Multiple-tracer tests for contaminant transport process identification in saturated municipal solid waste.

Two column tests were performed in conditions emulating vertical flow beneath the leachate table in a biologically active landfill to determine dominant transport mechanisms occurring in landfills. An improved understanding of contaminant transport process in wastes is required for developing better predictions about potential length of the long term aftercare of landfills, currently measured in timescales of centuries. Three tracers (lithium, bromide and deuterium) were used. Lithium did not behave conservatively. Given that lithium has been used extensively for tracing in landfill wastes, the tracer itself and the findings of previous tests which assume that it has behaved conservatively may need revisiting. The smaller column test could not be fitted with continuum models, probably because the volume of waste was below a representative elemental volume. Modelling compared advection-dispersion (AD), dual porosity (DP) and hybrid AD-DP models. Of these models, the DP model was found to be the most suitable. Although there is good evidence to suggest that diffusion is an important transport mechanism, the breakthrough curves of the different tracers did not differ from each other as would be predicted based on the free-water diffusion coefficients. This suggested that solute diffusion in wastes requires further study.

Investigating the effect of compression on solute transport through degrading municipal solid waste.

The effect of applied compression on the nature of liquid flow and hence the movement of contaminants within municipal solid waste was examined by means of thirteen tracer tests conducted on five separate waste samples. The conservative nature of bromide, lithium and deuterium tracers was evaluated and linked to the presence of degradation in the sample. Lithium and deuterium tracers were non-conservative in the presence of degradation, whereas the bromide remained effectively conservative under all conditions. Solute diffusion times into and out of less mobile blocks of waste were compared for each test under the assumption of dominantly dual-porosity flow. Despite the fact that hydraulic conductivity changed strongly with applied stress, the block diffusion times were found to be much less sensitive to compression. A simple conceptual model, whereby flow is dominated by sub-parallel low permeability obstructions which define predominantly horizontally aligned less mobile zones, is able to explain this result. Compression tends to narrow the gap between the obstructions, but not significantly alter the horizontal length scale. Irrespective of knowledge of the true flow pattern, these results show that simple models of solute flushing from landfill which do not include depth dependent changes in solute transport parameters are justified.

Use of the passive lower lingual arch in the management of anterior mandibular crowding in the mixed dentition.

Leeway space preservation in the mixed dentition is a well-documented method of space management. In the mandibular arch it may be saved for utilisation in the correction of minor anterior crowding by the placement of a passive lower lingual arch (LLA) during the transition from the mixed dentition to the permanent dentition.

Clogging of landfill tyre and aggregate drainage layers by methanogenic leachate and implications for practice.

This paper reports the results of pilot scale tests carried out to investigate the clogging of shredded and baled tyres in comparison with aggregates when percolated by leachates representative of those generated by methanogenic stage landfills. Realistic lifetime loading rates of methanogenic leachate were applied, and clogging was not generally apparent in any of the drainage media studied. This is in apparent contrast to many other studies that have demonstrated the susceptibility of all forms of drainage media to biological and chemical clogging when percolated with high strength organic and calcium rich leachates. The reasons for this difference are identified, the implications for landfill drainage system design are discussed and some suggestions for operational practice are presented for discussion.

Early identification and management of mandibular canine ectopia.

Mandibular canine impaction and transmigration have serious consequences for the patient, as removal of the tooth or teeth in question is often the only solution. The loss of one or both mandibular canines complicates orthodontic treatment. Early warning signs of mandibular canine ectopia are explored in this paper as well as how to assess the potential for displacement, impaction and/or transmigration. This paper highlights the value of interceptive treatment once the early signs of an aberrant mandibular canine have been detected.

Maxillary canine management in the pre-adolescent: a guideline for general practitioners.

This paper focuses on the identification of ectopic eruption patterns of the maxillary canines from the dental ages of approximately 8 to 12 years. The timing and suitability of interceptive treatment in pre-adolescents are discussed.

Combination antibiotics as a treatment for chronic Chlamydia-induced reactive arthritis: a double-blind, placebo-controlled, prospective trial.

