Three difficult cases: the challenge of autoimmunity, immunodeficiency and recurrent infections in patients with Good syndrome.

Good syndrome (GS) is a rare, adult-acquired primary combined immunodeficiency syndrome arising in the context of previous or current thymoma. Patients with GS frequently develop recurrent sinopulmonary infections and are also at high risk of autoimmune manifestations, including skin conditions such as lichen planus. We report three middle-aged patients with GS complicated by multiple autoimmune and infectious manifestations. The combination of immunodeficiency, autoimmunity and recurrent infections seen in patients with GS continues to present a management challenge, particularly in patients with oral mucosal disease and recurrent candidiasis. Clinicians should be prompted to investigate an underlying immunodeficiency in patients with multiple autoimmune conditions and recurrent sinopulmonary infections.

Report on World Workshops on Oral Medicine (WWOM) IV and V: research themes and citation impact: WWOM VI steering committee.

The first World Workshop on Oral Medicine (WWOM) was held in 1988. The portfolio has continued to expand in scope and impact over the past 26 years. Five World Workshops were conducted between 1988 and 2010, focusing on creation of systematic reviews in biomedicine and health care of importance to the international oral medicine community. WWOM VI was conducted in April 2014 and further extended this modeling. This most recent Workshop also fostered creation of the inaugural joint meeting between the American Academy of Oral Medicine and the European Association of Oral Medicine, together with The British Society for Oral Medicine and the Oral Medicine Academy of Australasia. The goal of the WWOM portfolio is to strategically enhance international oral medicine research, education, and clinical practice. To this end, this report summarizes subject areas for WWOM IV (2004) and research recommendations for WWOM V (2010), as well as citation metrics relative to publications from these two conferences. The information is designed to provide research and clinical context for key issues in oral medicine as delineated by the WWOM portfolio over the past 10 years, as well as for projected outcomes of WWOM VI over the next 12 months.

Spontaneous subarachnoid hemorrhage and negative initial vascular imaging--should further investigation depend upon the pattern of hemorrhage on the presenting CT?

BACKGROUND: Multiple investigations are usually performed in patients with spontaneous SAH who have negative initial angiography. This study aimed to evaluate the most appropriate use of additional imaging studies and how this may be influenced by the findings of the initial CT. METHODS: A retrospective analysis was performed on a prospectively collected cohort of patients referred with spontaneous SAH and negative initial angiography. The patients were divided into four categories based upon the distribution of blood on the initial CT: perimesencephalic (pSAH), diffuse (dSAH), sulcal (sSAH) and CT negative (CSF positive for xanthochromia) (nCT-pLP). The number and nature of the subsequent imaging investigations were reviewed, and the results were correlated with the findings of the presenting CT. RESULTS: One hundred fourteen patients were included in the study. Repeat imaging found five relevant abnormalities. Three cases of vasculitis were diagnosed on the first DSA following a negative CTA. A case of dissecting aneurysm was revealed on the third neurovascular study. A hemorrhagic spinal tumor presented with xanthochromia. No subsequent abnormality was found on the third DSA or MRI head. No case of pSAH had a subsequent positive finding if the initial CTA was negative. CONCLUSIONS: Certain patterns of SAH are associated with a low yield of abnormalities on repeat imaging if the initial angiography is normal. The authors believe that the pattern of hemorrhage on the presenting CT should be used to guide the most appropriate use of further imaging modalities and present a diagnostic algorithm for this purpose.

Intent matters: how flow and forms of information impact collective navigation.

The phenomenon of collective navigation has received considerable interest in recent years. A common line of thinking, backed by theoretical studies, is that collective navigation can improve navigation efficiency through the 'many-wrongs' principle, whereby individual error is reduced by comparing the headings of neighbours. When navigation takes place in a flowing environment, each individual's trajectory is influenced by drift. Consequently, a potential discrepancy emerges between an individual's intended heading and its actual heading. In this study, we develop a theoretical model to explore whether collective navigation benefits are altered according to the form of heading information transmitted between neighbours. Navigation based on each individual's intended heading is found to confer robust advantages across a wide spectrum of flows, via both a marked improvement in migration times and a capacity for a group to overcome flows unnavigable by solitary individuals. Navigation based on individual's actual headings is far less effective, only offering an improvement under highly favourable currents. For many currents, sharing actual heading information can even lead to journey times that exceed those of individual navigators.

Impaired cardiac function in chronic fatigue syndrome measured using magnetic resonance cardiac tagging.

