Drug resistance mediating Plasmodium falciparum polymorphisms and clinical presentations of parasitaemic children in Uganda.

BackgroundPlasmodium falciparum genetic polymorphisms that mediate altered drug sensitivity may impact upon virulence. In a cross-sectional study, Ugandan children with infections mutant at pfcrt K76T, pfmdr1 N86Y, or pfmdr1 D1246Y had about one-fourth the odds of symptomatic malaria compared to those with infections with wild type (WT) sequences. However, results may have been confounded by greater likelihood in those with symptomatic disease of higher density mixed infections and/or recent prior treatment that selected for WT alleles.MethodsPolymorphisms in samples from paired episodes of asymptomatic and symptomatic parasitaemia in 114 subjects aged 4-11 years were followed longitudinally in Tororo District, Uganda. Paired episodes occurred within 3-12 months of each other and had no treatment for malaria in the prior 60 days. The prevalence of WT, mixed, and mutant alleles was determined using multiplex ligase detection reaction-fluorescent microsphere assays.ResultsConsidering paired episodes in the same subject, the odds of symptomatic malaria were lower for infections with mutant compared to WT or mixed sequence at N86Y (OR 0.26, 95% CI 0.09-0.79, p = 0.018), but not K76T or D1246Y. However, symptomatic episodes (which had higher densities) were more likely than asymptomatic to be mixed (for N86Y OR 2.0, 95% CI 1.04-4.0, p = 0.036). Excluding mixed infections, the odds of symptomatic malaria were lower for infections with mutant compared to WT sequence at N86Y (OR 0.33, 95% CI 0.11-0.98, p = 0.046), but not the other alleles. However, if mixed genotypes were grouped with mutants in this analysis or assuming that mixed infections consisted of 50% WT and 50% mutant genotypes, the odds of symptomatic infection did not differ between infections that were mutant or WT at the studied alleles.ConclusionsAlthough infections with only the mutant pfmdr1 86Y genotype were associated with symptomatic infection, this association could primarily be explained by greater parasite densities and therefore greater prevalence of mixed infections in symptomatic children. These results indicate limited association between the tested polymorphisms and risk of symptomatic disease and highlight the value of longitudinal studies for assessing associations between parasite factors and clinical outcomes

Discriminating active from latent tuberculosis in patients presenting to community clinics.

BACKGROUND: Because of the high global prevalence of latent TB infection (LTBI), a key challenge in endemic settings is distinguishing patients with active TB from patients with overlapping clinical symptoms without active TB but with co-existing LTBI. Current methods are insufficiently accurate. Plasma proteomic fingerprinting can resolve this difficulty by providing a molecular snapshot defining disease state that can be used to develop point-of-care diagnostics. METHODS: Plasma and clinical data were obtained prospectively from patients attending community TB clinics in Peru and from household contacts. Plasma was subjected to high-throughput proteomic profiling by mass spectrometry. Statistical pattern recognition methods were used to define mass spectral patterns that distinguished patients with active TB from symptomatic controls with or without LTBI. RESULTS: 156 patients with active TB and 110 symptomatic controls (patients with respiratory symptoms without active TB) were investigated. Active TB patients were distinguishable from undifferentiated symptomatic controls with accuracy of 87% (sensitivity 84%, specificity 90%), from symptomatic controls with LTBI (accuracy of 87%, sensitivity 89%, specificity 82%) and from symptomatic controls without LTBI (accuracy 90%, sensitivity 90%, specificity 92%). CONCLUSIONS: We show that active TB can be distinguished accurately from LTBI in symptomatic clinic attenders using a plasma proteomic fingerprint. Translation of biomarkers derived from this study into a robust and affordable point-of-care format will have significant implications for recognition and control of active TB in high prevalence settings

Lateral cephalometric analysis of asymptomatic volunteers and symptomatic patients with and without bilateral temporomandibular joint disk displacement