OBJECTIVE: Chlamydia trachomatis and Chlamydophila (Chlamydia) pneumoniae are known triggers of reactive arthritis (ReA) and exist in a persistent metabolically active infection state in the synovium, suggesting that they may be susceptible to antimicrobial agents. The goal of this study was to investigate whether a 6-month course of combination antibiotics is an effective treatment for patients with chronic Chlamydia-induced ReA. METHODS: This study was a 9-month, prospective, double-blind, triple-placebo trial assessing a 6-month course of combination antibiotics as a treatment for Chlamydia-induced ReA. Eligible patients had to be positive for C trachomatis or C pneumoniae by polymerase chain reaction (PCR). Groups received 1) doxycycline and rifampin plus placebo instead of azithromycin; 2) azithromycin and rifampin plus placebo instead of doxycycline; or 3) placebos instead of azithromycin, doxycycline, and rifampin. The primary end point was the number of patients who improved by 20% or more in at least 4 of 6 variables without worsening in any 1 variable in both combination antibiotic groups combined and in the placebo group at month 6 compared with baseline. RESULTS: The primary end point was achieved in 17 of 27 patients (63%) receiving combination antibiotics and in 3 of 15 patients (20%) receiving placebo. Secondary efficacy end points showed similar results. Six of 27 patients (22%) randomized to combination antibiotics believed that their disease went into complete remission during the trial, whereas no patient in the placebo arm achieved remission. Significantly more patients in the active treatment group became negative for C trachomatis or C pneumoniae by PCR at month 6. Adverse events were mild, with no significant differences between the groups. CONCLUSION: These data suggest that a 6-month course of combination antibiotics is an effective treatment for chronic Chlamydia-induced ReA.

The mixed dentition pantomogram: a valuable dental development assessment tool for the dentist.

The mixed dentition pantomogram is routinely used in paediatric patients. This paper discusses the value of the pantomogram for early identification of problems in dental development during the mixed dentition stage. Aspects regarding dental maturity, leeway space, the sequence of eruption of the permanent teeth, anomalies and the development of the canines will be reviewed.

Psoriasiform lesions induced by tumour necrosis factor antagonists: a skin-deep medical conundrum.

Rarely, tumour necrosis factor (TNF)alpha antagonist therapy has been associated with de novo psoriasiform eruptions. This is unusual in that these same drugs are used to treat psoriasis. Most of these cases involve the palms and soles, yet palmoplantar pustular psoriasis represents only 1.7% of all cases of psoriasis. Keratoderma blenorrhagicum is a psoriasiform rash that occurs primarily on the palms and soles of some patients with reactive arthritis. It is grossly and histologically indistinguishable from pustular psoriasis. Chlamydia trachomatis is a common aetiological agent for reactive arthritis, and in vitro studies have shown that chlamydial replication is inversely proportional to TNFalpha levels. Three patients taking TNFalpha antagonists are presented who developed such lesions and who were found to be positive for C trachomatis DNA in the affected skin. It is proposed that these psoriasiform lesions may not be psoriasis, but rather keratoderma blenorrhagicum.

Infraocclusion of primary molars: a review of the literature.

Infraocclusion of primary molar teeth is a relatively common clinical finding and decision-making concerning the successful management of such cases can present a challenge to the general dental practitioner. This paper reviews the epidemiology, aetiology, diagnosis, treatment rationale and includes flow charts for easy reference to the various treatment options for infraoccluded primary molar teeth.

Dentoskeletal and soft-tissue changes in growing class II malocclusion patients during nonextraction orthodontic treatment.

An investigation was conducted to determine the outcome of nonextraction edgewise orthodontic treatment of thirty-five caucasian patients with Class II molar relationships (13 division 1 and 22 division 2 cases). Twenty-three females and 12 males aged between 10 and 16 years old were treated using Class II intermaxillary elastics worn with 0.016" x 0.022" stainless steel archwires and without extra-oral traction. Thirty cephalometric landmarks were identified and digitized, and used to calculate 41 parameters. Space analyses were conducted on pretreatment study models. Most of the cases had between 0-4 mm space shortage in both maxillary and mandibular dentitions. Results of this study indicated that the mean SNA angle decreased by 1.580 degrees, and that this change was largely due to posterior movement of point A. The mean pre-treatment ANB value was 4.490 degrees which decreased to a mean posttreatment value of 2.810 degrees (p<0.05). No significant changes in the growth direction of the jaws were found, showing that the use of Class II intermaxillary elastics in this sample had no detrimental effect on this parameter (p<0.05). The SNB angle increased by a mean of 0.110 degrees, which can be attributed to anterior mandibular growth. The dentoalveolar changes included a mean overjet reduction of 3.816mm (mean posttreatment overjet was 2.2mm) and proclination of the lower incisors relative to the APo line and the mandibular plane, probably caused by the use of Class II intermaxillary elastics. The lower lip advanced relatively more than the upper lip, and this contributed to an improvement of the lip relationship. The amount of nose growth observed during the study was normal for this age group, and compared favourably with other data in the literature.

