[New regulation for graduate education for the specialist in urology. Rights, responsibilities and possibilities for development of urologic assistants].
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Clinical Competence↗
Biomedical subjects
J Simon
Publications and source records attributed to J Simon.
[Local recurrence following radical cystectomy for bladder cancer. Diagnostic and therapeutic options].
The prognosis for patients with local recurrence following cystectomy for urothelial bladder cancer is poor. Only a small proportion of patients with good performance status are candidates for any form of therapy at all. Clinical experience shows that local recurrence is often accompanied or followed by systemic tumor spread. Therefore, palliative systemic chemotherapy is the cornerstone of treatment. Local radiotherapy or local tumor resection is reserved for subgroups of patients and to ease local symptoms or complications. Only a few patients are candidates for multimodal therapeutic approaches with curative intent. Despite such efforts, the survival of patients with local recurrence is limited in nearly all cases.
Antineoplastic Agents↗
Workgroup III: facilitating screening for colorectal cancer: quality assurance and evaluation. UICC International Workshop on Facilitating Screening for Colorectal Cancer, Oslo, Norway (29 and 30 June 2002).
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Colorectal Neoplasms↗
Detection of receptor activator of NF-kappa beta ligand in apical periodontitis.
A novel protein known as receptor activator of NF-kappa beta ligand (RANK-L) has been identified as a potential osteoclast differentiation factor. However, comparatively little is known about the expression of RANK-L in the pathogenesis of periradicular lesions. In this study, RANK-L expression was evaluated in biopsy specimens from apical periodontitis. Tissue samples from 21 periapical lesions were collected. RANK-L mRNA was isolated by using the guanidinium isothiocyanate acid phenol method. This was followed by generation of cDNA using specific primer for RANK-L by reverse transcription polymerase chain reaction amplification. RANK-L expression in each periapical sample was assessed by agarose gel electrophoresis. Gel electrophoresis analysis showed a single band of 385 bp corresponding to RANK-L in every periapical lesion. By contrast, normal control tissue showed no detectable RANK-L mRNA expression. In conclusion, RANK-L may play a role in apical periodontitis-induced bone resorption.
Alveolar Bone Loss↗
Renal transplantation in children with severe bladder dysfunction.
PURPOSE: Renal transplantation in children with bladder dysfunction carries a risk for the renal graft. We report our experience with transplantation in 15 patients 6 to 18 years old with severe abnormalities of the lower urinary tract. MATERIALS AND METHODS: A total of 18 renal transplants were performed in 15 children with bladder dysfunction secondary to myelomeningocele (3), occult spina bifida (1), malformation/agenesis of the sacrum (5), posterior urethral valves (4), female hypospadias (1) and bladder exstrophy (1) between 1979 and 2003. Urological surgery was performed before transplantation in 14 cases-7 bladder augmentations, 5 incontinent urinary conduits/reservoirs and 2 vesicostomies. Voiding was maintained by intermittent catheterization in 9 cases and incontinent ostomies in 6. Graft implantation was performed by extraperitoneal route with ureteral anastomosis to the native bladder in cases of bladder augmentation. Immunosuppression consisted of triple therapy with polyclonal/monoclonal antibodies. RESULTS: Urological complications consisted of urethral obstruction due to mucus hypersecretion (1), urinary fistula (1), ureterovesical obstruction (1), stone formation (3), urinary tract incrustation by Corynebacterium urealyticum (1) and pyelonephritis (2). Graft survival rates at 1 and 5 years were 77% and 62%, respectively, with a median of 79 months (95% CI 51 to 107). Three graft losses were related to urological disease. CONCLUSIONS: Renal transplantation in children with severe bladder dysfunction can achieve similar results to those obtained in the general population. Meticulous selection of patients and surgical reparative techniques ensuring voiding and adequate control of urinary infections are mandatory. Augmentation cystoplasty and intermittent catheterization are appropriate techniques currently used for achieving this outcome.
Adolescent↗
Pharmacokinetic profile of recombinant human N-acetylgalactosamine 4-sulphatase enzyme replacement therapy in patients with mucopolysaccharidosis VI (Maroteaux-Lamy syndrome): a phase I/II study.
