Quality assessment of clinical practice guidelines used in oral and maxillofacial surgery.

An assessment of the quality of oral and maxillofacial surgery clinical practice guidelines is lacking. The aim of this investigation was to assess the quality of guidelines using the RIGHT (Reporting Items for practice Guidelines in HealThcare) checklist. The primary outcome was to assess the score (quality) of guidelines based on the RIGHT checklist and to identify predictors (region, type, single or multi-centre, and speciality/non-speciality) influencing the quality score. In this review, following a search of electronic databases and national society websites, a total of 25 guidelines were independently assessed by two assessors against the 22-item RIGHT checklist. Inter-assessor reliability was assessed. Deficiencies in the reporting of items relating to limitations, funding, declaration and management of interests, healthcare questions, and quality assurance were evident. The median overall score for the guidelines was 28 (range 14-66). Guidelines produced by multiple centres (ß=57.15, 95% confidence interval -26.62 to 87.68, P= 0.001, multivariate analysis) and non-speciality societies (ß=20, 95% confidence interval -0.03 to 40.03, P=0.05, univariate analysis) tended to have higher quality scores. Overall, the quality of clinical practice guidelines used in oral and maxillofacial surgery was deemed suboptimal. If clinical practice guidelines are to be used in making treatment decisions for patients, clinicians should be aware of their possible limitations.

Information for oral and maxillofacial patients: can it be improved?

The aim and objective of this study was to evaluate the quality and readability of leaflet and online Oral and Maxillofacial Surgery patient information leaflets (PILs). The quality, readability and grade level of each PIL was assessed using the DISCERN, Flesch Reading Ease and Flesh-Kincaid Grade Level instruments respectively. In total, 140 patient information leaflets were assessed. For both leaflet and online PILs, many items of the DISCERN instrument were deemed of low quality and poorly reported. The median overall quality score was 30.2. Variation in the quality and readability scores between leaflet and online PILs and those produced by various societies was evident. Overall, PILs were deemed to be of moderate quality. Online PILs were of lower quality, more difficult to read and aimed at a higher reading age level.

National clinical guidelines for the management of unerupted maxillary incisors in children.

This article summarises recently updated guidelines produced by the Clinical Governance Directorate of the British Orthodontic Society through the Clinical Standards Committee of the Faculty of Dental Surgery, Royal College of Surgeons of England (FDSRCS) on the management of unerupted maxillary incisor teeth in children. The maxillary incisor teeth usually erupt in the early mixed dentition but eruption disturbances can occur and are often attributable to local factors. A failure of eruption will affect the developing occlusion and potentially influence psychological development of the child. The general principles of management for delayed eruption or impaction of these teeth is to ensure that adequate space exists in the dental arch and to remove any obstruction to eruption. Consideration should also be given to further promoting eruption through surgical exposure of the incisor, with or without subsequent orthodontic traction. A number of factors influence the decision-making process, including patient age, medical history, potential compliance, aetiology and position of the unerupted incisor. Treatment planning should be complemented by careful clinical assessment and the use of appropriate special investigations. To optimise the treatment outcome a multidisciplinary specialist approach is recommended.

Intraoral Spitz naevus: a case report.

Intraoral occurrences of Spitz naevus are very rare, there being only one previously documented case in the literature. Here is reported a case of a young male who presented with a pigmented lesion of the upper labial mucosa which had the clinical appearance of a simple naevus. Excision biopsy confirmed this to be a Spitz naevus. This lesion shares histopathological similarities with malignant melanoma. Spitz naevus is a benign lesion, but malignant transformation has been reported and close monitoring is recommended.

Arteriovenous malformation of the mandible--a case report.

Both arteriovenous malformations (AVMs) and solitary bone cysts of the mandible are uncommon lesions. The latter can be considered fairly innocuous but AVMs require careful management. The following is a description of a case where an arteriovenous malformation of the mandible presented with mental nerve paraesthesia. However, radiographically the features appeared to be consistent with a solitary bone cyst. It is important for clinicians in both a primary and secondary care setting to be aware that this type of lesion can have life threatening complications.