Differential expression of collagen, MMP, TIMP and fibrogenic-cytokine genes in the granulomatous colon of Schistosoma mansoni-infected mice.

Schistosomiasis mansoni is a major helminthic disease of the tropics characterised by chronic hepatic and intestinal granulomatous inflammation and fibrosis. The fibrotic response is regulated by the amount of collagen deposited in the tissues and the degradation of that collagen by matrix metalloproteinases (MMP). In the murine model of the disease, although hepatic granuloma formation and the ensuing fibrosis have been thoroughly examined, there is a dearth of information on the intestinal fibrotic process. The expression of fibrosis-related genes in the colons of chronically infected mice has therefore been investigated. Compared with that seen in uninfected mice, the expression of the genes coding for collagen of types I, III and IV was upregulated. Similarly, the messages for MMP-2, MMP-3 and MMP-8 were elevated, indicating the potential for collagen degradation. The genes for two tissue inhibitors of metalloproteinases (TIMP), TIMP-1 and TIMP-4, were, however, expressed at higher levels than those coding for the MMP. As a corollary, expression of the genes coding for three fibrogenic cytokines, transforming growth factor-beta, tumour necrosis factor and interleukin-4, was elevated. These data indicate that an imbalance in MMP:TIMP expression and enhanced levels of the messages for fibrogenic cytokines underlie the mechanism(s) of the colonic fibrosis seen in mice chronically infected with Schistosoma mansoni.

Synovial Chlamydia trachomatis up regulates expression of a panel of genes similar to that transcribed by Mycobacterium tuberculosis during persistent infection.

BACKGROUND: Synovial tissues in patients with Chlamydia associated arthritis are persistently infected by C trachomatis, an organism for which genetic manipulation is not possible. M tuberculosis also engages in persistent infection, and because this bacterium is genetically tractable many groups have been able to define transcriptional characteristics of mycobacterial growth and persistence. OBJECTIVE: To investigate whether the pattern of gene expression underlying chlamydial persistence is similar to that underlying mycobacterial persistence. METHODS: 194 genes in M tuberculosis that are transcriptionally up regulated to support in vivo growth and persistence of that organism have previously been identified. Each of those genes was compared with the C trachomatis genome to identify orthologues. Expression of selected chlamydial orthologues so identified was assessed by real time RT-PCR in an in vitro model of chlamydial persistence and synovial tissues from patients who were PCR positive for C trachomatis at that site. RESULTS: 67 C trachomatis genes were identified as being orthologous to mycobacterial persistence related genes, representing 35% of the genes tested. The chlamydial orthologues fell into similar metabolic and other categories as those in M tuberculosis. Expression of a majority of selected chlamydial orthologues was strongly up regulated in an in vitro model of chlamydial persistence and in synovial tissues of relevant patients, compared with their expression during active infection. CONCLUSIONS: These observations provide new insight into the molecular genetic basis underlying chlamydial persistence, and indicate that this information can be obtained, in some instances, by extrapolating observations made in other biological systems and/or organisms.

A novel nonsteroidal antifibrotic oligo decoy containing the TGF-beta element found in the COL1A1 gene which regulates murine schistosomiasis liver fibrosis.

Schistosomiasis mansoni disseminated worm eggs in mice and humans induce granulomatous inflammations and cumulative fibrosis causing morbidity and possibly mortality. In this study, intrahepatic and I.V. injections of a double-stranded oligodeoxynucleotide decoy containing the TGF-beta regulatory element found in the distal promoter of the COL1A1 gene into worm-infected mice suppressed TGF-beta1, COL1A1, tissue inhibitor of metalloproteinase-1, and decreased COL3A1 mRNAs to a lesser extent. Sequence comparisons within the mouse genome found homologous sequences within the COL3A1, TGF-beta1, and TIMP-1 5' flanking regions. Cold competition gel mobility shift assays using these homologous sequences with 5' and 3' flanking regions found in the natural COL1A1 gene showed competition. Competitive gel mobility assays in a separate experiment showed no competition using a 5-base mutated or scrambled sequence. Explanted liver granulomas from saline-injected mice incorporated 10.45 +/- 1.7% (3)H-proline into newly synthesized collagen, whereas decoy-treated mice showed no collagen synthesis. Compared with the saline control schistosomiasis mice phosphorothioate double-stranded oligodeoxynucleotide treatment decreased total liver collagen content (i.e. hydroxy-4-proline) by 34%. This novel molecular approach has the potential to be employed as a novel antifibrotic treatment modality.

