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PubMed2024

Enhanced transgene expression from single-stranded AAV vectors in human cells in vitro and in murine hepatocytes in vivo.

We identified that distal 10 nucleotides in the D-sequence in AAV2 inverted terminal repeat (ITR) share partial sequence homology to 1/2 binding site of glucocorticoid receptor-binding element (GRE). Here, we describe that (1) purified GR binds to AAV2 D-sequence, and the D-sequence competes with GR binding to its cognate binding site; (2) dexamethasone-mediated activation of GR pathway significantly increases the transduction efficiency of AAV2 vectors in human cells; (3) human osteosarcoma cells, U2OS, which lack expression of GR, are poorly transduced by AAV2 vectors, but stable transfection with a GR expression plasmid restores vector-mediated transgene expression; (4) replacement of the distal 10 nucleotides in the D-sequence of the AAV2 ITR with a full-length GRE consensus sequence significantly enhances transgene expression in human cells in vitro and in murine hepatocytes in vivo; and (5) none of the ITRs in AAV1, AAV3, AAV4, AAV5, and AAV6 genomes contains the GRE 1/2 binding site, and insertion of a full-length GRE consensus sequence in the AAV6-ITR also significantly enhances transgene expression from AAV6 vectors, both in vitro and in vivo. These novel vectors, termed generation Y AAV vectors, which are serotype, transgene, or promoter agnostic, should be useful in human gene therapy.

AAV vectors↗

PubMed2025

Use of an oversized AAV8 vector for CPS1 deficiency results in long-term survival and ammonia control.

Carbamoyl phosphate synthetase 1 (CPS1) deficiency, a urea-cycle disorder, results in hyperammonemia initiating a sequence of adverse events that can lead to coma and death if not treated rapidly. There is a high unmet need for an effective therapeutic for this disorder, especially in early neonatal patients where mortality is excessive. However, development of an adeno-associated virus (AAV)-based approach is hampered by large cDNA size and high protein requirement. We developed an oversized AAV vector as a gene therapy to treat CPS1 deficiency. In order to constrain genome size, we utilized small liver-specific promoter/enhancers and a minimal polyadenylation signal. Long-term survival (9 months, end of study) with ammonia control was achieved in AAV8.CPS1-administered Cps1flox/flox mice, while all null vector-injected controls died with marked hyperammonemia; female mice demonstrated improved survival over treated males. While glutamine remained elevated compared to controls, ammonia was controlled in surviving animals. Mice maintained their weights and were not sarcopenic. While drinking water did contain carglumic acid, no nitrogen scavengers were administered. Although there were concerns with vector genomic integrity, these findings demonstrate proof of concept for an oversized gene-therapy approach for a challenging urea-cycle disorder where high-level hepatic protein is essential for survival.

MT: Delivery Strategies↗

PubMed2000

Engineering membrane proteins for nuclear medicine: applications for gene therapy and cell tracking.

Nuclear imaging techniques such as PET and SPECT imaging are expected to play major roles in evaluating the efficacy of in vivo gene therapy. In particular, the quantification of vector delivery and imaging the efficacy of gene expression are of key interests in testing new treatment paradigms and in designing novel vectors. In this review article we illustrate how nuclear imaging can be used to image novel cell-surface expressed fusion proteins and how this strategy can be used to probe for phenotypic changes in genetically manipulated cells. Since the described approach uses new fusion proteins, typically not present on eukaryotic cells, such "artificial receptors" can be designed to bind radioisotopes currently in clinical use. The described fusion proteins consist of 1) a binding domain such as a peptide based chelator that binds 99mTc oxotechnetate and 2) a membrane anchoring domain. A variety of fusion proteins have been tested so far and the most promising one to date consists of a metallothionein (MT)-derived C-terminal peptide fused to a type II membrane protein markers containing the N-terminal membrane anchoring domain of neutral endopeptidase (PEP). Cell-surface expression of MT in transfected cells has been demonstrated using monoclonal antibodies in vitro. Both in vitro and in vivo transchelation experiments have confirmed expression of 99mTc-binding sites in eukaryotic cells. We expect the described approach to evolve into a useful strategy to "tag" transfected cells with 99mTc and thus assessing efficiency of gene delivery and expression.

