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D Greenhalgh

Publications and source records attributed to D Greenhalgh.

17 recordsLinked to original sources
PubMed1996

Effects of heterogeneity on the spread of HIV/AIDS among intravenous drug users in shooting galleries.

In this article we study the effects of heterogeneity on the spread of HIV and AIDS among a population of injecting drug users. We allow for variability in the rate at which addicts visit shooting galleries, their choice of shooting gallery, and whether or not they clean their needles before use. If the sizes of the different groups of drug users remain constant then there is a key parameter R0, which determines the behavior of the epidemic. If R0 is less than or equal to one then the disease will die out, whereas if R0 exceeds one then the fractions of infected individuals and the fractions of infected needles tend to their unique equilibrium values. These are global results. If we allow for recruitment of new susceptible drug users and deaths from AIDS in the population then the unique endemic equilibrium may become unstable and limit cycles can arise by Hopf bifurcation.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Modelling epidemics with variable contact rates.

In this paper we look at models for epidemics where the contact rate is a monotone increasing function of the population density. The background death rate also depends on the population density. We first examine the case of a constant contact rate (motivated by AIDS) and here obtain some global stability results. We consider an SIR model where a typical individual starts off susceptible, at some stage catches the disease and after a short infectious period becomes permanently immune. We also look at the effects of vaccination. First we perform an equilibrium and local stability analysis. Next we reformulate the model in terms of the proportions of individuals susceptible, infected, and immune to obtain some global stability results. We find three possible equilibrium values: one where the population is extinct, one where the disease has died out but the population has not died out, and a unique equilibrium where disease is present. We determine conditions for global stability of these equilibria. For certain parameter values none of these equilibria are locally stable. In this case there is a formal proportional endemic equilibrium with a strictly positive proportion of infected individuals. We expect the population size to die out but the proportions of susceptible, infected, and immune individuals to tend to this endemic proportional equilibrium. We find two critical contact rates which help determine the behaviour of the system. Next we extend some of these results to the case where the contact rate depends on population density. Finally the paper examines these results further using numerical methods.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Some bounds on estimates for reproductive ratios derived from the age-specific force of infection.

In this paper we shall look at estimation of reproductive ratios for common childhood infections such as chickenpox, measles, mumps, and hepatitis A with and without a vaccination program. The paper starts with a survey of previous work in this area. We suppose that we are given data in the form of an age-related serological profile with a given vaccination program. This is used to estimate the reproductive ratio and evaluate vaccination campaigns. The effect of different mixing patterns, such as homogeneous mixing, assortative mixing, proportional mixing, and symmetric mixing are discussed. R phi denotes the reproductive ratio when a steady-state vaccination campaign phi is used. Assortative mixing maximizes the reproductive ratio R phi. A mixing pattern which minimizes R phi and a lower bound for R phi for the important symmetric mixing case are found. The most usual situation is that we are given the age-serological profile with no vaccination so that we have bounds for the basic reproductive ratio R0. These results are illustrated with an application to vaccination against hepatitis A in Bulgaria. Numerical evaluations of the effect of different elimination vaccination strategies are examined.

Adult↗
PubMed1993

Cotransfection of HPV-18 and v-fos DNA induces tumorigenicity of primary human keratinocytes.

Human keratinocytes were cotransfected with the FBJ/R v-fos oncogene and the HPV-18 genome and selected on the basis of their resistance to inducers of terminal differentiation. Unlike keratinocytes immortalized by HPV-18 DNA alone, the HPV-18/v-fos transformants exhibited prominent intracellular vacuolization and formed progressively growing, squamous cell tumors when injected subcutaneously into nude mice. Cytogenetic analysis of two clonally selected transformed cell lines (18/fos clone 1 and 18/fos clone 2) revealed minimal alterations in karyotype, although a consistent rearrangement of chromosome 10, iso(10q), was observed. Further analysis of 18/fos clone 1 confirmed the expression of the fos gene as well as the HPV-18 E7 protein. Alterations in fos gene expression, which appear to be an important facet of epidermal differentiation in vivo, could potentially contribute to the malignant progression of HPV immortalized cells.

Animals↗
PubMed1992

Development of an in vitro model to study carcinogen-induced neoplastic progression of initiated mouse epidermal cells.

