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Biomedical subjects

B Peters

Publications and source records attributed to B Peters.

At least 19 recordsLinked to original sources

Self-fabricated fenestrated Amplatzer occluders for transcatheter closure of atrial septal defect in patients with left ventricular restriction: midterm results.

To avoid left ventricular failure after transcatheter closure of atrial septal defects in elderly patients with restrictive left ventricular physiology, partial occlusion by fenestrated devices may be an option. If complete defect closure is not possible in these patients, significant reduction of left to right shunting usually results in clinical benefit. We report two patients in whom deterioration of left ventricular function could be avoided by implantation of self-fabricated fenestrated Amplatzer Septal Occluders (ASO) in patients with ongoing restrictive left ventricular physiology. We describe technical preparation of the standard occluder, the specific implantation technique, and the initial and the intermediate term results up to 24 months.

Aged↗

Close localization of DAP-kinase positive tumour-associated macrophages and apoptotic colorectal cancer cells.

The death-associated protein kinase (DAP-kinase) is a cytoskeleton-associated protein crucially involved in the induction of early apoptotic pathways. Aberrant hypermethylation of the DAP-kinase promoter plays a major role in tumorigenesis. We aimed to investigate the inactivation of DAP-kinase and its association with apoptotic cell death in 94 colorectal carcinomas. DAP-kinase promoter hypermethylation and mRNA expression were investigated using methylation-specific PCR and real-time RT-PCR, respectively. The expression of DAP-kinase, Fas, and Fas-ligand (FasL) proteins was studied by immunohistochemistry and immunofluorescence. Apoptosis of tumour cells was investigated using the TUNEL assay. DAP-kinase was expressed in tumour cells and tumour-invading macrophages and was closely associated with high numbers of apoptotic tumour cells. DAP-kinase expression co-localized with FasL overexpression in tumour-associated macrophages, and aberrant promoter hypermethylation was verified in more than 50% of carcinomas. There was a tendency for proximal tumours to show DAP-kinase promoter methylation more frequently (p = 0.07). Promoter methylation resulted in a decrease or loss of DAP-kinase protein expression in tumour cells and tumour-associated macrophages. Simultaneously, a decreased apoptotic count and loss of Fas/FasL expression was observed in tumour cells. Our study is the first to demonstrate DAP-kinase expression in invading tumour-associated macrophages in colorectal cancer. The presence of similar expression levels of DAP-kinase in tumour cells and associated macrophages, and their dependence on the promoter methylation status of the tumour cells, suggests cross talk between these cell types during apoptotic cell death.

Aged↗

A computational resource for the prediction of peptide binding to Indian rhesus macaque MHC class I molecules.

Non-human primates, in general, and Indian rhesus macaques, specifically, play an important role in the development and testing of vaccines and diagnostics destined for human use. To date, several frequently expressed macaque MHC molecules have been identified and their binding specificities characterized in detail. Here, we report the development of computational algorithms to predict peptide binding and potential T cell epitopes for the common MHC class I alleles Mamu-A*01, -A*02, -A*11, -B*01 and -B*17, which cover approximately two thirds of the captive Indian rhesus macaque populations. We validated this method utilizing an SIV derived data set encompassing 59 antigenic peptides. Of all peptides contained in the SIV proteome, the 2.4% scoring highest in the prediction contained 80% of the antigenic peptides. The method was implemented in a freely accessible and user friendly website at . Thus, we anticipate that our approach can be utilized to rapidly and efficiently identify CD8+ T cell epitopes recognized by rhesus macaques and derived from any pathogen of interest.

Algorithms↗

Left ventricular conditioning in the elderly patient to prevent congestive heart failure after transcatheter closure of atrial septal defect.

