pathophysiologic role played by IL-6 in specific diseases.

Activities of Daily Living↗

The use of itraconazole to treat cutaneous fungal infections in children.

BACKGROUND: Cutaneous mycoses such as tinea capitis, onychomycosis and some cases of tinea corporis/cruris, and tinea pedis/manus require oral antifungal therapy. There is relatively limited data regarding the use of the newer oral antifungal agents, e.g. itraconazole, in the treatment of these mycoses in children. OBJECTIVE: We wished to determine the efficacy and safety of itraconazole continuous therapy in the management of cutaneous fungal infections in children. METHODS: Children with cutaneous mycoses were treated with itraconazole in an open-label manner in 4 studies. For tinea capitis, the treatment regimens using itraconazole continuous therapy were: study 1, 3 mg/kg/day for 4 or 8 weeks; study 2, 5 mg/kg/day for 6 weeks, and study 3, 5 mg/kg/ day for 4 weeks. In a different trial, study 4, itraconazole continuous therapy 5 mg/kg/day was used to treat toenail onychomycosis (duration: 12 weeks), tinea corporis/ cruris (duration: 1 week) and tinea pedis/manus (duration: 2 weeks). RESULTS: The efficacy rates at follow-up 12 weeks from the start of therapy in children with tinea capitis treated using the itraconazole continuous regimen were: clinical cure (CC) and mycological cure (MC) in study 1 (n = 10, Trichophyton violaceum all patients), CC 50%, MC 86%; in study 2 (n = 35, Microsporum canis 22 patients, Trichophyton sp. 12 patients), CC 82.8%, MC 80%, and in study 3 (n = 16, M. canis 11 patients, Trichophyton sp. 5 patients), (CC 66.7%, MC 78.5%. Itraconazole was also effective in the treatment of dermatomycoses in 24 children (study 4). The CC and MC rates at the follow-up 8 weeks from the start of therapy in children with dermatomycoses and 12 months in children treated for onychomycosis were: onychomycosis (n = 1, T. rubrum), CC 100%, MC 100%; tinea corporis (n = 12, M. canis 10 patients), CC 100%, MC 90%; tinea cruris (n = 3, Trichophyton sp. 2 patients), CC 100%, MC 100%; tinea manus (n = 1, T. rubrum), CC 100%, MC 100%, and tinea pedis (n = 7, T. rubrum), CC 100%, MC 100%). Adverse effects consisted of a cutaneous eruption in 1 (1.2%) of the 85 children, with mild, transient, asymptomatic elevation of liver function tests (less than twice the upper limit of normal) in 2 (3.4%) of 58 children in whom monitoring was performed. CONCLUSIONS: Itraconazole is effective and safe in the treatment of tinea capitis and other cutaneous fungal infections in children.

Antifungal Agents↗

Information Theory, Scaling Laws and the Thermodynamics of Evolution.

Renormalization symmetry and the Legendre transformation are imposed on a parametized form of ergodic source uncertainty, a widely-applied model for "languages" ranging from the spoken word to genetic codes. Using the Shannon-McMillan theorem to identify a duality between source uncertainty and free energy density, this procedure: (i) suggests that a punctuated "phase change" and resulting sudden fragmentation or coalescence should be the norm for "language"-based phenomena, particularly the transfer of "genetic" information within reproducing populations; (ii) gives a power law for that phase change near transition; (iii) provides a "disorder" construct similar to an entropy which may trigger higher degrees of punctuation in social systems than is suggested from simple physical analogs; and (iv) gives "equations of state" relating ensemble averages which should be observable within coalesced systems. The general formalism is explicitly applied to problems of speciation, coevolution and group selection, and comparison made with the work of Eigen and his associates.Copyright 1998 Academic Press Limited

Journal Article↗

Scales of geography, time, and population: the study of violence as a public health problem.

OBJECTIVES: In this study, data on violent deaths in the Bronx, New York City, from the 1970, 1980, and 1990 censuses were analyzed. METHODS: The incidence and areal density of intentional deaths were mapped by health area. Simple and stepwise regressions between violent death measures and other factors were performed. RESULTS: The incidence of deaths at levels of those in the highest 1970 quintile spread so that by 1990 only 2 areas saw incidences at levels of the lowest 1970 quintile. Overcrowding, socioeconomic status, population, population change, and drug deaths in simple regressions and overcrowding, socioeconomic status, and low-weight births in stepwise regressions correlated significantly with violent death incidence or density. CONCLUSIONS: Understanding the spatiotemporal development of violence can contribute to public policy on violence.

Censuses↗

Intronic sequences modulate the sensitivity of beta-lactoglobulin transgenes to position effects.