AIM: Mucopolysaccharidosis VI (Maroteaux-Lamy syndrome) is a lysosomal storage disease caused by a deficiency of the enzyme-N-acetylgalactosamine 4-sulphatase (ASB). Enzyme replacement therapy with recombinant human ASB (rhASB) has been studied in a randomized, double-blind, two-dose (0.2 and 1.0 mg/kg/week) phase I/II study (n = 7) followed by an open-label single dose (1.0 mg/kg/week) extension study. We report the pharmacokinetic profile of rhASB and the impact of antibody development. METHODS: Pharmacokinetic analysis was performed at weeks 1, 2, 12, 24, 83, 84 and 96. Infusions were administered over 4 hours using a ramp-up protocol. Plasma ASB and rhASB antibody concentrations and urine glycosaminoglycan (GAG) concentrations were determined. RESULTS: The area under the plasma concentration-time curve (AUC(0-t)) for the high-dose group increased from week 1 to week 2, but remained unchanged at weeks 12 and 24. A large difference in mean AUC(0-t) was observed between the low- and high-dose groups. Pharmacokinetic results at weeks 83, 84 and 96 were similar to those at week 24. Six patients developed antibodies to rhASB. One patient developed high antibody levels in combination with a high ASB concentration, while a second patient also developed high antibody levels with undetectable ASB concentrations. Antibodies from the second patient blocked detection of ASB. By week 72, antibody levels had decreased in all patients. The high-dose rhASB produced a more rapid and greater percentage reduction in urinary GAG concentrations than the lower dose (70% versus 55% at 24 weeks). Antibody levels did not appear to influence urinary GAG concentrations. CONCLUSION: Pharmacokinetic parameters appear to be independent of the duration of treatment and are not linear between the 0.2 and 1.0 mg/kg/week doses. Antibodies to rhASB develop in most patients, but their concentration decreases over time. Antibody formation may influence pharmacokinetic parameters during the early phases of treatment, although it appears to have limited impact on biochemical efficacy.
Adolescent↗
A highly immunogenic trivalent T cell receptor peptide vaccine for multiple sclerosis.
BACKGROUND: T cell receptor (TCR) peptide vaccination is a novel approach to treating multiple sclerosis (MS). The low immunogenicity of previous vaccines has hindered the development of TCR peptide vaccination for MS. OBJECTIVE: To compare the immunogenicity of intramuscular injections of TCR BV5S2, BV6S5 and BV13S1 CDR2 peptides in incomplete Freunds adjuvant (IFA) with intradermal injections of the same peptides without IFA. METHODS: MS subjects were randomized to receive TCR peptides/IFA, TCR peptides/saline or IFA alone. Subjects were on study for 24 weeks. RESULTS: The TCR peptides/IFA vaccine induced vigorous T cell responses in 100% of subjects completing the 24-week study (9/9) compared with only 20% (2/10) of those receiving the TCR peptides/saline vaccine (P =0.001). IFA alone induced a weak response in only one of five subjects. Aside from injection site reactions, there were no significant adverse events attributable to the treatment. CONCLUSIONS: The trivalent TCR peptide in IFA vaccine represents a significant improvement in immunogenicity over previous TCR peptide vaccines and warrants investigation of its ability to treat MS.
Adult↗
The digital pen and paper. Evaluation and acceptance of a new data acquisition device in clinical settings.
OBJECTIVES: To evaluate the efficiency and acceptance of digital pen and paper technology for real-time clinical data acquisition. METHODS: A prospective interventional unblinded study involving consecutive patients in two clinical settings during a defined time-frame was proposed. The first trial was designed as a stress test to evaluate acceptance in a workload-intensive environment. Acceptance was assessed using observations and a satisfaction questionnaire. The second trial was intended to determine the reliability of data acquisition in a controlled environment. Reliability was assessed by comparing the performance of the digital pen against scanner analysis and a double human blinded acquisition. RESULTS: Overall, users were satisfied with the use of the digital pen (median 3 on a Likert-scale (-5, 5)). Without any specific user training, successful data acquisition was greater than 80%. Use of this technology required less adaptation than standard computer devices, and was easy to learn and use. Ergonomic problems shaded the perception of the technology by inducing an increased cognitive load. Digitalized data was missing either because of a bug or due to lack of data validation. The reliability obtained with the digital pen was significantly lower to that obtained with the scanner. CONCLUSIONS: Natural technology such as the digital pen proved to be a good tool in stressful clinical environments without interfering with the normal workload or increasing the time for data acquisition. However, in order to improve quality of data acquisition, designing acquisition forms specifically for the use of digital pens is of paramount importance.