Initiation and promotion in mouse skin carcinogenesis produce multiple benign tumors, squamous papillomas, but only a few squamous cell carcinomas. The spontaneous conversion from the benign to the malignant phenotype occurs over many months and in stages, but induced malignant conversion can be accomplished more rapidly by exposure of papilloma-bearing mice to mutagens or by transfection of papilloma cell lines with specific oncogenes. The analysis of genetic targets responsible for carcinogen-induced neoplastic progression would be facilitated by the development of in vitro models where the process is rapid, focal, and quantitative. To this end, primary newborn mouse keratinocytes were initiated in vitro by the introduction of the v-rasHa oncogene via a defective retrovirus. Recipient cells produce squamous papillomas and have a high proliferation rate in culture medium with 0.05 mM Ca2+, but fail to grow in medium with 0.5 mM Ca2+ which is permissive for growth of malignant keratinocytes. When v-rasHa-keratinocytes were exposed to mutagens in vitro, proliferative foci emerged after culture in 0.5 mM Ca2+ for 4 weeks. These foci stained intensely red with rhodamine stain, could be easily quantitated, and readily incorporated bromodeoxyuridine. Dose-response studies with several mutagens indicated that the number of foci increased with concentration to the point where excessive cytotoxicity developed. Mutagens varied in potency for producing foci in the following order: cis-diamminedichloroplatinum greater than or equal to benzo(a)pyrene diolexpoxide I greater than N-methyl-N'-nitro-N-nitrosoguanidine greater than or equal to 4-nitroquinoline-N-oxide greater than N-acetoxy-acetyl- aminofluorene. The tumor promoter 12-O-tetradecanoylphorbol-13-acetate was inactive in the assay. A subset of cell lines derived from foci produced malignant tumors in vivo, while others were not tumorigenic. Analysis of DNA from cell lines and tumors revealed that most tumorigenic cell lines maintained the v-rasHa genome, whereas the viral sequences were deleted in nontumorigenic cell lines. Immunohistochemical analysis indicated that proliferative foci and quiescent v-rasHa keratinocytes expressed keratin 8, a marker of v-rasHa expression in cultured keratinocytes. Cells in foci, but not v-rasHa control cells, expressed keratin 13, a marker which is strongly associated with the malignant progression of skin tumors in vivo. This in vitro assay provides a quantitative model to study chemically induced focal neoplastic progression at the cellular level and to identify agents which may be selective for enhancing malignant conversion.

Animals↗
PubMed1992

Vaccination in density-dependent epidemic models.

This paper examines the effect of vaccination for an epidemic model where the death rate depends on the number of individuals in the population. The basic model which is described is based on measles or other childhood diseases in developing countries or viral diseases such as rabies in animal populations. An equilibrium analysis of the model and the local stability of small perturbations about the equilibrium values are discussed. The biological implications of these results are examined and similar results presented for modifications of the basic model.

Animals↗
PubMed1992

Some threshold and stability results for epidemic models with a density-dependent death rate.

Most classical models for infectious diseases assume that the birth and death rates of individuals and the meeting rates between susceptible and infected individuals do not depend on the total number of individuals in the population. While these assumptions are valid in some situations they are less valid in others. For example, for diseases in animal an insects populations competition for scarce resources might well mean that the death rate depends on the number of individuals. The present paper examines two epidemic models where the death rate is density dependent. For each model the possible equilibrium levels of disease incidence are determined and the stability of these equilibrium levels to small perturbations is discussed. The biological interpretation of these results is presented together with the results of some numerical simulations.

Birth Rate↗
PubMed1992

Some results for an SEIR epidemic model with density dependence in the death rate.

This paper deals with an SEIR epidemic model for an infectious disease where the death rate depends on the number of individuals in the population. It is also assumed that there is an additional death rate suffered by infected individuals. It is found that there are three steady-state values: one where the population is extinct, one where the population maintains itself at a constant level and the disease is extinct, and one where there is a unique equilibrium with disease present. An interesting and unusual feature is that it is possible for this third equilibrium to exist and be locally unstable. Numerical work and simulation show that we can have cycles of disease incidence with increasing amplitude, a constant amplitude, and a decreasing amplitude, depending on the parameter values of the model.

Animals↗
PubMed1990

Vaccination campaigns for common childhood diseases.

Mathematical models exist for vaccination programs for common childhood diseases such as measles, chickenpox, polio, rubella, and mumps. In compartmental models, the population is divided into compartments containing susceptible, infected, and immune individuals, and the model also takes account of the age structure in the population. An equilibrium analysis is performed on the resulting partial differential equations to determine the vaccination program that just eliminates the disease. The stability of the resulting equilibrium solutions is also examined. Particular attention is paid to multistage vaccination strategies that vaccinate given proportions of susceptible individuals at various ages. Finally, some numerical results are analyzed to see what these vaccination coverages mean for certain common childhood diseases.

Child↗
PubMed1990

An epidemic model with a density-dependent death rate.

This paper deals with a mathematical model for a disease where the death rate depends on the number of people in the population. This sort of model would be suitable for diseases in developing countries or for diseases amongst animal and insect populations. We also assume that the population under consideration is regulated by the disease so that there is a mortality induced by the disease. We use a compartmental model and perform an equilibrium and stability analysis to find that there is a threshold condition. If the threshold is exceeded, then there is a unique equilibrium with disease present which is locally stable to small perturbations. We conclude by looking at several specific models and seeing how the results relate to previous work.

