Electrocardiographic Changes Associated with Smoking and Smoking Cessation: Outcomes from a Randomized Controlled Trial

Introduction

Cardiovascular disease (CVD) can be detected and quantified by analysis of the electrocardiogram (ECG); however the effects of smoking and smoking cessation on the ECG have not been characterized.

Methods

Standard 12-lead ECGs were performed at baseline and 3 years after subjects enrolled in a prospective, randomized, placebo-controlled clinical trial of smoking cessation pharmacotherapies. ECGs were interpreted using the Minnesota Code ECG Classification. The effects of (i) smoking burden on the prevalence of ECG findings at baseline, and (ii) smoking and smoking cessation on ECG changes after 3 years were investigated by multivariable and multinomial regression analyses.

Results

At baseline, 532 smokers were (mean [SD]) 43.3 (11.5) years old, smoked 20.6 (7.9) cigarettes/day, with a smoking burden of 26.7 (18.6) pack-years. Major and minor ECG criteria were identified in 87 (16.4%) and 131 (24.6%) of subjects, respectively. After adjusting for demographic data and known CVD risk factors, higher pack-years was associated with major ECG abnormalities (p = 0.02), but current cigarettes/day (p = 0.23) was not. After 3 years, 42.9% of subjects were abstinent from smoking. New major and minor ECG criteria were observed in 7.2% and 15.6% of subjects respectively, but in similar numbers of abstinent subjects and continuing smokers (p>0.2 for both). Continuing smokers showed significant reduction in current smoking (–8.4 [8.8] cigarettes/day, p<0.001) compared to baseline.

Conclusions

In conclusion, major ECG abnormalities are independently associated with lifetime smoking burden. After 3 years, smoking cessation was not associated with a decrease in ECG abnormalities, although cigarettes smoked/day decreased among continuing smokers.     

Non-Invasive Drosophila ECG Recording by Using Eutectic Gallium-Indium Alloy Electrode: A Feasible Tool for Future Research on the Molecular Mechanisms Involved in Cardiac Arrhythmia

Background

Drosophila heart tube is a feasible model for cardiac physiological research. However, obtaining Drosophila electrocardiograms (ECGs) is difficult, due to the weak signals and limited contact area to apply electrodes. This paper presents a non-invasive Gallium-Indium (GaIn) based recording system for Drosophila ECG measurement, providing the heart rate and heartbeat features to be observed. This novel, high-signal-quality system prolongs the recording time of insect ECGs, and provides a feasible platform for research on the molecular mechanisms involved in cardiovascular diseases.

Methods

In this study, two types of electrode, tungsten needle probes and GaIn electrodes, were used respectively to noiselessly conduct invasive and noninvasive ECG recordings of Drosophila. To further analyze electrode properties, circuit models were established and simulated. By using electromagnetic shielded heart signal acquiring system, consisted of analog amplification and digital filtering, the ECG signals of three phenotypes that have different heart functions were recorded without dissection.

Results and Discussion

The ECG waveforms of different phenotypes of Drosophila recorded invasively and repeatedly with n value (n>5) performed obvious difference in heart rate. In long period ECG recordings, non-invasive method implemented by GaIn electrodes acts relatively stable in both amplitude and period. To analyze GaIn electrode, the correctness of GaIn electrode model established by this paper was validated, presenting accuracy, stability, and reliability.

Conclusions

Noninvasive ECG recording by GaIn electrodes was presented for recording Drosophila pupae ECG signals within a limited contact area and signal strength. Thus, the observation of ECG changes in normal and SERCA-depleted Drosophila over an extended period is feasible. This method prolongs insect survival time while conserving major ECG features, and provides a platform for electrophysiological signal research on the molecular mechanism involved in cardiac arrhythmia, as well as research related to drug screening and development.     

Right Bundle Branch Block: A Predictor of Mortality in Early Systemic Sclerosis

Objective

To evaluate the prognostic significance of baseline electrocardiogram (ECG) abnormalities in a multiethnic cohort of patients with early systemic sclerosis (SSc) and to determine the serological, clinical, and echocardiogram correlates of ECG findings.

Methods

SSc patients with disease duration of≤5 years were enrolled in the GENISOS (Genetics versus Environment in Scleroderma Outcome Study) cohort. At the first visit, a standard 12 lead ECG was obtained along with demographic information, clinical data, and autoantibodies. The results of echocardiograms were also recorded. All ECGs were interpreted by a cardiologist unaware of the patients'' clinical data.