OBJECTIVES: Impaired cardiac function has been confirmed in patients with chronic fatigue syndrome (CFS). Magnetic resonance cardiac tagging is a novel technique that assesses myocardial wall function in vivo. We hypothesized that patients with CFS may have impaired development and release of myocardial torsion and strain. METHODS: Cardiac morphology and function were assessed using magnetic resonance imaging and cardiac tagging methodology in 12 CFS patients (Fukuda) and 10 matched controls. RESULTS: Compared to controls, the CFS group had substantially reduced left ventricular mass (reduced by 23%), end-diastolic volume (30%), stroke volume (29%) and cardiac output (25%). Residual torsion at 150% of the end-systolic time was found to be significantly higher in the patients with CFS (5.3 ± 1.6°) compared to the control group (1.7 ± 0.7°, P = 0.0001). End-diastolic volume index correlated negatively with both torsion-to-endocardial-strain ratio (TSR) (r = -0.65, P = 0.02) and the residual torsion at 150% end-systolic time (r = -0.76, P = 0.004), so decreased end-diastolic volume is associated with raised TSR and torsion persisting longer into diastole. Reduced end-diastolic volume index also correlated significantly with increased radial thickening (r = -0.65, P = 0.03) and impaired diastolic function represented by the ratio of early to late ventricular filling velocity (E/A ratio, r = 0.71, P = 0.009) and early filling percentage (r = 0.73, P = 0.008). CONCLUSION: Patients with CFS have markedly reduced cardiac mass and blood pool volumes, particularly end-diastolic volume: this results in significant impairments in stroke volume and cardiac output compared to controls. The CFS group appeared to have a delay in the release of torsion.

Abnormal negative feedback processing in first episode schizophrenia: evidence from an oculomotor rule switching task.

BACKGROUND: Previous studies have shown that patients with schizophrenia are impaired on executive tasks, where positive and negative feedbacks are used to update task rules or switch attention. However, research to date using saccadic tasks has not revealed clear deficits in task switching in these patients. The present study used an oculomotor 'rule switching' task to investigate the use of negative feedback when switching between task rules in people with schizophrenia. METHOD: A total of 50 patients with first episode schizophrenia and 25 healthy controls performed a task in which the association between a centrally presented visual cue and the direction of a saccade could change from trial to trial. Rule changes were heralded by an unexpected negative feedback, indicating that the cue-response mapping had reversed. RESULTS: Schizophrenia patients were found to make increased errors following a rule switch, but these were almost entirely the result of executing saccades away from the location at which the negative feedback had been presented on the preceding trial. This impairment in negative feedback processing was independent of IQ. CONCLUSIONS: The results not only confirm the existence of a basic deficit in stimulus-response rule switching in schizophrenia, but also suggest that this arises from aberrant processing of response outcomes, resulting in a failure to appropriately update rules. The findings are discussed in the context of neurological and pharmacological abnormalities in the conditions that may disrupt prediction error signalling in schizophrenia.

An international survey in postgraduate training in Oral Medicine.

OBJECTIVES: The aim of this preliminary study was to investigate postgraduate Oral Medicine training worldwide and to begin to identify minimum requirements and/or core content for an International Oral Medicine curriculum. MATERIALS AND METHODS: Countries where there was believed to be postgraduate training in Oral Medicine were identified by the working group. Standardized emails were sent inviting participants to complete an online survey regarding the scope of postgraduate training in Oral Medicine in their respective countries. RESULTS: We received 69 total responses from 37 countries. Of these, 22 countries self-identified as having postgraduate Oral Medicine as a distinct field of study, and they served as the study group. While there is currently considerable variation among Oral Medicine postgraduate training parameters, there is considerable congruency in clinical content of the Oral Medicine syllabi. For example, all of the training programs responded that they did evaluate competence in diagnosis and management of oral mucosal disease. CONCLUSIONS: This preliminary study provides the first evidence regarding international Oral Medicine postgraduate training, from which recommendations for an international core curriculum could be initiated. It is through such an initiative that a universal clinical core syllabus in postgraduate Oral Medicine training may be more feasible.

Coinfections associated with human immunodeficiency virus infection: workshop 1A.