Animals↗

PubMed2003

Overcoming the blood-brain barrier to taxane delivery for neurodegenerative diseases and brain tumors.

The blood-brain barrier (BBB) effectively prevents microtubule (MT)-stabilizing drugs from readily entering the central nervous system (CNS). A major limiting factor for microtubule-stabilizing drug permeation across the BBB is the active efflux back into the circulation by the overexpression of the multidrug-resistant gene product 1 (MDR1) or P-glycoprotein (P-gp). This study has focused on strategies to overcome P-gp-mediated efflux of Taxol analogs, MT-stabilizing agents that could be used to treat brain tumors and, potentially, neurodegenerative diseases such as Alzheimer's disease. However, taxol is a strong P-gp substrate that limits its distribution across the BBB and therapeutic potential in the CNS. We have found that addition of a succinate group to the C-10 position of paclitaxel (Taxol) results in an agent, Tx-67, with reduced interactions with P-gp and enhanced permeation across the BBB in both in vitro and in situ models. Our studies demonstrate the feasibility of making small chemical modifications to Taxol to generate analogs with reduced affinity for the P-gp but retention of MT-stabilizing properties, i.e., a taxane that may reach and treat therapeutic targets in the CNS.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2004

Myoblast transplantation for inherited myopathies: a clinical approach.

Myoblast transplantation (MT) is an experimental strategy for the potential treatment of myopathies. MT has two properties that make it potentially beneficial: genetic complementation and myogenic potential. Preclinical experiments on monkeys have shown that promising results can be obtained with MT in large muscles of primates depending on two conditions: appropriate immunosuppression and cell delivery by a method of high-density injections. Preclinical work on MT is being, or may be, addressed to: develop efficient methods of donor cell delivery applicable to clinics; control or avoid acute rejection by methods with the fewest secondary effects; understand the factors that condition the early survival of donor cells following transplantation; increase the success of each individual injection; re-engineer a functional structure in muscles that degenerates to fibrosis and fat substitution; and search for precursor cells with potential advantages over myoblasts.

Animals↗

PubMed2004

In vitro and in vivo transport and delivery of phosphorothioate oligonucleotides with cationic liposomes.

A recent strategy in gene therapy has been using antiviral genes that are delivered to uninfected cells, either as RNA or DNA, to provide intracellular protection from human immunodeficiency virus type-1 (HIV-1) infection. Antisense oligonucleotides that are complementary to specific target genes suppress gene expression. A variety of techniques are available to enhance the cellular uptake and pharmacological effectiveness of antisense oligonucleotides, both in vitro and in vivo. We investigated the intracellular and tissue uptake of an oligonucleotide/cationic lipid complex, using a fluorescently labeled oligonucleotide. The antisense oligonucleotide was designed against the HIV-1 gag gene sequence. A T-cell line (MT-4) and PHA-stimulated peripheral blood mononuclear cells (PBMCs) were both infected with HIV-1(NL432) at an MOI of 0.01. One h later, both cultures were washed and treated with medium containing 1 microM antisense oligonucleotide. After a 3-day interval, the HIV-1 antigen expression was monitored by an indirect immunofluorescence assay. At 3 days post infection, we confirmed that p24 antigen production was inhibited by the antisense oligonucleotide/cationic lipid complex at a 1/10 ratio in the PBMCs, using enzyme-linked immunosorbent assay (ELISA). We also confirmed the intracellular existence of the complex by fluorescent microscopy. We investigated different means of transporting the antisense oligonucleotide/cationic lipid complex to mouse tissues by intravenous, intraperitoneal and subcutaneous injections. We observed that the anti-HIV-1 activity of the antisense oligonucleotide/cationic lipid complex was the result of enhanced cellular uptake, both in vitro and in vivo. Therefore, the antisense oligonucleotide/cationic lipid complex is an excellent system for the transport and delivery of genes to target cells, as it is effective both in vitro and in vivo.