Results

Of 265 SSc patients with average disease duration at enrollment of 2.5 years, 140 (52.8%) had abnormal ECG findings. These findings were not associated with SSc disease type or autoantibody profile but were associated with more severe heart and lung involvement. A total of 75 patients (28.3%) died over a follow up time of 9.9 years. Complete right bundle branch block (± left anterior hemiblock) on ECG, present in 7 (2.6%) patients, predicted a higher risk of mortality (HR: 5.3; 95% CI: 2.1 to 13.4; p<0.001). The predictive significance of right bundle branch block was independent of age at enrollment, gender, ethnicity and risk factors for coronary artery disease.

Conclusion

ECG abnormalities are common in patients with early SSc and are associated with the severity of lung and heart involvement. Right bundle branch block is an independent predictor of mortality, and should be considered a marker of disease severity in SSc.     

The Application of Root Mean Square Electrocardiography (RMS ECG) for the Detection of Acquired and Congenital Long QT Syndrome

Background

Precise measurement of the QT interval is often hampered by difficulty determining the end of the low amplitude T wave. Root mean square electrocardiography (RMS ECG) provides a novel alternative measure of ventricular repolarization. Experimental data have shown that the interval between the RMS ECG QRS and T wave peaks (RT_PK) closely reflects the mean ventricular action potential duration while the RMS T wave width (TW) tracks the dispersion of repolarization timing. Here, we tested the precision of RMS ECG to assess ventricular repolarization in humans in the setting of drug-induced and congenital Long QT Syndrome (LQTS).

Methods

RMS ECG signals were derived from high-resolution 24 hour Holter monitor recordings from 68 subjects after receiving placebo and moxifloxacin and from standard 12 lead ECGs obtained in 97 subjects with LQTS and 97 age- and sex-matched controls. RT_PK, QT_RMS and RMS TW intervals were automatically measured using custom software and compared to traditional QT measures using lead II.

Results

All measures of repolarization were prolonged during moxifloxacin administration and in LQTS subjects, but the variance of RMS intervals was significantly smaller than traditional lead II measurements. TW was prolonged during moxifloxacin and in subjects with LQT-2, but not LQT-1 or LQT-3.

Conclusion

These data validate the application of RMS ECG for the detection of drug-induced and congenital LQTS. RMS ECG measurements are more precise than the current standard of care lead II measurements.     

Evaluation of Differences in Automated QT/QTc Measurements between Fukuda Denshi and Nihon Koden Systems

Background

Automatic measurement becomes a preference, and indeed a necessity, when analyzing 1000 s of ECGs in the setting of either drug-inducing QT prolongation screening or genome-wide association studies of QT interval. The problem is that individual manufacturers apply different computerized algorithms to measure QT interval. We conducted a comparative study to assess the outcomes with different automated measurements of QT interval between ECG machine manufacturers and validated the related heart rate correction methods.

Methods and Results

Herein, we directly compared these different commercial systems using 10,529 Fukuda Denshi ECGs and 72,754 Nihon Kohden ECGs taken in healthy Japanese volunteers. Log-transformed data revealed an equal optimal heart rate correction formula of QT interval for Fukuda Denshi and Nihon Kohden, in the form of QTc = QT/RR^−0.347. However, with the raw data, the optimal heart rate correction formula of QT interval was in the form of QTc = QT+0.156×(1-RR) for Fukuda Denshi and QTc = QT+0.152×(1-RR) for Nihon Kohden. After optimization of heart rate correction of QT interval by the linear regression model using either log-transformed data or raw data, QTc interval was ∼10 ms longer in Nihon Kohden ECGs than in those recorded on Fukuda Denshi machines. Indeed, regression analysis revealed that differences in the ECG machine used had up to a two-fold larger impact on QT variation than gender difference. Such an impact is likely to be of considerable importance when ECGs for a given individual are recorded on different machines in the setting of multi-institutional joint research.

Conclusions

We recommend that ECG machines of the same manufacturer should be used to measure QT and RR intervals in the setting of multi-institutional joint research. It is desirable to unify the computer algorithm for automatic QT and RR measurements from an ECG.     

