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PubMed1998

The incidence and Dukes' staging of colorectal cancer over 3 decades.

AIMS: Two previous studies (1966-1971 and 1979-1983) of patients with colorectal cancer (CRC) have been reported from our hospital. A large increase in the incidence of CRC was noted, and an improvement in Dukes' staging of tumours at treatment. We report a series of patients admitted with newly diagnosed CRC to evaluate this trend further. METHODS: A prospective study was made of all patients with newly diagnosed CRC admitted to the John Radcliffe Hospital, Oxford in 1995. Means of diagnosis and Dukes' staging were recorded. RESULTS: In 1 year 177 patients were admitted with newly diagnosed CRC. Previous studies had shown an increase from 52.8 to 103.4 patients per year. The number of patients diagnosed by colonoscopy doubled from 19.4% in 1979-1983 to 41% in 1995. No significant change in the proportion of patients with Dukes' A or B tumours was found. CONCLUSION: The number of patients treated annually with CRC in a stable population has more than trebled in the last 3 decades. A real increase in the incidence of CRC is likely as this rise cannot be explained solely by changing referral patterns or an ageing community. There are no significant changes in presentation patterns despite the availability of colonoscopy since 1975.

Aged↗
PubMed2000

Identifying persons with chronic conditions in a managed care setting. A comparison of methods.

PURPOSE: Together, the sophisticated computerized information systems and defined, stable populations within Health Maintenance Organizations (HMOs) can reduce imprecision associated with modeling disease incidence and prevalence. Such data are useful for resource allocation, intervention planning, epidemiological study and surveillance. Identifying all cases of illness within such a defined population is vital to these aims, yet detailed diagnostic information is lacking in many pre-paid plans. In this presentation, diagnostic and prescription data are compared for their ability to assess the treatment prevalence for 28 chronic medical conditions.METHODS: Group Health Cooperative is a mixed model HMO in Western WA state. Automated records for calendar year 1999 were examined for 182,174 commercially insured patients age 20-64. Prescription drug data and International Classification of Disease-9(th) Clinical Modification codes (ICD-9CM) were used to identify 28 chronic medical conditions among patients. Chi square tests were performed to compare results produced by the two methods.RESULTS: The diagnostic method worked best for conditions with no clear pharmacologic treatment. However, the pharmacy-based method better identified patients with chronic illnesses initially diagnosed prior to 1999, and with disorders for which standard diagnostic codes are inconsistently utilized, such as mental health conditions.CONCLUSIONS: While both diagnostic and pharmacy-based methods perform well in identifying a limited set of conditions, each performs poorly under certain circumstances. A hybrid method utilizing both diagnostic and pharmacy data may be more appropriate for an HMO setting. Additional research is needed to develop and refine such a method.

Journal Article↗
PubMed1998

Health promotion for end-stage renal disease patients.

Health promotion is the desired objective of dialysis treatment. Achieving the highest level of functioning not only improves the life of the patient but rewards the staff through the positive feedback that improvement produces. The facility is rewarded by a stable population producing a more secure stream of income. The therapeutic environment is improved through better communication, positive attitudes, and more active participation of patients in their care. When maximum health is the focus of care, activities to achieve health are part of routine clinical contact, not additional effort requiring more staff. Fundamental to achieving health is adequate dialysis, control of anemia, good nutrition, and attention to comorbid conditions. The "Five Es" Life Options model of rehabilitation is a pattern for pursuing health and life enhancement. Encouragement is the positive attitude and expectations for each patient. Evaluation is individualized planning and periodic assessment of progress. Education prepares the patient for participation and responsibility. Exercise (on dialysis and off) improves physical capacity and well being. Employment is sought for those of working age and capability. A number of facilities have shown the effectiveness and benefits of these practices. In addition, using health status/quality of life measures to obtain patient-reported assessment of condition allows objective scoring. Comparisons and compilations can be made to evaluate the effect of interventions or illness on status. This can be accomplished for groups or individuals to document the effect of health promotion.

Health Promotion↗
PubMed1985

The identity of Leishmania tarentolae Wenyon 1921.

A double clone of Trypanosoma platydactyli Catouillard, 1909, derived from a single trypomastigote from the blood of the Moorish gecko, Tarentola mauritanica, was grown in vitro. Morphogenesis of the parasites led to a stable population of promastigotes which were identical, in general morphology, ultrastructure and the electrophoretic mobility of 8 enzymes, to those cultures previously considered to be Leishmania tarentolae Wenyon, 1921. These cultures included the strain isolated from the type locality in Algeria by Parrot (1949) and later used as a laboratory model for the genus Leishmania. T. platydactyli and L. tarentolae are synonymized and the present status of saurian Leishmania parasites is discussed.