Animals↗

PubMed1998

The dental caries experience of 12-year-old children in the United Kingdom. Surveys coordinated by the British Association for the Study of Community Dentistry in 1996/97.

DESIGN: This paper reports the results of standardised clinical caries examinations of 129,941 twelve-year-old children from across the United Kingdom and the Isle of Man. These 1996/97 coordinated surveys are the latest in a series which seek to monitor the dental health of children and to assess the delivery of dental services. METHOD: The criteria and conventions of the British Association for the Study of Community Dentistry were used. Representative samples were drawn from participating health authorities and boards and caries was diagnosed at the caries into dentine (D3) threshold using a visual method without radiography or fibre-optic transillumination. RESULTS: These demonstrated once again a wide variation in prevalence across the United Kingdom, with mean values for D3MFT for the current English 'regions' (of the National Health Service) and the other UK 'territories' ranging from 0.66 in Thames South to 2.55 in Northern Ireland. The mean value for D3MFT across the United Kingdom was 1.13 (D3T = 0.48, MT = 0.10, FT = 0.54). Overall, 44% of children had evidence of caries experience at the dentinal level of detection (D3MFT > 0), although the means ranged between 31% (Thames South) and 72% (Northern Ireland). The mean D3MFT for those with disease at this threshold was 2.55. Trends over time demonstrate an improvement of 15% in overall D3MFT for Great Britain since 1992/93, compared to the 20% seen over the previous four year period. Over recent years the overall trend in this age group seems to be towards lower values. However, there has been no improvement in either mean DT or mean MT since 1992/93, while FT and care index have fallen. The number of fillings provided in 1996/97 and thus the care index, remain low, on average across the UK, only 48% of the dentinal caries experience identified by survey examinations of permanent teeth was seen as fillings (range in individual districts and boards: 27 to 76). CONCLUSION: Taken together, these findings demonstrate the continuing need for more effective preventive strategies and treatment services for this important age group.

Child↗

PubMed2003

Transcriptional activation of the metallothionein I gene by electric pulses in vivo: basis for the development of a new gene switch system.

BACKGROUND: In vivo gene transfer to skeletal muscle is a promising strategy for the treatment of muscular disorders and for the systemic delivery of therapeutic proteins. Nevertheless, for a safe and effective protein production, the spatial and temporal control of gene expression is critical. The existing regulating systems rely on the use of an exogenously regulatory protein and/or an inducer drug whose pharmacological properties are of major concerns for therapeutic applications in humans. Therefore, new strategies based on endogenous regulatable elements have been explored. METHODS: Gene expression profiles of skeletal muscle submitted or not to electrical pulses and harvested at different times were compared using the Affymetrix GeneChip technology. The endogenous metallothionein promoter was studied by Northern blot and semiquantitative and quantitative RT-PCR. The inducibility of the metallothionein I promoter placed in a plasmid exogenous context was studied using the murine SEAP reporter gene. RESULTS: The expression of metallothionein I mRNA is significantly increased 6 h after electric pulses delivery. This induction is transient. Identical MT-I expression level is observed after several sequential series of pulses delivery. We demonstrated as well that the MT-II promoter was sensitive to electric pulses delivery. Moreover, the metallothionein I promoter, placed in a plasmid context in front of a reporter gene, was also activated by the application of transient electric field. CONCLUSIONS: We identified a promoter highly inducible by the controlled electric stimuli applied for electrotransfer experiments. The use of the metallothionein promoter is promising for the time-control by physical stimuli of the expression of a therapeutic gene.

Animals↗

PubMed1998

Retroviral vector-mediated expression in primary human T cells of an endoplasmic reticulum-retained CD4 chimera inhibits human immunodeficiency virus type-1 replication.

