The detection of sensitivity of proprioception by a new clinical test: The dual joint position test

Objectives

To date, very few studies have paid attention to the joint sense (proprioception) of toes other than the big toe. We evaluated the sensitivity of joint position sense at the joint of the great toe in comparison to other digits, and with that determined by the dual digit stimulation test, in a sample of healthy normal controls and patients with clinical diagnosis of the lemniscal system dysfunction.

Material and methods

Seventy-two patients with lemniscal system dysfunction (55 clinically definitive multiple sclerosis, 17 vasculitis) and 110 healthy volunteers participated in the study. All subjects underwent the joint position sense test of all digits of upper and lower extremities. The position sense resulting from the combined operation of the joints of the second and the fourth digits (simultaneous two digits position sense) was also measured and subsequently compared with the results of the great toe position sense.

Results

Upper extremities: no difference was found in recognition of the position sense in the single digits of the upper extremities between patients and healthy volunteers. There was a significant difference in the dual joint position test of the right upper extremity between patients and the case group (p < 0.05) but not in the left upper extremity. Lower extremities: there was no significant difference in proprioception of the great toe neither in the right and nor in the left side between patients and normal subjects. However, the joint position sense of other single digits was deteriorated in the patients, a difference that was significant compared to normal controls (p < 0.05). Additionally, patients and normal controls displayed a difference in dual digit position sense of the right and left lower extremities (p < 0.05).

Conclusions

We show in this paper that the proprioception of simultaneous dual digits is diminished in patients when compared to a single digit position sense. Moreover, the great toe proprioception is less sensitive than other digits. Taken together, these observations lend evidence for a new clinical method which we named as dual joint position test. We suggest this novel method offers clinical utility to demonstrate lemniscal system dysfunction.     

Salivary infectious agents and periodontal disease status

Saygun I, Nizam N, Keskiner I, Bal V, Kubar A, Aç?kel C, Serdar M, Slots J. Salivary infectious agents and periodontal disease status. J Periodont Res 2011; 46: 235–239. © 2011 John Wiley & Sons A/S Background and Objectives: The potential of salivary microorganisms to diagnose periodontal disease and to guide periodontal treatment is a research topic of current interest. This study aimed to determine whether the salivary counts of periodontopathic microbes correlated with the periodontal pocket counts of the same infectious agents, and whether the salivary counts of the test infectious agents could distinguish among individuals with periodontal health and various types of periodontal disease. Material and Methods: The study included 150 systemically healthy adults, of whom 37 were periodontally healthy, 31 had gingivitis, 46 had chronic periodontitis and 36 had aggressive periodontitis. Each study subject contributed microbial samples from the two deepest periodontal pockets of the dentition and from whole saliva. Aggregatibacter actinomycetemcomitans, Campylobacter rectus, Fusobacterium nucleatum, Porphyromonas gingivalis, Prevotella intermedia, Tannerella forsythia and Epstein–Barr virus were identified using the TaqMan real‐time PCR methodology. Statistical analysis was performed using the Mann–Whitney U‐test and the receiver operating characteristic statistics. Results: C. rectus, F. nucleatum, P. gingivalis, P. intermedia and T. forsythia occurred with significantly higher copy‐counts in salivary samples from patients with gingivitis, chronic periodontitis and aggressive periodontitis than from periodontally healthy individuals. A. actinomycetemcomitans only showed higher salivary copy‐counts in subjects with aggressive periodontitis compared with subjects with healthy periodontium, and the salivary copy‐counts of Epstein–Barr virus did not reveal any significant difference among the four subject groups studied. The diagnostic sensitivity for periodontitis was 89.19 for P. gingivalis and for T. forsythia and 86.49 for P. intermedia, with specificities ranging from 83.78 to 94.59. The optimal copy‐counts per mL saliva for identifying periodontitis were 40,000 for P. gingivalis, 700,000 for T. forsythia and 910,000 for P. intermedia. Conclusion: Salivary copy‐counts of P. gingivalis, T. forsythia and P. intermedia appear to have the potential to identify the presence of periodontitis, whereas the salivary level of the other test infectious agents may possess little or no diagnostic utility. Longitudinal studies are warranted to determine the ability of salivary copy‐counts of major periodontopathic bacteria to predict future periodontal breakdown.     