Crystal structure of the B7-1/CTLA-4 complex that inhibits human immune responses.

Optimal immune responses require both an antigen-specific and a co-stimulatory signal. The shared ligands B7-1 and B7-2 on antigen-presenting cells deliver the co-stimulatory signal through CD28 and CTLA-4 on T cells. Signalling through CD28 augments the T-cell response, whereas CTLA-4 signalling attenuates it. Numerous animal studies and recent clinical trials indicate that manipulating these interactions holds considerable promise for immunotherapy. With the consequences of these signals well established, and details of the downstream signalling events emerging, understanding the molecular nature of these extracellular interactions becomes crucial. Here we report the crystal structure of the human CTLA-4/B7-1 co-stimulatory complex at 3.0 A resolution. In contrast to other interacting cell-surface molecules, the relatively small CTLA-4/B7-1 binding interface exhibits an unusually high degree of shape complementarity. CTLA-4 forms homodimers through a newly defined interface of highly conserved residues. In the crystal lattice, CTLA-4 and B7-1 pack in a strikingly periodic arrangement in which bivalent CTLA-4 homodimers bridge bivalent B7-1 homodimers. This zipper-like oligomerization provides the structural basis for forming unusually stable signalling complexes at the T-cell surface, underscoring the importance of potent inhibitory signalling in human immune responses.

1.9 A crystal structure of interleukin 6: implications for a novel mode of receptor dimerization and signaling.

Interleukin 6 (IL-6) has many biological activities in vivo, and deregulation has been implicated in many disease processes. IL-6, a 185 amino acid polypeptide was refolded, purified and crystallized. The crystals diffracted to beyond 1.9 A and the structure was solved using single isomorphous replacement. The X-ray structure of IL-6 is composed of a four helix bundle linked by loops and an additional mini-helix. 157 out of 185 residues are well defined in the final structure, with 18 N-terminal and 8 A-B loop amino acids displaying no interpretable electron density. The three-dimensional structure has been used to construct a model of IL-6 interacting with the IL-6 receptor (alpha-chain) and gp130 (beta-chain) that gives new insight into the process of molecular recognition and signaling. Based on this model, we predict a fourth binding site on IL-6, a low affinity IL-6-IL-6 interaction, which may be necessary for the sequential assembly of a functional hexameric IL-6 receptor complex.

Complete 1H, 15N and 13C assignments, secondary structure, and topology of recombinant human interleukin-6.

Essentially complete backbone and side-chain 1H, 15N and 13C resonance assignments for the 185-amino-acid cytokine interleukin-6 (IL-6) are presented. NMR experiments were performed on uniformly [15N]- and [15N,13C]-labeled recombinant human IL-6 (rIL-6) using a variety of heteronuclear NMR experiments. A combination of 13C-chemical shift, amide hydrogen-bond exchange, and 15N-edited NOESY data allowed for analysis of the secondary structure of IL-6. The observed secondary structure of IL-6 is composed of loop regions connecting five alpha-helices, four of which are consistent in their length and disposition with the four-helix bundle motif present in other related cytokines and previously postulated for IL-6. In addition, the topology of the overall fold was found to be consistent with a left-handed up-up-down-down four-helix bundle based on a number of long-range interhelical NOEs. The results presented here provide deeper insight into structure-function relationships among members of the four-helix bundle family of proteins.

Human immunodeficiency virus 1 reverse transcriptase. Template binding, processivity, strand displacement synthesis, and template switching.

