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Biomedical subjects

J Hess

Publications and source records attributed to J Hess.

At least 55 records · Page 3Linked to original sources

Results of biventricular repair of congenital cardiac malformations: definitive corrective surgery?

OBJECTIVES: Congenital cardiac malformations are usually corrected in the neonatal period or in early infancy. Corrective surgery may not always be definitive, especially in complex malformations. Long-term morbidity is influenced by reoperations and their risk. METHODS: This study analyzes our single-center experience over more than 20 years in a selected group of patients. Data were gathered, with special focus on causes and incidence for reoperations, respectively. RESULTS: Freedom from reoperation after 5, 10, and 15 years for each cardiac malformation was determined. The numbers describe in the following order patient years (y), number of patients (n), and freedom from reoperation at follow-up interval (%), respectively: atrial septal defect (15,864y, n=1198, 99+/-0/99+/-0/99+/-0), partial atrioventricular septal defect (2506y, n=234, 95+/-2/93+/-2/93+/-2), total anomalous pulmonary venous connection (742y, n=141, 93+/-1/91+/-0/91+/-0), complete atrioventricular septal defect (1715y, n=377, 81+/-3/76+/-3/72+/-4), tetralogy of Fallot <1 year (1503y, n=197, 94+/-4/85+/-1/74+/-3), transposition of great arteries (1459y, n=375, 88+/-2/83+/-4/73+/-7), interrupted aortic arch (IAA) (481y, n=98, 63+/-6/52+/-7/45+/-8), common arterial trunk (CAT) (599y, n=109, 64+/-6/24+/-6/11+/-5). CONCLUSIONS: In most congenital malformations surgical correction is definitive and the rate of reoperations is low. In complex anomalies, such as CAT and IAA, reoperations at long-term are more common. Analysis of such results and recognition of a sometimes inevitable operative morbidity helps to predict long-term outcome and influences the follow-up.

Age Factors↗

Balloon dilation for aortic recoarctation: morphology at the site of dilation and long-term efficacy.

OBJECTIVES: We undertook this study to assess the immediate and long-term outcome of balloon angioplasty performed for recurrent or residual coarctation of the aorta, and to assess the changes in the vessel wall caused by this procedure. METHODS: Clinical, echocardiographic, angiographic and hemodynamic data from 71 patients who underwent balloon angioplasty for recoarctation between January 1987 and January 1998 were analysed retrospectively. RESULTS: Angioplasty was performed after a median of 82.6 months (range 1.4 mo-20.9 y, mean 88.5 mo) following surgery for coarctation. Mean systolic pressure gradients were reduced from 27 +/- 15 mmHg to 11 +/- 11 mmHg after angioplasty (p < 0.0001). The mean diameter at the site of recoarctation increased from 5.5 +/- 2.5 to 7.5 +/- 2.7 mm (p < 0.0001). Outpouchings of contrast agents, indicating the disruption of the inner layers of the vessel wall, were defined as extravasations. They were observed in one-quarter of the angiograms performed immediately after the intervention. Immediate success of angioplasty was achieved in 71%, and persisted in 69% of patients during long-term follow up. The main determinant for immediate success was the age at the time of the procedure (p < 0.05), while the main determinant for long-term success was the increase achieved in diameter. Extravasations did not progress to aneurysms, neither acutely nor during echocardiographic follow-up studies. For further follow-up, more sensitive imaging techniques will be necessary to delineate the morphology of the site of extravasation observed immediately after angioplasty.

Adolescent↗

Cognitive, and behavioural and emotional functioning of young children awaiting elective cardiac surgery or catheter intervention.

AIMS: To assess the cognitive, and behavioural and emotional functioning of children aged 3 months to 7 years shortly before elective cardiac surgery or elective interventional catheterisation. METHODS: We used the Bayley Scales of Infant Development, and the McCarthy Scales of Children's Abilities, to measure cognitive functioning. The Child Behavior Checklist was used to assess behavioural and emotional problems. RESULTS: We found no significant differences in mean cognitive scores for children scheduled for cardiac surgery or interventional catheterisation when compared with reference groups. This was also the case for children awaiting cardiac surgery as opposed to those awaiting interventional catheterisation, and for those below as compared to those above the age of 2.5 years. Overall, our results regarding behavioural and emotional functioning were comparable to those of normative reference groups. The only difference found was that the children scheduled for cardiac surgery and aged from 2 to 3 years had significantly higher scores on the Child Behavior Checklist than did peers from normative groups. CONCLUSION: Cognitive, and behavioural and emotional functioning, both for young children awaiting elective cardiac surgery and interventional catheterisation, can be considered as quite favourable.