Transcatheter closure of atrial septal defects (ASDs) is a safe and effective treatment. Over the past years, an increasing number of elderly patients (age > 60 years) have been admitted for transcatheter closure to prevent ongoing congestive heart failure from volume overload. However, recent data point to the risk of serious acute left ventricular dysfunction leading to pulmonary edema immediately after surgical or transcatheter ASD closure in some patients. In this study, we used a technique described before to recognize in advance patients at risk of left heart failure after ASD closure. Those patients at risk were then treated with preventive conditioning medication for 48-72 hr before definitive transcatheter ASD closure was performed. Fifty-nine patients aged over 60 years (range, 60-81.8 years; median, 68 years) were admitted to our institution for transcatheter closure of an atrial septal defect. All patients received evaluation of atrial pressures before and during temporary balloon occlusion of the ASD. Patients with left ventricular restriction due to increased mean atrial pressures (> 10 mm Hg) during ASD occlusion received anticongestive conditioning medication with i.v. dopamine, milrinone, and furosemide for 48-72 hr before definitive ASD closure with an Amplatzer septal occluder was performed. In 44 patients without any signs of left ventricular restriction, ASD closure was performed within the first session. Fifteen (25%) out of 59 patients showed left ventricular restriction. In the majority of patients with LV restriction, the mean left atrial pressures with occluded ASD were significantly decreased after 48-72 hr of conditioning medication. Definitive ASD closure was then performed in a second session. Only two patients received a fenestrated 32 mm Amplatzer occluder due to persistent increased atrial pressures > 10 mm Hg even after conditioning medication. There were no significant differences in shunt, device size, or defect size between the two groups. Balloon occlusion of atrial septal defects identifies patients with left ventricular restrictive physiology before ASD closure. Intravenous anticongestive conditioning medication seems to be highly effective in preventing congestive heart failure after interventional closure of an ASD in the elderly patient with a restrictive left ventricle.

Aged↗

Modeling the MHC class I pathway by combining predictions of proteasomal cleavage, TAP transport and MHC class I binding.

Epitopes presented by major histocompatibility complex (MHC) class I molecules are selected by a multi-step process. Here we present the first computational prediction of this process based on in vitro experiments characterizing proteasomal cleavage, transport by the transporter associated with antigen processing (TAP) and MHC class I binding. Our novel prediction method for proteasomal cleavages outperforms existing methods when tested on in vitro cleavage data. The analysis of our predictions for a new dataset consisting of 390 endogenously processed MHC class I ligands from cells with known proteasome composition shows that the immunological advantage of switching from constitutive to immunoproteasomes is mainly to suppress the creation of peptides in the cytosol that TAP cannot transport. Furthermore, we show that proteasomes are unlikely to generate MHC class I ligands with a C-terminal lysine residue, suggesting processing of these ligands by a different protease that may be tripeptidyl-peptidase II (TPPII).

ATP-Binding Cassette Transporters↗

The CP stent--short, long, covered--for the treatment of aortic coarctation, stenosis of pulmonary arteries and caval veins, and Fontan anastomosis in children and adults: an evaluation of 60 stents in 53 patients.

OBJECTIVE: To evaluate the feasibility and usefulness of the Cheatham platinum (CP) stent in a broad spectrum of lesions. METHODS: Retrospective analysis of 60 implanted CP stents (11-80 mm lengths, 12 covered) between September 2001 and March 2004. PATIENTS: 53 patients aged 2.5-68 years (median 17 years). Body weight ranged from 12-95 kg (median 52 kg). Thirty six patients had aortic (re)coarctation; seven of them had functionally interrupted aortic arches. Thirteen patients had pulmonary artery stenosis and four had stenosis of caval veins or conduits in a total cavopulmonary connection (TCPC). RESULTS: Arterial pressure gradients dropped from 33 mm Hg (range 20-80 mm Hg) to 5 mm Hg (range 0-10 mm Hg) and pressure gradients in TCPC or caval veins dropped from 4 mm Hg (range 4-20 mm Hg) to 0 mm Hg (range 0-3 mm Hg). All stents were placed in the target lesion without complications. Three stent fractures without clinical instability were noted. CONCLUSIONS: The CP stent is suitable for the treatment of vessel stenosis in congenital heart diseases from childhood to adulthood. Whether these good results will be stable in the long term needs to be investigated.

Adolescent↗

Psychological effects of occupational exposure to organic solvent mixtures on printers.

PURPOSE: Neuropsychiatric symptoms associated with long-term exposure to organic solvents have been investigated for a long time in many occupational studies. The aim of our study was to identify preclinical effects of low-level chronic solvent exposure on the cognitive performance of silk-screen printers. METHODS: A cross-sectional study was conducted including 38 printers which were exposed to organic solvent mixtures and 45 controls without neurotoxic exposure. The psychometric test battery included nine tests and two questionnaires. RESULTS: The sum of scales or the total score of the PNF was also significantly (p <0.001) higher in the exposed group than in the non-exposed. The printers performed worse in some psychometric tests than did controls. Cross validation with the psychometric performances resulted in 69.6% of participants being correctly classified (55.9% printers and 80% controls). Highly significant differences (p<0.001) between both groups of exposed and non-exposed workers were found for the mean values of the multidimensional psychometric score. CONCLUSIONS: These results of our study proved not only that chronic exposure to organic solvent mixtures could induce a psychological effect but also that the psychological/psychometrical tests performed in this study were capable of predicting neurotoxicity.

