Asymptomatic Healthy Controls Research Articles

Myocardial perfusion at rest in patients with Diabetes Mellitus Type 1 compared with healthy controls assessed with Multi Detector Computed Tomography

AimType 1 diabetes mellitus (T1DM) is associated with an increased risk of ischemic heart disease (IHD). The relative contribution of structural and functional abnormalities of the coronary circulation determining clinically manifested IHD remains unknown. The aim of this study was to assess potential differences in myocardial perfusion at rest and coronary atherosclerosis between asymptomatic T1DM patients and healthy controls. MethodsLeft ventricular (LV) myocardial perfusion at rest measured as LV myocardial Attenuation Density/LV blood pool Attenuation Density (MyoAD-ratio) and coronary artery atherosclerosis were evaluated with 320-multidetector computed tomography angiography in 57 asymptomatic T1DM patients and 114 sex and age matched controls. ResultsIn both groups median age was 53 years (p5,p95: 42,67) and 59.6% were men. Median duration of diabetes in the T1DM group was 35 years (p5,p95: 17,49). Median coronary calcium score was higher in T1DM patients (51 vs. 2, p=0.037) compared with controls. However, a similar frequency of >50% stenosis in one or more coronary arteries was found in T1DM patients and controls (18% vs. 14%, p=0.49). LV myocardial perfusion at rest (MyoAD-ratio) was 18% higher in T1DM patients than controls (0.13 vs. 0.11, p<0.0001). This difference was noted throughout all the LV myocardial segments. In a multiple regression analysis including diabetes, sex, age, cardiovascular risk factors, heart rate, calcium score and coronary stenosis >50%, MyoAD-ratio remained significantly higher in T1DM patients (p=0.0001). ConclusionsLV myocardial perfusion at rest is higher in T1DM patients compared with controls independent of coronary atherosclerosis and cardiovascular risk factors.

Utility of Salivary Biomarkers for Demonstrating Acute Myocardial Infarction

The comparative utility of serum and saliva as diagnostic fluids for identifying biomarkers of acute myocardial infarction (AMI) was investigated. The goal was to determine if salivary biomarkers could facilitate a screening diagnosis of AMI, especially in cases of non-ST elevation MI (NSTEMI), since these cases are not readily identified by electrocardiogram (ECG). Serum and unstimulated whole saliva (UWS) collected from 92 AMI patients within 48 hours of chest pain onset and 105 asymptomatic healthy control individuals were assayed for 13 proteins relevant to cardiovascular disease, by Beadlyte technology (Luminex®) and enzyme immunoassays. Data were analyzed with concentration cut-points, ECG findings, logistic regression (LR) (adjusted for matching for age, gender, race, smoking, number of teeth, and oral health status), and classification and regression tree (CART) analysis. A sensitivity analysis was conducted by repetition of the CART analysis in 58 cases and 58 controls, each matched by age and gender. Serum biomarkers demonstrated AMI sensitivity and specificity superior to that of saliva, as determined by LR and CART. The predominant discriminators in serum by LR were troponin I (TnI), B-type natriuretic peptide (BNP), and creatine kinase-MB (CK-MB), and TnI and BNP by CART. In saliva, LR identified C-reactive protein (CRP) as the biomarker most predictive of AMI. A combination of smoking tobacco, UWS CRP, CK-MB, sCD40 ligand, gender, and number of teeth identified AMI in the CART decision trees. When ECG findings, salivary biomarkers, and confounders were included, AMI was predicted with 80.0% sensitivity and 100% specificity. These analyses support the potential utility of salivary biomarker measurements used with ECG for the identification of AMI. Thus, saliva-based tests may provide additional diagnostic screening information in the clinical course for patients suspected of having an AMI.

Postural response to vibration of triceps surae, but not quadriceps muscles, differs between people with and without knee osteoarthritis

Although proprioceptive impairments are reported in knee osteoarthritis (OA), there has been little investigation of the underlying causes. Muscle spindles make an important contribution to proprioception. This study investigated whether function of quadriceps, triceps surae, and tibialis anterior muscle spindles is altered in individuals with knee OA. Thirty individuals with knee OA (17 females, 66 ± 7 [mean ± SD] years) and 30 healthy asymptomatic controls (17 females, 65 ± 8 years) stood comfortably and blindfolded on a force plate. Mechanical vibration (60 Hz) was applied bilaterally over the quadriceps, triceps surae, or tibialis anterior muscles for the middle 15 s (Vibration) of a 45 s trial (preceded and followed by 15 s Baseline and Recovery periods). Two trials were recorded for each muscle site. Mean anterior-posterior displacement of centre of pressure was analysed. Although there were no differences between groups for trials with vibration applied to the quandriceps or tibialis anterior, participants with knee OA were initially perturbed more by triceps surae vibration and accommodated less to repeated exposure than controls. This indicates that people with knee OA have less potential to detect or compensate for disturbed input to triceps surae, possibly due to an inability to compensate using muscles spindles in the quadriceps muscle.

