Rapid and sustained control of itch and reduction in Th2 bias by dupilumab in a patient with Sézary syndrome.

BACKGROUND: Sézary syndrome is a leukaemic variant of cutaneous T-cell lymphoma with poor prognosis. With the exception of stem cell transplantation, current treatments for SS are not curative. Rather, they aim at reducing disease burden and improving quality of life. Yet, pruritus - the major cause for impaired quality of life in these patients - is notoriously difficult to treat. Thus, supportive treatments addressing agonizing pruritus are urgently needed. OBJECTIVES: To explore the clinical and immunological effects of type 2 cytokine blockade with dupilumab as supportive treatment in Sézary syndrome. METHODS: A Sézary syndrome patient with stable disease but intractable pruritus was treated with dupilumab in combination with continued extracorporeal photopheresis. Close clinical and immunological monitoring on blood and skin samples from the patient was performed over 44 weeks. In vitro assays with patient's lymphoma cells were performed to address effects of dupilumab on Sézary cell's response to Th2 cytokines. RESULTS: Clinically, dupilumab treatment induced rapid and sustained reduction in itch and improvement of skin and lymph node involvement. In both blood and skin, a reduction in Th2 bias was observed. Intriguingly, lymphocyte counts and Sézary cells in blood increased and later stabilized under dupilumab treatment. In vitro, dupilumab abrogated the anti-apoptotic and activating effects of Th2 cytokines on Sézary cells. CONCLUSIONS: In this Sézary patient, inhibition of IL-4 and IL-13 signalling was associated with striking clinical benefit in terms of quality of life, pruritus and use of topical corticosteroids. While safety remains an important concern, our data support the future exploration of Th2 modulation for supportive care in Sézary Syndrome.

Adults seeking orthodontic treatment: expectations, periodontal and TMD issues.

The growth in adult orthodontics presents new challenges to both the general dental practitioner and the orthodontist. Although many of the main objectives of orthodontic treatment are similar for adults, young adults and children, adult patients frequently bring significant challenges in several areas not often seen in the younger patient group. In areas such as planning realistic treatment outcomes, it is paramount that the patient's expectations are identified, respected and managed where appropriate. The adult patient's dental health often dictates deviation from the ideal treatment plan and periodontal problems are a common example. Based on current evidence, this paper presents an overview of some of the difficulties in the management of these issues, as well as highlighting developments with regard to pain conditions and their relevance to orthodontic treatment and its effects on temporomandibular joint disorders (TMD) management.

TMD and occlusion part I. Damned if we do? Occlusion: the interface of dentistry and orthodontics.

OBJECTIVES: To review how occlusion, facial growth, TM disc position and malocclusion may relate to TMD; to review clinical studies investigating TMD pre- and post-orthodontic treatment as well as other studies linking occlusal features with TMD highlighting their limitations; and to make suggestions for improved study designs in the future in order to provide an evidence-base for clinical practice. DESIGN: Review article. METHODS: Electronic databases (MEDLINE and the Cochrane Database of Systematic Reviews) were used to select relevant and frequently cited studies (mean: 28 citations). Citation rate was confirmed using the Web of Science. Study designs are reviewed and weaknesses discussed. RESULTS: Evidence is lacking to suggest static occlusal factors cause TMD. CONCLUSIONS: Poor study designs have led to much of the controversy over whether occlusal factors (including orthodontics) 'cause' TMD. In order to provide an evidence-base for future clinical practice, suggestions to improve study designs are made.

TMD and occlusion part II. Damned if we don't? Functional occlusal problems: TMD epidemiology in a wider context.