Few studies of dentofacial and orthodontic structural relationships relative to temporomandibular joint (TMJ) dysfunction have been reported. We undertook this investigation to determine any correlation of orthodontic and dentofacial characteristics with TMJ bilateral disc displacement. The population of patients was selected from a TMJ clinic where a control group of asymptomatic volunteers had been previously established and standardized. Differences in skeletal structural features were determined among three study groups: (1) asymptomatic volunteers with no TMJ disk displacement, (2) symptomatic patients with no TMJ disc displacement, and (3) symptomatic patients with bilateral TMJ disk displacement. Thirty-two asymptomatic volunteers without disk displacement (25 female, 7 male) were compared with the same number each of symptomatic patients without TMJ disk displacement and symptomatic patients with bilateral TMJ disk displacement. All subjects had undergone a standardized clinical examination, bilateral TMJ magnetic resonance imaging, and lateral cephalometric radiographic analysis. The groups were matched according to sex, TMJ status, age, and Angle classification of malocclusion. Seventeen lateral cephalometric radiographic cranial base, maxillomandibular, and vertical dimension variables were evaluated and compared among the study groups. The mean angle of SNB, or the intersection of the sella-nasion plane and the nasion–point B line (indicating mandibular retrognathism relative to cranial base), of the symptomatic patients-with-displacement group was significantly smaller than that in the asymptomatic volunteers and symptomatic patients without bilateral disk displacement (p \u3c 0.05). Female subjects showed smaller linear measurements of mandibular length, lower facial height, and total anterior facial height than male subjects in all three groups (p \u3c 0.05). The mean angle of ANB, or the intersection of the nasion–point A and nasion–point B planes (indicating retrognathism of mandible relative to maxilla), was significantly greater in female than in male subjects, in all groups (p \u3c 0.05). Symptomatic patients with bilateral disk displacement had a retropositioned mandible, indicated by a smaller mean SNB angle compared with that in asymptomatic volunteers and symptomatic patients with no disk displacement on either side. Lateral cephalometric radiographic assessment may improve predictability of TMJ disk displacement in orthodontic patients but is not diagnostic; nor does the assessment explain any cause-and-effect relationship. (Am J Orthod Dentofacial Orthop 1998;114:248-55.

Iodinated contrast media and cerebral hemorrhage after intravenous thrombolysis

<p>Background and Purpose: Iodinated contrast is increasingly used in CT perfusion or angiographic examinations in acute stroke. Increased risk of intracranial hemorrhage (ICH) complicating microcatheter contrast injections has recently been reported in the second Interventional Management of Stroke (IMS 2) trial with contrast toxicity potentially contributory.</p> <p>Methods: We reviewed clinical and radiological data on all patients treated with intravenous alteplase at a single center between May 2003 and November 2008.</p> <p>Results: Of 312 patients treated with intravenous alteplase, 69 (22.1%) received intravenous iodinated contrast in volumes between 50 and 150 mL. Incidence of symptomatic ICH defined as per European Cooperative Acute Stroke Study 2 was 16 of 312 (5.1%; 95% CI, 2.7% to 7.6%); among patients not given contrast, it was 12 of 243 (4.9%; 2.2% to 7.7%) compared with 4 of 69 (5.8%; 0.3% to 11.3%) in those given contrast. Incidence of symptomatic ICH defined as per Safe Implementation of Thrombolysis in Stroke-MOnitoring Study (SITS-MOST) criteria was 12 of 312 (3.9%; 1.7% to 6%), 9 of 243 (3.7%; 1.3% to 6%) among those not given contrast, and 3 of 69 (4.4%; 95% CI, -0.5% to 9.2%) among those given contrast. Patients with symptomatic ICH were older, had higher pretreatment National Institutes of Health Stroke Scale, and blood glucose than those without symptomatic ICH. In logistic regression analysis, pretreatment blood glucose was the only significant predictor of symptomatic ICH by either definition (OR, 1.23; 95% CI, 1.03 to 1.48 per mmol/L increment; P=0.024). Contrast administration or dose was not associated with symptomatic ICH.</p> <p>Conclusions: Intravenous iodinated contrast in doses typically required for CT angiography and perfusion imaging was not associated with symptomatic intracranial hemorrhage in patients treated with alteplase.</p&gt

Relationship of the medial clavicular head to the manubrium in normal and symptomatic degenerated sternoclavicular joints

Background: Clavicular prominence is common in patients with symptomatic degenerative sternoclavicular arthritis. It is unclear if this is caused by enlargement or subluxation of the clavicle. The aim of this report is to describe a reproducible measurement technique to evaluate the relationship of the medial clavicular head to the manubrium. Methods: One hundred normal sternoclavicular joints, twenty-five sternoclavicular joints with symptomatic degenerative arthritis, and twenty-five non-symptomatic sternoclavicular joints on the contralateral side were studied with three-dimensional (3D) reconstruction with use of computer modeling. The greatest width (anterior-posterior distance) and height (superior-inferior distance) of the clavicle in the sagittal plane were measured, and the positions of the anterior and superior borders of the medial clavicle and their distances to the frontal and axial planes, respectively, were evaluated. The ratio of the anterior-posterior distance to the anterior-frontal plane distance was measured to evaluate the anterior-posterior position of the clavicle and the ratio of the superior-inferior distance to the superior-axial plane distance was measured to evaluate its superoinferior position. If the ratio was not in the 95% normal range, the clavicle was defined as subluxated. The reproducibility of this technique was evaluated on the basis of the interobserver and intraobserver reliability. Results: This technique showed good interobserver and intraobserver reliability. The mean anterior-posterior and superior-inferior distances were significantly larger in association with symptomatic sternoclavicular arthritis than in the normal sternoclavicular joints (p < 0001). The clavicle was subluxated anteriorly in twenty-two of the twenty-five cases of symptomatic sternoclavicular arthritis, but it was not subluxated superiorly. Conclusions: The medial clavicular head in patients with degenerative sternoclavicular arthritis is significantly larger than it is in the normal population, and it is usually subluxated anteriorly

