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Biomedical subjects

J Snoeck

Publications and source records attributed to J Snoeck.

At least 19 recordsLinked to original sources

Bayesian network analysis of resistance pathways against HIV-1 protease inhibitors.

Interpretation of Human Immunodeficiency Virus 1 (HIV-1) genotypic drug resistance is still a major challenge in the follow-up of antiviral therapy in infected patients. Because of the high degree of HIV-1 natural variation, complex interactions and stochastic behaviour of evolution, the role of resistance mutations is in many cases not well understood. Using Bayesian network learning of HIV-1 sequence data from diverse subtypes (A, B, C, F and G), we could determine the specific role of many resistance mutations against the protease inhibitors (PIs) nelfinavir (NFV), indinavir (IDV), and saquinavir (SQV). Such networks visualize relationships between treatment, selection of resistance mutations and presence of polymorphisms in a graphical way. The analysis identified 30N, 88S, and 90M for nelfinavir, 90M for saquinavir, and 82A/T and 46I/L for indinavir as most probable major resistance mutations. Moreover we found striking similarities for the role of many mutations against all of these drugs. For example, for all three inhibitors, we found that the novel mutation 89I was minor and associated with mutations at positions 90 and 71. Bayesian network learning provides an autonomous method to gain insight in the role of resistance mutations and the influence of HIV-1 natural variation. We successfully applied the method to three protease inhibitors. The analysis shows differences with current knowledge especially concerning resistance development in several non-B subtypes.

Bayes Theorem↗

Optimization of a genotypic assay applicable to all human immunodeficiency virus type 1 protease and reverse transcriptase subtypes.

Genotypic assays are used often to guide clinicians in decisions concerning the treatment of patients. An optimized sequence-based genotypic assay was used to determine the whole protease and reverse transcriptase (RT) gene, including the gag cleavage site region and RNase H region. Since non-B subtypes are increasing in countries where subtype B was the most prevalent subtype, and treatment becomes more available in developing countries where the epidemic is characterized by a high prevalence of non-B subtypes, it was important that the genotypic test was evaluated using a panel of different subtypes. Amplification was successful for different subtypes: A, B, C, D, F, G, H, J, CRF01_AE, CRF02_AG, CRF11_cpx, CRF13_cpx and an uncharacterized recombinant sample. The detection limit of the PCR was 1000 copies/ml, except for 1 subtype C sample (PL3) and 1 CRF02_AG sample (PL8). The detection limit for these samples was 5000 copies/ml. A sequence could be obtained in both directions for most of the samples.

DNA Primers↗

Evaluation of two commercial kits for the detection of genotypic drug resistance on a panel of HIV type 1 subtypes A through J.

We compared the two commercially available sequencing kits for HIV-1 drug resistance testing, the ViroSeq Genotyping System (Applied Biosystems, Foster City, CA, U.S.A.) and the TRUGENE HIV-1 Genotyping Kit (Visible Genetics, Inc., Toronto, Ontario, Canada), with our in-house genotyping system. Fifteen viral isolates from African patients (6 treated and 9 untreated) covering a panel of HIV-1 subtypes A through J and 7 plasma samples from Belgian and African patients (2 treated and 5 untreated) were tested. All the samples could be amplified and sequenced by the three systems; however, for all systems, alternative amplification/sequencing primers had to be used for some samples belonging to subtype B as well as to other subtypes. The consensus sequence was partially derived from only one strand for the in-house system and for the ViroSeq Genotyping System. The TRUGENE HIV-1 Genotyping Kit scored the highest number of ambiguities, followed by the ViroSeq Genotyping System and the in-house system. For 11 samples, these differences in reporting mixtures affected 14 resistance-related positions, which altered the interpretation toward protease inhibitors for 2 samples when using version 1.2 RetroGram software (Virology Networks, Utrecht, The Netherlands). All three systems were able to sequence diluted samples with a viral load down to 10 3 or 10 4 RNA copies/ml. Our data therefore suggest that the performance of amplification and sequencing primers must be improved to allow fast and reliable resistance testing for all HIV-1 subtypes.

Drug Industry↗

An outbreak of Burkholderia cepacia with septicemia on a cardiology ward.

During a 3-day period, eight patients developed septicemia with Burkholderia cepacia. Heparin injection was found to be a risk factor. Heparin was diluted with dextrose solution, which was aspirated from a 1-L bag. B cepacia, genotypically identical to the blood isolates, was isolated from this bag.