We have analysed the expression of beta-lactoglobulin (BLG) gene constructs with combinations of introns deleted to further define the role of intronic regions in directing position-independent mammary expression of BLG transgenes. Intron removal had no obvious effect on hormonal induction of BLG expression in vitro but dramatically reduced expression in vivo, in that removal of intron pairs always resulted in a proportion of the transgenic lines generated failing to express the transgene in the mammary gland. Position-dependent expression was seen for all intron-deleted transgenes regardless of which introns were removed and the ability of the intron-deleted transgenes to be expressed bore no relationship to transgene copy number. Thus, intron removal per se increases the sensitivity of BLG transgenes to position effects.

Animals↗

Socioeconomic determinants of health: community marginalisation and the diffusion of disease and disorder in the United States.

This article describes the cascading diffusion of "inner city problems" of disease and disorder in the United States--from the huge marginalised inner city communities of the largest municipalities, first along national travel routes to smaller cities, and then from central cities into surrounding more affluent suburbs-following the pattern of the daily journey to work. Public policies and economic practices which increase marginalisation act to damage the "weak ties" of the community social networks which bind central city neighbourhoods into functioning units. Spreading disease and disorder can be interpreted as indices of the resulting social disintegration, which is driven by policy. This "failure of containment" in the United States should serve as a warning for cities in Europe against reducing the municipal and other services that they provide to "unpopular" subpopulations.

Acquired Immunodeficiency Syndrome↗

The hierarchical diffusion of AIDS and violent crime among U.S. metropolitan regions: inner-city decay, stochastic resonance and reversal of the mortality transition.

Census data on migration within and between the 25 largest U.S. metropolitan areas-containing more than 113 million people-permit construction of a probability-of-contact matrix corresponding to a particular Markov process dominated by the nation's largest cities, a hierarchical structure. Regression models based on vectors associated with that process find the large-scale diffusion of AIDS in the U.S.A. depends strongly on national patterns of contact with the original AIDS outbreaks in New York City and San Francisco as modulated by the violent crime rate, a local index of social disintegration resulting from the marginalization of minority ethnic urban communities. Violent crime is itself undergoing a recognizably similar hierarchical diffusion from the largest U.S. cities into smaller metropolitan regions. Further analysis suggests that continuation of public policies of "benign neglect" and "planned shrinkage" directed against marginalized urban populations may trigger a strong stochastic resonance which can significantly degrade public health and public order for much of the three-quarters of the U.S. population living in or near cities, in effect reversing the mortality transition of the last century.

Acquired Immunodeficiency Syndrome↗

Transgene rescue in the mammary gland is associated with transcription but does not require translation of BLG transgenes.

Many transgenes, particularly those comprising cDNA sequences fail to be expressed when they are introduced into transgenic mice. We have previously shown that this problem can be overcome in the mammary gland by co-integrating a poorly expressed cDNA transgene, comprising the sheep beta-lactoglobulin promoter, with the efficiently expressed, unmodified beta-lactoglobulin gene. In this report we demonstrate that the transcription of the beta-lactoglobulin gene is associated with this effect because co-integration with a non-transcribed beta-lactoglobulin gene fails to rescue expression. By contrast, co-integration with a translationally inactivated beta-lactoglobulin transgene does rescue the expression of the second gene, but without the co-production of beta-lactoglobulin protein.

Animals↗

Beneficence toward whom? Ethical decision-making in a maternal-fetal conflict.

Ethical dilemmas and conflicts occur frequently in critical care units. When these dilemmas involve a pregnant patient, the conflicts are further complicated, because they also involve the interests of the fetus. Using an ethical decision-making process facilitates the analysis of ethical dilemmas and their resolutions. This process is used to analyze the dilemma of selecting appropriate treatment for a woman at 30 weeks' gestation, diagnosed with acute lymphocytic leukemia. The case is examined from the perspective of the mother and the fetus, using the decision-making process. The medical indications include the patient's physical state, disease process, and treatment options. Patient preferences are the ethical and legal center of the patient-physician, and patient-nurse relationship. Contextual features include religious beliefs, cultural values, family dynamics, and financial and legal aspects of the care options. Finally, the ethical principles, relevant and in conflict, are assessed. Exploring these areas clarifies the best treatment option in consideration of the issues and facts of the case.

Adult↗

Epidemiological, clinical, and neuropathological study of apolipoprotein E genotype in Alzheimer's disease.

