[Current concepts in chronic lymphocytic leukemia. Better chances for young patients].
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Biomedical subjects
Publications and source records attributed to B Schmitt.
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INTRODUCTION: Assessment of systolic and diastolic ventricular function in children and adults with morphologically and functionally univentricular heart is difficult using the conventional echocardiographic methods. Quantitative assessment of systolic and diastolic wall motion by TDE may provide information on abnormal systolic and diastolic ventricular function. Thus, the object of this study was to analyze the patterns of anterior and posterior wall motions in children with univentricular heart after palliative Fontan operation in comparison to normal subjects. PATIENTS AND METHODS: We investigated 21 patients of an average age of 10.1 years (range 4.2 to 32 years) with the primary diagnosis of univentricular heart and tricuspid atresia after a median period of 4.3 (range 1.2 to 8) years after cavo-pulmonary anastomosis (Fontan procedure) and in comparison to a normal collective of children without cardiovascular malformations. For investigation we used the novel tissue Doppler echocardiography (TDE) (EchoPack 6.3.6, Vingmed, Norway). Thereby we chose the standardized apical view and evaluated the left and right annular systolic (S(T)), early diastolic (E(T)) and atrial (A(T)) motion. We also registered the acceleration and deceleration time of each obtained curve. RESULTS: In comparison to the posterior myocardial wall the velocities at the anterior wall of the rudimentary ventricle were significantly reduced in all patients with tricuspid atresia and univentricular heart (p<0.0001). Particularly the annular systolic and diastolic wall motions of the rudimentary ventricle as well as their deceleration and acceleration time in patients with univentricular hearts differed significantly from those in healthy persons. CONCLUSION: Abnormal myocardial wall motion is detectable in children and adults with univentricular heart after palliative cardiac procedures using tissue Doppler echocardiography. The hemodynamic value of the measured abnormal wall motions, however, need further comparative studies.
OBJECTIVES: Two randomized trials found that monitoring labor by analyzing the fetal electrocardiogram (STAN) appears to offer better sensitivity and specificity in screening for metabolic acidosis than cardiotocography (CTG) does. We report here the results of a descriptive study of 173 cases between 1 June 2001 and 31 May 2002, the objectives of which were twofold: to determine the number of possible false negatives (defined by neonatal metabolic acidosis with a pH less than 7.05 and base deficit (BD) greater than 12 mmol/l, in the absence of a STAN decisions event more than 30 min before birth), and to assess whether STAN indicated the need for operative intervention too late in cases of fetal distress. PATIENTS AND METHODS: Our study was conducted on an at-risk population with CTG changes. STAN was used with a scalp electrode to monitor labor according to a protocol based upon the FIGO CTG classification and the clinical instructions used in the Swedish trial. Accordingly, we compared two groups: in group 1, a STAN decision event required a rapid conclusion to labor, while in group 2, the absence of any STAN decision event meant that labor continued, despite the changes in the tracing. RESULTS: We found seven cases with a neonatal pH less than 7.05, but only one may involve a false negative by this method. The mean arterial pH and the number of fetuses born with an arterial pH less than 7.10 did not differ significantly between the two groups, nor were there any significant differences in the mean BD at birth, or the number of children with a BD greater than 12 mmol/l. CONCLUSION: The results appear to indicate that use of STAN with the usual CTG enables an appropriate response to cases of fetal distress, but it remains difficult to determine the real benefits that can be expected from this method in France. Longer assessment in our population is required before we can assess its actual advantages.