Adult↗

[Transcatheter closure of congenital ventricular septal defects].

We report on the transcatheter closure of ventricular septal defects (VSD) in 26 patients with Amplatzer Occluders and Nit- Occlud Coil Systems. Twenty-one patients had a perimembranous and 5 patients a muscular VSD. Patients' age range was 5 months to 59 years (median 8 years) and their body weight 4.5 kg to 167 kg (median 28 kg). Defect diameters were 3-11 mm (median 5 mm). Sixteen patients had left ventricular volume overload and 7 patients pulmonary hypertension (median 50% of systemic pressure). Seven patients suffered from trivial or mild aortic regurgitation. Twenty-eight devices (4-12 mm; median 8 mm) were implanted (16 Amplatzer, 12 Nit-Occlud) through sheaths of 4F to 9F (median 7F). Fluoroscopy times were 8.3- 56.5 min (median 26.2 min). One coil was surgically explanted directly after intervention. One patient needed pulmonary banding due to additional VSDs. After a follow-up of 7 months (1-12 months), 2 patients had a small and 9 a minimal residual shunt. Thirteen defects were completely closed. Transcatheter closure of VSDs with new devices seems to be a promising therapy for suitable defects in different hemodynamic conditions in patients of every age.

Adolescent↗

[Influence of long term occupational exposure to solvents on colour vision].

BACKGROUND: The study was designed to determine the influence of chronic occupational exposition of organic solvent mixtures on colour vision of car painters. SUBJECTS AND METHODS: The 123 subjects (2 groups differing in organic solvents exposure and 1 control group) were examined using Ishihara-Panel, Lanthony Desaturated Panel D-15, Velhagen-Panel, and Tritan-Album. RESULTS: In the Velhagen-Panel 3% of the probands currently exposed to organic solvents, and 11% of formerly exposed probands developed a blue/yellow vision defect for the right eye. All control subjects perfectly finished this panel. In the Tritan-Album 3% of currently exposed subjects and 26% of formerly exposed painters expressed a blue/yellow vision defect for the right eye, but also 7% of controls showed anomalies. Similar results were found for both panels with the left eye. The CCI difference in the D-15 test was significant between all three groups. CONCLUSION: The impaired colour vision may also be an important indicator of neuro-ophthalmological effects after long-term occupational exposure to organic solvents.

Adult↗

Therapeutic drug monitoring of clozapine and relapse--a retrospective study of routine clinical data.

OBJECTIVE: Therapeutic drug monitoring (TDM) of the atypical antipsychotic drug clozapine is recommended. Clinical studies have indicated a therapeutic window for clozapine serum levels in schizophrenic and schizo-affective patients during acute treatment, i.e. for patients who do not respond to treatment with typical antipsychotics. However, despite the frequent use of clozapine also in maintenance treatment, very few data are available showing the relationship between serum levels of clozapine and the prevention of relapse. Thus, the primary objective of the study was to investigate the relationship between serum levels ofclozapine and relapse during maintenance treatment. METHODS: A retrospective study of routine TDM-data was conducted. Samples obtained on an acute treatment ward from patients with < 4 days hospitalization (recent admissions) were regarded as samples associated with relapse. Samples which can be attributed to an intoxication were identified as described in the TDM-form. The serum level of clozapine, as well as age, gender, smoking habits, concurrent drugs, psychiatric diagnosis and dose of clozapine were evaluated. Data analysis was performed on individual samples and, alternatively, on multiple samples from a single patient which are summarized according to a typical clinical situation. RESULTS: 404 serum levels were measured in 86 patients. After exclusion of patients receiving acute treatment, 65 relevant clinical situations were identified in 50 patients: 12 relapses, 8 intoxications (a total of 20 situations with poor outcome) and 45 situations involving patients with good maintenance outcome. Samples involving relapse had serum levels of 198 +/- 211 ng/ml (10-624), intoxications had serum levels of 1,969 +/- 705 ng/ml (900-2,900) and those with good outcome had serum levels of 384 +/- 255 ng/ml (56-1,028) (mean +/- SD (range)). By means of sensitivity of receiver operating characteristic curves (ROC) a lower limit of the therapeutic window can be estimated at about 50-250 ng/ml and an upper limit at about 745-1,050 ng/ml. The frequencies of good and poor outcome were significantly different within and outside these ranges, e.g. chi2 = 11.8 and p < 0.001 for 250 to 745 ng/ml. Comparison of only good outcome and relapse provided a significant difference in the serum level of clozapine (Student's t-test p = 0.024). However, 67% of relapses were predicted in a model of logistic regression only if the variables serum level and concurrent treatment with other psychotropic drugs were included simultaneously as independent variables. Neither variable was able to predict relapse if used as a single variable in separate models. Finally, it was found that serum levels of clozapine were increased in women, in aged patients and in nonsmokers. CONCLUSIONS: It is tentatively concluded that serum levels of clozapine < 50 ng/ml are related to relapse irrespective of concurrent psychotropic drugs. In cases where there are no concurrent psychotropic drugs, serum levels of clozapine < 250 ng/ml are associated with relapse. The risk of relapse is low for serum levels of clozapine > 250 ng/ml irrespective of concurrent psychotropic drugs. The risk of intoxication is increased with serum levels > 750 ng/ml. The TDM of clozapine is recommended during maintenance treatment.