Oral rinse MMP‐8 point‐of‐care immuno test identifies patients with strong periodontal inflammatory burden

Oral Diseases (2010) 17 , 115–122 Objective: To determine whether oral rinse matrix metalloproteinase (MMP)‐8 levels, measured by three different methods, tissue inhibitor of matrix metalloprotease‐1 (TIMP‐1) levels and elastase activity differentiate subjects with different periodontal condition; and second, to find out if MMP‐8 levels were comparable among the methods used. Methods: MMP‐8 levels were analysed with an immunofluorometric method (IFMA), dentoELISA and commercial ELISA. Also TIMP‐1 levels and elastase activity were measured. For statistical analysis 214 study subjects were categorized into four groups, specified by the presence and number of moderate (4–5 mm) and deep (≥6 mm) periodontal pockets, and bleeding on probing percentage. Results: MMP‐8 levels especially measured by dentoELISA and adjusted to the number of teeth per subject differentiated the study group with strong periodontal inflammatory burden from groups with lower levels. This was also verified with receiver operating characteristic ( ROC) analysis. Elastase activity associated with higher IFMA and dentoELISA MMP‐8 levels. IFMA MMP‐8/TIMP and dentoELISA MMP‐8/TIMP‐1 tended to be higher with the increasing level of periodontal inflammatory burden. TIMP‐1 levels decreased with increasing age. Conclusions: Oral rinse MMP‐8 together with TIMP‐1 analysis may have potential in complementary periodontal diagnostics. dentoELISA can be applied in quantitative oral rinse chair side biomarker diagnostics.     

Use of high-sensitivity digital ELISA improves the diagnostic performance of circulating brain-specific proteins for detection of traumatic brain injury during triage

ABSTRACT

Background: Historically, limited sensitivity associated with traditional immunoassay methods has prevented the use of brain-specific proteins as blood biomarkers of traumatic brain injury (TBI) during triage, as these proteins exhibit low circulating concentrations. Digital ELISA is a newly-developed technique that is up to 1000 times more sensitive than conventional ELISA methods. The purpose of this study was to determine whether the use of digital ELISA over conventional ELISA improves the performance of brain-specific proteins as blood biomarkers of TBI during triage.

Methods: Blood was sampled from TBI patients (n = 13) at emergency department admission, as well as from neurologically normal controls (n = 72). Serum levels of two brain-specific proteins, neurofilament light chain (NfL) and Tau, were measured via digital ELISA. Estimated conventional ELISA measures were generated by adjusting values according to the lower limits of detection achievable with commercially available conventional ELISA assays, and receiver operating characteristic (ROC) analysis was used to compare the diagnostic performance of digital ELISA measures to estimated conventional ELISA measures in terms of their ability to discriminate between TBI patients and controls.

Results: Used in combination, digital ELISA measures of NfL and Tau could discriminate between groups with 100% sensitivity and 91.7% specificity. Estimated conventional ELISA measures could only discriminate between groups with 7.7% sensitivity and 94.4% specificity. This difference in diagnostic performance was statistically significant when comparing areas under ROC curves.

Conclusions: The use of digital ELISA over conventional ELISA methods improves the diagnostic performance of circulating brain-specific proteins for detection of TBI during triage.     

Application of salivary noncoding microRNAs for the diagnosis of oral cancers

Oral cancer is on the rise globally and survival rates, despite improvements in clinical care, have not significantly improved. Early detection followed by immediate intervention is key to improving patient outcomes. The use of biomarkers has changed the diagnostic landscape for many cancers. For oral cancers, visual inspection followed by a tissue biopsy is standard practice. The discovery of microRNAs as potential biomarkers has attracted clinical interest but several challenges remain. These microRNAs can be found in bodily fluids such as blood and saliva which have been investigated as potential sources of biomarker discovery. As oral cancer is localized within the oral cavity, saliva may contain clinically relevant molecular markers for disease detection. Our review provides an outline of the current advances for the application of salivary microRNAs in oral cancer. We also provide a technical guide for the processing of salivary RNAs to ensure accurate clinical measurement and validation.     