PURPOSE: To assess the new method of 3-dimensional echocardiography in comparison to the "gold standard" MRI as to its ability to calculate left ventricular volumes in patients with congenital heart disease. MATERIALS AND METHODS: Eighteen patients between the ages of 3.9 to 37.3 years (mean: 12.8 +/- 9.7) with a geometrically abnormal left ventricle were examined using a 1.5T scanner with a fast gradient-echo sequence (TR = 14 ms, TE = 2.6 - 2.9 ms, FOV = 300 - 400 mm, flip angle = 20 degrees, matrix = 128 : 256, slice thickness = 5 mm, retrospective gating) in multislice-multiphase technique. Transthoracic 3D-echocardiography was performed with a 3.5 MHz transducer and a Tomtec (Munich, Germany) system for 3D reconstruction. RESULTS: Volume calculation was possible in all patients with 3D-echocardiography, but the muscle mass calculation only succeeded in 11 of 18 patients (61 %) due to inadequate visualization of the entire myocardium. Comparing MRI and 3D-echocardiography, the correlation was r = 0.97 for the end-systolic volumes, r = 0.98 for the end-diastolic volumes, r = 0.79 for the end-systolic muscle mass and r = 0.77 for the end-diastolic muscle mass. The agreement between both methods was considered good for the calculated end-diastolic volumes and sufficient for the calculated end-systolic volumes. The muscle mass calculations showed larger differences especially for the end-systolic mass. Mean intraobserver variability was 18.6 % for end-systolic and 8.3 % for end-diastolic volumes. CONCLUSION: In patients with an abnormal left ventricular configuration due to congenital heart disease, the new method of 3D-echocardiography is sufficient for volume calculations in preselected patients. The high intraobserver variability is still a limitation of transthoracic 3D-echocardiography in comparison to MRI.
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INTRODUCTION: Fifty-eight patients (mean age 27 years, range 17-44) with primary spontaneous pneumothorax (PSP) underwent resection of apical bullae and partial apical pleurectomy via mini-thoracotomy or thoracoscopy, in 12 cases bilaterally, between 1982 and 1999. METHOD: After a mean follow-up period of 111 (16-212) months, 26 patients with 31 operated lungs were reassessed by high-resolution CT (HRCT) to demonstrate postoperative morphological changes. RESULTS: Neither relevant clinical symptoms nor recurrence of a pneumothorax were found. However, HRCT revealed new apical bleb formations in 22 (71%) of 31 lungs. Neither the surgical approach, the technique of resection nor giving up smoking could be correlated to the tissue alterations. Surgical excision of the apex of the lung does not stop bleb formation. CONCLUSION: This study confirms earlier results from a different institution, when blebs recurred in 50% of the cases. The presence of these new apical formations neither influenced the clinical outcome nor predisposed to recurrence of PSP. Parietal (partial) pleurectomy seems mandatory to prevent PSP in the long-term.
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AIM: The effect of ABT-229, a new macrolide with no antibacterial activity, on gastro-oesophageal reflux, oesophageal motility and gastric emptying in patients with gastro-oesophageal reflux disease was investigated. METHODS: Twenty-one patients were treated with a placebo and ABT-229 (2.5, 5 or 10 mg b.d.) in a randomized, incomplete crossover study design. Ambulatory 24-h pH manometry was performed and gastric emptying was assessed by the 13C-octanoic acid breath test on the seventh day of treatment. RESULTS: A significant decrease was found in the mean (+/- s.e.) percentage of reflux time (intra-oesophageal pH < 4) for ABT-229 5 mg b.d. and 10 mg b.d., but not for 2.5 mg b.d., compared with placebo. For ABT-229 5 mg, it was 8.5 +/- 0.5% vs. 10.7 +/- 0.7% (P < 0.038) and, for ABT-229 10 mg, it was 6.6 +/- 0.5% vs. 8.4 +/- 0.5% (P < 0.019). There were no significant differences in any of the analysed manometric parameters. In addition, the gastric half-emptying time for all doses of ABT-229 did not differ significantly from that after placebo. CONCLUSIONS: ABT-229 is able to reduce slightly, but significantly, acid reflux in patients with gastro-oesophageal reflux disease. This effect does not appear to be due to a measurable improvement in oesophageal motility or gastric emptying.