Adult↗

Pathways to HIV testing and care by black African and white patients in London.

OBJECTIVE: To examine factors associated with uptake of HIV clinic services by black African HIV positive people living in London. DESIGN: Questionnaire survey of patients attending study clinic. SETTING: HIV outpatient clinic in south London, UK. SUBJECTS: All HIV positive patients attending the clinic between July 1999 and March 2000. MAIN OUTCOME MEASURES: Use of health services, delay in seeking HIV test, pre-HIV test concerns, delay in uptake of HIV care, barriers to clinic use, disclosure, sources of support. RESULTS: 392 questionnaires were completed. Respondents were 64% white, 26% black African, and 10% from other ethnic groups. Twenty eight per cent of black Africans suspected they were HIV positive before diagnosis (white patients 45% (p<0.01)). Before testing 11% of black Africans had previously attended a genitourinary medicine clinic, 80% had consulted a GP. Twenty per cent of black Africans expressed concern over entitlement to care and where to get an HIV test. The majority of black Africans (66%) received HIV care within 1 month of their diagnosis. They were significantly (p<0.01) less likely than white patients to disclose their HIV status to family and friends. CONCLUSION: This study suggests that although black Africans are a high risk group for HIV infection they generally do not suspect their status. While they may delay testing, their uptake of HIV clinic care and use of statutory and voluntary support services after diagnosis is similar to their white counterparts. However, they lack informal support networks. This study highlights the continuing need for health promotion work among London's African communities, to reduce the stigma surrounding HIV/AIDS and to raise awareness of the benefits of testing.

Adult↗

Comparison of real-time and intermittent triggered myocardial contrast echocardiography for quantification of coronary stenosis severity and transmural perfusion gradient.

BACKGROUND: Both intermittent triggered and real-time myocardial contrast echocardiography (MCE) have been proposed to detect impaired myocardial perfusion. We compared the ability of these 2 methods to quantify altered myocardial blood flow (MBF) and transmural distribution of MBF produced by graded coronary stenoses. METHODS AND RESULTS: In 8 open-chest dogs, we created 4 graded left anterior descending coronary artery (LAD) stenoses: 3 levels of reduced adenosine hyperemia (non-flow-limiting at rest) and 1 grade of flow-limiting at rest. Real-time MCE was performed with SonoVue infusion using low-energy power pulse inversion (ATL) imaging, whereas ECG-gated intermittent triggered imaging used high energy at pulsing intervals from 1:1 to 1:10. LAD signal intensity (SI) was plotted versus time by real-time MCE and versus pulsing intervals by triggered MCE and was fitted to a 1-exponential function to obtain plateau SI (A) and the rate of SI rise (b). Visual detection of decreased opacification was equivalent by triggered and real-time MCE. Fluorescent microsphere-derived MBF ratio in LAD/left circumflex artery beds demonstrated close correlation with both real-time imaging (b, r=0.79; Axb, r=0.81) and triggered imaging (b, r=0.78; Axb, r=0.80). The endocardial/epicardial ratio of MBF in the LAD bed demonstrated closer correlation with the endocardial/epicardial ratios of b (r=0.71) and Axb (r=0.67) obtained by real-time than triggered imaging (b, r=0.42; Axb, r=0.52). CONCLUSIONS: Real-time and triggered MCE are equivalent in their ability to identify coronary stenosis and quantify altered MBF.