Morphometry of the Pelvic Floor Muscles in Women With and Without Provoked Vestibulodynia Using 4D Ultrasound

It has been suggested that pelvic floor muscles (PFMs) play an important role in provoked vestibulodynia (PVD) pathophysiology. Controversy in determining their exact contribution may be explained by methodological limitations related to the PFM assessment tools, specifically the pain elicited by the measurement itself, which may trigger a PFM reaction and introduce a strong bias. The aim of this study was to compare PFM morphometry in women suffering from PVD to asymptomatic healthy control women using a pain-free methodology, transperineal four-dimensional (4D) ultrasound. Fifty-one asymptomatic women and 49 women suffering from PVD were recruited. Diagnosis of PVD was confirmed by a gynecologist following a standardized examination. All the participants were nulliparous and had no other urogynecological conditions. The women were evaluated in a supine position at rest and during PFM maximal contraction. Transperineal 4D ultrasound, which consists of a probe applied on the surface of the perineum without any vaginal insertion, was used to assess PFM morphometry. Different parameters were assessed in sagittal and axial planes: anorectal angle, levator plate angle, displacement of the bladder neck, and levator hiatus area. The investigator analyzing the data was blinded to the clinical data. Women with PVD showed a significantly smaller levator hiatus area, a smaller anorectal angle, and a larger levator plate angle at rest compared with asymptomatic women, suggesting an increase in PFM tone. During PFM maximal contraction, smaller changes in levator hiatus area narrowing, displacement of the bladder neck, and changes of the anorectal and of the levator plate angles were found in women with PVD compared with controls, which may indicate poorer PFM strength and control. Using a reliable and pain-free methodology, this research provides sound evidence that women with PVD display differences in PFM morphometry suggesting increased tone and reduced strength.

Differential Early Secreted Antigen Target (ESAT) 6 kDa–induced IFN-γ and SOCS1 expression distinguishes latent and active tuberculosis

Expression of Suppressor of cytokine signaling (SOCS)-1 molecules is increased in patients with tuberculosis (TB). Early Secreted Antigen Target (ESAT)-6 kDa - induced IFN-γ responses indicate Mycobacterium tuberculosis infection. The effect of ESAT6- stimulation on SOCS1 in the host is not known. Healthy asymptomatic controls had a negative (n = 16) or a positive ( n = 13) tuberculin skin test (TST). ESAT6-induced IFN-γ responses classified these controls as positive (EC ESAT6 IFN-γ (+), n = 5) or negative (EC ESAT6 IFN-γ (-), n = 24) responders. Patients had pulmonary (n = 21) or extra-pulmonary (n = 30) tuberculosis. Peripheral blood cells were stimulated with ESAT6 and mRNA expression of IFN-γ and SOCS1 was determined. ESAT6-induced IFN-γ expression was raised in EC ESAT6 IFN-γ (+) as compared with EC ESAT6 IFN-γ (-), p = 0.019. ESAT6-induced SOCS1 mRNA expression was increased in both pulmonary TB and extra-pulmonary TB patients as compared with both EC groups. ESAT6-induced IFN-γ/SOCS1 mRNA expression ratio was decreased in TB patients as compared with both EC groups. M. tuberculosis infection induces increased ESAT6-induced IFN-γ responses in both latent and active TB. Our data shows down-regulation of IFN-γ / SOCS1 expression to be induced only in active TB cases, distinguishing them from healthy individuals likely to have latent TB. A decreasing IFN-γ /SOCS1 ratio may leads to reduced Th1 immunity which contributes to inability of the host to control clinical disease.