Age Factors↗

Creation of genome-wide protein expression libraries using random activation of gene expression.

Here we report the use of random activation of gene expression (RAGE) to create genome-wide protein expression libraries. RAGE libraries containing only 5 x 10(6) individual clones were found to express every gene tested, including genes that are normally silent in the parent cell line. Furthermore, endogenous genes were activated at similar frequencies and expressed at similar levels within RAGE libraries created from multiple human cell lines, demonstrating that RAGE libraries are inherently normalized. Pools of RAGE clones were used to isolate 19,547 human gene clusters, approximately 53% of which were novel when tested against public databases of expressed sequence tag (EST) and complementary DNA (cDNA). Isolation of individual clones confirmed that the activated endogenous genes can be expressed at high levels to produce biologically active proteins. The properties of RAGE libraries and RAGE expression clones are well suited for a number of biotechnological applications including gene discovery, protein characterization, drug development, and protein manufacturing.

Cell Line↗

New normal limits for the paediatric electrocardiogram.

AIMS: Previous studies that determined the normal limits for the paediatric ECG had their imperfections: ECGs were recorded at a relatively low sampling rate, ECG measurements were conducted manually, or normal limits were presented for only a limited set of parameters. The aim of this study was to establish an up-to-date and complete set of clinically relevant normal limits for the paediatric ECG. METHODS AND RESULTS: ECGs from 1912 healthy Dutch children (age 11 days to 16 years) were recorded at a sampling rate of 1200 Hz. The digitally stored ECGs were analysed using a well-validated ECG computer program. The normal limits of all clinically relevant ECG measurements were determined for nine age groups. Clinically significant differences were shown to exist, compared with previously established normal limits. Sex differences could be demonstrated for QRS duration and several amplitude measurements. CONCLUSIONS: These new normal limits differ substantially from those commonly used and suggest that diagnostic criteria for the paediatric ECG should be adjusted.

Adolescent↗

PEDMEANS: a computer program for the interpretation of pediatric electrocardiograms.

The interpretation pediatric electrocardiograms (ECGs) is complicated because of the strong age-dependency of the diagnostic criteria. We wanted to develop and evaluate a computer program for the interpretation of pediatric 12-lead ECGs. Continuous age-dependent normal limits were established based on ECGs from 1,912 healthy Dutch children. Additionally, a reference interpretation was obtained for 1,718 ECGs recorded at the Sophia Children's Hospital. The total set of ECGs was divided in a training set of 1076 ECGs and a test set of 642 ECGs. All ECGs were recorded at a sampling rate of 1,200 Hz. Based on the normal limits and the training set, diagnostic rules were formalized in an iterative process by using expert interviews and automatic rule induction. The resultant rules were evaluated on the test set. The performance of the program, on our study population, appears to justify its use in a clinical setting. Preferably, the program should also be evaluated in other clinical centers.

Algorithms↗

Long-term problems after cavopulmonary anastomosis: diagnosis and management.

After nearly three decades, the "Fontan-like" surgical approach for tricuspid atresia and other forms of functional univentricular heart disease have substantially improved life expectancy and functional status of these patients. However, over the years, complications such as persisting or reoccurring cyanosis, dysrhythmia, thromboembolism, protein-losing enteropathy and exercise intolerance have increasingly been reported. The management of these complications are related to their association with residual or recurrent structural lesions, which can be treated by catheter intervention or surgery, and to pathophysiological sequelae, directly associated to the specific characteristics of "Fontan-like" circulation. The recent modification might reduce this type of complication; however, hard data on this are not available yet.

Arrhythmias, Cardiac↗

Cisapride does not improve precolonoscopy bowel preparation with either sodium phosphate or polyethylene glycol electrolyte lavage.