The Novel Deacetylase Inhibitor AR-42 Demonstrates Pre-Clinical Activity in B-Cell Malignancies In Vitro and In Vivo

Background

While deacetylase (DAC) inhibitors show promise for the treatment of B-cell malignancies, those introduced to date are weak inhibitors of class I and II DACs or potent inhibitors of class I DAC only, and have shown suboptimal activity or unacceptable toxicities. We therefore investigated the novel DAC inhibitor AR-42 to determine its efficacy in B-cell malignancies.

Principal Findings

In mantle cell lymphoma (JeKo-1), Burkitt''s lymphoma (Raji), and acute lymphoblastic leukemia (697) cell lines, the 48-hr IC₅₀ (50% growth inhibitory concentration) of AR-42 is 0.61 µM or less. In chronic lymphocytic leukemia (CLL) patient cells, the 48-hr LC₅₀ (concentration lethal to 50%) of AR-42 is 0.76 µM. AR-42 produces dose- and time-dependent acetylation both of histones and tubulin, and induces caspase-dependent apoptosis that is not reduced in the presence of stromal cells. AR-42 also sensitizes CLL cells to TNF-Related Apoptosis Inducing Ligand (TRAIL), potentially through reduction of c-FLIP. AR-42 significantly reduced leukocyte counts and/or prolonged survival in three separate mouse models of B-cell malignancy without evidence of toxicity.

Conclusions/Significance

Together, these data demonstrate that AR-42 has in vitro and in vivo efficacy at tolerable doses. These results strongly support upcoming phase I testing of AR-42 in B-cell malignancies.     

Early PTSD Symptom Trajectories: Persistence,Recovery, and Response to Treatment: Results from the Jerusalem Trauma Outreach and Prevention Study (J-TOPS)

Context

Uncovering heterogeneities in the progression of early PTSD symptoms can improve our understanding of the disorder''s pathogenesis and prophylaxis.

Objectives

To describe discrete symptom trajectories and examine their relevance for preventive interventions.

Design

Latent Growth Mixture Modeling (LGMM) of data from a randomized controlled study of early treatment. LGMM identifies latent longitudinal trajectories by exploring discrete mixture distributions underlying observable data.

Setting

Hadassah Hospital unselectively receives trauma survivors from Jerusalem and vicinity.

Participants

Adult survivors of potentially traumatic events consecutively admitted to the hospital''s emergency department (ED) were assessed ten days and one-, five-, nine- and fifteen months after ED admission. Participants with data at ten days and at least two additional assessments (n = 957) were included; 125 received cognitive behavioral therapy (CBT) between one and nine months.

Approach

We used LGMM to identify latent parameters of symptom progression and tested the effect of CBT on these parameters. CBT consisted of 12 weekly sessions of either cognitive therapy (n = 41) or prolonged exposure (PE, n = 49), starting 29.8±5.7 days after ED admission, or delayed PE (n = 35) starting at 151.8±42.4 days. CBT effectively reduced PTSD symptoms in the entire sample.

Main Outcome Measure

Latent trajectories of PTSD symptoms; effects of CBT on these trajectories.

Results

Three trajectories were identified: Rapid Remitting (rapid decrease in symptoms from 1- to 5-months; 56% of the sample), Slow Remitting (progressive decrease in symptoms over 15 months; 27%) and Non-Remitting (persistently elevated symptoms; 17%). CBT accelerated the recovery of the Slow Remitting class but did not affect the other classes.

Conclusions

The early course of PTSD symptoms is characterized by distinct and diverging response patterns that are centrally relevant to understanding the disorder and preventing its occurrence. Studies of the pathogenesis of PTSD may benefit from using clustered symptom trajectories as their dependent variables.     

Tomotherapy archive structure and new software tool for loading and advanced analysis of data contained in it

Aim

The main objective of the study was to analyze the structure of data contained in the archives exported from a tomotherapy treatment planning system. An additional aim was to create an application equipped with a user-friendly interface to enable automatic reading of files and data analysis, also using external algorithms. Analyses had to include image registration, dose deformation and summation.

Materials and methods

Files from the archive exported from the tomotherapy treatment planning system (TPS) were analyzed. Two programs were used to analyze the information contained in the archive files: XML Viewer by MindFusion Limited and HxD hex editor by Maël Hora. To create an application enabling loading and analyzing the data, Matlab by MathWorks, version R2009b, was used.