OBJECTIVES: To review studies investigating how functional occlusion may relate to TMD and how bruxism may relate to TMD; to review the epidemiology of TMD and relate this to the context of clinical occlusal studies and other aetiological factors. Deficiencies in study design are highlighted and suggestions made to improve future study designs in order to provide an evidence-base for clinical practice. DESIGN: Review article. METHODS: Electronic databases (MEDLINE and the Cochrane Database of Systematic Reviews) were used to select relevant and frequently cited studies (mean: 40 citations). Citation rate was confirmed using the Web of Science. Study designs are reviewed and weaknesses and implications discussed. RESULTS: Evidence is lacking to suggest functional occlusal factors cause TMD. Investigation of other aetiological factors has been relatively neglected. CONCLUSIONS: Neither static nor dynamic occlusal factors (including orthodontics) can be said to 'cause' TMD. However, other potential aetiological factors exist which would benefit from more investigation. This, together with improved study designs, would help provide a stronger evidence-base for clinical practice in the future.

Teamwork in orthodontics: limiting the risks of root resorption.

Orthodontic treatment is not without risk. The risks may be due to patient factors (which may not always be evident before treatment) or may come about because of the treatment itself. While the common types of risk are well documented, less information is available as to how some of the more unusual problems can best be managed when they arise; often the need for teamwork between the patient, orthodontist and general dental practitioner (GDP) are underestimated. This paper presents three patients in whom various root-related problems existed either before orthodontic treatment or which arose during orthodontic treatment; demonstrates how they were managed; and highlights the need for teamwork to ensure a 'least harmful' outcome. All patients were followed up for over a year.

Chlorhexidine-modified glass ionomer for band cementation? An in vitro study.

OBJECTIVE: To compare the mean retentive strength, predominant site of band failure, amount of cement remaining on the tooth at deband and survival time of orthodontic micro-etched bands cemented with chlorhexidine-modified (CHXGIC) or conventional glass ionomer cement (GIC). DESIGN: In vitro study. SETTING: Dental Materials Laboratory. MATERIALS AND METHODS: One-hundred-and-twenty intact, caries-free third molars were collected from patients attending for third molar surgery. These were stored for 3 months in distilled water and decontaminated in 0.5% chloramine. To assess retentive strength, 80 teeth were randomly selected and 40 were banded with each cement. Testing was undertaken using a Nene M3000 testing machine at a cross-head speed of 1 mm/min. Following debanding, the predominant site of failure was recorded as cement-enamel or cement-band interface. The amount of cement remaining on the tooth surface following deband was assessed and coded. Survival time for another 40 banded specimens, 20 cemented with each cement, was assessed following application of mechanical stress in a ball mill. MAIN OUTCOME MEASURES: Retentive strength, predominant site of failure, amount of cement remaining on the tooth surface, survival time. RESULTS: Mean retentive strength for bands cemented with CHXGIC (0.32 MPa, SD 0.09) or GIC (0.28 MPa, SD 0.07) did not differ significantly (p=0.05). All bands failed at the enamel-cement interface. There was no significant difference in the amount of cement remaining on the tooth surface after deband for each cement type (p=0.23). The mean survival time of bands cemented with CHXGIC or GIC was 7.0 and 6.4 hours, respectively (p=0.23). CONCLUSIONS: There was no significant difference in mean retentive strength, amount of cement remaining on the tooth after deband or mean survival time of bands cemented with CHXGIC or GIC. Bands cemented with either cement failed predominantly at the enamel-cement interface. The results suggest that CHXGIC may have comparable clinical performance to GIC for band cementation.

Relationship between lip position and drooling in children with cerebral palsy.

AIM: This was to determine whether there is any relationship between lip position and drooling in children with cerebral palsy (CP). METHODS: One hundred and sixty individuals with CP (aged 4-18 years) agreed to take part in the study. The following data were collected in two ways. Firstly the presence or absence of drooling, the dental age, the incisal relationship and lip position were obtained by direct observation of the children. Secondly other data for age, sex, learning disability and type of CP were collected using a questionnaire/form. STATISTICS: This was by simple Chi squared analysis. RESULTS: A significantly greater number of CP children who drooled had incompetent lips (p<0.002). When comparing CP children with drooling (mild + moderate + severe) and those without drooling there was a clear difference in distribution of it between those with and those without competent lips. This difference was found to be highly significant (p<0.005). CONCLUSION: Lip position and oral seal share a potentially important association with drooling.