BACKGROUND: Oral sodium phosphate solution (NAP) and polyethylene glycol-electrolyte lavage (PEG-EL) are used for precolonoscopy bowel preparation. The benefit of adding cisapride to PEG-EL is controversial, and its influence on the effectiveness of NAP has not been investigated. The primary aim of this study was to determine whether cisapride improves the effectiveness and/or tolerableness of bowel preparation with either NAP or PEG-EL. METHODS: In 187 patients undergoing colonoscopy, a randomized, double-blind, placebo-controlled trial with a Latin square design was conducted to compare 4 different bowel preparations: NAP plus either cisapride (10 mg; 2 doses) or placebo, or PEG-EL plus either cisapride (10 mg; 1 dose) or placebo. Quality of the bowel preparation was graded by the endoscopist according to the amount of stool present in the colon (excellent, satisfactory, unsatisfactory). To assess tolerability, patients rated 8 symptoms, the taste of the lavage solution, and the ease of preparation on a 5-point scale (1: easy; 5: distressing). RESULTS: Endoscopists scored the bowel preparation as either excellent or satisfactory as follows: NAP: cisapride 50% versus placebo 61% (p = 0.3); PEG-EL: cisapride 80% versus placebo 78% (p = 1.0). Cisapride did not improve tolerability or the frequency of adverse symptoms associated with either solution. The ease of bowel preparation was significantly better in the NAP group versus PEG-EL group (mean score 1.8 versus 2.8; p < 0.0001). CONCLUSIONS: Cisapride does not improve the quality of bowel preparation with either NAP or PEG-EL. NAP is better tolerated by patients than PEG-EL; however, PEG-EL results in better bowel preparation.

Administration, Oral↗

Development of live recombinant vaccine candidates against tuberculosis.

We report on 2 recombinant (r) live vaccine candidates that use different strategies to improve cell-mediated immunity for TB control: (i) the current TB vaccine strain Mycobacterium bovis BCG, endowed with a pore-forming cytolysin; and (ii) rSalmonella typhimurium secreting a single immunodominant antigen shared by BCG and M. tuberculosis.

Animals↗

The B lymphocyte-specific coactivator BOB.1/OBF.1 is required at multiple stages of B-cell development.

The transcriptional coactivator BOB.1/OBF.1 confers B-cell specificity on the transcription factors Oct1 and Oct2 at octamer site-containing promoters. A hallmark of the BOB.1/OBF.1 mutation in the mouse is the absence of germinal center development in secondary lymphoid organs, demonstrating the requirement for BOB.1/OBF.1 in antigen-dependent stages of B-cell differentiation. Here we analyzed earlier stages of B lymphopoiesis in BOB.1/OBF.1-deficient mice. Examination of B-cell development in the bone marrow revealed that the numbers of transitional immature (B220(+) IgM(hi)) B cells were reduced and that B-cell apoptosis was increased. When in competition with wild-type cells, BOB.1/OBF.1(-/-) bone marrow cells exhibited defects in repopulating the bone marrow B-cell compartment and were unable to establish a presence in the periphery of host mice. The defective bone marrow populations in BOB.1/OBF.1(-/-) mice were rescued by conditional expression of a BOB.1/OBF.1 transgene controlled by the tetracycline gene expression system. However, the restored populations did not restore the numbers of IgD(hi) B cells in the periphery, where the BOB.1/OBF.1 transgene was not expressed. These results show that BOB.1/OBF.1(-/-) B cells exhibit multistage defects in B-cell development, including impaired production of transitional B cells and defective maturation of recirculating B cells.

Animals↗

Patient follow up screening evaluations. Examples with regard to congenital hip dislocation and congenital heart disease.

OBJECTIVE: To discuss the merits of the patient follow up study design for the evaluation of some specific mass screening programmes. DESIGN: Theoretical evaluation illustrated by two examples. SETTING: Department of Public Health Erasmus University Rotterdam. MAIN RESULTS: The gold standard for evaluation of favourable effects of screening is the randomised controlled trial (RCT). Application of an RCT, however, is often not feasible, in which cases observational studies will have to be relied on. The case-control study design is generally considered to be second best. In some situations, however, a patient follow up study design may be applicable and may have some major advantages. The use of the patient follow up design for screening evaluation will often be very problematic or even unacceptable, particularly as far as screening for cancer is concerned. The most important objections are resulting from lead time bias, length bias, selection bias and over-treatment bias. For the evaluation of screening for congenital heart disease and congenital hip dislocation in Dutch child health care, however, these objections may relatively simply be overcome. Lead time bias will be of little importance, as the ages of onset of these disorders are fixed, namely at birth, and their ultimate outcomes may be expected within relatively short time. Length bias may largely be avoided by correction for severity of the disorder, which can be adequately assessed by modern diagnostic procedures. Selection bias is generally hard to rule out, but in these cases it probably plays a minor part. Over-treatment can be avoided by the policy of "watchful waiting", which in these disorders can be applied with little risk for fatal outcomes. In principle bias might be avoided more successfully in a case-control screening evaluation than in a patient follow up study. However, the patient follow up study is for both screening programmes discussed here the more feasible design and can provide more supplementary information. The results of two example studies suggest that both screenings probably yield considerable benefits CONCLUSION: Under a number of specific conditions a patient follow up study is an efficient alternative to more customary designs for screening evaluation.