Less small airway dysfunction in asymptomatic bronchial hyperresponsiveness than in asthma

Bronchial hyperresponsiveness (BHR) can be present in subjects without any respiratory symptoms. Little is known about the role of the small airways in asymptomatic subjects with BHR. We investigated small airway function assessed by spirometry and impulse oscillometry, as well as Borg dyspnea scores at baseline and during a methacholine provocation test in 15 subjects with asymptomatic BHR, 15 asthma patients, and 15 healthy controls. At baseline, small airway function (R5 -R20 and X5 ) was comparable between subjects with asymptomatic BHR and healthy controls, whereas asthma patients showed small airway dysfunction as reflected by higher R5 -R20 and lower X5 values. During methacholine provocation, small airway dysfunction was more severe in asthma patients than in subjects with asymptomatic BHR. Interestingly, a higher increase in small airway dysfunction during methacholine provocation was associated with a higher increase in Borg dyspnea scores in subjects with asymptomatic BHR, but not in asthma patients. Subjects with asymptomatic BHR may experience fewer symptoms in daily life because they have less small airway dysfunction.

Abstract 150: Carotid Artery Atherosclerosis: Biomarkers of Plaque Instability

Objective To identify intraplaque and plasma biomarkers of carotid atherosclerotic plaque instability. We hypothesized that comparison of plaques and plasma from symptomatic and asymptomatic patients would show differences in proteolytic and inflammatory proteins, identifying them as potential markers of an unstable plaque. Methods 42 symptomatic and asymptomatic patients (22 women, 20 men, 52-89 years) presenting for carotid endarterectomy had blood samples drawn and carotid plaques processed for protein extraction. The intraplaque expression of proteolytic enzymes (uPA, tPA, PAI-1 and MMP-2) and inflammatory markers (TF, TSP-1, and TNF-α) were evaluated by Western blot analysis. Plasma analyte concentrations were assayed with LUMINEX CVD1 and Cytokine panels using LUMINEX technology. Results Intraplaque expression of tPA and uPA was 5.9x and 4.5x higher (n=15, p&lt; .05) respectively in the symptomatic group when compared to the asymptomatic group. The symptomatic group also demonstrated a 4.3x increase in active MMP-2 and a 3.6x increase in PAI-1 expression. Investigation of inflammatory proteins demonstrated 2.7-, 4.7-, and 3.3-fold increases in the expression of TNF- α, TSP-1, and TF, respectively. Plasma levels of MPO, MMP-9, IL8, MCP-1 and TNFα were significantly elevated in both the symptomatic and asymptomatic groups when compared to healthy controls (n=7, p&lt;0.05). While there was no change in ICAM-1 levels between asymptomatic patients and healthy controls, symptomatic patients demonstrated a 35% decrease (n=7, p&lt;0.05) when compared to controls. Also, plasma PAI-1 levels in asymptomatic patients were 55% lower than in symptomatic patients and 75% lower than in healthy controls. Conclusion Elevated expression of certain inflammatory markers and proteolytic enzymes in carotid plaques was demonstrated in symptomatic patients. Marked differences were also observed in ICAM-1 and PAI-1 expression in the plasma of symptomatic patients relative to asymptomatic patients and healthy controls. This leaves promising avenues for further inquiry into the roles of these proteins in atherosclerotic disease and their potential as clinical biomarkers of an unstable atherosclerotic plaque.

Longitudinal rates of change in subchondral bone size in healthy knees and knees with radiographic osteoarthritis