Animals↗
PubMed1998

Epidemiology and direct economic impact of hydrocephalus: a community based study.

BACKGROUND: The cost of care for hydrocephalic patients is not well established. METHODS: This retrospective study for the years 1990-1996 analyzed the cost of surgical intervention and hospitalization of hydrocephalic patients in the community-based setting of Manitoba, Canada, with a stable population of 1.138 million. RESULTS: The number of discharges with a primary diagnosis of hydrocephalus was greater than 200 annually. The mean duration of hospital stay was 12.4 to 21.9 days, depending on the etiology of hydrocephalus. Approximately 80 shunt procedures were performed annually. The total annual cost of care, excluding outpatient costs and chronic non-hospital based costs which could not be determined accurately, was estimated to be CDN$ 3.5 million in this community. CONCLUSIONS: Hydrocephalus is a chronic condition which puts substantial monetary demands on society and therefore deserves greater attention.

Adult↗
PubMedDate not supplied

Development of the rabbit retina, III: Differential retinal growth, and density of projection neurons and interneurons.

To provide a quantitative description of postnatal retinal expansion in rabbits, a new procedure was developed to map the retinae, which cover the inner surface of hemispheres or parts of rotation ellipsoids, in situ, onto a single plane. This method, as well as the known distribution of Müller cells per unit retinal surface area, were used to estimate the redistribution of specific subpopulations of Müller cells within different topographic regions of the retinae. Müller cells are known to exist as a stable population of cells 1 week after birth and can therefore be used as "markers" for determining tissue expansion. Our results show that differential retinal expansion occurs during development. Peripheral retinal regions expand at least twice as much as the central ones. Furthermore, there is a greater vertical than horizontal expansion. This differential retinal expansion leads to a corresponding redistribution of 5-hydroxytryptamine (5-HT) accumulating amacrine cells. Differential retinal expansion, however, does not account for all of the changes in the centro-peripheral density gradient of cells in the ganglion cell layer (GCL)--mostly retinal ganglion cells--during postnatal development. The changes in the ganglion cell layer were evaluated in Nissl-stained wholemount retinal preparations. Additionally, the difference between expansion-related redistribution of cells in the GCL and Müller cells was confirmed in wholemount preparations where Müller cells (identified as vimentin positive) and cells in the GCL (identified by fluorescent supravital dyes) were simultaneously labeled. It is assumed that many of the ganglion cells within the retinal center are not translocated during retinal expansion, possibly because their axons are fixed. In contrast, 5-HT accumulating amacrine cells--which are interneurons without a retinofugal axon--display a passive redistribution together with the surrounding retinal tissue.

Animals↗
PubMed2000

Avian pneumoviruses and emergence of a new type in the United States of America.

Avian pneumovirus (APV) primarily causes an upper respiratory disease recognized as turkey rhinotracheitis (TRT) or swollen head syndrome (SHS) in chickens. The virus was first isolated in South Africa during the early 1970s and has subsequently been reported in Europe, Asia and South America. In February 1997, a serologically distinct APV isolate was officially reported in the USA following an outbreak of TRT during the previous year. This was the first report of these virus types in the USA; they were previously considered exotic to the USA and Canada. The predicted matrix (M) proteins of European APV type A and B isolates share 89% identity in their amino acid sequence. However, the predicted M protein of APV/CO is only 78% similar to the APV type A and 77% similar to the APV type B protein sequence. The predicted amino acid sequence of the US APV isolate's fusion (F) protein has 72% sequence identity to the F protein of APV type A and 71% sequence identity to the F protein of type B. This compares with the 83% sequence identity between the predicted amino acid sequences of the F proteins of APV types A and B. The lack of sequence heterogeneity among the US APV isolates over 2 years suggests that these viruses have maintained a relatively stable population since the first outbreak of TRT. Phylogenetic analysis of the M and F proteins, together with the serological uniqueness of the US APV isolates, supports their classification as a new APV, designated type C.

Amino Acid Sequence↗
PubMed2005

Pot and field studies on bioremediation of p-nitrophenol contaminated soil using Arthrobacter protophormiae RKJ100.