Child↗

Altered arterial expression patterns of inducible and endothelial nitric oxide synthase in pulmonary plexogenic arteriopathy caused by congenital heart disease.

Flow-associated pulmonary hypertension leads to pulmonary plexogenic arteriopathy (PPA), a specific pulmonary vascular disease that includes vascular lesions characterized by abnormal vasodilatation and endothelial cell proliferation. Increased local production of NO has been suggested in this condition. Because reported data on the expression of endothelial NO-synthase (ecNOS) have been contradictory, we speculated that the expression of the inducible isoform of NOS (iNOS) is enhanced in this form of pulmonary hypertension. We investigated immunohistochemically the expression of ecNOS and iNOS in lung tissue of patients with flow-associated pulmonary hypertension (n = 18) and compared the findings with those in patients with increased pulmonary blood flow but normal pulmonary artery pressure (n = 10), with congestive vasculopathy (n = 6) and control subjects (n = 4). Immunoreactivity for ecNOS and iNOS was present both in normal and diseased pulmonary arteries. Marked immunoreactivity to both isoforms was present within the advanced lesions of PPA, including plexiform lesions. Semiquantitative analysis of immunoreactivity, both for ecNOS and iNOS, showed no correlation with the severity of morphologic vascular lesions (p = 0.29 and p = 0.23, respectively). In contrast to ecNOS, immunoreactivity for iNOS was increased in patients with flow-associated pulmonary hypertension compared with other patients (p = 0.02). The present study has demonstrated enhanced expression of iNOS in patients at risk for advanced PPA, but not in patients with other forms of pulmonary arteriopathy. Moreover, high expression of both ecNOS and iNOS were present in advanced lesions of PPA. These data suggest differentiated roles for different isoforms of NOS in the pathogenesis of this specific pulmonary arteriopathy.

Analysis of Variance↗

Bacterial carriers and virus-like-particles as antigen delivery devices: role of dendritic cells in antigen presentation.

Replicating attenuated strains of intracellular bacteria like Salmonella typhimurium, Listeria monocytogenes or Mycobacterium bovis Bacille Calmette Guérin (BCG), and non-replicating virus-like-particles (VLP) consisting, for instance, of the VP1-surface component of polyoma virus offer great potential as heterologous carriers delivering foreign protein antigens for immune recognition. Moreover, attenuated S. typhimurium and L. monocytogenes strains hold also great promise as delivery vehicles for DNA vaccines. Polyoma virus-specific VLP consisting of VP1-pentamers are also of interest as carrier devices for eukaryotic expression plasmids. At first sight these different replicating and non-replicating types of vehicles have little in common, but from an immunological point of view viable bacteria and non-viable VLP are both well suited for evoking protective immune responses via several routes of vaccine administration. As these antigen carriers generate humoral and cell-mediated immunity, the heterologous antigens are not only targeted to appropriate pathways of major histocompatibility (MHC) class I and class II antigen processing and presentation, but also generate an adequate cytokine milieu for promoting antigen-specific responses. The most prominent advantage of these carrier devices is presented by their capacity to directly target antigenic proteins or DNA vaccines to immature dendritic cells (DC) along their maturation pathway. Mature DC are the key antigen presenting cell population which efficiently mediates antigen transport to organised lymphoid tissues for the initiation of T cell responses. In general, uptake of these diverse antigen delivery systems by antigen presenting cells (APC) finally lead to efficacious immune responses in the control of pathogenic microorganisms and tumours.

Animals↗

Immune response against Mycobacterium tuberculosis: implications for vaccine development.

Tuberculosis remains a major health problem globally. Although this threat would best be controlled by a combination of chemotherapy and vaccination, satisfactory vaccines are not available yet. Rational design of a novel vaccine generation against tuberculosis has become possible on the basis of recent achievements in molecular genetics of the pathogen and immunology of the host. Currently, two different strategies are pursued. First, the subunit vaccine approach attempting to induce efficacious immunity by unique antigens in defined adjuvants. Second, the whole bacterial vaccine approach relying on multiple antigens and built-in adjuvanticity. Time will tell which type of vaccine is best suited for eradication of tuberculosis.