s / Osteoarthritis and Cartilage 21 (2013) S63–S312 S242 (non-transduced cells). A set of 53 downregulated genes pertaining to the, canonical, planar, Cell Growth & Profileration and Cell Migration, were identified. One of them, DAAM1, have been already described as direct targets of mir-335. Conclusions: Our results indicate a lower expression of mir335 in OAMSCs patients and suggest that the downregulation in Wnt related genes during the initial stages of differentiation that could be partly restored after mir335 overexpression. Therefore, we hypothesize that a diminished expression of mir335 could contribute to the altered function of MSCs in OA. 456 LONGITUDINAL RATES OF CHANGE IN SUBCHONDRAL BONE SIZE IN HEALTHY KNEES AND KNEES WITH RADIOGRAPHIC OSTEOARTHRITIS M. Hudelmaier y, W. Wirth y, M. Nevitt z, F. Eckstein y. for the OAI investigatorsy Paracelsus Med. Univ., Salzburg, Austria; zUniv. of California, OAI Coordinating Ctr., San Francisco, CA, USA Purpose: Several studies reported that an increase of subchondral bone area (tAB) is associatedwith features of radiographic knee osteoarthritis (rOA), such as osteophytes, joint space narrowing or subchondral defects. One cross-sectional study reported that tABs were larger in knees with higher KL grades, based on site readings from the OA initiative (OAI). Here we test the hypotheses that knees with rOA show greater rates of longitudinal tAB change than knees with risk factors but not definite radiographic OA (pre-rOA) or healthy knees without. Methods: Coronal FLASHwe MR images of 899 right knees from OAI participants (539 women, 360 men; age 61.6 9.5; BMI 28.9 4.8) were acquired at baseline and 12 month follow-up (public use datasets 0.E.1 and 1.E.1). Based on central radiographic readings (Boston University), 101 knees were classified asymptomatic healthy controls (bilateral KLG 0, no OA risk factors), 254were pre-rOA (KLG 0&1, with risk factors), and 544 had definite rOA (KLG 2-4). The tAB of the medial and lateral tibia (MT/LT) and weight-bearing (central) femoral condyles (cMF/cLF) were segmented by experienced readers, by matching numbers of slices processed per plate in scan pairs, but with blinding to acquisition order. The size of the tAB was calculated in 3D. Because an increase in tAB was expected, 1-sided non-paired t-tests were used to compare groups, and significance of change was assessed with 1-sided paired t-tests. Results: tAB changes were less than 1% in all strata (Table 1) and were not significantly different from zero in healthy reference knees (SRM range -0.10 to +0.11). Pre-rOA knees had a significant (p<0.05) tAB increase in cMF (SRM +0.10) but not in other plates (SRM 0.05). rOA knees showed significant tAB increases in MT (SRM +0.14), cMF (SRM +0.21) and cLF (SRM +0.15), but not in LT (SRM +0.03). The changes were significantly greater than in rOA than in pre-rOA knees for MT and cLF (p< 0.05), and greater than in healthy controls for MT (p<0.05). In MT, the percent increase in tAB was greater in knees with higher KL grades. Conclusions: Knees with definite rOA show small but significant longitudinal increases in tAB, predominantly in the medial compartment. In the medial tibia, the rate of tAB changewas greater in rOA than in pre-rOA or healthy knees. The observed relationship between tAB change and rOAI status in the medial tibia may be due to rOA predominantly affecting the medial compartment (in general and in the OAI) and because femorotibial loading is known to be greater medially than laterally. The current results suggest that longitudinal change in tABs is a feature of structural progression associated with rOA status.

Positive association of adiponectin with soluble thrombomodulin, von Willebrand factor and soluble VCAM-1 in dyslipidemic subjects

ObjectivesBoth decreased and increased risk of cardiovascular events/mortality have been reported with high adiponectin levels. Only a few studies have reported an association of adiponectin with markers of hemostasis/endothelial dysfunction which might explain the reported discrepancies. Design and methodsWe evaluated the association of total adiponectin with von Willebrand factor (vWF), plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (t-PA), soluble thrombomodulin (sTM), adhesion molecules sICAM-1 and sVCAM-1, lipids and markers of insulin resistance (IR) in 308 asymptomatic dyslipidemic subjects and healthy controls. Subjects were divided into 4 dyslipidemic phenotypes (DLP): DLP1 (TG<1.5mmol/L+ApoB<1.2g/L), DLP2 (TG≥1.5+ApoB<1.2), DLP3 (TG<1.5+ApoB≥1.2) and DLP4 (TG≥1.5+ApoB≥1.2). The results were evaluated also according to the presence (+) and absence (−) of metabolic syndrome (MS). ResultsIn hyperlipidemic subjects (DLP2–4), PAI-1, t-PA and sICAM-1 correlated with markers of IR but only t-PA correlated inversely with adiponectin. In contrast positive association of adiponectin with vWF, sTM and sVCAM-1 was found but none of these parameters correlated with markers of insulin resistance. In multiple regression analysis, adiponectin remained independently associated with vWF [in DLP3, DLP4, DLP2–4, MS(−)], with sTM [in DLP2, DLP4, DLP2–4, MS(+)] and with sVCAM-1 [in DLP2, DLP3, DLP4, DLP2–4, MS(+)]. In healthy controls (DLP1), no association between adiponectin and markers of hemostasis/endothelial dysfunction was found. ConclusionThe independent positive association of adiponectin with vWF, sTM and sVCAM-1 deserves further evaluation in connection with the risk of atherothrombotic cardiovascular events.