Biodegradation of p-nitrophenol (PNP), a priority pollutant, was studied as a model system for bioremediation of sites contaminated with nitroaromatic/organic compounds. Bioremediation of PNP-containing soil was first carried out in pots using immobilized and free cells of Arthrobacter protophormiae RKJ100 in order to ascertain the role of a suitable carrier material. Results showed that stability of the introduced strain was enhanced upon immobilization and that the rate of PNP depletion decreased with increasing depth of soil. Small-scale field studies (in one square meter plots) were then conducted in which PNP-contaminated soil from an agricultural field was bioaugmented with strain RKJ100 under natural environmental conditions. PNP was totally depleted in 5 days by immobilized cells, whereas free cells were able to deplete 75% of PNP in the same time period. The fate of the released strain as monitored by plate counts, hybridization studies, and real-time polymerase chain reaction revealed fairly stable population of the cells upon immobilization on corncob powder throughout the period of study.

Arthrobacter↗
PubMed1999

Mechanisms of resistance to pathogenesis in muscular dystrophies.

A mechanistic definition of the dystrophic process is proposed, and the effects of growth factors vs. down-regulation of growth are critically analyzed. A conceptual scheme is presented to illustrate the steps leading to pathology, and various compensatory systems which ameliorate the pathology are examined, particularly in regards to the mdv mouse which is resistant to the deficiency of dystrophin, the main protein product of the Duchenne and Becker muscular dystrophy (DMD/BMD) gene. These compensatory systems are analyzed in terms of the differential resistance of fiber types to pathogenesis. The generation of a stable population of maturationally arrested centronucleated fibers which express the mature adult myosin isoforms is proposed to be the main strategy of mdx muscle to minimize apoptosis. Physiological properties of these fibers, such as utrophin expression, and high mitochondrial and endoplasmic reticulum content, together with probable increased glycerophosphorylcholine concentrations and facile access to the vascular system, are hypothesized to be instrumental in their resistance to pathogenesis. It is proposed that the major element that determines the susceptibility of most human muscles to the dystrophic process is their inability to arrest the maturation of regenerated fibers at the centronucleated stage with a concomitant expression of the adult myosins.

Animals↗
PubMed2001

The role of apoptosis in regulating hematopoietic stem cell numbers.

The importance of apoptosis, in combination with proliferation, in maintaining stable populations has become increasingly clear in the last decade. Perturbation of either of these processes can have serious consequences, and result in a variety of disorders. Moreover, as the players and pathways gradually emerge, it turns out that there are strong connections in the regulation of cell cycle progression and apoptosis. Apoptosis, proliferation, and the disorders resulting from aberrant regulation have been studied in a variety of cell types and systems. Hematopoietic stem cells (HSC) are defined as primitive mesenchymal cells that are capable of both self-renewal and differentiation into the various cell lineages that constitute the functioning hematopoietic system. Many (but certainly not all) mature hematopoietic cells are relatively short-lived, sometimes with a half-life in the order of days. Homeostasis requires the production of 10(8) (mouse) to 10(11) (human) cells each day. All of these cells are ultimately derived from HSC that mostly reside in the bone marrow in adult mammals. The study of the regulation of HSC numbers has focussed mainly on the choice between self-renewal and differentiation, symmetric and asymmetric cell divisions. Recently, however, it has been directly demonstrated that apoptosis plays an important role in the regulation of hematopoietic stem cells in vivo.

Animals↗
PubMed1977

Burrows of wild and albino rats: effects of domestication, outdoor raising, age, experience, and maternal state.

Burrows dug by albino rats were compared with those of wild Norway rats in an outdoor pen and in observation chambers in the laboratory. Burrows, in terms of measurements, configurations, or sequential development, were indistinguishable in wild and domestic rats. Burrowing for both wild and domestic rats was unaffected by raising in outdoor burrows, by availability of nesting material, or by pregnancy. Prior experience in burrowing did make it more efficient in a second trial, which suggests that learning may have a limited role in what appears to be a behavior with a strong genetic basis. Feralization of domestic rats in the outdoor pen was especially productive in answering claims of degeneracy in these animals: Albino rats were hardy throughout climatic extremes, they maintained a stable population for two years, they constructed and lived in burrows, and they showed a vaiety of wild-type behaviors.

Age Factors↗
PubMed2004

Upregulation of tissue inhibitor of metalloproteinases (TIMP)-2 promotes matrix metalloproteinase (MMP)-2 activation and cell invasion in a human glioblastoma cell line.