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BACKGROUND: Enterococcus species are major nosocomial pathogens and are exhibiting vancomycin resistance with increasing frequency. Previous studies have not resolved whether vancomycin resistance is an independent risk factor for death in patients with invasive disease due to Enterococcus species or whether antibiotic therapy alters the outcome of enterococcal bacteremia. OBJECTIVE: To determine whether vancomycin resistance is an independent predictor of death in patients with enterococcal bacteremia and whether appropriate antimicrobial therapy influences outcome. DESIGN: Prospective observational study. SETTING: Four academic medical centers and a community hospital. PATIENTS: All patients with enterococcal bacteremia. MEASUREMENTS: Demographic characteristics; underlying disease; Acute Physiology and Chronic Health Evaluation (APACHE) II scores; antibiotic therapy, immunosuppression, and procedures before onset; and antibiotic therapy during the ensuing 6 weeks. The major end point was 14-day survival. RESULTS: Of 398 episodes, 60% were caused by E. faecalis and 37% were caused by E. faecium. Thirty-seven percent of isolates exhibited resistance or intermediate susceptibility to vancomycin. Twenty-two percent of E. faecium isolates showed reduced susceptibility to quinupristin-dalfopristin. Previous vancomycin use (odds ratio [OR], 5.82 [95% CI, 3.20 to 10.58]; P < 0.001), previous corticosteroid use (OR, 2.43 [CI, 1.22 to 4.86]; P = 0.01), and total APACHE II score (OR, 1.06 per unit change [CI, 1.02 to 1.10 per unit change]; P = 0.003) were associated with vancomycin-resistant enterococcal bacteremia. The mortality rate was 19% at 14 days. Hematologic malignancy (OR, 3.83 [CI, 1.56 to 9.39]; P = 0.003), vancomycin resistance (OR, 2.10 [CI, 1.14 to 3.88]; P = 0.02), and APACHE II score (OR, 1.10 per unit change [CI, 1.05 to 1.14 per unit change]; P < 0.001) were associated with 14-day mortality. Among patients with monomicrobial enterococcal bacteremia, receipt of effective antimicrobial therapy within 48 hours independently predicted survival (OR for death, 0.21 [CI, 0.06 to 0.80]; P = 0.02). CONCLUSIONS: Vancomycin resistance is an independent predictor of death from enterococcal bacteremia. Early, effective antimicrobial therapy is associated with a significant improvement in survival.
BACKGROUND: The epithelial cell adhesion molecule (EpCAM) is a homophilic and Ca2+ independent adhesion molecule that is expressed de novo in squamous cell carcinoma (SCC) but is absent in the majority of healthy squamous epithelia. EpCAM expression correlates with cell proliferation and dedifferentiation along with a progression in tumorigenicity. To date, nothing is known about the molecular mechanisms responsible for the regulation of the EpCAM gene. METHODS: The authors analyzed the regulation of a fragment of the EpCAM promoter. RESULTS: The analyzed fragment has significant activity in EpCAM positive cells, and it is regulated negatively by tumor necrosis factor alpha (TNFalpha). This negative regulation results in diminished mRNA expression and in the down-regulation of EpCAM protein at the cell surface in SCC cells. Both effects can be mimicked by the treatment of cells with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA). TNFalpha-induced inhibition of the EpCAM expression is mediated by TNF receptor 1 through the TNF receptor-associated death domain protein (TRADD) and by the activation of nuclear factor kappaB (NF-kappaB), and it can be blocked by dominant-negative variants of TRADD and the NF-kappaB inhibitor, IkappaB. The authors provide further evidence that NF-kappaB represses EpCAM expression by competing for the transcriptional coactivator p300/CREB binding protein (p300/CBP). CONCLUSIONS: The current results provide the first insights into the regulation of EpCAM expression, which is regulated negatively by TNFalpha and TPA through the activation of NF-kappaB. The repression may rely on the competition of NF-kappaB for p300/CBP histone acetyl transferase activity, because the overexpression of p300 reverts TNFalpha effects.
