Biomedical subjects
D Clements
Publications and source records attributed to D Clements.
Determining the spatial distribution of viable and nonviable bacteria in hydrated microcosm dental plaques by viability profiling.
AIMS: The aim of this study was to use confocal laser scanning microscopy (CLSM) to examine the spatial distribution of both viable and nonviable bacteria within microcosm dental plaques grown in vitro. Previous in vivo studies have reported upon the distribution of viable bacteria only. METHODS AND RESULTS: Oral biofilms were grown on hydroxyapatite (HA) discs in a constant-depth film fermenter (CDFF) from a saliva inoculum. The biofilms were stained with the BacLight LIVE/DEAD system and examined by CLSM. Fluorescence intensity profiles through the depth of the biofilm showed an offset between the maximum viable intensity and the maximum nonviable intensity. Topographical differences between the surface properties of the viable and nonviable biofilm virtual surfaces were also measured. CONCLUSIONS: The profile of fluorescence intensity from viable and nonviable staining suggested that the upper layers of the biofilm contain proportionally more viable bacteria than the lower regions of the biofilm. SIGNIFICANCE AND IMPACT OF STUDY: Viability profiling records the transition from predominantly viable to nonviable bacteria through biofilms suggesting that this technique may be of use for quantifying the effects of antimicrobial compounds upon biofilms. The distribution of viable bacteria was similar to that found in dental plaque in vivo suggesting that the CDFF produces in vitro biofilms which are comparable to their in vivo counterparts in terms of the spatial distribution of viable bacteria.
Delayed post-traumatic osteonecrosis of a vertebral body (Kummell's disease).
Kummell's disease is a rare spinal disorder characterized as avascular necrosis of a vertebral body occurring in a delayed fashion after minor trauma. The disease derives its name from the German surgeon Hermann Kummell, who described a series of patients with the disorder in 1895. Kummell's disease is distinguished from typical osteoporotic compression fractures, by virtue of the fact that patients with Kummell's disease develop symptoms in delayed fashion. In addition, Kummell's disease exhibits different signal characteristics on magnetic resonance imaging when compared to osteoporotic compression fractures. In this review we discuss the pathophysiology, histopathology and treatment of this interesting disorder.
Initiation and early patterning of the endoderm.
We review the early stages of endoderm formation in the major animal models. In Amphibia maternal molecules are important in initiating endoderm formation. This is followed by successive signaling events that establish and then pattern the endoderm. In other organisms there are differences in endodermal development, particularly in the initial, prephylotypic stages. Later many of the same key families of transcription factors and signaling cassettes are used in all animals, but more work will be needed to establish exact evolutionary homologies.
Changes in embryonic cell fate produced by expression of an endodermal transcription factor, Xsox17.
Many molecules induce the ectopic expression of tissue-specific genes in Xenopus embryos. Conversely, interfering with their activity disrupts patterns of gene expression, implicating them in normal development. Does this mean that they control cell fate (i.e. position, as well as differentiation)? Xsox17alpha and beta can induce ectopic expression of endodermal markers; inhibiting their function suppresses expression of endodermal marker genes in the developing gut (Cell 91 (1997) 397). Here we show the effect of these manipulations on cell lineage. Expressing Xsox17 in a cells normally fated to become ectoderm causes their descendants either to relocate into the embryonic gut or to die at a late developmental stage. Conversely, disrupting Xsox17 activity in cells normally fated to be endodermal causes them to enter mesodermal and ectodermal lineages.
Reverse genetics. Screening plant populations for gene knockouts.
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Interference of antibody production to hepatitis B surface antigen in a combination hepatitis A/hepatitis B vaccine.
A randomized trial comparing 3 manufacturing consistency lots of a combination hepatitis A/hepatitis B vaccine to each other and to hepatitis A vaccine and hepatitis B vaccine given separately and concurrently was done to evaluate safety, tolerability, and immunogenicity. Healthy volunteers >/=11 years of age were divided into 4 groups. Each of 3 groups received a separate consistency lot of the combination vaccine, and 1 group received separate but concurrent injections of hepatitis A and hepatitis B vaccines. Injections were given at weeks 0 and 24. The combination vaccine was generally well tolerated. The hepatitis A portion of the combination vaccine produced clinically acceptable high seropositivity rates 4 and 52 weeks after the first injection. The hepatitis B portion of the vaccine did not produce clinically acceptable seropositivity rates 4 weeks after the second injection. Lack of antibody production may be attributed, at least in part, to immunologic interference.