We have analyzed the kinetics of DNA synthesis catalyzed by reverse transcriptase from human immunodeficiency virus 1 (HIV-1). Reverse transcriptase, overproduced in Escherichia coli and purified to homogeneity, has polymerase and RNase H activity. Reverse transcriptase forms a stable complex with poly(rA).oligo(dT) primer-templates in the absence of Mg2+ and dTTP with an equilibrium dissociation constant of 3 nM. Synthesis from these preformed complexes can be initiated, and restricted to a single processive cycle, by the simultaneous addition of Mg2+, dTTP, and excess competitor RNA. Preformed complexes decay with a maximal half-life of 2-3 min. Synthesis on poly(rA) templates is processive with an incorporation rate of 10-15 nucleotides/s at 37 degrees C. Processivity varies widely with the template used, increasing from a few to greater than 300 nucleotides in the order: poly(dA) less than double-stranded DNA less than single-stranded DNA less than single-stranded RNA less than poly(rA). On double-stranded DNA reverse transcriptase catalyzes limited strand-displacement synthesis of up to 50 nucleotides. On RNA-DNA hybrids significant DNA synthesis is observed only after degradation of the RNA strand by the RNase H activity of reverse transcriptase. Intermolecular strand switching occurs with poly(rA) templates. At low ionic strength reverse transcriptase can use multiple templates with a single primer, leading to products of greater than template length. Reverse transcriptase and primer do not have to dissociate during the exchange of template strands, thus allowing processive DNA synthesis across template borders.

Human IL-3 and GM-CSF act synergistically in stimulating hematopoiesis in primates.

Interleukin-3 (IL-3) is a member of a family of growth factors, each of which supports the proliferation and development of hematopoietic precursors in culture. Although the biologic effects of the different hematopoietic growth factors have been well documented in different culture systems, it has only recently become possible to study the activities of these molecules in vivo. In comparison with the later acting hematopoietic growth factors granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor, IL-3 elicited a delayed and relatively modest leukocytosis when continuously infused intravenously in primates. The IL-3 infusion, however, greatly potentiated the responsiveness of the animal to subsequent administration of a low dose of GM-CSF. These results suggest that IL-3 expands an early cell population in vivo that subsequently requires the action of a later acting factor such as GM-CSF to complete its development. Optimal stimulation of hematopoiesis may be achieved with combinations of hematopoietic growth factors.

Response of resting human peripheral blood natural killer cells to interleukin 2.

The present study shows that recombinant interleukin 2 (IL-2) purified to homogeneity induces a rapid and potent enhancement of spontaneous cytotoxicity of human peripheral blood lymphocytes. The cells mediating cytotoxicity after 18-h treatment with IL-2 have surface markers of natural killer (NK) cells and are generated from the peripheral blood subset containing spontaneous cytotoxic cells. A parallel production of gamma interferon (IFN-gamma) is induced by recombinant IL-2 (rIL-2), and NK cells appear to be the major producer cells, whereas T cells are unable to produce IFN-gamma under these experimental conditions. However, the kinetics of the enhancement of cytotoxicity are faster than those of IFN-gamma production, and monoclonal anti-IFN-gamma antibodies do not suppress this effect, making it unlikely that the IFN-gamma produced is responsible for the enhancement. The enhancement of NK cell activity induced by rIL-2 precedes any proliferative response of the lymphocytes, which is instead observed in longer-term cultures of both NK and T cells.

5-Aminolevulinic acid dehydratase: alkylation of an essential thiol in the bovine-liver enzyme by active-site-directed reagents.

1. 5-Aminolevulinic acid dehydratase from bovine liver has been shown to be inactivated by 5-halolevulinic acids and 3-halolevulinic acids. 2. The substrate, 5-aminolevulinic acid, protects the enzyme from modification by 5-halolevulinic acids. 3. Using tritiated chlorolevulinic acids, it was shown that four of the subunits in the octameric enzyme are preferentially modified. 4. The susceptible enzyme group modified is an --SH group of a reactive cysteine at or near the active site. 5. Oxidized enzyme is not affected by either 5-chlorolevulinic acid or 3-chlorolevulinic acid. 6. Evidence is presented which suggests that 5-chlorolevulinic acid is acting as an active-site-directed reagent.