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In humans, eating is assumed to be regulated within a neuronal circuitry integrating hypothalamic "feeding centers" with neocortical regions. Here, DC potentials were recorded in food deprived men to demonstrate a graded tuning of neocortical excitability in conjunction with meal ingestion. In the beginning of food ingestion a pronounced negative DC potential shift developed (P<0.01) which was replaced by a gradual positive potential shift reaching a maximum within 5 min after cessation of food intake (P<0.05). Both negative and positive shifts showed a widespread cortical distribution. The initial negative DC potential presumably reflecting increased depolarisation of apical cortical dendrites, may serve to facilitate eating behavior. The succeeding positivity points to a growing inhibitory influence on cortical processing with increasing satiety that may support termination of meal intake.
Chronic lymphocytic leukemia of the B-cell type (B-CLL) is the most frequently occurring leukemia in the Western hemisphere. Until 10 years ago, the basic medical approach to this disease was expectative and palliative. Chemotherapy with alkylating agents such as chlorambucil used to be the main therapeutic option, and only patients at advanced stages of B-CLL were treated. With the advent of new treatments such as purine analogs, high-dose therapy followed by hematopoietic progenitor support, monoclonal antibodies, and further immunotherapies, this paradigm is about to change. By using these combinations, younger patients with active disease are now treated with the goal of a long-lasting remission. More sophisticated techniques allow characterization of some of the underlying molecular genetic aberrations and (together with new serum parameters) more accurate prediction of individual prognoses than with the clinical staging systems. With the help of these developments, patients with B-CLL will be managed according to their individual risk with a watch-and-wait strategy in patients with the most indolent form of the disease, conventional chemotherapy with alkylating agents and/or purine analogs in patients at intermediate risk, and aggressive high-dose chemotherapy (followed by immunotherapy) in patients with the most aggressive form of the disease.
OBJECTIVES: Combined androgen blockade with medical or surgical castration plus a nonsteroidal antiandrogen for metastatic prostate cancer has been the subject of 20 randomized trials. The findings range from no expected increase in survival in 17 studies to an estimated 3.7 to 7 months' survival improvement noted in 3 studies. Most recently, a 1999 evidence report from the Agency for Healthcare Research and Quality and a 2000 overview from the Prostate Cancer Trialists Collaborative Group indicated that combined androgen blockade was associated with an approximately 3% to 5% increase in 5-year survival. We report herein a systematic review on combined androgen blockade performed by the Cochrane Collaborative Review Group on Prostate Diseases. METHODS: Controlled trials that included a randomization of immediate nonsteroidal antiandrogens with castration versus castration alone for metastatic prostate cancer and provided information on survival were reviewed. Information on overall survival, toxicity, progression-free survival, cancer-specific survival, and type of nonsteroidal antiandrogen and castration therapies was abstracted by two independent reviewers. RESULTS: Twenty trials (n = 6320 patients) were included. The pooled odds ratio (OR) for overall survival with combined androgen blockade was 1.03 (95% confidence interval [CI] 0.85 to 1.25; n = 4970 from 13 trials), 1.16 (95% CI 1.00 to 1.33; n = 5286 from 14 trials), and 1.29 (95% CI 1.11 to 1.50; n = 3550 from 7 trials) at 1, 2, and 5 years, respectively. Progression-free survival was improved at 1 year (OR = 1.38; 95% CI 1.15 to 1.67; n = 2278 from 7 trials). Cancer-specific survival was improved at 5 years (OR = 1.58; 95% CI 1.05 to 2.37; n = 781 from 2 trials). When analysis was limited to studies identified as being of high quality, the pooled OR for overall survival progressively increased but was not significant at any follow-up interval. CONCLUSIONS: We find that there is a 5% improvement in the percentage of men surviving at 5 years (30% vs. 25%) with combined androgen blockade with nonsteroidal antiandrogens as well as improvements in progression-free survival at 1 year. Appropriate patients with metastatic prostate cancer should be informed of the potential benefits, toxicities, and out-of-pocket expenditures.
Genes encoding glutamate receptor channel subunits were identified in genomes from Drosophila melanogaster and Caenorhabditis elegans by homology search with amino acid sequences that participate in the conserved channel pore. The predicted sequences of the putative glutamate receptor subunits revealed a distinct channel pore signature for each receptor subtype and for most of them, related members were found in C. elegans and Drosophila.