Intracellular expression of genes that inhibit key steps in the human immunodeficiency virus (HIV-1) replicative cycle could offer an alternative therapy for AIDS treatment. One of these approaches involves the inhibition of env protein maturation through the expression of CD4 molecules with added exogenous sequences that promote their retention in the endoplasmic reticulum (ER). We have tested this strategy using a CD4 chimera (CD4epsilon10) containing an ER retention sequence derived from the TCR CD3-epsilon chain. Transfection of CD4epsilon10 in the human T cell line Jurkat made it resistant to infection with two different HIV-1 isolates, which was evaluated by measuring p24 antigen production, induction of apoptosis, and syncytia formation. Furthermore, polymerase chain reaction (PCR) analysis of genomic DNA showed no traces of the proviral HIV-1 genome in CD4epsilon10-transfected cells, suggesting it was not maintained latently in these cells. To facilitate the delivery of the CD4epsilon10 chimera to primary cells from AIDS patients, a Moloney-based retroviral vector was constructed that expresses CD4epsilon10 under the transcriptional control of the HIV-1 long terminal repeat (LTR) promoter. Transduction of the MT-2 human T cell line with this vector rendered it resistant to infection with HIV-1 by a process that involved the inhibition of gp160 proteolytic processing. Finally, transduction of the CD4epsilon10 chimera into T lymphoblasts derived from asymptomatic HIV-infected individuals demonstrated a protective effect, resulting in both an increased cellular proliferation rate and an increased percentage of CD4+ cells. These results suggest that it is feasible to use retroviral transduction of CD4epsilon10 as a gene therapy approach for AIDS treatment.

CD4 Antigens↗

PubMed2001

Local administration of dendritic cells inhibits established breast tumor growth: implications for apoptosis-inducing agents.

Dendritic cells (DCs) can efficiently acquire foreign antigen(s) from apoptotic cells and induce MHC class I-restricted, antigen-specific CTLs. An accumulation of DCs within solid tumor masses in situ has been associated indirectly with a more favorable prognosis. Therefore, DCs may offer an efficient means for triggering immune responses within tumors, particularly in those masses containing significant apoptosis. We examined whether delivery of DCs could, alone, impact on the progressive growth of a tumor with a relatively high apoptotic index. We detected significant early apoptosis within the mass of a s.c. growing murine MT-901 breast carcinoma. DCs could efficiently engulf MT-901 tumor apoptotic cells in vitro. Intratumoral injections of syngeneic but not allogeneic DCs resulted in significant inhibition of MT-901 tumor growth. Histological examination of the tumor revealed intense mononuclear cell infiltration during and after DC injections. Tumor growth inhibition was relatively radiosensitive and dependent on host-derived CD8+ T cells. The baseline level of tumor apoptosis could be increased substantially by tumor necrosis factor alpha administration, leading to a greater DC-mediated antitumor effect. The antitumor effect could also be enhanced by first pulsing DCs with the foreign helper protein, keyhole limpet hemocyanin, prior to intratumoral delivery and combining it with the systemic administration of interleukin 2. Splenocytes from treated animals showed heightened levels of specific CTL activity and production of cytokines. The level of in situ tumor apoptosis appears to play a critical role in DC-mediated antitumor effects. The potential implication of these findings in DC-based tumor therapy strategies is discussed.

Animals↗

PubMed2006

The dental caries experience of 11-year-old children in Great Britain. Surveys coordinated by the British Association for the Study of Community Dentistry in 2004 / 2005.