Dynamics of collagen, MMP and TIMP gene expression during the granulomatous, fibrotic process induced by Schistosoma mansoni eggs.

In schistosomiasis mansoni, granulomatous inflammation and fibrotic resolution are the major pathogenetic factors. The outcome of fibrosis is influenced by the deposition of collagen and degradation mediated by matrix metalloproteinases (MMP). There is a dearth of data on the expression of MMP and the tissue inhibitors of metalloproteinase (TIMP) during the fibrosis associated with schistosomiasis. In this study, the dynamics of collagen, MMP and TIMP gene expression were analysed during murine Schistosoma mansoni infection. Expression within the granulomatous liver tissue of the genes coding for collagen of types I, III and IV was up-regulated at the onset of granuloma development, and the dominant type-I expression peaked at the chronic, fibrotic stage. The amount of deposited hepatic collagen increased with the chronicity of the infection, indicating cumulative fibrosis. Collagenase, gelatinase, stromelysin, matrilysin-specific gene activities were similarly up-regulated, but only MMP-8 (collagenase-2) expression peaked at the height of fibrosis. TIMP-1 gene expression gradually increased during the course of the disease and, along with TIMP-2, peaked at the chronic, fibrotic stage. Granuloma myofibroblasts expressed both MMP and TIMP-1 genes. In ELISA of the splenic cytokines, high levels of fibrogenic interleukin-13 and moderate production of transforming growth factor-beta were found to be concurrent with fibrosis. These data indicate that an imbalance in MMP:TIMP expression and fibrogenic cytokine production are associated with cumulative fibrosis.

Modelling the compression behaviour of landfilled domestic waste.

This paper discusses the mechanisms involved in the compression of domestic waste, and how the resulting compression behaviour may be modelled. Reference is made to experimental data illustrating the effect of gas content and pore water pressure on bulk density and drainable porosity, and a theoretical model able to reproduce some but not all features of the data is presented.

Dendritic cells co-localize with activated CD4+ T cells in giant cell arteritis.

OBJECTIVE: Giant cell arteritis (GCA) is a vasculitis predominantly affecting medium- and large-sized arteries. Recent data show the co-localization of dendritic cells and Chlamydia pneumoniae in vascular biopsies from GCA patients. Here we define the topographical relation of dendritic cells and these activated T-cells to determine the antigen presenting cell in GCA, and to examine several auxiliary biochemical and genetic aspects relating to the role of bacteria such as C. pneumoniae in eliciting GCA. METHODS: 18 paraffin-embedded temporal artery biopsy specimens from 14 patients with GCA that were PCR-positive for C. pneumoniae were examined by two-color immunohistochemistry for the topographical relationship between dendritic cells and activated T-cells. In addition the presence of GTP-binding proteins. Tumor necrosis factor alpha (TNF alpha), and Toll-like receptor 4 (TLR4) was investigated. 15 temporal artery specimens from 10 patients without GCA served as controls. RESULTS: In all GCA specimens, dendritic cells co-localized in the immediate vicinity of activated CD4+ Talin-expressing T cells, and these were predominantly found in granulomatous infiltrates. Confocal microscopy confirmed the cell-cell contact of dendritic cells with activated T cells. Results further showed that RhoA and Rac1 were predominantly present in the region of granulomatous infiltrates. TNF alpha production and expression was found in dendritic cells and macrophages, predominantly in granulomatous infiltrates and in endothelial cells of the vasa vasorum dispersed in the adventitial and medial layers of the temporal artery. No control specimens showed TNF alpha expression. More than 95% of dendritic cells were positive for TLR4; macrophages and endothelial cells localized in the adventitia showed TLR4 production. CONCLUSIONS: The immediate co-localization of dendritic cells and activated T cells indicate a high probability that the former represent the antigen presenting cells in GCA. In addition, because of the presence of Rho A and Rac1 in the granulomatous infiltrates, we speculate that they provide the right environment for cell-cell contact and adhesion, and that they may promote the internalization of bacteria. TNF alpha is expressed at high levels in the granulomatous infiltrates of temporal artery specimens from patients with GCA. Since TLR4 is produced in the same cell types, and predominantly in the adventitial layer of the temporal artery, we suggest that these receptors are coupled to signal transduction pathways that control TNF alpha expression.

Chlamydia pneumoniae infection promotes the transmigration of monocytes through human brain endothelial cells.