Local invasiveness is a characteristic feature of glioblastoma that makes surgical resection nearly impossible and accounts in large part for its poor prognosis. To identify mechanisms underlying glioblastoma invasion and motility, we used Transwell invasion chambers to select for a more potently invasive subpopulation of U87MG human glioblastoma cells. The stable population of tumor cells (U87-C1) obtained through this in vitro selection process were three times more invasive than parental U87MG cells and demonstrated faster monolayer wound healing and enhanced radial motility from cell spheroids. This enhanced invasiveness was associated with an 80% increase in matrix metalloproteinase 2 (MMP-2) activation. No differences in expression levels of pro-MMP-2, membrane-type matrix metalloproteinase I (MT1-MMP), or integrin alphavbeta3 (mediators of MMP-2 activation) were detected. However, U87-C1 cells exhibited two-fold elevation of tissue inhibitor of metalloproteinases (TIMP)-2 mRNA and protein relative to parental cells. Exogenous addition of comparable levels of purified TIMP-2 to parental U87MG cells increased MMP-2 activation and invasion. Similarly, U87MG cells engineered to overexpress TIMP-2 at the same levels as U87-C1 cells also demonstrated increased MMP-2 activation, indicating that an increase in physiological levels of TIMP-2 can promote MMP-2 activation and invasion in glioblastoma cells. However, exogenous administration or recombinant overexpression of higher amounts of TIMP-2 in U87MG cells resulted in inhibition of MMP-2 activation. These results demonstrate that the complex balance between TIMP-2 and MMP-2 is a critical determinant of glioblastoma invasion, and indicate that increasing TIMP-2 in glioblastoma patients may potentially cause adverse effects, particularly in tumors containing high levels of MT1-MMP and MMP-2.

Cell Line, Tumor↗
PubMed2000

The likelihood of homoploid hybrid speciation.

New species may be formed through hybridization and without an increase in ploidy. The challenge is for hybrid derivatives to escape the homogenizing effects of gene flow from parental species. The mechanisms hypothesized to underlie this process were modelled using a computer simulation. The model is of recombinational speciation, in which chromosomal rearrangements between parental species result in poor fertility of F1 hybrids, but through recombination, novel homozygous types are formed that have restored fertility. In simulations, stable populations bearing the recombinant karyotypes originated frequently and were maintained when the fertility of F1 hybrids was high. However, this high rate of origination was offset by low genetic isolation, and lower F1 hybrid fertility increased the evolutionary independence of derived populations. In addition, simulations showed that ecological and spatial isolation were required to achieve substantial reproductive isolation of incipient species. In the model, the opportunity for ecological isolation arose as a result of adaptation to extreme habitats not occupied by parental species, and any form of spatial isolation (e.g. founder events) contributed to genetic isolation. Our results confirmed the importance of the combination of factors that had been emphasized in verbal models and illustrate the trade-off between the frequency at which hybrid species arise and the genetic integrity of incipient species.

Animals↗
PubMed1999

Ultrastructural identification of small granule prolactin (PRL) cells in goat adenohypophysis by the colloidal-gold method.

We describe ultrastructural characteristics of PRL cells with small secretory granules, immunostained with ovine antiserum, in adult Murciano-Granadina milking goats during anoestrus, the last third of gestation and lactation. This cell subtype is considered to comprise a stable population that decreases numerically during gestation and lactation, and that may change during these stages to show large granules.

Anestrus↗
PubMedDate not supplied

Scleroderma in South Australia: epidemiological observations of possible pathogenic significance.

BACKGROUND: Scleroderma is an autoimmune disorder of unknown cause. Previous epidemiological studies have suggested some regional clustering and associations with occupations involving exposure to silica dusts and hydrocarbons. AIMS: To determine: (i) prevalence and incidence of scleroderma in South Australia (SA), a state with a stable population living in well-defined urban, rural and industrial regions, (ii) hospital separation rates, (iii) cumulative survival rates, (iv) gender and disease subclassification, (v) geographical residency and occupations, (vi) familial associations and (vii) age at onset versus age-specific incidence rate. METHODS: Creation of the South Australian Scleroderma Register (SASR) to identify demographics and clinical and serological features of all scleroderma patients resident in SA. RESULTS: Scleroderma occurs in South Australia with a point prevalence of 23 per 10(5) and an incidence of approximately 1/15th of this. However, this prevalence is high compared with other regional world studies. Scleroderma is predominantly a female disease, with most patients having the limited form of scleroderma characterized by the presence of the anticentromere antibody and a mean survival of 27.6 years. In contrast, diffuse scleroderma is a less benign disease occurring at an early age of onset and has a mean survival of 9.6 years. Scleroderma occurs throughout SA without regional localization. Weak associations are seen in males, but not females, with occupations involving possible environmental exposure to silica or hydrocarbons. Scleroderma rarely occurs in families. CONCLUSION: No strong genetic or environmental influences were found to account for the relatively common occurrence of scleroderma in SA. The age at onset versus age-specific incidence curve suggests that scleroderma can be considered as a stochastic illness involving a number of random events occurring in a predisposed population. These random events may involve mutations of pivotal somatic genes.