OBJECTIVE: This paper reports the results of standardized clinical caries examinations of 11-year-old children from across England and Wales, Scotland, Isle of Man, and Jersey in 2004/5. These co-ordinated surveys are the latest in a series which seek to monitor the dental health of children and to assess the delivery of dental services. METHOD: The criteria and conventions of the British Association for the Study of Community Dentistry were used. Representative samples were drawn from participating strategic health authorities (SHAs), primary care trusts (PCTs), health boards (HBs), and local health boards (LHBs). Caries was diagnosed at the caries into dentine threshold using a visual method without radiography or fibre-optic transillumination. RESULTS: The results again demonstrated a wide variation in disease prevalence and care strategies across Great Britain. Mean values for D3MFT within the current English strategic health authorities ranged from 0.19 in Harlow to 1.32 in North Manchester and in Salford; in Wales mean values ranged from 0.69 in Vale of Glamorgan to 2.09 in Blaenau Gwent; while in Scotland they ranged from 0.59 in Orkney to 1.77 in Western Isles. Mean D3MFT across England was 0.64 (D3T = 0.32, MT = 0.06, FT = 0.25), across Wales it was 1.09 (D3T = 0.48, MT 0.11, FT = 0.50), and across Scotland values were 1.29 (D3T = 0.52, MT = 0.17, FT = 0.60). Overall, 31.3% of children in England & Wales and 47.1% of children inspected in Scotland had evidence of caries experience in dentine (D3MFT > 0, including visual dentine caries). As in previous surveys, the distribution of caries was highly skewed. Thus the mean caries experience for those with dentinal decay in England and Wales was 2.12, as opposed to the overall mean of 0.66; in Scotland the corresponding values were 2.74 and 1.29. Trends over time demonstrate an improvement in overall mean D3MFT for England and Wales since the 2000/2001 of 12-year-olds, although part of this difference is accountable to the younger age, at examination, in this survey. The mean value for those with dentine decay experience was also marginally less at 2.12 compared with 2.35 in the previous survey. (Figures for Scotland were not included in the 2000/2001 survey.) The care index was also found to be marginally lower than previously at 41% compared with 48% but again the younger age of the children would influence this value. CONCLUSION: Dental health of 11-year-old children has been surveyed in Great Britain, Jersey, and the Isle of Man: being a slightly younger mean age than in previous BASCD surveys. Geographic variation in oral health is marked at both the local and national levels. Overall, the provision of operative care for those with dentinal decay is around 42%. While many children enjoy good oral health, sizable groups remain within the population of 11-year-old children who have a clinically significant burden of preventable dental disease.

Age Factors↗

PubMed2005

Selective gene transfer in vitro to tumor cells via recombinant Newcastle disease virus.

We developed a novel strategy to target recombinant Newcastle disease virus (NDV) to tumor cells for gene therapy. Modifying the virus with a bispecific fusion protein allowed virus receptor-independent tumor cell binding and gene transfer. The targeting molecule (alpha)HN-IL-2 contains an scFv antibody cloned from a neutralizing hemagglutinin-neuraminidase (HN)-specific hybridoma linked to the human cytokine IL-2. A recombinant NDV expressing the enhanced green fluorescent protein (NDFL-EGFP) was applied to show the expression of foreign genes in virus-infected tumor cells. At 24 hours after infection with the modified virus (NDFL-EGFP/(alpha)HN-IL-2), FACS analysis and fluorescence microscopy revealed neutralization of natural infection in IL-2 receptor-negative Jurkat leukemia cells, but targeted expression of EGFP in IL-2 receptor-positive human leukemia-derived MT-2 cells. The targeted gene delivery of NDFL-EGFP/(alpha)HN-IL-2 in MT-2 cells was blocked by the target ligand human IL-2. Selective virus entry to IL-2 receptor bearing tumor cells was also observed in a mixture of Jurkat and MT-2 cell lines. These results demonstrate that a recombinant NDV carrying a foreign gene can be successfully targeted to a specific tumor through a bispecific protein, which thereby increases the selectivity of gene transfer.

Animals↗

PubMed2005

The dental caries experience of 5-year-old children in England and Wales (2003/4) and in Scotland (2002/3). Surveys co-ordinated by the British Association for the Study of Community Dentistry.