The importance of opportunistic pathogens in HIV disease has been demonstrated from the onset of the epidemic. This workshop aimed to review the evidence for the role of oral microorganisms in HIV-related periodontal disease and HIV transmission and the effect of HIV therapy on periodontal disease. Despite being a common copathogen, tuberculosis seems to have limited oral presentation. The oral manifestations seem to have little impact on the individual and, once diagnosed, are responsive to chemotherapy. The participants debated the available evidence on the role of microorganisms and whether further research was warranted and justified. Although the effects of lipodystrophy on facial aesthetics may be profound and may markedly affect quality of life, there is no evidence to suggest a direct effect on the oral cavity. Though of interest to oral health care workers, lipodystrophy and associated metabolic syndromes were thought to be further investigated by other, more appropriate groups.

Global oral health inequalities: oral infections-challenges and approaches.

Four oral mucosal infections were identified as Global Oral Health Priorities: (a) HIV and associated viral, bacterial, and fungal infections; (b) tuberculosis; (c) NOMA; and (d) sexually transmitted diseases. Huge global inequalities exist in all four. HIV-associated infections constitute the major challenge. Oral manifestations of AIDS can be specifically diagnostic, indicating a significant role for dentists within health teams. The World Workshops in Oral Health & Disease in AIDS have identified a research program, elements of which are being implemented. Data on oral mucosal involvement in tuberculosis, syphilis, and gonorrhea are incomplete in developed countries and virtually non-existent in low- and middle-income countries, indicating the need for further epidemiological studies. Oral manifestations of tuberculosis and sexually transmitted diseases are largely associated with general health, so action programs should be integrated with agencies treating the systemic diseases. NOMA is very much in the oral health domain. It is a preventable disease associated with malnutrition and unidentified bacterial factors. Prevalence is probably grossly overestimated at present; but nevertheless it constitutes a challenge to the profession, especially in the NOMA belt. Current treatment is surgical, but plans for its eradication should be achievable. The global oral health community, especially the IADR, has a major role to play.

Mucosal (oral and vulval) lichen planus in women: are angiotensin-converting enzyme inhibitors protective, and beta-blockers and non-steroidal anti-inflammatory drugs associated with the condition?

AIM: To determine whether there is an association between the use of angiotensin-converting enzyme (ACE) inhibitors, beta-blockers and nonsteroidal anti-inflammatory drugs (NSAIDS) in women with mucosal (oral and vulval) lichen planus (LP) compared with a control population. METHODS: This was a retrospective review of medical records in dedicated vulval and oral clinics in hospitals. The study population comprised 141 women with vulval LP and 106 women with oral LP. Medications taken at the time of diagnosis were recorded. RESULTS: Patients with mucosal LP were more likely to be on NSAIDS and beta-blockers, but less likely to be on ACE inhibitors compared with controls. All three groups were found to have an inverse relationship with ACE inhibitors, but no association was found between patients with oral LP and beta-blockers. CONCLUSIONS: Beta-blockers and NSAIDS are associated with LP, suggesting that withdrawal of these drugs should be considered. Further studies are needed to confirm or refute the inverse relationship between mucosal LP and use of ACE inhibitors.

Onset and progression of clinical manifestations of orofacial granulomatosis.

BACKGROUND: There remain few studies describing in detail the early occurrence and long-term progression of clinical manifestations of orofacial granulomatosis (OFG) in a substantial number of patients. OBJECTIVES: The aim of this study was to determine the early and late clinical manifestations of a large case series of patients with OFG. PATIENTS/METHODS: Clinically relevant data of 49 patients with OFG who attended an Oral Medicine unit in the UK were examined retrospectively. The analyzed parameters included occurrence and typology of initial manifestations at onset and with respect to long-term follow-up. RESULTS: Five major patterns of disease onset were observed. Recurrent facial swelling with/without intra-oral manifestations was the single most common presentation at onset followed by intra-oral ulcers, and other intra-oral and neurological manifestations. The majority of patients later developed a spectrum of additional features. CONCLUSIONS: OFG results in multiple manifestations at different time points. The disease onset is characterized by manifestations other than facial swelling in about half of affected individuals. However, patients can develop cosmetically unacceptable lip/facial swelling at a later stage. Nearly all affected individuals ultimately develop lip/facial swelling while about half of all patients develop oral ulceration.

Relations between endogenous androgens and estrogens in postmenopausal women with suspected ischemic heart disease.