Potential Impact of Microarray Diagnosis of T Cell–Mediated Rejection in Kidney Transplants: The INTERCOM Study

We previously developed a microarray‐based test for T cell‐mediated rejection (TCMR) in a reference set of 403 biopsies. To determine the potential impact of this test in clinical practice, we undertook INTERCOM, a prospective international study of 300 indication biopsies from 264 patients ( ClinicalTrials.gov NCT01299168). Biopsies from six centers—Baltimore, Barcelona, Edmonton, Hannover, Manchester and Minneapolis—were analyzed by microarrays, assigning TCMR scores by an algorithm developed in the reference set and comparing TCMR scores to local histology assessment. The TCMR score correlated with histologic TCMR lesions—tubulitis and interstitial infiltration. The accuracy for primary histologic diagnoses (0.87) was similar to the reference set (0.89). The TCMR scores reclassified 77/300 biopsies (26%): 16 histologic TCMR were molecularly non‐TCMR; 15 histologic non‐TCMR were molecularly TCMR, including 6 with polyoma virus nephropathy; and all 46 “borderline” biopsies were reclassified as TCMR (8) or non‐TCMR (38). Like the reference set, discrepancies were primarily in situations where histology has known limitations, for example, in biopsies with scarring and inflammation/tubulitis potentially from other diseases. Neither the TCMR score nor histologic TCMR was associated with graft loss. Thus the molecular TCMR score has potential to add new insight, particularly in situations where histology is ambiguous or potentially misleading.     

Automated diagnosis of epilepsy using EEG power spectrum

Interictal electroencephalography (EEG) has clinically meaningful limitations in its sensitivity and specificity in the diagnosis of epilepsy because of its dependence on the occurrence of epileptiform discharges. We have developed a computer‐aided diagnostic (CAD) tool that operates on the absolute spectral energy of the routine EEG and has both substantially higher sensitivity and negative predictive value than the identification of interictal epileptiform discharges. Our approach used a multilayer perceptron to classify 156 patients admitted for video‐EEG monitoring. The patient population was diagnostically diverse; 87 were diagnosed with either generalized or focal seizures. The remainder of the patients were diagnosed with nonepileptic seizures. The sensitivity was 92% (95% confidence interval [CI] 85–97%) and the negative predictive value was 82% (95% CI 67–92%). We discuss how these findings suggest that this CAD can be used to supplement event‐based analysis by trained epileptologists.     

Snowboarding injuries: a review of the literature and an analysis of the potential use of portable ultrasound for mountainside diagnostics

Snowboarding has become a popular recreational and professional sport. Participants suffer a variety of injuries, especially of the extremities, that require medical evaluation. This article reviews the reported injuries to both leisure and elite athletes. To many, an injured extremity requires travel to a medical facility for accurate evaluation. Musculoskeletal ultrasound is an accurate and portable technology that can be used for real time, mountainside diagnoses of these injuries.     

Diagnostic Instability Over Time in the Late-Onset Frontal Lobe Syndrome: When Can We Say it's FTD?

ObjectivesDistinguishing sporadic behavioral variant of frontotemporal dementia (bvFTD) from late-onset primary psychiatric disorders (PPD) remains challenging with the lack of robust biomarkers. An early bvFTD misdiagnosis in PPD cases and vice-versa is common. Little is known about diagnostic (in)stability over longer period of time. We investigated diagnostic instability in a neuropsychiatric cohort up to 8 years after baseline visit and identified which clinical hallmarks contribute to diagnostic instability.DesignDiagnoses of participants of the late-onset frontal lobe (LOF) study were collected from the baseline visit (T0) and the 2-year follow-up visit (T2). Clinical outcomes were retrieved 5–8 years after baseline visit (T_final). Endpoint diagnoses were categorized into bvFTD, PPD and other neurological disorders (OND). We calculated the total amount of participants that switched diagnosis between T0-T2 and T2-T_final. Clinical records of participants that switched diagnosis were assessed.ResultsOf the 137 patients that were included in the study, the final diagnoses at T_final were bvFTD 24.1% (n = 33), PPD 39.4% (n = 54), OND 33.6% (n = 46) and unknown 2.9% (n = 4). Between T0 and T2, a total of 29 (21.2%) patients switched diagnosis. Between T2 and T_final, 8 (5.8%) patients switched diagnosis. Prolonged follow-up identified few cases with diagnostic instability. Major contributors to diagnostic instability where a nonconverting diagnosis of possible bvFTD and a probable bvFTD diagnosis based on informant-based history and an abnormal FDG-PET scan whilst having a normal MRI.ConclusionConsidering these lessons, a FTD diagnosis remains stable enough to conclude that 2 years is sufficient to say if a patient with late-life behavioral disorder has FTD.