OBJECTIVE: This paper reports the results of standardized clinical caries examinations of 5 year old children from across England and Wales in 2003/4 and Scotland in 2002/3. These co-ordinated surveys are the latest in a series which seek to monitor the dental health of children and to assess the delivery of dental services. METHOD: The criteria and conventions of the British Association for the Study of Community Dentistry were used. Representative samples were drawn from participating strategic health authorities (SHAs), primary care trusts (PCTs) and health boards (HBs). Caries was diagnosed at the caries into dentine threshold using a visual method without radiography or fibre-optic transillumination. Data for Jersey and the Isle of Man are also included. RESULTS: The results again demonstrated a wide variation in disease prevalence and care strategies across Great Britain. Mean values for d3mft within the current English Strategic Health Authorities ranged from 0.47 in Maidstone Weald (South) to 3.69 in North Kirklees (North); in Wales mean values ranged from 1.48 in Flintshire (NW) to 3.73 in Merthyr (SE); while in Scotland they ranged from 1.29 in Borders to 3.67 in Argyll & Clyde. Mean d3mft across England was 1.49 (d3t = 1.12, mt = 0.19, ft = 0.18), across Wales it was 2.42 (d3t = 1.70, mt = 0.43, ft = 0.29) and across Scotland values were 2.76 (d3t = 1.87, mt = 0.65, ft = 0.24). Overall, 39.6% of children in England & Wales and 55.4% of children inspected in Scotland had evidence of caries experience in dentine (d3mft > 0, including visual dentine caries). The distribution of caries was highly skewed. Thus the mean caries experience for those with dentinal decay in England and Wales was 3.90, as opposed to the overall mean of 1.55; in Scotland the corresponding values were 4.98 and 2.76. Trends over time demonstrate virtually no change in the overall mean d3mft for England and Wales since 2001/2, although the mean value for those with dentine decay experience increased marginally from 3.83 to 3.90. In Scotland there had been deterioration in the overall mean (2.76 as compared to the 2.55 reported in 1999). The care index has also fallen (for example in England & Wales to 12% from 13.2% in 2001/2002 and 14.3% in 1999/2000). CONCLUSION: There has been no overall improvement in the dental health of 5 year old children over the last 2 years. Geographic variation in oral health is marked at both the local and national levels. Overall, the provision of operative care for those with dentinal decay has again decreased slightly. While many children enjoy good oral health, sizable groups remain within the population of 5 year old children who have a clinically significant burden of preventable dental disease.

Child, Preschool↗

PubMed2026

Next-generation macrophage engineering in cancer therapy: From TAM reprogramming to CAR-macrophages.

Macrophages are central regulators of the tumor microenvironment (TME), shaping immune suppression, angiogenesis, metabolism, and therapeutic resistance in solid cancers. While early strategies sought to deplete tumor-associated macrophages (TAMs) or block monocyte recruitment, limited efficacy and compensatory mechanisms revealed the need for functional reprogramming rather than elimination. Recent advances in viral vectors, CRISPR-Cas genome editing, and RNA-based delivery platforms have enabled precise genetic modification of macrophages, giving rise to chimeric antigen receptor macrophages (CAR-Ms) and related engineered products. Beyond antigen targeting, effective macrophage engineering requires stabilization of pro-inflammatory identity, resistance to tumor-induced repolarization, metabolic reinforcement, and integration of checkpoint modulation pathways. This review synthesizes current strategies across DNA, mRNA, and siRNA-based platforms, highlighting convergent design principles that connect TAM reprogramming with CAR-M development. We discuss reshaping phagocytosis checkpoints, metabolic and transcriptional stabilization, cytokine augmentation, and synthetic receptor architecture, emphasizing combinatorial and context-aware engineering, while proposing new candidate gene targets. Engineered macrophages are thus evolving from simple effector cells into programmable immune coordinators capable of converting immunologically "cold" tumors into inflamed, therapy-responsive niches.

CAR-M↗

PubMed2002

The dental caries experience of 12-year-old children in England and Wales. Surveys coordinated by the British Association for the Study of Community Dentistry in 2000/2001.