Results

Archive exported from the TPS is a directory with several files. It contains three types of data: .xml, .img and .sin. Tools available in Matlab offer great opportunities for analysis and transformation of loaded information. Proposed application automates the loading of necessary information and simplifies data handling. Furthermore, the application is equipped with a graphical user interface (GUI). The main application window contains buttons for opening the archives and analyzing the loaded data.

Conclusion

The analysis of data contained in the archive exported from the tomotherapy treatment planning system allowed to determine the way and place of saving information of our interest, such as tomography images, structure sets and dose distributions. This enabled us to develop and optimize methods of loading and analyzing this information.     

Automatic identification and characterization of radial files in light microscopy images of wood

Background and Aims

Analysis of anatomical sections of wood provides important information for understanding the secondary growth and development of plants. This study reports on a new method for the automatic detection and characterization of cell files in wood images obtained by light microscopy. To facilitate interpretation of the results, reliability coefficients have been determined, which characterize the files, their cells and their respective measurements.

Methods

Histological sections and blocks of the gymnosperms Pinus canariensis, P. nigra and Abies alba were used, together with histological sections of the angiosperm mahogany (Swietenia spp.). Samples were scanned microscopically and mosaic images were built up. After initial processing to reduce noise and enhance contrast, cells were identified using a ‘watershed’ algorithm and then cell files were built up by the successive aggregation of cells taken from progressively enlarged neighbouring regions. Cell characteristics such as thickness and size were calculated, and a method was developed to determine the reliability of the measurements relative to manual methods.

Key Results

Image analysis using this method can be performed in less than 20 s, which compares with a time of approx. 40 min to produce the same results manually. The results are accompanied by a reliability indicator that can highlight specific configurations of cells and also potentially erroneous data.

Conclusions

The method provides a fast, economical and reliable tool for the identification of cell files. The reliability indicator characterizing the files permits quick filtering of data for statistical analysis while also highlighting particular biological configurations present in the wood sections.     

An Automated System for Rapid Non-Destructive Enumeration of Growing Microbes

Background

The power and simplicity of visual colony counting have made it the mainstay of microbiological analysis for more than 130 years. A disadvantage of the method is the long time required to generate visible colonies from cells in a sample. New rapid testing technologies generally have failed to maintain one or more of the major advantages of culture-based methods.

Principal Findings

We present a new technology and platform that uses digital imaging of cellular autofluorescence to detect and enumerate growing microcolonies many generations before they become visible to the eye. The data presented demonstrate that the method preserves the viability of the microcolonies it detects, thus enabling generation of pure cultures for microbial identification. While visual colony counting detects Escherichia coli colonies containing about 5×10⁶ cells, the new imaging method detects E. coli microcolonies when they contain about 120 cells and microcolonies of the yeast Candida albicans when they contain only about 12 cells. We demonstrate that digital imaging of microcolony autofluorescence detects a broad spectrum of prokaryotic and eukaryotic microbes and present a model for predicting the time to detection for individual strains. Results from the analysis of environmental samples from pharmaceutical manufacturing plants containing a mixture of unidentified microbes demonstrate the method''s improved test turnaround times.

Conclusion

This work demonstrates a new technology and automated platform that substantially shortens test times while maintaining key advantages of the current methods.     

The accuracy of the electrocardiogram during exercise stress test based on heart size

Background

Multiple studies have shown that the exercise electrocardiogram (ECG) is less accurate for predicting ischemia, especially in women, and there is additional evidence to suggest that heart size may affect its diagnostic accuracy.

Hypothesis

The purpose of this investigation was to assess the diagnostic accuracy of the exercise ECG based on heart size.

Methods

We evaluated 1,011 consecutive patients who were referred for an exercise nuclear stress test. Patients were divided into two groups: small heart size defined as left ventricular end diastolic volume (LVEDV) <65 mL (Group A) and normal heart size defined as LVEDV ≥65 mL (Group B) and associations between ECG outcome (false positive vs. no false positive) and heart size (small vs. normal) were analyzed using the Chi square test for independence, with a Yates continuity correction. LVEDV calculations were performed via a computer-processing algorithm. SPECT myocardial perfusion imaging was used as the gold standard for the presence of coronary artery disease (CAD).

Results

Small heart size was found in 142 patients, 123 female and 19 male patients. There was a significant association between ECG outcome and heart size (χ² = 4.7, p = 0.03), where smaller hearts were associated with a significantly greater number of false positives.