Orthodontic preparation for orthognathic surgery: how long does it take and why? A retrospective study.

We investigated the duration of pre-operative orthodontic treatment of patients who had combined orthodontic and orthognathic treatment and examined the variables that influenced this. Records of patients who had undergone such treatment in the past 5 years were collected (n=65) from three consultant orthodontists and one Senior Specialist Registrar/Fixed Term Training Appointment (FTTA). The number of days from placement of the first active orthodontic component to the day that final planning impressions were taken was used to calculate the duration of treatment before the patient was ready for operation. The variables investigated were: sex, age, malocclusion, extractions (excluding third molars), and the clinician. The median duration of pre-operative treatment was 17 months (range 7-47). Only the orthodontist appeared to affect this duration, but this requires further investigation as it may merely reflect variation in other factors such as compliance. We conclude that patients should be informed that the pre-operative phase may last 12-24 months.

Evidence for an extensive collagen type III/VI proximal domain in the rat femur. I. Diminution with ovariectomy.

Collagenous proteins other than Type I have received little attention in hypogonadal bone loss. Using femora from 25 young (2.5 months) and older (11 months) control and ovariectomized adult rats killed 1-4 months postoperation, cancellous atrophy was histologically confirmed, and the immunolocalization of collagen Type III was examined. This occurred as numerous immunofluorescent Sharpey-like fibers, 5-25 microm thick, regularly associated with collagen Type VI, which ramified the femoral cortex. Sequential transverse cryosections enabled the mapping of the fibers in three-dimensions, demonstrating that they constituted an extensive subperiosteal domain which may be a lasting legacy of early skeletal development. Fiber density was greatest in the trochanters and femoral neck. The domain tapered distally and was apparently anchored into the mid-shaft by intracortical cartilaginous islands, staining for collagen Type VI (as well as Type II and fibronectin). Ovariectomy caused disconnection of the fibers and reduced the proximal domain of both young and older animals, previously positive areas of the cortex becoming negative. It is concluded that collagen Type III/VI occupies a substantial, discrete domain in the rat proximal femur as a complex extension of the periosteum. Diminution of this cortical domain with trabecular atrophy suggests that it has a proactive or reactive role in determining bone mass and strength by facilitating musculoskeletal exchange in a form that is disengaged by ovariectomy.

Evidence for an extensive collagen type III proximal domain in the rat femur. II. Expansion with exercise.

Exercise in youth may affect bone "quality" as well as quantity. Using the rat model, 1.5-month-old females were divided into four weight-matched groups, exercised short-term (6 weeks, E(s), n = 20) and long-term (14 weeks, E(L), n = 10) by access to monitored running wheels, and corresponding "sedentary" controls (S(S) short-term, n = 20; S(L) long-term, n = 10). Femora were either plastic-embedded or fresh-frozen. Transverse histological slices, 100 microm thick, were cut midshaft, while similar cryosections, 8 microm thick, were prepared from the same site and also coronal to the femoral neck region. An image analyser measured femoral neck and midshaft microarchitecture, while immunostaining localized collagen type III-rich fibres (CIII, an index of Sharpey fibre insertions) and osteopontin-rich osteons (OPN, an index of remodelling). Exercise increased cortical bone (proximal width +18%, midshaft area +7%). It also raised cancellous bone volume (+25%) by trabecular thickening (+30%) with more intraosseous vascularity and new trabecular interconnections (node-terminus ratio, +57%; trabecular pattern factor, -147%; marrow star volume. -48%). In the cortex a prominent discrete subperiosteal domain became wider (+50% midshaft) with exercise and contained more numerous (+15%) CIII-stained fibres. In contrast the encircled inner bone developed more numerous (+14%) OPN-rich osteons. It is concluded that short-term voluntary exercise augments both cortical and cancellous microarchitecture. It also alters protein composition, such that expanding arrays of Sharpey's fibres within a circumferential proximal domain (Part I) interconnect more powerfully with the musculature and interface more robustly with the core bone that in response becomes more vascular and biodynamic, providing further insight into how muscle mass may be skeletally translated.