DESIGN: This paper reports the results of standardised clinical caries examinations of 106,694 twelve-year-old children from England, Wales, the Isle of Man and Jersey. These 2000/01 coordinated surveys are the latest in a series which seek to monitor the dental health of children and to assess the delivery of dental services. METHOD: The criteria and conventions of the British Association for the Study of Community Dentistry were used. Representative samples were drawn from participating health authorities and boards, and caries was diagnosed at the caries into dentine (D3) threshold using a visual method without radiography or fibre-optic transillumination. RESULTS: Once again a wide variation in caries prevalence across the United Kingdom was demonstrated, with mean values for D3MFT for the English 'regions' (of the National Health Service) and Wales ranging from 0.63 in the West Midlands to 1.31 in Wales. The mean value for DMFT across England Wales was 0.89 (D3T=0.39, MT=0.07, FT=0.43). Overall, 38% of children had evidence of caries experience at the dentinal level of detection (D3MFT>0), although the means ranged between 30% (West Midlands) and 51% (Wales). The mean D3MFT for those with disease at this threshold was 2.35. Trends over time demonstrate an improvement of 11% in overall D3MFT since 1996/97, compared to the 15% seen over the previous four year period. FT and care index fell. The number of fillings provided in 2000/01 and thus the care index, remained low. On average across England and Wales, only 48% of the dentinal caries experience identified by survey examinations of permanent teeth was seen as fillings (range in individual districts: 30% to 78%). The use of the SiC index highlights dental health inequalities. CONCLUSION: Taken together, these findings demonstrate the continuing need for more effective preventive strategies and treatment services for this important age group.

Child↗

PubMed2000

The dental caries experience of 14-year-old children in the United Kingdom. Surveys coordinated by the British Association for the Study of Community Dentistry in 1998/99.

DESIGN: This paper reports the results of standardised clinical caries examinations of 121.550 14-year-old children from across the United Kingdom, Jersey and the Isle of Man. These 1998/99 coordinated surveys are the latest in a series which seeks to monitor the dental health of children and to assess the delivery of dental services. METHOD: The criteria and conventions of the British Association for the Study of Community Dentistry were used. Representative samples were drawn from participating health authorities and boards and caries was diagnosed at the caries into dentine (D3) threshold using a visual method without radiography or fibreoptic transillumination. RESULTS: These demonstrated, once again, a wide variation in prevalence across the United Kingdom, with mean values for D3MFT for the current English regional offices (of the National Health Service) and the other UK countries ranging from 1.17 in West Midlands to 3.65 in Northern Ireland. The mean value for D3MFT across the United Kingdom was 1.76 (D3T=0.59, MT=0.15, FT=1.02). Overall, 54% of children had evidence of caries experience at the dentinal level (D3MFT>0), although the means ranged between 43% (South East) and 78% (Northern Ireland). The mean D3MFT for those with disease at this threshold was 3.24. Trends over time demonstrate an improvement of 10% in overall D3MFT for Great Britain since 1994/95, compared to the 21% seen over the previous four year period. Over recent years the overall trend in this age group seems to be towards lower values. However, there has been no improvement in mean MT since 1994/95, while FT and care index have fallen. The number of fillings provided in 1998/99 and thus the care index, remains low, on average across the UK, only 58% of the dentinal caries experience identified by survey examinations of permanent teeth was seen as fillings (range in individual districts and boards: 34% to 83%). CONCLUSION: Taken together, these findings demonstrate the continuing need for more effective preventive strategies and treatment services for this important age group.

Adolescent↗

PubMed2004

The dental caries experience of 14-year-old children in England and Wales. Surveys co-ordinated by the British Association for the Study of Community Dentistry in 2002/2003.