Bacteremia↗

Nosocomial septicaemias in a cardiologic ward. A case-control study.

Nosocomial septicaemias were studied in a cardiologic ward at the University Hospital of Antwerp, Belgium. The incidence of nosocomial infections was found to be 2.7 per 1,000 admissions per year. A case-control study suggested that in contrast with coronarography and pacemaker implantation, percutaneous transluminal coronary angioplasty may be a risk factor for nosocomial septicaemia (OR 4.5, 95% confidence interval 0.7-33.4).

Aged↗

High atrial pacing impedance: efficient or wasteful? A comparison of an active and a passive fixation lead.

We compared the stimulation characteristics of two atrial fixation leads: the CPI model 4269 (n = 45) and Cordis-Telectronics model 327-752 (n = 42). The CPI lead uses an active fixation method, whereas the Cordis-Telectronics lead is fixated passively. Impedance and threshold were measured at implant and during 12 months of follow-up. P wave sensing was good with both types of leads. Follow-up of these 87 leads showed that both the impedance and threshold increased with the active leads, but not with the passive fixation leads. In the active fixation group, regardless of the high atrial pacing impedance, 93% could still be programmed to 2.5 V-0.6 msec (with a 2:1 threshold safety margin). It is concluded that the high chronic pacing impedance of the active fixation leads will be beneficial on current drain if no major increase in pacing threshold occurs simultaneously.

Cardiac Pacing, Artificial↗

Apical hypertrophic cardiomyopathy.

Illustrated by a case report, which was rather suggestive of coronary ischemic heart disease, the principle characteristics of apical hypertrophic cardiomyopathy are outlined. Outside East Asia, it remains a very uncommon variant of hypertrophic cardiomyopathy. The electrocardiogram in basal conditions showed giant negative T-waves (-14 mm) in the precordial leads, while the ventriculogram in RAO projection revealed the typical, so called "ace of spades" configuration. Based on the present literature and the follow-up of these patients a review of apical hypertrophic cardiomyopathy is presented. One of the most important consequences of the identification of this variant seems to be the rather good prognosis when compared to other forms of hypertrophic cardiomyopathy.

Biopsy↗

Capnocytophaga canimorsus endocarditis.

We report a case of aortic valve endocarditis, caused by Capnocytophaga canimorsus (previously known as CDC Group DF-2) secondary to a dog bite. Vegetations were documented by cross-sectional echocardiography and bacteraemia by positive haemocultures for this unusual gram-negative bacillus.

Animals↗

External vibration interference of activity based rate responsive pacemakers.

The change of the pacing rate in response to external vibration interference was assessed in four rate responsive pacemakers with a piezoelectric crystal (Medtronic Activitrax 8403, Siemens Sensolog 3, Biotronik Ergos 01, and Medtronic Legend 8417) and one with an accelerometer (CPI Excel VR 1119). They were tested in the laboratory. External vibration was simulated in vitro by exposing the different pacemakers to a controlled sinusoidal vibration force generated by a Millar pressure vibration amplifier type MGM-30 (Millar Instruments, Inc., Houston, TX, USA). All pacemakers were programmed at standard settings. Two types of vibration forces were applied: (1) one with varying amplitude but with constant vibration frequency; and (2) one with varying frequency but with constant vibration amplitude. In this manner curves of pacing rate versus vibration forces versus vibration frequency were obtained. High vibration forces and low vibration frequencies were associated with the highest pacing rate response. In this experimental setting, the pacemaker based on the accelerometer principle apparently was the least sensitive to high frequency vibrations, which are known to be related to environmental interference. It also seemed more appropriately responsive in the lower frequency range, which is more appropriate for the detection of true physiological activity.

Acceleration↗

Predictive value of the P wave at implantation for atrial fibrillation after VVI pacemaker implantation.

This study assesses the value of P wave measurements on the surface ECG at implantation, in the prediction of atrial fibrillation in VVI paced patients. From a consecutive series of 320 pacemaker implantations 172 VVI paced patients for symptomatic atrioventricular block (AVB) (n = 126; mean age 69 +/- 14) or sick sinus syndrome (SSS) (n = 56; mean age 68.6 +/- 12) and in sinus rhythm at implantation were used in this study. P wave duration in V1 is correlated with the incidence of atrial fibrillation during 5 years of follow-up. V1 at implantation was significantly longer (114.6 +/- 2.7 msec) in the patients who developed atrial fibrillation than in those who did not (91.9 +/- 2.7 msec) (P < 0.001). Although positive predictive accuracy increases progressively for higher V1 values for AVB and SSS, the negative predictive and diagnostic accuracy of V1 criteria were less in SSS. Application of the Bayes' theorem showed that in SSS the probability to develop atrial fibrillation is 33% for V1 < 110 msec and is for V1 < 90 msec still higher than that reported in DDD paced patients. In the AVB group the probability to develop atrial fibrillation is 8% for V1 < 110 msec and 6% for V1 < 100 msec. It seems, therefore, that atrial stimulation (AAI or DDD) is always indicated in SSS. In AVB with V1 < 100 msec, DDD pacing, if not needed for other indications, apparently does not offer much benefit in the prophylaxis of atrial fibrillation.