Optimizing outcomes in ADHD treatment: From clinical targets to novel delivery systems

Our knowledge and understanding of the underlying neurobiology and symptomatic expression of ADHD has advanced dramatically over the past decade. Associated with these advances has been a similar explosion of new treatment options to individualize treatment for our patients.This article will:∙review strategies to measure ADHD symptoms and functional difficulties while seeking to achieve full symptomatic remission throughout the day∙summarize recent findings regarding the management and prioritization of ADHD and comorbid conditions and∙discuss the various pharmacologic treatment options with a focus on recently developed molecules and novel delivery systems</jats:p

Quantification of white matter cellularity and damage in preclinical and early symptomatic Alzheimer\u27s disease

Interest in understanding the roles of white matter (WM) inflammation and damage in the pathophysiology of Alzheimer disease (AD) has been growing significantly in recent years. However, in vivo magnetic resonance imaging (MRI) techniques for imaging inflammation are still lacking. An advanced diffusion-based MRI method, neuro-inflammation imaging (NII), has been developed to clinically image and quantify WM inflammation and damage in AD. Here, we employed NII measures in conjunction with cerebrospinal fluid (CSF) biomarker classification (for β-amyloid (Aβ) and neurodegeneration) to evaluate 200 participants in an ongoing study of memory and aging. Elevated NII-derived cellular diffusivity was observed in both preclinical and early symptomatic phases of AD, while disruption of WM integrity, as detected by decreased fractional anisotropy (FA) and increased radial diffusivity (RD), was only observed in the symptomatic phase of AD. This may suggest that WM inflammation occurs earlier than WM damage following abnormal Aβ accumulation in AD. The negative correlation between NII-derived cellular diffusivity and CSF Aβ42 level (a marker of amyloidosis) may indicate that WM inflammation is associated with increasing Aβ burden. NII-derived FA also negatively correlated with CSF t-tau level (a marker of neurodegeneration), suggesting that disruption of WM integrity is associated with increasing neurodegeneration. Our findings demonstrated the capability of NII to simultaneously image and quantify WM cellularity changes and damage in preclinical and early symptomatic AD. NII may serve as a clinically feasible imaging tool to study the individual and composite roles of WM inflammation and damage in AD. Keywords: Inflammation, White matter damage, Diffusion basis spectrum imaging, Neuro-inflammation imaging, Cerebrospinal fluid, Preclinical Alzheimer disease, Early symptomatic Alzheimer disease, Magnetic resonance imagin

Computational fluid dynamics modeling of symptomatic intracranial atherosclerosis may predict risk of stroke recurrence.

BackgroundPatients with symptomatic intracranial atherosclerosis (ICAS) of ≥ 70% luminal stenosis are at high risk of stroke recurrence. We aimed to evaluate the relationships between hemodynamics of ICAS revealed by computational fluid dynamics (CFD) models and risk of stroke recurrence in this patient subset.MethodsPatients with a symptomatic ICAS lesion of 70-99% luminal stenosis were screened and enrolled in this study. CFD models were reconstructed based on baseline computed tomographic angiography (CTA) source images, to reveal hemodynamics of the qualifying symptomatic ICAS lesions. Change of pressures across a lesion was represented by the ratio of post- and pre-stenotic pressures. Change of shear strain rates (SSR) across a lesion was represented by the ratio of SSRs at the stenotic throat and proximal normal vessel segment, similar for the change of flow velocities. Patients were followed up for 1 year.ResultsOverall, 32 patients (median age 65; 59.4% males) were recruited. The median pressure, SSR and velocity ratios for the ICAS lesions were 0.40 (-2.46-0.79), 4.5 (2.2-20.6), and 7.4 (5.2-12.5), respectively. SSR ratio (hazard ratio [HR] 1.027; 95% confidence interval [CI], 1.004-1.051; P = 0.023) and velocity ratio (HR 1.029; 95% CI, 1.002-1.056; P = 0.035) were significantly related to recurrent territorial ischemic stroke within 1 year by univariate Cox regression, respectively with the c-statistics of 0.776 (95% CI, 0.594-0.903; P = 0.014) and 0.776 (95% CI, 0.594-0.903; P = 0.002) in receiver operating characteristic analysis.ConclusionsHemodynamics of ICAS on CFD models reconstructed from routinely obtained CTA images may predict subsequent stroke recurrence in patients with a symptomatic ICAS lesion of 70-99% luminal stenosis

P003. NSAIDs for symptomatic treatment of headache

Background and aims Clinical observations suggest that the use of non-steroidal anti-inflammatory drugs (NSAIDs) for symptomatic treatment of headache is not in line with recommendations by international guidelines [1]. The aim of the study was to evaluate NSAIDs use for episodic headache at the Headache Centre of the Chieti University in the period: January 2000-February 2013