Gastric Emptying in Patients With Functional Dyspepsia and Patients With Migraine

TO THE EDITOR: I read the paper by Yu et al1 entitled Gastric emptying in migraine: a comparison with functional dyspepsia. The authors measured gastric emptying time in 27 patients with migraine, 32 patients with functional dyspepsia (FD) and 12 healthy controls in order to investigate whether delayed gastric emptying plays a pathogenic role in FD patients or migraine patients without any gastrointestinal symptoms during the interictal periods, and whether delayed gastric emptying is associated with specific dyspeptic symptoms in those patients. FD is believed to be a heterogeneous disorder in which diverse pathophysiologic mechanisms are involved. Delayed gastric emptying has been considered to be one of the major pathophysiologic mechanisms in FD.2,3 A meta-analysis of 17 studies reported that delayed solid gastric emptying was present in about 40% of patients with FD.4 However, larger studies reported delayed gastric emptying in 20-30% of patients with FD.3 The study by Yu et al1 revealed that the proportions of patients with mildly delayed and delayed gastric emptying were 24.1% and 58.6% in the FD group, respectively. The proportion of normal gastric emptying in the FD group was 17.3%. These proportions are very different from those reported in previous studies. The grading criteria of gastric emptying used in that study5 should be validated in the author's institution, because the methodology to measure gastric emptying including the type of meal used and a normal range of gastric emptying in asymptomatic healthy controls may be different. Indeed, mildly delayed and delayed gastric emptying were present in 25.0% and 33.3% of the healthy controls, suggesting the possibility that the grading criteria of gastric emptying were not appropriate. Regarding the association between gastric emptying parameters and dyspeptic symptoms in patients with FD, small studies have shown controversial results. Whereas, larger studies have shown the association of postprandial fullness and nausea with delayed gastric emptying.6,7 Because the sample size of the study by Yu et al1 is small, it does not have any superiority over the previous studies. The authors failed to find the association of delayed gastric emptying with any dyspeptic symptoms. This negative association might be attributed to the small sample size. The authors recommended further study for the association of migraine with FD. However, they excluded those who had experienced gastrointestinal symptoms during the interictal period from the migraine group. Upper abdominal symptoms are reported to be more frequent in patients with migraine compared with healthy controls.8 Therefore, in order to investigate the association between migraine and FD, it seems to be more rational that migraine patients with upper abdominal symptoms are included in the study. The investigation of the gastric mechanism associated with nausea and vomiting occurring during ictal period is likely to be difficult to perform because gastric function should be measured during ictal period.

Sero-immunoproteomics of Leishmania infantum: a reappraisal of the role of antibodies in protection to the development of kala-azar and antigen discovery for the design of biomarkers and vaccines.

Sero-immunoproteomics of Leishmania infantum: a reappraisal of the role of antibodies in protection to the development of kala-azar and antigen discovery for the design of biomarkers and vaccines.

Cognitive performance in healthy women during induced hypogonadism and ovarian steroid addback.

Gynecology clinic-based studies have consistently demonstrated that induced hypogonadism is accompanied by a decline in cognitive test performance. However, a recent study in healthy asymptomatic controls observed that neither induced hypogonadism nor estradiol replacement influenced cognitive performance. Thus, the effects of induced hypogonadism on cognition might not be uniformly experienced across individual women. Moreover, discrepancies in the effects of hypogonadism on cognition also could suggest the existence of specific risk phenotypes that predict a woman's symptomatic experience during menopause. In this study, we examined the effects of induced hypogonadism and ovarian steroid replacement on cognitive performance in healthy premenopausal women. Ovarian suppression was induced with a GnRH agonist (Lupron) and then physiologic levels of estradiol and progesterone were reintroduced in 23 women. Cognitive tests were administered during each hormone condition. To evaluate possible practice effects arising during repeated testing, an identical battery of tests was administered at the same time intervals in 11 untreated women. With the exception of an improved performance on mental rotation during estradiol, we observed no significant effects of estradiol or progesterone on measures of attention, concentration, or memory compared with hypogonadism. In contrast to studies in which a decline in cognitive performance was observed in women receiving ovarian suppression therapy for an underlying gynecologic condition, we confirm a prior report demonstrating that short-term changes in gonadal steroids have a limited effect on cognition in young, healthy women. Differences in the clinical characteristics of the women receiving GnRH agonists could predict a risk for ovarian steroid-related changes in cognitive performance during induced, and possibly, natural menopause.