Conclusions

This study suggests a possible explanation for the poor diagnostic accuracy of exercise stress testing, especially in women, as the overwhelming majority of patients with small heart size were women.     

Open label study of escalating doses of oral treprostinil diethanolamine in patients with systemic sclerosis and digital ischemia: pharmacokinetics and correlation with digital perfusion

Introduction

Treprostinil diethanolamine is an innovative salt form of the prostacyclin analogue, treprostinil sodium, developed as an oral sustained release (SR) osmotic tablet. The availability of a formulation permitting convenient systemic delivery might have applicability to scleroderma vascular complications. We evaluated pharmacokinetics and perfusion in scleroderma patients with digital ischemia following escalating twice-daily doses of treprostinil diethanolamine SR.

Methods

Scleroderma patients with digital ulcers were enrolled in this dual-center, open-label, phase I pharmacokinetic study. Drug concentrations and perfusion, quantified by laser Doppler imaging, were measured over 12 hours at the 2 mg and 4 mg (or maximally tolerated) doses. Pharmacokinetic parameters were determined from individual plasma concentration versus time profiles using non-compartmental analysis methods. Digital perfusion and skin temperature were modeled as a function of log-transformed drug concentration and other covariates by performing repeated measures analyses using random effects models.

Results

Nineteen scleroderma patients (84% female, 53% limited scleroderma) received treprostinil diethanolamine SR with dose titration up to 4 mg twice daily as tolerated. Peak concentrations (mean maximum plasma concentration (C_max) = 1,176 and 2,107 pg/mL) occurred approximately 3.6 hours after dose administration, and overall exposure (under the plasma concentration-time curve from time 0 to 12 hours post dose (AUC_0-12) = 7,187 and 12,992 hr*pg/mL) was linear between the 2 mg and 4 mg doses. Perfusion and digital skin temperature were positively associated with log-transformed plasma concentration at the 4 mg dose (P = 0.015 and P = 0.013, respectively). The most frequent adverse events were similar to those seen with prostacyclin analogues.

Conclusions

Oral treprostinil diethanolamine was effectively absorbed in patients with scleroderma. Drug administration was temporally associated with improved cutaneous perfusion and temperature. Treprostinil diethanolamine may provide a new therapeutic option for Raynaud''s phenomenon and the peripheral vascular disease of scleroderma.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00848939","term_id":"NCT00848939"}}NCT00848939.

Electronic supplementary material

The online version of this article (doi:10.1186/ar4216) contains supplementary material, which is available to authorized users.     

Diagnostic dilemma of cardiac syncope in pediatric patients

Aims

Syncope is defined as temporary loss of consciousness and postural tone resulting from an abrupt transient decrease in cerebral blood flow. The present work aimed at determining how diagnostic tests are used in the evaluation of pediatric syncope at a tertiary pediatric referral center and to report on the utility and the yield of these tests.

Settings and Design

Retrospective study conducted at a tertiary referral arrhythmolology service

Methods and Material

The clinical charts of 234 pediatric patients presenting with a primary complaint of syncope with an average age of 7.48 ± 3.82(3.5-16) years were reviewed by the investigators.

Statistical analysis used

Statistical Package of social science (SPSS) version 9,0 was used for analysis of data.

Results

The commonest trigger for syncope in the study population was early following exercise (n=65) and the commonest prodrome was palpitation, noted in 25 patients. A murmur was present in 19 of our patients (8.3%) while 10.7% (n=25) had abnormal ECGs. Of the 106 echocardiograms done, 14 (13.2%) were abnormal. Only two of them were missed by ECG. All patients were offered ambulatory 24 hour ECG. One patient with sick sinus syndrome was diagnosed only with Holter.

Conclusions

Clues to the presence of cardiac syncope may include acute onset of syncope, frequent episodes, low difference between blood pressure readings in supine and erect positions (after standing for 2 minutes) and most importantly an abnormal 12 lead ECG. Transthoracic echo and Holter monitoring have low yield in pediatric syncope.     

Comparative,double-blind,controlled study of intra-articular hyaluronic acid (Hyalubrix?) injections versus local anesthetic in osteoarthritis of the hip

Introduction

Comparison of intra-articular bacterial-derived hyaluronic acid (Hyalubrix^®) (HA) with local analgesia (mepivacaine) for osteoarthritis (OA) of the hip.