Anesthesia, Obstetrical↗
[Epidemiological study of hypothyroidism as cardiovascular risk in population].
BACKGROUND: Prevalence of hypothyroidism (HT) markedly differs among various populations. We aimed to establish the prevalence of HT in the Czech population and to assess its association with conventional cardiovascular risk factors. METHODS AND RESULTS: 1240 subjects (629 m, 611 f; mean age 52.3); a random, population-based sample were evaluated. Cut-off points for thyroid parameters were defined as follows: thyreostimulating hormone (TSH) 0.58-3.65 mU/I, free thyroxine (fT4) 9-22 pmol/l and thyroid peroxidase antibodies (TPOAb) < or = 14 IU/A. The overall prevalence of HT was 6.8% in males and 13.8% in females (p < 0.0001); subclinical HT (high TSH, normal fT4) was found in 3.0% and 8.0%, overt-untreated (high TSH, low fT4) in 3.2% and 3.0% and overt-treated HT in 0.6% and 2.8% of males and females, respectively. Moreover, in euthyroid subjects, 4.6% of males and 9.3% of females showed positive TPO-Ab (p < 0.0001). The adjusted relative risk of hypothyroidism was significantly increased in males with manifest vascular disease (odds ratio 3.48 (1.56-7.74)]), in females aged > or = 55 years (2.08 (1.29-3.36)) or hypertension (1.80 (1.03-3.13)), and moreover, in males and females with positive TPOAb (5.81 (2.57-13.13) and 5.92 (3.38-10.36), resp.) CONCLUSIONS: Hypothyroidism was found in Czech population highly prevalent and it can contribute to the coronary risk, produced by conventional factors.
Adult↗
Integrated real-time control for a sequencing batch reactor plant and a combined sewer system.
Integrated real-time control (RTC) concepts, which are trying to operate drainage systems and WWTPs depending on the current capacities of both systems, are becoming more and more important. While almost all publications in this field have been concentrating on continuous flow systems, this paper will present a project which has been initiated to realise an integrated RTC strategy for a Sequencing Batch Reactor (SBR) plant in simulation as well as in full-scale. The results of the simulation are that SBR plants can handle high hydraulic loads. The cost-benefit analysis shows that an integrated operation is reasonable concerning environmental and economic aspects. In order to verify the simulation results, full-scale operation has been started in January 2004. The first results seem to confirm the results of the simulation study.
Bioreactors↗
[Association between free thyroxin concentration and degree of heart failure in patients with chronic heart insufficiency].
BACKGROUND: It is evident, that overt thyroid dysfunction (both, hypo- or hyperthyroidism) could be associated with heart failure. The aim of our study was to establish whether also mild changes in free thyroxin (fT4) may influence the degree of heart failure in patients with chronic heart insufficiency. METHODS AND RESULTS: There were included 148 patients (m 121, f 27, mean age 63.8 +/- 1.14) with clinical chronic heart failure were, with fT4 levels within the normal range (9-22 pmol/l) and without thyroid suppression or substitution treatment. Degree of heart failure was quantified by plasma B-type natriuretic peptide (BNP), N-terminal pro-BNP (NT-proBNP) and big endothelin. Patients with fT4 in the range 11.9-14.6 pmol/l (optimal, 3rd-6th decile) had significantly lower NT-proBNP (718 +/- 70.4 pg/ml), than those with fT4 < or = 11.8 (low-normal, bottom two deciles) (1236 +/- 223.6 pg/ml; p < 0.03) and those with fT4 over 14.6 pmol/l [high-normal, top four deciles] (1192 +/- 114.9 pg/ml; p < 0.0002). These differences remain significant also if adjusted for age, gender and other confounders; adjusted odds ratio was 1.30 (1.05-1.59) for optimal vs. low-normal and 1.27 (1.04-1.55) for optimal vs. high-normal. Similar statistical differences were found also in BNP and high endothelin, but only between optimal and high-normal fT4 strata. CONCLUSIONS: The degree of heart failure could be influenced also by mild changes in fT4 concentration.