Our studies of the APOE genotype in AD confirm a strong association of the epsilon 4 allele with development of AD and a decreased risk associated with epsilon 2. From a clinical/neuropathological perspective, the major effects of APOE epsilon 4 are to lower the age of onset and to increase the amount of A beta deposit in the brain. Neither rate of progression nor number of neurofibrillary tangles were affected. We also carried out a longitudinal population-based assessment of the APOE genotype to determine the risk for developing cognitive impairment of someone in the general population based on APOE genotype. APOE epsilon 4 carried about 1.4-fold increased risk, and APOE epsilon 2 about 1.7-fold decreased risk. Thus, inheritance of APOE epsilon 4 is a major biological risk factor for AD, but it has limited utility as a prognostic indicator for development of dementia in an individual.

Age of Onset↗

Lack of association of trinucleotide repeat polymorphisms in very-low-density lipoprotein receptor gene with Alzheimer's disease.

Inheritance of the apolipoprotein E epsilon 4 allele is a risk factor for Alzheimer's disease (AD). A recent report studying Japanese patients suggested that a polymorphism of a trinucleotide repeat in the 5' untranslated region of an apolipoprotein E receptor, the very-low-density lipoprotein receptor, is genetically associated with AD, with overrepresentation of the allele containing five copies of the repeat. We determined the allele frequencies of the very-low-density lipoprotein receptor in 3 white populations totaling 469 individuals. In contrast to the previous report, we found no differences in allele frequencies between case patients and control subjects. The discrepancy could be due to differences in Japanese and white populations. Nonetheless, these data weaken the likelihood that this polymorphism in the very-low-density lipoprotein receptor gene is strongly associated with AD.

Alleles↗

Apolipoprotein E and cognitive change in an elderly population.

The apolipoprotein E (apoE) epsilon 4 allele is overrepresented, and the apoE epsilon 2 allele underrepresented, in Alzheimer's disease. To assess the risk of cognitive impairment in individuals with these genotypes in the general population, we studied a population-based sample of 1,899 individuals 65 years and older as a follow-up to the Iowa 65+ Rural Health Study. Multiple regression and logistic regression analyses demonstrated significant effects of apoE epsilon 4 and apoE epsilon 2 in predicting performance on a delayed recall task over a 4- to 7-year period. The magnitude of this effect was, however, fairly modest, with odds ratios for developing impairment of approximately 1.37 (95% confidence interval: 1.007, 1.850; p = 0.045) for apoE epsilon 4 and 0.53 (95% confidence interval: 0.368, 0.777; p = 0.001) for apoE epsilon 2. These effects were more pronounced in women than men. Importantly, 85% of elderly apoE E4/4 individuals (average age, 81) scored in the unimpaired range on a screening mental status test. Thus, many individuals reach old age without cognitive impair- ment despite inheritance of one or two apoE epsilon 4 alleles. This suggests that apoE genotyping will have limited utility as a diagnostic or prognostic indicator of cognitive decline in individuals.

Aged↗

Aids, violence and behavioral coding: information theory, risk behavior and dynamic process on core-group sociogeographic networks.

Elsewhere we have presented a traveling-wave analysis of HIV transmission on a tightly self-interactive, geographically-focused core group social network (Wallace R. Soc. Sci. Med. 32, 847, 1991; Soc. Sci. Med. 33, 1155, 1991; Environ. Plan. A. 26, 767, 1994; Wallace R. and Fullilove M. Environ. Plan. A. 23, 1701 1991). Here we reanalyze the problem in probability space and recover a close analog of the Shannon Coding Theorem of information theory. Subsequent direct application of information-theoretic methods provides striking insight regarding the spread of disease along the sociogeographic networks of marginalized subgroups, suggesting that 'risk behaviors' for infection may constitute essential components of a behavioral code for the transmission of information within the noisy channel of a marginalized community's social networks. The code's form, including the incorporation of risk behaviors, arises as a direct consequence of the external oppressive forces which structure marginalization. This viewpoint suggests an explanation of the sometime-observed rapid transmission of both infection and of control strategies for infection along the same network, but suggests further that if risk behaviors are indeed parts of a behavioral code for the transmission of group norms, statements of individual worth or resource sharing, then high rates of relapse are inevitable, given the persistence of the external oppression which gives those behaviors symbolic value. We suggest that violent acts in particular may emerge as key behavioral symbols for 'sending a message' in socially disorganized communities, implying that school-based or other individual-oriented harm reduction strategies for violence prevention, in the absence of a comprehensive, multifactorial reform program, cannot significantly reverse the effects of continuing economic and social constraints or of public policies of planned shrinkage and benign neglect, factors primarily responsible for the disorganization of urban minority communities within the United States.

Acquired Immunodeficiency Syndrome↗