Epidermal growth factor gene polymorphism 61A/G in patients with chronic liver disease for early detection of hepatocellular carcinoma

Overexpression of epidermal growth factor (EGF) in the liver induces transformation into hepatocellular carcinoma (HCC) in animal models. Polymorphisms in the EGF gene modulate EGF levels. To evaluate the effect of EGF gene single nucleotide polymorphism and to assess its correlation with the risk of HCC in patients with chronic liver diseases. The present study included 80 participants divided into four groups: group 1 included 20 asymptomatic healthy control volunteers, group 2 included 20 patients with chronic hepatitis C viral (HCV) infection, group 3 included 20 patients with liver cirrhosis, and group 4 included 20 patients with HCC. For all participants, the following investigations were performed: routine laboratory investigations including complete blood count, liver function tests, sero markers of hepatitis viruses HBsAg, HCV-RNA by quantitative polymerase chain reaction, and α-fetoprotein. DNA was extracted from whole blood for detection of single nucleotide polymorphism of the EGF by polymerase chain reaction, followed by restriction fragment length polymorphism. We found a significant difference between both patients with HCC and HCV versus controls in terms of the G carrier (GG and GA; 80 vs. 40%, P<0.05). In addition, the cirrhotic and chronic hepatitis C patients with GG had three-fold and 2.3-fold odds ratio for developing HCC, respectively. The EGF 61GG genotype might be associated with a high risk for the development of HCC in Egyptian patients with chronic liver disease.

Generation of dyspeptic symptoms by direct acid and water infusion into the stomachs of functional dyspepsia patients and healthy subjects

The mechanisms of the development of symptoms in functional dyspepsia (FD) patients have not been fully elucidated. We previously reported that acid directly infused into the stomach causes dyspeptic symptoms in asymptomatic healthy controls (HCs); however, the response to acid infusion of FD patients was not determined. To investigate the severity of dyspeptic symptoms induced by direct acid infusion in FD subjects and HCs. This was a multi-centre, cross-over, randomised, double-blind study in 23 FD subjects and 32 HCs. FD was defined using the Rome III criteria. All subjects were Helicobacter pylori negative. Each subject received two tests; 0.1 mol/L hydrochloric acid and water infused into the stomach. The presence and severity of 12 dyspeptic symptoms were assessed using a visual analogue scale. The proportion of subjects developing symptoms by acid or water infusion was significantly greater in FD subjects than HCs. All of the FD subjects experienced at least one symptom by water or acid infusion. In the FD subjects, the severity of symptoms was significantly greater with acid infusion than water infusion. The severity of symptoms in total and the scores for eight of the 12 symptoms induced by acid infusion was significantly greater in FD subjects than in HCs. The severity of dyspeptic symptom generation induced by direct acid infusion into the stomach was significantly greater in functional dyspepsia subjects than in healthy controls, suggesting that hypersensitivity to acid is one of the important mechanisms of the development of symptoms in functional dyspepsia patients.

Dynamic Imaging and Function of Partial Supraspinatus Tendon Tears

It was the purpose of this study to identify and document normal and abnormal supraspinatus tendon function in vivo using real-time ultrasound. We defined 4 groups of 20 individuals each: partial tear (group 1), full-thickness tear (group 2), successfully repaired tear (group 3), and healthy asymptomatic controls (group 4). Except for group 4, all patients underwent magnetic resonance arthrography to confirm the diagnosis. All underwent ultrasound imaging of the supraspinatus tendon with the adducted arm at rest and under maximal isometric abduction. Tendon deformation was dynamically assessed and measured with tendon thickness changes at 0.5, 1, 1.5, and 2 cm from the tendon insertion. The clinical assessment consisted of absolute and relative Constant score, subjective shoulder value, and strength measurements. Without muscle contraction, the tendons of the 4 groups were not of significantly different thickness, with the least variation at 1.5 cm from the insertion site. On contraction, the normal tendon thickness significantly increased at a distance of 2 cm, whereas it did not for the full-thickness and partial supraspinatus tears. Thus contraction of the muscle resulted in measurable deformation of the tendon. Partially torn supraspinatus tendons can be functionally incompetent, leading to a biomechanical deformation of the musculotendinous unit that is not different from that of a unit with a full-thickness tendon tear. The dynamic sonographic finding of a successful repair of a supraspinatus tendon is similar to that of a normal tendon, even though the previously injured muscle appears unable to generate the same strength as a normal muscle. Level III, case-control study.