Chronic Disease↗
Observation of a narrow charm-strange meson D(+)(sJ)(2632)-->D(+)(s)eta and D(0)K(+).
We report the first observation of a charm-strange meson D(+)(sJ)(2632) at a mass of 2632.5+/-1.7 MeV/c(2) in data from SELEX, the charm hadro-production experiment E781 at Fermilab. This state is seen in two decay modes, D(+)(s)eta and D0K+. In the D(+)(s)eta decay mode we observe a peak with 101 events over a combinatoric background of 54.9 events at a mass of 2635.4+/-3.3 MeV/c(2). There is a corresponding peak of 21 events over a background of 6.9 at 2631.5+/-2.0 MeV/c(2) in the decay mode D0K+. The decay width of this state is <17 MeV/c(2) at 90% confidence level. The relative branching ratio Gamma(D0K+)/Gamma(D(+)(s)eta) is 0.14+/-0.06. The mechanism that keeps this state narrow is unclear. Its decay pattern is also unusual, being dominated by the D(+)(s)eta decay mode.
Journal Article↗
Mutational analysis of mucopolysaccharidosis type VI patients undergoing a trial of enzyme replacement therapy.
Mucopolysaccharidosis type VI (MPS VI), or Maroteaux-Lamy syndrome, is a lysosomal storage disorder caused by a deficiency of N-acetylgalactosamine-4-sulfatase (ARSB). Seven MPS VI patients were chosen for the initial clinical trial of enzyme replacement therapy. Direct sequencing of genomic DNA from these patients was used to identify ARSB mutations. Each individual exon of the ARSB gene was amplified by PCR and subsequently sequenced. Nine substitutions (c.289C>T [p.Q97X], c.629A>G [p.Y210C], c.707T>C [p.L236P], c.936G>T [p.W312C], c.944G>A [p.R315Q], c.962T>C [p.L321P], c.979C>T [p.R327X], c.1151G>A [p.S384N], and c.1450A>G [p.R484G]), two deletions (c.356_358delTAC [p.Y86del] and c.427delG), and one intronic mutation (c.1336+2T>G) were identified. A total of 7 out of the 12 mutations identified were novel (p.Y86del, p.Q97X, p.W312C, p.R327X, c.427delG, p.R484G, and c.1336+2T>G). Two of these novel mutations (p.Y86del and p.W312C) were expressed in Chinese hamster ovary cells and analyzed for residual ARSB activity and mutant ARSB protein. The two common polymorphisms c.1072G>A [p.V358M] and c.1126G>A [p.V376M] were identified among the patients, along with the silent mutation c.1191A>G. Cultured fibroblast ARSB mutant protein and residual activity were determined for each patient, and, together with genotype information, were used to predict the expected clinical severity of each MPS VI patient.
Alternative Splicing↗
[Urological education improvement--two paths to a goal].
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Certification↗
Interest of interferon alpha in systemic mastocytosis. The French experience and review of the literature.
Systemic mastocytosis (SM) are defined by an abnormal growth and accumulation of mast cells in bone marrow and/or other extracutaneous organs. There is currently no cure for this disease. Because of similarities and/or association of mastocytosis with myeloproliferative disorders, interferon alpha has been tested but with contradictory reported results. A first prospective multicenter phase II trial was then started in France. From 1994 to 1997, 20 adult patients with confirmed bone marrow involvement received interferon alpha-2b for at least 6 months, (from 1 million U per day up to 5 million U/m(2)/day). Thirteen patients who presented systemic and/or specific cutaneous manifestations, demonstrated objective responses: seven (35%) were partial, six (30%) minor but no complete response could be observed at the time of analysis. The bone marrow remained unchanged in 12/13. Thus, interferon should be offered to patients with severe systemic manifestations, who have not responded to symptomatic therapies, even in case of non-aggressive mastocytosis, with or without corticosteroids the first weeks. Long-term therapy should be offered to patients with initial positive response. To control more aggressive SM or mastocytosis associated with clonal hematologic non-mast cell lineage or leukaemia mast cell, other chemotherapeutic regimens should be proposed like Cladribine (2-chlorodeoxyadenosine, 2-CDA) or polychemotherapies including interferon as it is being tested in France in a new multicentric protocol, coordinated by the association AFIRMM, with interferon and oral cytarabine.