Aged↗

[P wave changes and atrial fibrillation after implantation of VVI type pacemaker].

The P waves of patients with VVI pacemakers were compared with those of DDD pacemakers at implantation and then regularly for 5 years. A certain number of cardiac pathologies are known to cause P wave changes. The incidence of atrial fibrillation (AF) was much higher in VVI than in DDD patients. In the VVI group, the incidence was much greater in patients paced for sinus node disease than in patients paced for AVB. Analysis of sinus P wave characteristics in 320 patients with VVI pacemakers shows progressive abnormalities of atrial function with time. The expression of this atrial dysfunction is a statistically significant prolongation of the P wave in V1 and dII and of the terminal part of the P wave in V1. The factors responsible for this abnormality and which favours the occurrence of AF are quasi-permanent pacing, the presence of retrograde conduction and an abnormality of atrial activation at the time of implantation.

Aged↗

Evolution of P wave characteristics after pacemaker implantation.

This study is an investigation of the long-term effects of VVI pacing on the atrium as derived from the evolution of P wave characteristics of 285 patients. The occurrence of left and right atrial disease is demonstrated as well as the evolution of left atrial hypertrophy in some cases. A comparison is made with DDD pacing and special attention is given to the progression to atrial fibrillation.

Aged↗

Simultaneous bipolar pacing and sensing during EPs.

Bipolar pacing and sensing-recording on the same electrode is a problem during pacemaker implantation as well as during electrophysiological studies. A method is described that makes this possible. By using bipolar simultaneous sensing-pacing on the same electrode, the system can record local repolarization after a depolarization controlled by stimulation. The bipolar-paced evoked potential is useful as an indicator to drive a bipolar QT rate responsive pacemaker. Even more, during EPS it can be used to detect capture during tachycardia stimulation and to measure the exact refractory period.

Carbon↗

Diagnostic value of R wave amplitude changes during exercise testing after myocardial infarction.

To determine the diagnostic value of R wave amplitude changes occurring during exercise testing after myocardial infarction, exercise ECG's and coronary angiograms were reviewed in 76 postinfarction patients and in 40 patients with normal coronary arteries. During exercise, an increase in R wave amplitude (mean: + 2.7 +/- 1.3 mm) was observed in the postinfarction patients, significantly different (P less than 0.001) from the decrease (mean: - 2.6 +/- 1.1 mm) observed in the group with normal coronary arteries. Although this change increased with the number of diseased coronary arteries, the difference between 1-vessel and multi- or 3-vessel disease was not significant. Extension of infarct size from one to more akinetic segments on the left ventricular angiogram was associated with a significant (P less than 0.001) increase of the R wave amplitude change during exercise (mean: + 1.6 +/- 1.1 vs 3.3 +/- 1.3 mm). It is concluded that the abnormal increase in R wave amplitude observed during exercise testing after myocardial infarction is more strongly related to infarct size then to the number of diseased coronary arteries. Furthermore exercise induced R wave amplitude changes have no diagnostic value in the prediction of multi- or 3-vessel disease in postinfarction patients.

Angiocardiography↗

Prosthetic valve endocarditis due to methicillin-resistant Staphylococcus epidermidis and Micrococcus species successfully treated with rifampicin combined with other antibiotics.

Two patients with prosthetic valve endocarditis due to methicillin-resistant Gram-positive cocci (Staphylococcus epidermidis and Micrococcus spp.) are described. They were successfully treated with rifampicin combined first with an aminoglycoside and later with co-trimoxazole or co-trimoxazole plus vancomycin. The addition of rifampicin to these antibiotics resulted in enhanced serum bactericidal activity. High doses of rifampicin (1200-1800 mg) for 7-8 weeks did not cause any serious side-effect. Surgery was not required. During surveillance for more than 2 years endocarditis did not recur.

Adult↗