CONTEXT: Because androgens are obligatory precursors of estrogens, it is reasonable to assume that their serum concentrations would exhibit positive correlations. If so, then epidemiologic studies that examine the association between androgens and pathological processes should adjust the results for the independent effect of estrogens. OBJECTIVE: The objective of the study was to examine the interrelationships among testosterone (T), androstenedione, estradiol (E2), estrone, and SHBG in postmenopausal women. DESIGN: This was a cross-sectional study of women participating in the National Heart, Blood, and Lung Institute-sponsored Women's Ischemia Syndrome Evaluation study. SETTING: The study was conducted at four academic medical centers. PATIENTS: A total of 284 postmenopausal women with chest pain symptoms or suspected myocardial ischemia. MAIN OUTCOME MEASURES: Post hoc analysis of the relationships among sex steroid hormones with insulin resistance, body mass index (BMI), and presence or absence of coronary artery disease as determined by coronary angiography. RESULTS: BMI was significantly associated with insulin resistance, total E2, free E2, bioavailable E2, and free T. Highly significant correlations were found for total T, free T, and androstenedione with total E2, free E2, bioavailable E2, and estrone and persisted after adjustment for BMI and insulin resistance. A significant relationship was present between total and free T and the presence of coronary artery disease after adjustment for the effect of E2. CONCLUSIONS: Serum levels of androgens and estrogens track closely in postmenopausal women referred for coronary angiography for suspected myocardial ischemia. Epidemiological studies that relate sex steroid hormones to physiological or pathological processes need to control for the independent effect of both estrogens and androgens.

Postmenopausal women with a history of irregular menses and elevated androgen measurements at high risk for worsening cardiovascular event-free survival: results from the National Institutes of Health--National Heart, Lung, and Blood Institute sponsored Women's Ischemia Syndrome Evaluation.

BACKGROUND: Women with polycystic ovary syndrome (PCOS) have a greater clustering of cardiac risk factors. However, the link between PCOS and cardiovascular (CV) disease is incompletely described. OBJECTIVE: The aim of this analysis was to evaluate the risk of CV events in 390 postmenopausal women enrolled in the National Institutes of Health-National Heart, Lung, and Blood Institute (NIH-NHLBI) sponsored Women's Ischemia Syndrome Evaluation (WISE) study according to clinical features of PCOS. METHODS: A total of 104 women had clinical features of PCOS defined by a premenopausal history of irregular menses and current biochemical evidence of hyperandrogenemia. Hyperandrogenemia was defined as the top quartile of androstenedione (> or = 701 pg/ml), testosterone (> or = 30.9 ng/dl), or free testosterone (> or = 4.5 pg/ml). Cox proportional hazard model was fit to estimate CV death or myocardial infarction (n = 55). RESULTS: Women with clinical features of PCOS were more often diabetic (P < 0.0001), obese (P = 0.005), had the metabolic syndrome (P < 0.0001), and had more angiographic coronary artery disease (CAD) (P = 0.04) compared to women without clinical features of PCOS. Cumulative 5-yr CV event-free survival was 78.9% for women with clinical features of PCOS (n = 104) vs. 88.7% for women without clinical features of PCOS (n = 286) (P = 0.006). PCOS remained a significant predictor (P < 0.01) in prognostic models including diabetes, waist circumference, hypertension, and angiographic CAD as covariates. CONCLUSION: Among postmenopausal women evaluated for suspected ischemia, clinical features of PCOS are associated with more angiographic CAD and worsening CV event-free survival. Identification of postmenopausal women with clinical features of PCOS may provide an opportunity for risk factor intervention for the prevention of CAD and CV events.

Diabetes mellitus, hypothalamic hypoestrogenemia, and coronary artery disease in premenopausal women (from the National Heart, Lung, and Blood Institute sponsored WISE study).

Diabetes mellitus (DM) portends a higher risk of coronary heart disease mortality in women compared with men. This relationship appears to be independent of traditional cardiac risk factors, and the role of reproductive hormones has been postulated. We assessed the relationship between DM, hypothalamic hypoestrogenemia (HHE), angiographic coronary artery disease (CAD), and major adverse cardiovascular events (MACE) during a median of 5.9 years in premenopausal women enrolled in the WISE Study. We evaluated 95 premenopausal women from WISE who underwent coronary angiography for suspected ischemia and were not using exogenous reproductive hormones. Results showed no difference in age between women with (n = 30) and without (n = 65) DM (43 +/- 6 years). DM was associated with hypertension, HHE, angiographic CAD, and coronary artery severity score (all p <0.05). Women with DM were twice as likely to have HHE (50% vs 26%; p = 0.02) compared with women without DM. The presence of both DM and HHE was associated with increased prevalence (40% vs 12% or 13%; p = 0.006) and severity of angiographic CAD (coronary artery severity score 19.9 +/- 19.2 vs 7.7 +/- 4.6 or 12.3 +/- 18.8; p = 0.008) compared with either HHE or DM alone, respectively. DM was moderately predictive of MACE. In conclusion, in premenopausal women undergoing coronary angiography for suspected myocardial ischemia, DM was associated with HHE. The presence of both DM and HHE predicted a greater burden of angiographic CAD. Prospective research is warranted to better understand causal relations between DM, endogenous hormones, and MACE in premenopausal women.