Methods

A pilot prospective, double-blind, 6-month randomized trial of 42 patients with hip OA. HA or mepivacaine was administered twice (once a month) under ultrasound guidance. Efficacy measurements included the Lequesne''s algofunctional index, a visual analog scale for pain, concomitant use of analgesia, patient and physician global measurement, and safety.

Results

Patients in the HA group exhibited a significantly reduced Lequesne''s algofunctional index 3 and 6 months after treatment (P < 0.001) and significantly reduced visual analog scale pain scores 3 and 6 months after treatment (P < 0.05) compared with the local anesthetic group. All primary and secondary measures were significantly improved versus baseline, but other than the above were not different from each other at 3 or 6 months. Adverse effects were minimal.

Conclusions

This comparative study suggests a beneficial effect and safety of intra-articular HA in the management of hip OA.

Trial registration number

ISRCTN39397064.     

Increased short-term variability of the QT interval in professional soccer players: possible implications for arrhythmia prediction

Background

Sudden cardiac death in competitive athletes is rare but it is significantly more frequent than in the normal population. The exact cause is seldom established and is mostly attributed to ventricular fibrillation. Myocardial hypertrophy and slow heart rate, both characteristic changes in top athletes in response to physical conditioning, could be associated with increased propensity for ventricular arrhythmias. We investigated conventional ECG parameters and temporal short-term beat-to-beat variability of repolarization (STV_QT), a presumptive novel parameter for arrhythmia prediction, in professional soccer players.

Methods

Five-minute 12-lead electrocardiograms were recorded from professional soccer players (n = 76, all males, age 22.0±0.61 years) and age-matched healthy volunteers who do not participate in competitive sports (n = 76, all males, age 22.0±0.54 years). The ECGs were digitized and evaluated off-line. The temporal instability of beat-to-beat heart rate and repolarization were characterized by the calculation of short-term variability of the RR and QT intervals.

Results

Heart rate was significantly lower in professional soccer players at rest (61±1.2 vs. 72±1.5/min in controls). The QT interval was prolonged in players at rest (419±3.1 vs. 390±3.6 in controls, p<0.001). QTc was significantly longer in players compared to controls calculated with Fridericia and Hodges correction formulas. Importantly, STV_QT was significantly higher in players both at rest and immediately after the game compared to controls (4.8±0.14 and 4.3±0.14 vs. 3.5±0.10 ms, both p<0.001, respectively).

Conclusions

STV_QT is significantly higher in professional soccer players compared to age-matched controls, however, further studies are needed to relate this finding to increased arrhythmia propensity in this population.     

Cardiac Alterations in Human African Trypanosomiasis (T.b. gambiense) with Respect to the Disease Stage and Antiparasitic Treatment

Background

In Human African Trypanosomiasis, neurological symptoms dominate and cardiac involvement has been suggested. Because of increasing resistance to the available drugs for HAT, new compounds are desperately needed. Evaluation of cardiotoxicity is one parameter of drug safety, but without knowledge of the baseline heart involvement in HAT, cardiologic findings and drug-induced alterations will be difficult to interpret. The aims of the study were to assess the frequency and characteristics of electrocardiographic findings in the first stage of HAT, to compare these findings to those of second stage patients and healthy controls and to assess any potential effects of different therapeutic antiparasitic compounds with respect to ECG changes after treatment.

Methods

Four hundred and six patients with first stage HAT were recruited in the Democratic Republic of Congo, Angola and Sudan between 2002 and 2007 in a series of clinical trials comparing the efficacy and safety of the experimental treatment DB289 to the standard first stage treatment, pentamidine. These ECGs were compared to the ECGs of healthy volunteers (n = 61) and to those of second stage HAT patients (n = 56).

Results

In first and second stage HAT, a prolonged QTc interval, repolarization changes and low voltage were significantly more frequent than in healthy controls. Treatment in first stage was associated with repolarization changes in both the DB289 and the pentamidine group to a similar extent. The QTc interval did not change during treatment.

Conclusions

Cardiac involvement in HAT, as demonstrated by ECG alterations, appears early in the evolution of the disease. The prolongation of the QTC interval comprises a risk of fatal arrhythmias if new drugs with an additional potential of QTC prolongation will be used. During treatment ECG abnormalities such as repolarization changes consistent with peri-myocarditis occur frequently and appear to be associated with the disease stage, but not with a specific drug.     