Age of Onset↗
PubMed2004

Nucleotide diversity and linkage disequilibrium in loblolly pine.

Outbreeding species with large, stable population sizes, such as widely distributed conifers, are expected to harbor relatively more DNA sequence polymorphism. Under the neutral theory of molecular evolution, the expected heterozygosity is a function of the product 4N(e)mu, where N(e) is the effective population size and mu is the per-generation mutation rate, and the genomic scale of linkage disequilibrium is determined by 4N(e)r, where r is the per-generation recombination rate between adjacent sites. These parameters were estimated in the long-lived, outcrossing gymnosperm loblolly pine (Pinus taeda L.) from a survey of single nucleotide polymorphisms across approximately 18 kb of DNA distributed among 19 loci from a common set of 32 haploid genomes. Estimates of 4N(e)mu at silent and nonsynonymous sites were 0.00658 and 0.00108, respectively, and both were statistically heterogeneous among loci. By Tajima's D statistic, the site frequency spectrum of no locus was observed to deviate from that predicted by neutral theory. Substantial recombination in the history of the sampled alleles was observed and linkage disequilibrium declined within several kilobases. The composite likelihood estimate of 4N(e)r based on all two-site sample configurations equaled 0.00175. When geological dating, an assumed generation time (25 years), and an estimated divergence from Pinus pinaster Ait. are used, the effective population size of loblolly pine should be 5.6 x 10(5). The emerging narrow range of estimated silent site heterozygosities (relative to the vast range of population sizes) for humans, Drosophila, maize, and pine parallels the paradox described earlier for allozyme polymorphism and challenges simple equilibrium models of molecular evolution.

Animals↗
PubMed2002

Policy analysis from first principles.

The argument of this paper is predicated on the view that social science should start with observation and the specification of a problem to be solved. On that basis, the appropriate properties and conditions of application of relevant tools of analysis should be defined. Evidence is adduced from data for sales volumes and values of a disparate range of goods to show that frequency distributions are commonly fat-tailed. This result implies that any stable population distribution will generally have infinite variance and perhaps undefined mean. Models with agents that reason about their behavior and are influenced by, but do not imitate, other agents known to them will typically generate fat-tailed time series data. A simulation model of intermediated exchange is reported that is populated by such agents and yields the same type of fat-tailed time series and cross-sectional data that is found in data for fast moving consumer goods and for retail outlets. This result supports the proposition that adaptive agent models of markets with agents that reason and are socially embedded have the same statistical signatures as real markets. Whereas this statistical signature precludes any conventional hypothesis testing or forecasting, these models do offer unique opportunities for validation on the basis of domain expertise and qualitative data. Perhaps the most striking conclusion is that neither current social theory nor any similar construct will ever support an effective policy analysis. However, adaptive agent modeling is an effective substitute when embedded in a wider policy analysis procedure.

Journal Article↗
PubMed2003

Identification of T cell-signaling pathways that stimulate latent HIV in primary cells.

Eradication of HIV infection depends on the elimination of a small, but stable population of latently infected T cells. After the discontinuation of therapy, activation of latent virus can rekindle infection. To purge this reservoir, it is necessary to define cellular signaling pathways that lead to activation of latent HIV. We used the SCID-hu (Thy/Liv) mouse model of HIV latency to analyze a broad array of T cell-signaling pathways and show in primary, quiescent cells that viral induction depends on the activation of two primary intracellular signaling pathways, protein kinase C or nuclear factor of activated T cells (NF-AT). In contrast, inhibition or activation of other important T cell stimulatory pathways (such as mitogen-activated protein kinase, calcium flux, or histone deacetylation) do not significantly induce virus expression. We found that the activation of NF-kappaB is critical to viral reactivation; however, all pathways that stimulate NF-kappaBdonot reactivate latent virus. Our studies further show that inhibition of NF-kappaB does not prevent activation of HIV by NF-AT, indicating that these pathways can function independently to activate the HIV LTR. Thus, we define several molecular pathways that trigger HIV reactivation from latency and provide evidence that latent HIV infection is maintained by the functional lack of particular transcription factors in quiescent cells.

Animals↗