We have investigated the effects of Chlamydia pneumoniae on human brain endothelial cells (HBMECs) and human monocytes as a mechanism for breaching the blood-brain barrier (BBB) in Alzheimer's disease (AD). HBMECs and peripheral blood monocytes may be key components in controlling the entry of C. pneumoniae into the human brain. Our results indicate that C. pneumoniae infects blood vessels and monocytes in AD brain tissues compared with normal brain tissue. C. pneumoniae infection stimulates transendothelial entry of monocytes through HBMECs. This entry is facilitated by the up-regulation of VCAM-1 and ICAM-1 on HBMECs and a corresponding increase of LFA-1, VLA-4, and MAC-1 on monocytes. C. pneumoniae infection in HBMECs and THP-1 monocytes up-regulates monocyte transmigration threefold in an in vitro brain endothelial monolayer. In this way, C. pneumoniae infection in these cell types may contribute to increased monocyte migration and promote inflammation within the CNS resulting from infection at the level of the vasculature. Thus, infection at the level of the vasculature may be a key initiating factor in the pathogenesis of neurodegenerative diseases such as sporadic AD.

Loss of mitochondrial DNA in rabbit bladder smooth muscle following partial outlet obstruction results from lack of organellar DNA replication.

When the rabbit bladder outlet is partially obstructed, the relative amount of mitochondrial (mt) DNA per cell in bladder smooth muscle falls rapidly. In order to assess whether this loss of organellar genome results from attenuation of mt DNA replication, we cloned portions of rabbit genes specifying the single-strand binding (SSB) protein required for initiation of mt DNA replication, and the catalytic subunit of DNA polymerase gamma (pol gamma), the replication enzyme itself. We then designed primer-probe systems for real-time RT-PCR (TaqMan) analyses for each gene. These were used to assess mRNA in preparations from bladder smooth muscle and mucosa from rabbits subjected to surgical obstruction of the bladder outlet for up to 14 days. mRNA from the pol gamma gene remained essentially at control level in smooth muscle and mucosa in all samples. In mucosa, mRNA from the SSB protein gene remained virtually at control levels in all samples, as did mt genome copy number. In smooth muscle, however, levels of this mRNA declined by >95% within 3 days of obstruction and remained at that level through 14 days; this attenuation of SSB protein mRNA paralleled the loss of mt DNA in the same smooth muscle samples. Thus, lack of mt SSB protein, and consequently attenuated mt DNA replication, is a primary factor in the loss of mt genome copies in bladder smooth muscle after outlet obstruction in the rabbit model of benign bladder dysfunction.

Cytokines in autoimmune lacrimal gland disease in MRL/MpJ mice.

PURPOSE: MRL/MpJ-+/+ (MRL/+) and MRL/MpJ-lpr/lpr (MRL/lpr) mice show spontaneous development of a T-cell-driven lacrimal gland inflammation that is a model for Sjögren syndrome. The lacrimal gland lesions in these mice were evaluated by quantitative RT-PCR for selected cytokine mRNA for the relative contributions of T-helper (Th)1 versus Th2 immune responses and by RT-PCR and immunohistochemistry for the contribution of the interleukin (IL)-2/IL-2 receptor (IL-2R) autocrine pathway. METHODS: RNA was isolated from lacrimal glands of MRL/+ mice ages 1 to 9 months and from MRL/lpr mice ages 1 through 5 months, and competitive RT-PCR was used to quantify mRNA for the cytokines IL-2, -4, -10, and -12 and interferon (IFN)-gamma. Frozen sections of lacrimal glands from MRL/+ and MRL/lpr mice ages 2 through 5 months were stained for the IL-2R. RESULTS: IL-2 and -12 mRNA transcripts were below the limit of detection (<10(-3) fg/pg hypoxanthine phosphoribosyl transferase gene; HPRT) in both MRL/+ and MRL/lpr mice of all ages. When detectable, IFN-gamma transcripts were present in low amounts and were below the limit of detection in most samples. IL-4 transcripts were present in 100- to 1000-fold greater amounts than IFN-gamma transcripts. IL-10 transcripts were detectable in both MRL/+ and MRL/lpr mice. IL-2R typically was detected on less than 10% of lymphocytes infiltrating lacrimal gland lesions in both substrains. CONCLUSIONS: On the basis of RT-PCR for cytokine mRNA, autoimmune lacrimal gland lesions in MRL/+ and MRL/lpr mice appear to be largely Th2-mediated. There does not appear to be a direct role for the IL-2/IL-2R autocrine pathway within the microenvironment of the lacrimal gland.