Association of MMP-2 and MMP-9 with clinical outcome of neurocysticercosis

Matrix metalloproteinases (MMPs) are the major endopeptidases involved in proteolysis of blood brain barrier (BBB) during central nervous system (CNS) infections. The present study detected serum levels and activities of MMP-2 and MMP-9 in patients with neurocysticercosis (NCC) and their association with symptomatic disease. In total, 68 individuals with NCC (36 symptomatic patients with active seizures and 32 asymptomatic individuals) and 37 healthy controls were enrolled for the study. Serum MMP-2 and MMP-9 levels and their activities were measured by ELISA and gel zymography respectively. Mean serum MMP-2 levels (ng/ml) were higher both in asymptomatic and symptomatic NCC cases compared to healthy controls. However, significantly higher levels of serum MMP-9 (ng/ml) were detected only in symptomatic NCC patients compared to asymptomatic NCC cases and healthy controls. Levels of both MMPs positively correlated with symptomatic NCC. Serum MMP-2 activities were significantly higher in symptomatic and asymptomatic NCC compared to healthy controls whereas serum MMP-9 activity was significantly associated with symptomatic NCC compared to healthy controls and asymptomatic NCC. In conclusion, the elevated level of MMP-9 in serum appears to play an important role in the development of symptoms i.e. active seizures in patients with NCC. However, further studies are needed to elucidate its precise role in disease pathogenesis.

Intrasession and interrater reliability of rehabilitative ultrasound imaging measures of the deep neck flexors: A pilot study

The purpose of this investigation was to examine the intrasession and interrater reliability of rehabilitative ultrasound imaging (RUSI) to measure the deep neck flexors (DNF). Two investigators traced the DNF muscle borders in eight female subjects aged 33 ± 11.2 years. Of the eight subjects, five subjects reported a greater than 6-month history of neck pain, and three subjects were asymptomatic healthy controls. Cross-sectional area (CSA) (cm2) of right and left muscle groups were calculated. The intraclass correlation coefficients (ICC) for CSA measures were 0.67 (95% CI: 0.27–0.87) for rater 1 with a standard error of measurement (SEM) of 0.06 cm2; 0.87 (95% CI: 0.65–0.96) for rater 2 with an SEM of 0.09 cm2; and 0.68 (95% CI: 0.44–0.87) for interrater reliability between rater 1 and rater 2 with an SEM of 0.11 cm2. The mean difference between CSA (cm2) measures were 0.00 ± 0.10 cm2 for rater 1 and 0.09 ± 0.13 cm2 for rater 2. The mean differences for CSA were 0.04 ± 0.12 cm2. This pilot investigation suggests that RUSI could be used to reliably assess the size of the deep neck flexors.

IL-25-Induced Immunotherapy Against Obesity and the Associated Metabolic Syndrome

Background/Aim: UES contractile reflex was described in 1957 by Creamer and Schlegel. The physiological role of this reflex in preventing pharyngeal reflux of gastric content and protecting the airway has been studied extensively. However, to date the defect of this reflex has not been described. Our aim was to characterize the UES pressure response to a variety of esophageal distensions in a group of patients with complaints of regurgitation and refluxattributed supraesophageal complications. Methods: We studied 8 patients (51 ± 20 yrs., 2F) with complaints of regurgitation and supraesophageal symptoms as well as 12 healthy asymptomatic controls (25 ± 5 yrs., 6F) in the supine position. Of the 8 patients, 6 had an intact esophagus, 1 had colonic interposition, and 1 had a partial esophagectomy and gastric pull-up. We tested the UES response to esophageal distension; simulating GE reflux by rapid and slow infusion of normal saline (10, 20, 30, and 60 mL) and air (10, 20, 30, 50 mL) and each injection was repeated 3 times. UES and esophageal pressures were monitored by high resolution intraluminal manometry. Pharyngeal reflux/regurgitation was monitored by high resolution esophagopharyngeal impedance recording. Patients were instructed to signal if pharyngeal reflux was perceived. Results: There were significant differences in the UES response to rapid and slow fluid injections between patients and controls (Chi-square< 0.0001) (Table). All patients but none of the controls reported pharyngeal reflux during slow and rapid esophageal fluid infusion. UES contraction(C) was absent during slow infusion only in patient group. Pharyngeal reflux was documented by impedance in six of eight patients with intact esophagus. All rapid fluid infusions produced UES contraction in the control group, while only 70-75% of rapid fluid infusions produced a UES contraction in patients. UES response to air distension, however, was relaxation(R) in both groups. Conclusions: UES contractile response to slow esophageal fluid distention is defective in patients with complaints of regurgitation and supraesophageal complications, allowing escape of refluxate into the pharynx. UES response to esophageal slow fluid infusion can serve as a test for recognizing this defect.