Mode of action of VegT in mesoderm and endoderm formation.
mRNA encoding the T-box transcription factor VegT is located throughout the vegetal pole of the Xenopus egg and is believed to play an important part in endoderm and mesoderm formation. We find that VegT generates endoderm both by cell-autonomous action and by generating TGF-beta family signals, the latter being entirely responsible for its mesoderm-inducing activity. Signalling molecules induced cell-autonomously by VegT include derrière, Xnr4 and activin B. Xnr1 and Xnr2 are also induced, but primarily in a non-autonomous manner. All of these signalling molecules are found in the blastula and gastrula vegetal pole and induce both endoderm and mesoderm in the animal cap assay, and hence are good candidates both for the endogenous zygotic mesoderm-inducing signal and for reinforcing the vegetal expression of endoderm markers.
Biomarkers of oxidative stress are significantly elevated in Down syndrome.
There is convincing epidemiological and in vitro evidence of chronic oxidative stress in individuals with Down syndrome (DS). These individuals develop Alzheimer like changes in the brain in their 30s and 40s. The incidence of autoimmune diseases and cataracts is significantly increased, and the overall ageing process is accelerated. In vitro studies show that impaired viability of DS neurons may be amended by simple chemical antioxidants, such as vitamin E, BHT and propyl gallate, clearly indicative of oxyl radical involvement. However, because of the lack of in vivo experiments, the role of oxidative stress in DS remains controversial. We report here on the results of the chemical analyses of urine samples of 166 individuals, where DS subjects were matched by their siblings. The levels of 8-hydroxy-2'-deoxyguanosine (2.35 +/- 1.69 in DS vs. 1.35 +/- 1.04 in controls, P = 0.00011), a biomarker of oxidative damage to DNA, and malondialdehyde (0.255 +/- 0.158 in DS vs. 0.204 +/- 0.128 in controls, P = 0.033), a biomarker of lipid peroxidation, are significantly elevated in individuals with DS. Dietary influences failed to show any significant correlation with the oxidative stress biomarkers. These results provide direct evidence for increased oxidative stress in individuals with DS.
Xsox17alpha and -beta mediate endoderm formation in Xenopus.
We have isolated two Xenopus relatives of murine Sox17 expressed in gastrula presumptive endoderm. Xsox17alpha and -beta expression can be induced in animal caps by activin, but not by FGF. Ectopic expression of these genes in animal caps induces the expression of endoderm markers; this induction is blocked by overexpression of a fusion of the Xsox17beta HMG domain to the Drosophila Engrailed repressor domain, as is induction of endoderm markers by activin and the expression of endodermal markers in whole embryos and isolated vegetal poles. These experiments, as well as the effects of the mRNAs on embryo phenotypes, suggest that the Xsox17 genes mediate an activin-induced endoderm differentiation pathway in animal caps and are involved in normal endoderm differentiation in embryos.
Semirigid instrumentation in the management of lumbar spinal conditions combined with circumferential fusion. A multicenter study.