Comparison of lip incompetence by remote video surveillance and clinical observation in children with and without cerebral palsy.

This study aimed to compare two methods of assessing lip position so that an appropriate method could be used to assess whether a relationship existed between lip position and drooling in children with cerebral palsy. This investigation compared the use of a new, remote video surveillance (RVS) technique with direct clinical assessment of lip position by determination of intra- and inter-examiner agreement. Lip position was assessed in both techniques using the Jackson lip classification. Two groups of school children took part: one group suffered from cerebral palsy (CP), but the second group consisted of unaffected individuals. Based on Kappa statistics, intra- and inter-examiner agreements were generally found to be moderate for the individual methods (kappa = 0.48-0.54), whilst agreement between the two methods was found to be good (kappa = 0.68). The results showed moderately good examiner-agreement in the assessment of lip position, using either method and the Jackson lip classification. Consequently, lip position can be assessed by either RVS or direct clinical assessment, the choice depending on the physical circumstances surrounding the assessor and operator preference. However, RVS may offer a more unobtrusive approach.

Orthodontics and the temporomandibular joint: where are we now? Part 1. Orthodontic treatment and temporomandibular disorders.

Orthodontists are concerned about the possibility of a link between the treatment they provide and temporomandibular disorders (TMD). The purpose of this article was to review the literature relating malocclusion and orthodontic treatment to problems of the temporomandibular joint (TMJ) and surrounding anatomy. In Part 1, the relationship of orthodontic treatment to TMD is discussed. In Part 2, the relationship of TMD to malocclusion will be addressed.

Orthodontics and the temporomandibular joint: where are we now? Part 2. Functional occlusion, malocclusion, and TMD.

In this second of two articles, the role of occlusion and malocclusion is assessed with respect to orthodontics and temporomandibular disorders (TMD). Some have suggested that malocclusion may cause TMD, or that by introducing a form of malocclusion, orthodontic treatment could be iatrogenic. Pertinent evidence relating to these issues will be assessed.

Orthodontic postgraduate training in Germany--have we anything to learn?

In 1996, the authors were able to visit the University Orthodontic Unit in Marburg, Germany. Author FL was able to undertake the visit as part of a discretionary secondment for specialist training and this article describes the author's (FL) experience of orthodontic, postgraduate training there, and highlights differences between training in the U.K. and Germany. In the current climate of change with regard to specialist training, it seemed timely to investigate how training occurs elsewhere in Europe.

A study to determine if changes to an undergraduate orthodontic course improved course quality and student satisfaction.

A study was carried out to determine if changes to the undergraduate orthodontic course at Leeds Dental Institute resulted in increased student satisfaction. The study was based on a questionnaire distributed to dental students comprising statements related to the undergraduate orthodontic course. Questionnaires were distributed in 1993 and 1995 to 2 groups of 4th year undergraduate dental students at the same stage of their course on both occasions. Questions were in the form of 16 statements with which students expressed a level of agreement, ranging from strongly agree to strongly disagree. The numbers of responses at each level of agreement were compared between the 2 groups. Statistical differences were determined using a Mann Whitney-U test. 8 of the 16 statements had more favourable responses in 1995 than in 1993. No statement received a less favourable response in 1995 than in 1993. It is concluded that changes in the undergraduate orthodontic course at Leeds Dental Institute aimed at increased problem-based learning and clinician-led tutorials, have resulted in improved student satisfaction with the teaching.