Glial Cell Line Derived Neurotrophic Factor Prevents High Fat Diet Induced Obesity

Background/Aim: UES contractile reflex was described in 1957 by Creamer and Schlegel. The physiological role of this reflex in preventing pharyngeal reflux of gastric content and protecting the airway has been studied extensively. However, to date the defect of this reflex has not been described. Our aim was to characterize the UES pressure response to a variety of esophageal distensions in a group of patients with complaints of regurgitation and refluxattributed supraesophageal complications. Methods: We studied 8 patients (51 ± 20 yrs., 2F) with complaints of regurgitation and supraesophageal symptoms as well as 12 healthy asymptomatic controls (25 ± 5 yrs., 6F) in the supine position. Of the 8 patients, 6 had an intact esophagus, 1 had colonic interposition, and 1 had a partial esophagectomy and gastric pull-up. We tested the UES response to esophageal distension; simulating GE reflux by rapid and slow infusion of normal saline (10, 20, 30, and 60 mL) and air (10, 20, 30, 50 mL) and each injection was repeated 3 times. UES and esophageal pressures were monitored by high resolution intraluminal manometry. Pharyngeal reflux/regurgitation was monitored by high resolution esophagopharyngeal impedance recording. Patients were instructed to signal if pharyngeal reflux was perceived. Results: There were significant differences in the UES response to rapid and slow fluid injections between patients and controls (Chi-square< 0.0001) (Table). All patients but none of the controls reported pharyngeal reflux during slow and rapid esophageal fluid infusion. UES contraction(C) was absent during slow infusion only in patient group. Pharyngeal reflux was documented by impedance in six of eight patients with intact esophagus. All rapid fluid infusions produced UES contraction in the control group, while only 70-75% of rapid fluid infusions produced a UES contraction in patients. UES response to air distension, however, was relaxation(R) in both groups. Conclusions: UES contractile response to slow esophageal fluid distention is defective in patients with complaints of regurgitation and supraesophageal complications, allowing escape of refluxate into the pharynx. UES response to esophageal slow fluid infusion can serve as a test for recognizing this defect.

Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) is a disorder of innate immunity and Th1 activation responsive to IL-1 blockade

The syndrome of periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) is the most common periodic fever disease in children. However, the pathogenesis is unknown. Using a systems biology approach we analyzed blood samples from PFAPA patients whose genetic testing excluded hereditary periodic fevers (HPFs), and from healthy children and pediatric HPF patients. Gene expression profiling could clearly distinguish PFAPA flares from asymptomatic intervals, HPF flares, and healthy controls. During PFAPA attacks, complement (C1QB, C2, SERPING1), IL-1-related (IL-1B, IL-1RN, CASP1, IL18RAP), and IFN-induced (AIM2, IP-10/CXCL10) genes were significantly overexpressed, but T cell-associated transcripts (CD3, CD8B) were down-regulated. On the protein level, PFAPA flares were accompanied by significantly increased serum levels of chemokines for activated T lymphocytes (IP-10/CXCL10, MIG/CXCL9), G-CSF, and proinflammatory cytokines (IL-18, IL-6). PFAPA flares also manifested a relative lymphopenia. Activated CD4(+)/CD25(+) T-lymphocyte counts correlated negatively with serum concentrations of IP-10/CXCL10, whereas CD4(+)/HLA-DR(+) T lymphocyte counts correlated positively with serum concentrations of the counterregulatory IL-1 receptor antagonist. Based on the evidence for IL-1β activation in PFAPA flares, we treated five PFAPA patients with a recombinant IL-1 receptor antagonist. All patients showed a prompt clinical and IP-10/CXCL10 response. Our data suggest an environmentally triggered activation of complement and IL-1β/-18 during PFAPA flares, with induction of Th1-chemokines and subsequent retention of activated T cells in peripheral tissues. IL-1 inhibition may thus be beneficial for treatment of PFAPA attacks, with IP-10/CXCL10 serving as a potential biomarker.