Apparent diffusion coefficient values obtained by unenhanced MRI predicts disease-specific survival in bladder cancer.

AIM: To assess the ability of apparent diffusion coefficient (ADC) measurements obtained by MRI to predict disease-specific survival (DSS) in patients with bladder cancer and compare it with established clinico-pathological prognostic factors. MATERIAL AND METHODS: The ethical review board approved this cross-sectional study. Patients with suspected bladder cancer receiving diagnostic 3 T diffusion-weighted imaging (DWI) of the bladder before transurethral resection of the bladder (TUR-B) or radical cystectomy were evaluated prospectively. Two independent radiologists measured ADC values in bladder cancer lesions in regions of interest. Associations between ADC values and pathological features with DSS were tested statistically. A combined model was established using artificial neuronal network (ANN) methodology. RESULTS: A total of 51 patients (median age 69 years, range 41-89 years) were included. Three patients were lost to follow-up, leaving 48 patients for survival analysis. Seven patients died during the 795 months studied. ADC showed significant potential to predict DSS (p<0.05). Except for grading, all pathological features as assessed by TUR-B could predict DSS (p<0.05, respectively). The combined ANN classifier showed the highest accuracy to predict DSS (0.889, 95% confidence interval: 0.732-1, p=0.001) compared to all single parameters. ADC was the second important predictor of the ANN. CONCLUSIONS: ADC measurements obtained by unenhanced MRI predicts DSS in bladder cancer patients. A combined classifier including ADC and clinico-pathological information showed high accuracy to identify patients at high risk for disease-related death.

Laparoscopic adenomectomy versus Eraser laser enucleation of the prostate.

PURPOSE: To evaluate functional outcomes and morbidity rates after laparoscopic adenomectomy (LA) and Eraser laser enucleation of the prostate (ELEP). MATERIALS AND METHODS: Forty patients with lower urinary tract symptoms suggesting bladder outlet obstruction, with a prostate heavier than 70 g on transrectal ultrasound, were selected to undergo laparoscopic adenomectomy or Eraser laser enucleation of the prostate. All patients were consecutively enrolled without randomization and assessed preoperatively, 3 and 6 months postoperatively. Baseline characteristics, perioperative data, and postoperative outcomes were compared. RESULTS: The total operating time was significantly longer in the LA group (138.8 ± 11.4 vs. 78.4 ± 10.0 min, p < 0.000001). Catheter removal was performed earlier (61.2 ± 21.3 vs. 174.0 ± 13.2 h, p < 0.000001) and the hospital stay was significantly shorter (62.4 ± 21.2 vs. 187.2 ± 12.6 h, p < 0.000001) in the ELEP group. The latter group experienced significantly less perioperative hemoglobin (Hb) loss (0.71 ± 0.25 vs. 2.15 ± 1.08 g/dl, p < 0.000001), and their postoperative Hb levels (14.1 ± 1.21 vs. 11.7 ± 1.31 g/dl, p < 0.000001) were significantly higher. The resected tissue was significantly greater in the LA group (58.5 ± 23.3 vs. 87.9 ± 22.4 g, p = 0.0002). Significant improvements in Qmax, Qol, and symptom scores from baseline to each follow-up time point were noted in both groups. No statistically significant difference in symptom scores or Qmax was registered between the LA and the ELEP group throughout the follow-up period. CONCLUSION: Laparoscopic adenomectomy and ELEP were equally effective for relieving bladder outflow obstruction and lower urinary tract symptoms. The advantages of ELEP include less blood loss, shorter catheterization times, and shorter hospital stays.

Tissue effects resulting from eraser laser enucleation of the prostate: in vivo investigation.

UNLABELLED: BACKGROUND/AIMS/OBJECTIVES: To describe the depth of the laser coagulation zone in vivo based on histological examinations and the functional outcome of a 1,318-nm diode laser for enucleation in benign prostatic enlargement (BPE). METHODS: A total of 20 patients with BPE were treated by laser Eraser® enucleation of the prostate (ELEP). Prostatic tissue wedges were evaluated to assess the depth of the ELEP coagulation zones. Additionally, patients were assessed preoperatively and 12 months postoperatively. RESULTS: The coagulation zones were 0.36 ± 0.17 mm in epithelial tissue, 0.28 ± 0.15 mm in stromal tissue, and 0.25 ± 0.12 mm in mixed tissue. The coagulation area at the cutting edge completely sealed capillary vessels, reaching a depth of 0.35 ± 0.15 mm. The diameter of the coagulated vessels measured 1.75 ± 0.83 mm. Mean blood loss was 115.54 ± 93.12 ml, catheter time 1.35 ± 0.33 days, and hospital stay 1.89 ± 0.52 days. The International Prostate Symptom Score, maximal flow rate, and quality of life significantly improved 12 months after the procedure. CONCLUSIONS: ELEP is safe and effective for BPE treatment and yields good results at a follow-up of 1 year. Because of the limited penetration depth, damage to the urinary sphincter is not expected.

Synthetic galactocerebrosides evoke myelination-inhibiting antibodies.