Proteomic analysis of the cyst stage of Entamoeba histolytica

Background

The category B agent of bioterrorism, Entamoeba histolytica has a two-stage life cycle: an infective cyst stage, and an invasive trophozoite stage. Due to our inability to effectively induce encystation in vitro, our knowledge about the cyst form remains limited. This also hampers our ability to develop cyst-specific diagnostic tools.

Aims

Three main aims were (i) to identify E. histolytica proteins in cyst samples, (ii) to enrich our knowledge about the cyst stage, and (iii) to identify candidate proteins to develop cyst-specific diagnostic tools.

Methods

Cysts were purified from the stool of infected individuals using Percoll (gradient) purification. A highly sensitive LC-MS/MS mass spectrometer (Orbitrap) was used to identify cyst proteins.

Results

A total of 417 non-redundant E. histolytica proteins were identified including 195 proteins that were never detected in trophozoite-derived proteomes or expressed sequence tag (EST) datasets, consistent with cyst specificity. Cyst-wall specific glycoproteins Jacob, Jessie and chitinase were positively identified. Antibodies produced against Jacob identified cysts in fecal specimens and have potential utility as a diagnostic reagent. Several protein kinases, small GTPase signaling molecules, DNA repair proteins, epigenetic regulators, and surface associated proteins were also identified. Proteins we identified are likely to be among the most abundant in excreted cysts, and therefore show promise as diagnostic targets.

Major Conclusions

The proteome data generated here are a first for naturally-occurring E. histolytica cysts, and they provide important insights into the infectious cyst form. Additionally, numerous unique candidate proteins were identified which will aid the development of new diagnostic tools for identification of E. histolytica cysts.     

Modelling seagrass growth and development to evaluate transplanting strategies for restoration

Background and Aims

Seagrasses are important marine plants that are under threat globally. Restoration by transplanting vegetative fragments or seedlings into areas where seagrasses have been lost is possible, but long-term trial data are limited. The goal of this study is to use available short-term data to predict long-term outcomes of transplanting seagrass.

Methods

A functional–structural plant model of seagrass growth that integrates data collected from short-term trials and experiments is presented. The model was parameterized for the species Posidonia australis, a limited validation of the model against independent data and a sensitivity analysis were conducted and the model was used to conduct a preliminary evaluation of different transplanting strategies.

Key Results

The limited validation was successful, and reasonable long-term outcomes could be predicted, based only on short-term data.

Conclusions

This approach for modelling seagrass growth and development enables long-term predictions of the outcomes to be made from different strategies for transplanting seagrass, even when empirical long-term data are difficult or impossible to collect. More validation is required to improve confidence in the model''s predictions, and inclusion of more mechanism will extend the model''s usefulness. Marine restoration represents a novel application of functional–structural plant modelling.     

Oral Doxycycline Reduces Pterygium Lesions; Results from a Double Blind,Randomized, Placebo Controlled Clinical Trial

Purpose

To determine whether oral doxycycline treatment reduces pterygium lesions.

Design

Double blind, randomized, placebo controlled clinical trial.

Participants

98 adult patients with primary pterygium.

Methods

Patients were randomly assigned to receive 100 mg oral doxycycline twice a day (49 subjects), or placebo (49 subjects), for 30 days. Photographs of the lesion were taken at the time of recruitment and at the end of the treatment. Follow-up sessions were performed 6 and 12 months post-treatment. Statistical analyses for both continuous and categorical variables were applied. p values of less than 0.05 were considered to indicate statistical significance.

Main Outcome Measures

The primary endpoint was the change in lesion size after 30 days of treatment.

Results

The primary endpoint was not met for the whole population but subgroup analysis showed that doxycycline was effective in patients of Caucasian origin while other ethnicities, mostly Hispanic, did not respond to the treatment. Moreover, there was a correlation between age and better response (p = 0.003). Adverse events were uncommon, mild, and in agreement with previous reports on short doxycycline treatments.

Conclusions

Oral doxycycline was superior to placebo for the treatment of primary pterygia in older Caucasian patients. These findings support the use of doxycycline for pterygium treatment in particular populations.

Trial Registration

European Union Clinical Trials Register EudraCT 2008-007178-39