Auto-inflammatory syndromes and oral health.

Auto-inflammatory diseases (periodic syndromes) are rare childhood-onset disorders which are characterized by fluctuating or recurrent episodes of fever and inflammation affecting serosal surfaces, joints, eyes and/or skin without significant autoantibody production or an identifiable underlying infection. They are disorders of innate immunity and the underlying genetic defect has been identified in most of the syndromes. Diagnosis relies on clinical symptoms and evidence of an elevated acute phase response during attacks, supported by finding mutations in the relevant genes. Several syndromes can lead to systemic AA amyloidosis. Aphthous-like oral ulceration has been reported as one manifestation in several of the syndromes, including periodic fever, aphthous-stomatitis, pharyngitis, adenitis (PFAPA) familial Mediterranean fever (FMF), hyperimmunoglobulinaemia D and periodic fever syndrome, tumour necrosis factor receptor associated periodic syndrome and pyogenic sterile arthritis, pyoderma gangrenosum, acne (PAPA). Chronic jaw recurrent osteomyelitis has been recorded in chronic recurrent multifocal osteomyelitis. Advances in the molecular pathogenesis of these syndromes and the regulation of innate immunity have enhanced diagnosis, and rationalized therapies. This article reviews the periodic fever syndromes relevant to oral health and the suggested association of FMF with Behçet's disease.

Are elderly pedestrians allowed enough time at pedestrian crossings in Cape Town, South Africa?

A descriptive, cross-sectional analytical study was conducted to determine whether the recommended walking speed of 1.2 ms(-1) would allow elderly pedestrians to safely clear pedestrian crossings in Cape Town, South Africa. Male and female volunteers (n = 47), aged 65-93 years and resident in four homes for older persons, were recruited. Pedestrian clearance intervals at 40 traffic lights within 5-km radius of the selected homes were measured. The mean walking speed required at these traffic lights was 0.86 +/- 0.32 ms(1). The maximal walking speed over 12 m was measured without carrying any load and when carrying a predetermined weight of an average shopping bag. Participants' emotions associated with pedestrian road safety were also assessed through an interview. The mean maximal unloaded and loaded walking speeds were 1.36 +/- 0.31 ms(-1) (0.73-2.03 ms(-1)), and 1.36 +/- 0.33 ms(-1) (0.58-2.12 ms(-1)), respectively. Over 30% of the participants walked slower than the recommended walking speed of 1.2 ms(-1). Participants felt that traffic lights did not allow for sufficient time to cross roads (51.1%) and reported emotions of apprehension (44.7%), anxiety (17.0%), and fear (10.6%) when crossing. A review of traffic planning and public policy is recommended to ensure older pedestrians safely clear pedestrian crossings.

Checklists for safe prescribing in oral medicine clinics.

Introduction Prescribing checklists are a means of managing risk related to systemic medications in oral medicine practice.Methods Checklists for workup and monitoring for azathioprine, mycophenolate mofetil (MMF) and dapsone were introduced to an oral medicine clinic. Compliance with the checklists was audited at six and 12-24 months post introduction, and compared to previous clinical practice.Results Azathioprine: compliance with viral serology screening improved from <10% to over 80% at 6 months post checklist introduction, and was 100% at 12 months. Documentation of counselling improved from 48% to 85% at six months, and was 100% at 12 months. Compliance with tuberculosis risk assessment improved from 5% to 50% at six months but declined to 4% at 12 months. Compliance with monitoring blood tests improved slightly. MMF: compliance with viral serology screening increased from nil to 100% at six months. Documented evidence of counselling increased from 20% to 100%. Monitoring blood test compliance for the first six weeks of therapy improved. Dapsone: documentation of patient counselling improved from 25% pre-checklist, to 50% at six months and 60% at 24 months. Monitoring blood test compliance improved at six months but had decreased by 24 months.Discussion and conclusion Clinical checklists led to a modest improvement in prescribing safety in our clinics. The usefulness of checklists depends on cultural changes and clinician engagement. Electronic medication safety programs may be a useful future strategy.