Synthetic galactodihydrocerebrosides with widely different fatty acid components can evoke myelination-inhibiting antibodies in rabbits. Whether these are the only such haptens involved in experimental immunizations of other species or in spontaneous human diseases is not yet known.

Species restriction of a monoclonal antibody reacting with residues 130 to 137 in encephalitogenic myelin basic protein.

A monoclonal antibody (immunoglobulin G1) has been produced that reacts against myelin basic protein present in or extracted from the brains of many mammals-with certain important exceptions. Because of known species differences in amino acid sequences of basic protein and of certain peptide fragments, the binding site for this particular antibody appeared likely to include residues 130 to 137. Confirmation of this hypothesis was obtained by amino acid composition of the major immunoreactive peptides produced by thermolysin digestion of human basic protein and isolated by high-performance liquid chromatography.

Density functional theory based screening of ternary alkali-transition metal borohydrides: a computational material design project.

We present a computational screening study of ternary metal borohydrides for reversible hydrogen storage based on density functional theory. We investigate the stability and decomposition of alloys containing 1 alkali metal atom, Li, Na, or K (M(1)); and 1 alkali, alkaline earth or 3d/4d transition metal atom (M(2)) plus two to five (BH(4))(-) groups, i.e., M(1)M(2)(BH(4))(2-5), using a number of model structures with trigonal, tetrahedral, octahedral, and free coordination of the metal borohydride complexes. Of the over 700 investigated structures, about 20 were predicted to form potentially stable alloys with promising decomposition energies. The M(1)(Al/Mn/Fe)(BH(4))(4), (Li/Na)Zn(BH(4))(3), and (Na/K)(Ni/Co)(BH(4))(3) alloys are found to be the most promising, followed by selected M(1)(Nb/Rh)(BH(4))(4) alloys.

Monoclonal antibodies reactive with myelin basic protein.

New monoclonal antibodies (MAbs) to myelin basic protein (BP) reveal epitopes to be in sequences 22-34, 75-82, 83-96, 118-131 and 125-131. Comparison of these results with those previously reported suggest that almost every sequence of about 10 amino acid residues may be sufficiently antigenic to make a single MAb but that certain regions are immunodominant, strong enough to make practically the same MAb repeatedly. One of these new MAbs (clone 3) has especially interesting reactivity, sharply limited to residues 75-82 in bovine and porcine BP: Lys-Ala-Gln-His-Gly-Arg-Pro. Whales presumably have the same sequence, since their BPs are fully reactive with clone 3 MAb, but all other species of BP, with known sequences of BP, have at least two changes in this sequence. Deletion of Lys75 (as in a tryptic peptide of porcine BP) reduces reactivity with the MAb about 10-fold, whereas substitution of Ala76 by Ser (as in all other species of BP) and either deletion of Gln77 (as in human, monkey and rabbit BP) or His78 (as in the guinea pig and rat BP) or substitution of Pro82 by Thr (as in human, monkey, rat and mouse BP) eliminates reactivity. We speculate that woodchuck and prairie dog BPs in this region closely resemble chicken BP, which has about 2% of the original reactivity. However, squirrel BP is unique, probably having only one of the changes in this region of BP, since it possesses 10-20 times the reactivity of chicken BP but still only 20-50% of the original reactivity with clone 3 MAb, a degree of reactivity not seen with any other species of BP.

28-Year Survival following Several Metastasectomies, Going through 8th Line Systemic Therapy in a Case of mRCC.

Metastatic renal cell carcinoma (mRCC) has been one of the most treatment-resistant cancers because of its unpredictable clinical course, resistance to chemo- and radiotherapy, and the limited response to immunotherapy and targeted agents. We present a case of long-term survival, that is, 28 years, after primary diagnosis (longest survival in the literature up to our knowledge) with mRCC after several metastasectomies (from local site recurrence, liver, and lung) and eight lines of systemic targeted therapy. This case report shows how crucial is the regular follow-up of patients with RCC after primary management and positive impact of early metastasectomy and systemic targeted therapy in case of mRCC on patients' condition and overall survival.

New monoclonal antibodies reactive with defined sequential epitopes in human myelin basic protein.

Three new IgG monoclonal antibodies are described which recognise sequential epitopes of the human myelin basic protein (MBP) molecule in amino acid sequences 36-50, 64-75 and 80-89. Two of the secreting hybridomas were prepared by immunisation of mice with synthetic peptides. This procedure appears to generate antibodies of similar affinities to those made using intact myelin basic protein as the immunogen. It has the advantage that antibodies to preselected regions of the molecule can be made at will and the problem of subsequent epitope localisation is simplified. It is possible with synthetic peptides to generate antibodies of specificities which it would be impossible to achieve by immunisation with intact myelin basic protein. The monoclonal antibodies described here should be useful tools in studies of myelin catabolism in vivo and in vitro. Of particular interest is our Clone 22, making an antibody which reacts equally well with intact human MBP and synthetic peptide sequence 80-89 in liquid phase assays. Antibodies of this rare specificity have been claimed to be able to react with the peptides of myelin basic protein found in the spinal fluid of patients with multiple sclerosis.