STUDY DESIGN: Patients with the diagnosis of degenerative disc conditions or spondylolisthesis undergoing circumferential fusion with posterior pedicle screw fixation using a semirigid rod were reviewed. OBJECTIVES: To determine the effectiveness of this approach in achieving a spinal fusion and satisfactory clinical outcome, and to determine the complications associated with the procedure. SUMMARY OF BACKGROUND DATA: The use of instrumentation to stabilize the lumbar motion segments and thereby enhance the fusion rate has been proposed in a number of studies. Semirigid fixation was believed to be effective in achieving these objectives without concern for stress-shielding, which was suggested by some authors using rigid fixation systems. METHODS: Patients who required spinal fusion with anterior and posterior approaches because of specific lumbar pathology or previous surgeries were selected. The surgery consisted of an anterior interbody fusion using allograft, followed by a posterolateral fusion and pedicle screw fixation. Fusion was determined by continuity of trabecular bridging, and outcomes were determined by pain reduction and return to previous levels of activity. Fusion was considered solid if the two posterolateral areas were fused (Zones one and two), if the anterior interbody area was fused (Zone three), or if all three zones were fused. Complications were documented during and after surgery. RESULTS: Sixty-two percent of patients had previous surgery with 25% of these patients having a diagnosis of pseudarthrosis. Fifty-five percent of patients had two or more levels fused, and 43% were heavy smokers. Ninety-seven percent of patients had successful fusions. Pain was significantly reduced on a pain analogue scale from 7.1 to 2.1 in the back and from 5.8 to 1.5 in the leg (p < 0.006 and 0.0001, respectively). Fifty-nine percent of patients returned to their previous level of activity, and 18% returned to lighter work or job retraining, for a total of 77% returning to the same or lighter levels of activity. Complications included metal failure, 4.9%; neurologic deficit, 1.2%; deep infection, 1.2%; deep venous thrombosis, 4.9%; and vascular injury, 2.4%. Fatal pulmonary embolus occurred in one patient. CONCLUSION: This technique produces a satisfactory fusion rate (97%) and a good clinical outcome based on pain reduction and return to a satisfactory level of activity (77%). It is associated with few, but significant, complications that compare well with other reported series in a difficult group of patients. This procedure should be reserved for patients who are considered to be at high risk for not achieving spinal fusion.
Distinct regulatory control of the Brachyury gene in axial and non-axial mesoderm suggests separation of mesoderm lineages early in mouse gastrulation.
Brachyury is required for the normal extension of the anteroposterior axis during mouse embryogenesis. A transgene comprising sequences from -500 to +150 relative to the start of Brachyury transcription, and the reporter gene lacZ, recapitulates some, but not all elements of Brachyury expression. Beta-Galactosidase expression is seen in the primitive streak from 6.5 d.p.c. but there is no detectable reporter expression in the node or notochord. Thus, the regulatory sequences required for the expression of Brachyury in the cells traversing the primitive streak are distinct from those required for the initiation of expression in the node. This suggests that different or additional signals are involved in activation of Brachyury in the node and notochord than those inducing Brachyury in the primitive streak. Additionally, the data suggest the possibility that axial and non-axial mesoderm are distinct from the earliest stages of Brachyury expression.
The report of the Clinical Care Group.
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Safety and cellular and humoral immune responses of a booster dose of varicella vaccine 6 years after primary immunization.
Four hundred nineteen children and adolescents immunized with live varicella vaccine 4-6 years earlier were enrolled in a study to evaluate the safety and immune response to a booster dose containing approximately 3300 pfu of virus. Of the subjects, 99% (414/419) maintained antibody to varicella zoster virus (VZV) with a geometric mean titer of 25.7 and mean stimulation index (SI) for VZV-specific lymphoproliferation response of 40.3 +/- 5.3 (SE). Some 7-10 days after the booster immunization, seropositivity rates increased to 100% (302/302), and GMT was 143.6 (anamnestic response). At 6 weeks after the booster inoculation, a subset of subjects had 100% seropositivity (74/74) with a GMT of 218.8 and an SI of 58.6. After 3 months, seropositivity was 100% (358/358), GMT was 119.0, and SI was 61.4.
Percutaneous aspiration of lumbar facet synovial cyst.
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Long term follow up of spinal trabecular bone mineral density in women with non-steroid treated rheumatoid arthritis.
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Audit of coding in gastrointestinal endoscopy.
The accuracy of the coding of gastrointestinal endoscopic procedures at Llandough Hospital was audited over 12 months. Although the endoscopy unit kept its own records, none of the staff were initially aware of the coding system used for endoscopic procedures for subsequent hospital activity analysis. Conventional typed discharge summaries were usually inadequate for coding purposes, and there was considerable variation in the proportion of procedures coded. Changes made to improve the accuracy and completeness of coding for endoscopic procedures were seen to be effective in a follow-up study.