OBJECTIVE: This paper reports the results of standardised clinical caries examinations of 77,693 14-year-old children from across England, Wales, Jersey and the Isle of Man. These 2002/3 coordinated surveys are the latest in a series which seeks to monitor the dental health of children and to assess the delivery of dental services. METHOD: The criteria and conventions of the British Association for the Study of Community Dentistry were used. Representative samples were drawn from participating health authorities and boards and caries was diagnosed at the caries into dentine (D3) threshold using a visual method without radiography or fibre-optic transillumination. RESULTS: These demonstrated, once again, a wide variation in prevalence across the area surveyed, with mean values for D3MFT for the current English government offices (of the National Health Service) and the local Health Boards in Wales ranging from 0.99 in the South East to 2.10 in Wales (2.41 in the Isle of Man). The mean value for across England and Wales was 1.48 (D3T=0.56, MT=0.10, FT=0.82). Overall 49 per cent of 14-year-old children in England and Wales had evidence of dentinal caries experience (D3MFT>0), the regional/country means ranged between 37 per cent (South-East) and) and 60 percent in Wales (65 per cent, Isle of Man). The mean D3MFT for those with disease at this threshold was 3.03. Trends over time demonstrate an improvement of 4% in overall D3MFT for England and Wales, there has been only small improvement in mean MT since 1994/95, while FT and care index have fallen. The number of fillings provided in 2002/3 and thus the care index, remains low, on average across England and Wales, only 55% of the dentinal caries experience identified by survey examinations of permanent teeth was seen as fillings (range in individual areas: 28% to 83%). CONCLUSION: These findings demonstrate a modest overall improvement in oral health, but a continuing need for more effective preventive strategies and treatment services for permanent teeth in this important age group. An average of half of the 14 year old children examined being affected by dentinal decay and a mean of three permanent teeth decayed into dentine for those children affected at this level of diagnosis is a poor start to charting oral health in the 21st Century in England and Wales.

Adolescent↗

PubMed1995

Assessment of nutritional, clinical, and immunologic status of HIV-infected, inner-city patients with multiple risk factors.

OBJECTIVE: To evaluate the nutritional, clinical, and immunologic factors associated with human immunodeficiency virus (HIV)-infected, inner-city patients with multiple risk factors. DESIGN: Prospective cross-sectional nutrition evaluation of patients with HIV infection. SETTING: Patients were interviewed at the outpatient clinic at Mt Sinai Medical Center, New York City, NY. SUBJECTS: Our subjects were men and women older than 18 years of age and at all stages of HIV infection (n = 56). OUTCOME MEASURES: Anthropometric measurements, history of weight changes (maintenance of preillness body weight or decrease from preillness weight status), 3-day food records, and clinical laboratory tests. STATISTICAL ANALYSES: Tests were used to compare patients who were at a stable weight with patients who had lost weight with regard to the anthropometric, dietary, and clinical variables. Spearman's rank correlation coefficient and chi 2 tests were applied to examine correlations between pairs and differences in proportions, respectively. RESULTS: Patients were classified into groups according to whether they were at a stable weight (n = 25) or had lost weight (n = 31). All anthropometric measurements, CD4 lymphocytes, and CD8 lymphocytes were significantly lower in the patients who had lost weight. No differences were observed between the groups for absolute lymphocyte count or transferrin, hemoglobin, and albumin levels. The mean energy intake of the 56 patients was 74% of the Recommended Dietary Allowance (RDA). Forty-seven patients (84%) took vitamin and/or mineral supplements within a range of 2% to 50,000% of the RDA. No significant positive correlations were observed between nutrient intake, CD4 cells, and absolute lymphocyte count. CONCLUSIONS/APPLICATIONS: All anthropometric measurements, CD4 lymphocytes, and CD8 lymphocytes were notably lower in patients with weight loss. The mean energy intake of the subjects was only 74% of the RDA. Megadoses of vitamin supplements were taken by a large number of patients, but no significant positive effects were observed for absolute lymphocyte count and CD4 cells. Although supplementation of micronutrients may influence the progression of HIV infection, a balanced, nutritious diet may be more beneficial in maintaining or improving the physiologic status of the patients. However, members of a high-risk population may benefit less from HIV-related social services and food or nutrition resources. With the growing number of injection-drug users in the acquired immunodeficiency syndrome population, it will be essential to develop comprehensive strategies to address the interconnected needs for medical and nutrition care. Ensuring that patients have adequate meals during an extended course of treatment in the outpatient clinic or that dietitians have meals available in group settings or through home-delivery service may be the most appropriate nutrition intervention in these high-risk patients.

Adult↗