Region-specific immunoassays for human myelin basic protein.

Three monoclonal antibodies reactive with human myelin basic protein have been used to develop immunoradiometric assays for this protein. Clone 1, a mouse IgG2a, is reactive with an epitope in the region 129-138. Clone 2, a mouse IgG1, is reactive with the region 119-131. Clone 12, a rat IgG, is reactive with the region 86-96. Competition experiments show that the reactions of Clone 1 and Clone 2 are mutually exclusive, probably because of steric effects. In contrast, when either Clone 1 or Clone 2 react they cause minimal interference with the subsequent binding of Clone 12. Less than 1 ng/ml of myelin basic protein can be detected in each of the two immunoradiometric assays developed. Clone 12 can also be used on its own in a competitive immunoassay to detect around 2 ng/ml. Using an extraction technique before the assay, serum or plasma can also be investigated. Assays for defined regions of myelin basic protein should prove valuable in identifying the products of myelin catabolism in patients with demyelinating disease.

Use of flexible ureteroscopy in the clinical practice for the treatment of renal stones: results from a large European survey conducted by the EAU Young Academic Urologists-Working Party on Endourology and Urolithiasis.

Treatment of renal stones using flexible ureteroscopy (fURS) is increasingly common despite the poor evidence in literature supporting its use and indications. With this study, we wanted to investigate the current use and indication of fURS for the treatment of renal stones in the clinical practice across the European countries. A survey was conducted using an emailed questionnaire consisting of 21 items; 2,894 recipients were selected via the EAU membership database. The questionnaires were collected through the SurveyMonkey system and the data were processed with the SPSS statistical package. Frequencies, cross tabs and Pearson correlation coefficients were applied as appropriate. 1,168 questionnaires were collected (response rate 40.4%). fURS was performed in 72.9% of the respondents' institutions, and 54.2% of the respondents were performing the procedure. For 95% of the users, fURS was considered first-line treatment, for stone of lower pole stone (45.9%) and <1 cm (44.2%) and 2 cm (43.8%) in size. The ureteral access sheaths were used routinely by more than 70% of the respondents. Lower pole stone repositioning technique was routinely performed by 45.9% of the surgeons. After fragmentation, 47.2% of the responders preferred to retrieve only the bigger fragments. At the end of fURS, lower volume surgeons were more likely to place routinely a double-J stent (p = 0.001). Higher volume surgeons estimated a higher durability of devices, both optical and digital ones (p < 0.001), and were more prone to consider fURS cost-effective when compared to other treatment modalities (p < 0.001). fURS is widely used for the treatment of renal stones and its use and indication can vary according to the age and surgeons' case volume. Higher volume surgeons are more prompt to extend international guidelines indications and to consider the technology cost-effective.

Fat embolism in kwashiorkor.

Fat embolism from the grossly fatty liver of an infant with kwashiorkor is described. Globules of fat were seen at necropsy in the hepatic veins, in the right atrium and ventricle of the heart and in the pulmonary artery. Sections of the lung showed fat emboli in numerous branches of the pulmonary artery. Examination of lung sections taken at necropsy from 40 patients who had severe kwashiorkor failed to show similar fat embolism.

Myelin basic protein and its free and bound antibodies in cerebrospinal fluid. All three must be determined on each specimen.

Myelin basic protein (BP) in the cerebrospinal fluid (CSF) is an important marker of brain damage, especially of white matter, but low or "normal" values can be misinterpreted if the CSF is not also examined for free and bound antibodies to BP. BP has many epitopes (antigenic determinants) and is very susceptible to fragmentation by proteolytic enzymes that are frequently very active in CSF, especially in patients with neurological diseases. This combination of factors permits BP to be degraded as it is released from myelin and to allow antibodies to those epitopes destroyed by enzymatic action to persist free in the CSF. Other free anti-BP antibodies may simply represent antibody excess. The relatively frequent formation of soluble antigen-antibody complexes with other epitopes on BP permits the existence of anti-BP antibodies bound to BP also in CSF. In addition to these factors that contribute to low values of free BP in CSF, if the analyses are not performed promptly on CSF collected in plastic tubes (polystyrene but preferably polypropylene), the "natural" adhesiveness of BP (immediately to glass, slowly to plastic) can remove it from the CSF, resulting in artifactually low values which can also be misinterpreted as "normal".

Myelin basic protein treatment of experimental allergic encephalomyelitis in monkeys.

Treatment of experimental allergic encephalomyelitis (EAE) in two strains of monkeys with large amounts of myelin basic basic protein (BP) fails unless an adjunct is also used. In both strains the adjunct by itself is more effective than BP by itself, but in the one strain which could be investigated sufficiently, the combination can be made almost totally effective in reversing EAE. The adjunct varies with the strain of monkey, an antibiotic in Macaca mulatta and a steroid in Macaca fascicularis. Similar adjunctive treatments should be considered in the management of multiple sclerosis, for EAE remains one of the best studied models.