Bone Marrow Cells↗
Evolution of preproinsulin gene in birds.
The coding region of the preproinsulin gene has been cloned and partly sequenced in a variety of marine and terrestrial birds (28 species). All genes showed the "ancestral" structure with a large intron-2. The size of intron-2 changed considerably during the evolution of birds (2.4-4.2kb). The hydrophobicity of signal peptides was conserved. Bird C-peptides were predicted to be 28 amino acids long, but circulating C-peptides would be only 26 amino acids long, with Passer as a possible exception. Bird C-peptides were found to lack the sequences identified in mammals as responsible for peptide bioactivity and the structure of the central part. In contrast, predicted insulin sequences were highly conserved. Only two types of analog were identified: the hypoactive form (GluA8), present only in Anseriformes and the hyperactive form (His A8), present in all other species. Based on 3'-nucleotide sequence analysis (extending into intron-2), birds appeared to be monophyletic. Five groups were clearly identified: Paleognathae, Galliformes, Anseriformes, Passeriformes, and Charadriiformes. Paleognathae were suggested as the basal group, supporting the traditional view of avian evolution. Subsequent branching identified a gallo-anserae group and a group containing all other Neognathae. Surprisingly, Columba livia (Columbiforme order) clustered with Galliformes. With represented species, Procellariiformes and possibly Ciconiiformes, and Pelicaniformes were suggested as paraphyletic, in agreement with conclusions from some studies based on mitochondrial DNA sequences.
Animals↗
Anti-CD4 monoclonal antibody treatment in acute and early chronic antigen-induced arthritis: influence on T helper cell activation.
To examine the effects of anti-CD4 mAb treatment in acute and chronic antigen-induced arthritis (AIA), C57BL/6 mice were treated intraperitoneally either with the depleting anti-CD4 mAb GK1.5 or with rat-IgG (control) on Days -1, 0, 1, 3, 5, and 7. Arthritis was monitored by assessment of joint swelling and histological evaluation in the acute (Day 3) and the chronic phase (Day 21) of AIA. To determine the effects on cellular immune responses, in vivo T-cell reactivity (delayed type hypersensitivity; DTH) was measured, as well as protein levels of TH1- (IL-2, IFN-gamma) and TH2-cytokines (IL-4, IL-10) in joint extracts and supernatants of ex vivo stimulated spleen and lymph node cells. The humoral immune response was analysed by measuring serum antibodies against methylated bovine serum albumine (mBSA) and extracellular matrix proteins. Treatment with GK1.5 reduced swelling, inflammation, and destruction of the arthritic joint. Unexpectedly, the effects were even more pronounced in the acute than in the chronic phase. The anti-inflammatory effect was accompanied by a diminished DTH against the arthritogen mBSA and a decrease of TH1-cytokine production in spleen and pooled body lymph nodes, whereas the TH2-cytokine production in these organs was unchanged and the humoral immune response was only moderately reduced. There was a failure of depleting CD4+ T-cells in the joint, reflected also by unchanged local cytokine levels. Therefore, systemic rather than local effects on the TH1/TH2 balance appear to underlie the therapeutic efficacy of anti-CD4 treatment in AIA.
Acute Disease↗
New V272A presenilin 1 mutation with very early onset subcortical dementia and parkinsonism.
In this report, we present the clinical and pathological details of a kindred of four individuals with a novel missense mutation (V272A) of the presenilin 1 gene (PSEN1) that experienced a subcortical dementia. The age of onset of symptoms ranged 26-36-year old, with an age at death of 36-46 years. Initial symptom was a marked mood disorder, with prominent parkinsonism in one case. The neuropsychological study, as well as the neuroimaging and PET in the proband were concordant with a subcortical dementia. The cerebral pathology showed in this patient, aside from the classical lesions of Alzheimer disease, Lewy bodies in cortex and substantia nigra, and widespread subcortical neuritic lesions. This clinical pattern and pathology expands the clinical spectrum of familial Alzheimer's disease and compel to include mutations of PSEN1 gene in the genetic study of subcortical dementia.
Adult↗