Bacterial Vaccines↗

Delivery of protein antigens and DNA by virulence-attenuated strains of Salmonella typhimurium and Listeria monocytogenes.

Two different plasmid-vector systems were developed which allow the efficient production and presentation of protein antigens in antigen-presenting cells (APC) by means of virulence-attenuated bacteria. The first antigen-delivery system is based on the secretion machinery of the Escherichia coli hemolysin (HlyA-type I secretion system), which transports proteins, possessing the specific HlyA secretion signal (HlyA(s)) at the C-terminus, across both membranes of gram-negative bacteria. This system functions in all gram-negative bacteria that possess the TolC-analogous protein in the outer membrane. This outer membrane protein is necessary for the stable anchoring of the type I secretion apparatus in the cell envelope. Suitable HlyA(s)-fused antigens are secreted with high efficiency by E. coli and by virulence-attenuated strains of Salmonella, Shigella, Vibrio cholerae and Yersinia enterocolitica. The other vector system expresses the heterologous antigen under the control of an eukaryotic promoter in a similar fashion as in plasmids commonly used for vaccination with naked DNA. This plasmid DNA is introduced into APCs with the help of virulence-attenuated self-destructing Listeria monocytogenes mutants. After synthesis of the heterologous protein, epitopes of the antigen are presented by the APC together with MHC class I molecules. This system functions in macrophages and dendritic cells in vitro and can also be used in a modified form in animal models.

Antigens, Bacterial↗

Isolation of RNA from mycobacteria grown under in vitro and in vivo conditions.

Isolation of RNA from mycobacteria is very difficult to perform, and the yields are generally very low. We describe an approach to isolate RNA from mycobacterial species which combines the disruption of mycobacterial cells by a silica/ceramic matrix in a reciprocal shaker with the ease and efficiency of subsequent RNA purification on spin columns with silica gel-based membranes. This method is rapid, easy to perform and yields high amounts of pure, intact total RNA. Due to its safety, this method is applicable even to group 3 biological hazard organisms like Mycobacterium tuberculosis. By combining a method for the isolation of phagosomal bacteria from infected primary macrophages with the novel RNA isolation technique, we are able to monitor gene expression during infection even in bacteria which are rather resistant to genetic manipulation, like Mycobacterium bovis.

Animals↗

Enhanced expression of vascular endothelial growth factor in pulmonary plexogenic arteriopathy due to congenital heart disease.

Congenital heart disease (CHD) leading to increased pulmonary blood pressure and flow is an important cause of pulmonary plexogenic arteriopathy (PPA). This type of arteriopathy tends to progress to an irreversible stage, hallmarked histologically by the emergence of a number of characteristic lesions, which include concentric laminar intimal proliferation and fibrosis, and plexiform lesions. The pathogenesis of these lesions, which connote a very poor prognosis, is not well understood. Since endothelial cell proliferation has been demonstrated in these lesions, it was hypothesized that vascular endothelial growth factor (VEGF), a key mediator of angiogenesis, might play a role in their pathogenesis. Thirty-nine patients with various types of CHD, who underwent cardiac catheterization and subsequent cardiac surgery, were studied prospectively. On the basis of a detailed assessment of the type of cardiac defect, the haemodynamic abnormalities, and the histopathological features evident from open lung biopsies, taken in all instances, patients were histologically grouped into cases with moderate PPA (n=18), advanced PPA (n=7), pulmonary congestive vasculopathy (PCV, n=5), and controls lacking pulmonary hypertension or increased pulmonary blood flow (n=4). Five patients were excluded from analysis because of inadequate sample size or quality. The presence of VEGF was assessed immunohistochemically using standard procedures and was correlated with haemodynamic and histological data. Immunoreactive VEGF was detected in pulmonary arterial smooth muscle cells and endothelial cells in 13 out of 34 cases and was more frequent and more pronounced in patients with the histological lesions of advanced PPA than in those with moderate PPA (p<0.01). VEGF positivity was particularly prominent in the lesions characteristic of advanced PPA. No difference in VEGF expression was observed between controls, PVC, and moderate PPA cases. Measured haemodynamic parameters did not differ significantly between VEGF-positive and VEGF-negative cases. We conclude that VEGF may play a role in the angioproliferative changes of advanced PPA.

Child↗