Animals↗

[Late complications following early childhood atrial switch operations for d-transposition of the great arteries. Incidence, diagnosis and therapy].

BACKGROUND AND OBJECTIVE: The atrial switch operation in patients with transposition of the great arteries have been replaced by the arterial switch operation in the neonatal period. However, an increasing number of atrial switch survivors has now reached adulthood. This study was aimed at evaluating the incidence and patterns of typical late complications in order to describe diagnostic and therapeutic options. PATIENTS AND METHODS: We retrospectively analysed the data of 40 adolescent and adult patients, who had an atrial switch operation a mean of 17,9 years ago (23 Senning, 17 Mustard operations). The mean age of the patients is 19,3 years with 40 % females. The follow up time in our institution was 4,7 years. RESULTS: The most frequent complications were cardiac rhythm disturbances (47,5 % loss of sinus rhythm, 22,5 % intermittent atrial flutter, 22,5 % junctional rhythm, 7,5 % paroxysmal supraventricular tachycardia, 17,5 % sick sinus syndrome, 5 % premature ventricular contractions), severe tricuspid regurgitation (15 %), severe right ventricular failure (5 %), baffle leaks (27,5 %), baffle obstructions (17,5 %), and pulmonary artery hypertension. CONCLUSION: The data demonstrate that adult patients who underwent atrial switch operation in early childhood need long term follow-up to allow early recognition and treatment of late complications, even in asymptomatic patients.

Adolescent↗

Controlled hypertension, a transgenic toggle switch reveals differential mechanisms underlying vascular disease.

A novel inbred rat model with inducible hypertension has been generated using a renin transgene under the transcriptional control of the cytochrome P450, Cyp1a1 promoter. The degree and duration of hypertension are regulated tightly by administration of the natural xenobiotic indole-3 carbinol and can be readily reversed. Induction experiments reveal distinct temporal and mechanistic responses to hypertensive injury in different vascular beds, which is indicative of differential susceptibility of organs to a hypertensive stimulus. The mesentery and heart exhibited the greatest sensitivity to damage, and the kidney showed an adaptive response prior to the development of malignant hypertensive injury. Quantitative analysis of morphological changes induced in mesenteric resistance arteries suggest eutrophic remodeling of the vessels. Kinetic evidence suggests that locally activated plasma prorenin may play a critical role in mediating vascular injury. This model will facilitate studies of the cellular and genetic mechanisms underlying vascular injury and repair and provide a basis for the identification of novel therapeutic targets for vascular disease.

Aldosterone↗

Comparative value of dobutamine and adenosine stress in the detection of coronary stenosis with myocardial contrast echocardiography.

BACKGROUND: Controversy continues as to whether adenosine or dobutamine is the superior pharmacological stress agent for myocardial contrast echocardiography (MCE). METHODS AND RESULTS: We compared real-time MCE refilling curves and wall thickening during adenosine and dobutamine stress in 14 open-chest dogs with left anterior descending and left circumflex coronary artery stenoses that reduced hyperemia by 40% to 60% and 70% to 90% (mild and severe non-flow-limiting stenosis, NFLS) and resting flow by 10% to 30% and 35% to 50% (mild and severe flow-limiting stenosis, FLS). MCE was performed with low-energy imaging during Optison infusion. After high-energy bubble destruction, time-intensity data from risk beds were fitted for an exponential function as y=A(1-e(-)(bt)), from which the rate of intensity increase (b) and maximal plateau intensity (A) were derived. Although severe NFLS and greater stenoses decreased b with both dobutamine and adenosine, with mild NFLS it was reduced in 58% of animals with dobutamine versus 8% with adenosine. The absolute decrease in b, however, was greater for adenosine than dobutamine with FLS. The A parameter was decreased with both adenosine and dobutamine only with the most severe FLS. Wall thickening was decreased with dobutamine in 33% of animals with severe NFLS and in all animals with any FLS; with adenosine, in all with severe FLS. CONCLUSIONS: Both dobutamine and adenosine significantly reduce MCE refilling rates in the setting of severe stenosis and in the absence of contractile abnormalities. Dobutamine decreases refilling rate and wall thickening at a less reduced flow grade than adenosine, but adenosine produces a greater magnitude of change than dobutamine.

Adenosine↗