Animals↗
PubMed1988

Analytical threshold and stability results on age-structured epidemic models with vaccination.

This paper examines mathematical models for common childhood diseases such as measles and rubella and in particular the use of such models to predict whether or not an epidemic pattern of regular recurrent disease incidence will occur. We use age-structured compartmental models which divide the population amongst whom the disease is spreading into classes and use partial differential equations to model the spread of the disease. This paper is particularly concerned with an analytical investigation of the effects of different types of vaccination schemes. We examine possible equilibria and determine the stability of small oscillations about these equilibria. The results are important in predicting the long-term overall level of incidence of disease, in designing immunisation programs and in describing the variations of the incidence of disease about this equilibrium level.

Age Factors↗
PubMed1988

Threshold and stability results for an epidemic model with an age-structured meeting rate.

This paper examines threshold and stability results for simple mathematical models for the transmission of infectious diseases with permanent natural immunity. Examples of such diseases are measles, chicken-pox, hepatitis, and mumps. An important feature of this work is the introduction of an age structure into the population amongst whom the disease is spreading and, in particular, the realization of the fact that the contact rate itself may depend on age. Equilibrium and stability analyses are performed on these models. These results are in part directed towards establishing conditions sufficient for the existence of a nonzero equilibrium disease level to be possible. Conjectures about the existence of a nonzero solution to a set of partial integrodifferential equations are examined. These conditions determine the circumstances under which the disease will persist. Particular emphasis is devoted to the case where the meeting rate depends on age.

Age Factors↗
PubMed1988

Isoflurane in the treatment of asthma.

A 22-month-old child developed severe bronchospasm. Prolonged ventilation of the lungs with isoflurane for 102 hours was used as treatment. The metabolism and fluoride levels obtained are discussed.

Administration, Inhalation↗
PubMed1987

Analytical results on the stability of age-structured recurrent epidemic models.

This paper examines the equilibrium and stability properties of relatively simple mathematical models for the transmission of infectious diseases such as measles, rubella, and mumps. We consider endemic diseases which are recurrent over a long time period. We discuss some simple models which incorporate an age structure into the population amongst whom the disease is spreading, since recent work has shown this feature to be important. The results are relevant in three ways: for predicting the long-term overall level of incidence of disease; for describing the oscillations of the incidence of disease around this equilibrium level; and for designing immunization programmes.

Age Factors↗
PubMed1987

Immunomodulators and wound healing.

The synthetic immunomodulators muramyl dipeptide (MDP), thymopoietin pentapeptide (TP5), and CP-46,665 were examined for their effects on wound healing in mice. We found no differences in wound disruption strength between immunomodulator-treated animals and saline controls on days 11, 14, and 21. The only exception was with high-dose CP-46,665, which produced weakened wounds on day 14 (p less than 0.05) and 21 (p less than 0.01). CP-46,665 was further studied by injecting high and low doses 48 hours before or after wounding. No differences were seen for these groups compared to controls at 11 and 21 days. Finally, to simulate a common clinical situation, mice were subjected to a 10% total body surface area (TBSA) burn to the right paraspinal region. Twenty-four hours later, a left paraspinal incision was performed with simultaneous injection of saline, Corynebacterium parvum (C. parvum), or low-dose TP-5, MDP, or CP-46,665. At 11 days, no detriment in wound healing was found for burned control or any of the immunomodulator-treated animals except in the C. parvum-treated mice, with significantly weakened skin strips (p less than 0.001). While C. parvum may be detrimental to wound healing, the synthetic modulators tested appear to have little effect on wound healing.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1986

Inhibition of wound healing by Corynebacterium parvum.

Corynebacterium parvum (C. parvum), an immunostimulant, was examined for its effects on wound healing in mice. Animals injected intraperitoneally with C. parvum, 1400 micrograms 48 hr prior to wounding had significantly decreased wound strength at 5, 7, 11, 14, and 21 days after wounding compared to saline-injected controls (P less than 0.05-P less than 0.001). Mice injected with C. parvum at 48 or 2 hr before wounding, synchronous with wounding and 2 or 48 hr after wounding had significantly decreased wound disruption strength of 11-day-old wounds (P less than 0.01-P less than 0.001). Formalin fixations of wound strips from C. parvum-treated animals were consistently weaker than similarly treated wound strips from controls (P less than 0.05-P less than 0.01). Histologic analysis of wounds from C. parvum-treated animals revealed decreased amounts of wound collagen and increased inflammatory reaction compared to saline-injected animals. While C. parvum can improve survival following injury or septic challenge, the potential for marked alterations in wound healing may limit its clinical application in surgical and trauma patients.

Animals↗