Retroperitoneal schwannomas of renal and pararenal origin: presentation of two case reports.

Retroperitoneal schwannomas are a rare entity. They originate from the Schwann cells of the nerve sheaths and may be of renal or pararenal origin. We report on two patients with retroperitoneal schwannomas, who received surgery under the suspicion of renal cell carcinoma.

Structures of a(n)* ions derived from protonated pentaglycine and pentaalanine: results from IRMPD spectroscopy and DFT calculations.

Infrared multiple-photon dissociation (IRMPD) spectroscopy and DFT calculations have been used to probe the most stable structures of a3(*) and a4(*) ions derived from both protonated pentaglycine (denoted G5) and pentaalanine (A5). The a3(*) and a4(*) ions derived from protonated A5 feature a CHR=N-CHR'- group at the N-terminus and an oxazolone ring at the C-terminus, as proposed previously [J. Am. Soc. Mass Spectrom. 19, 1788-1798 (2008)]. The isomeric a4(*) ion derived from A5 with a 3,5-dihydro-4H-imidazol-4-one ring structure was calculated to have a slightly better energy than the oxazolone, but the barrier to its formation is higher and there was no evidence of this ion in the IRMPD spectrum. By contrast, the a4(*) and [a4 - H2O](+) (denoted a4(0)) ions from G5 gave strikingly similar IRMPD spectra and both have the 3,5-dihydro-4H-imidazol-4-one ring structure similar to that recently reported for the [GGGG + H - H2O](+) ion [Int. J. Mass Spectrom. 316-318, 268-272 (2012)]. In the absence of a solvent molecule, the pathway to the oxazolone is calculated to be lower than those to thermodynamically more stable products, the a4(0) and the a4(*) with the 3,5-dihydro-4H-imidazol-4-one ring structure. Incorporation of one water molecule is sufficient to reduce the barrier to formation of the a4(0) of G5 to below that for formation of the oxazolone. On the equivalent potential energy surface for protonated A5 the barrier to formation of the a4(0) ion is 12.3 kcal mol(-1) higher than that for oxazolone formation and the a4(0) ion is not observed experimentally.

Urodynamic effect of 80 watt photoselective laser vaporization of the prostate.

OBJECTIVE: The aim of the analysis was to measure the pressure-flow urodynamic changes following GreenLight(™) laser vaporization of the prostate based on pressure-flow studies. MATERIAL AND METHODS: Sixty-two patients suffering from voiding dysfunction due to lower urinary tract symptoms underwent potassium titanyl phosphate (KTP) laser vaporization. A pressure-flow study was performed at baseline and at 3 months postoperatively. Symptoms and quality of life (QoL) were assessed using the International Prostate Symptom Score (IPSS) and questions regarding sexuality were assessed using the International Index of Erectile Function (IIEF). RESULTS: IPSS and QoL scores changed from 24 and 5 at baseline to 6 and 2 at 3 months, respectively. The initial median prostate volume was 35 ml (range 16-60 ml), the median maximum uroflow (Q max) was 9.2 ml/s (4-14.9 ml/s) and the median postvoiding residual urine was 80 ml (20-400 ml) (95% confidence interval 89.14, 135.44). The median IPSS and QoL score were significantly improved (p < 0.001). There was a significant decrease in median detrusor pressure at Q max from 83.1 to 40.45 cmH2O, and the median obstruction grade according to Schäfer's classification was also decreased significantly, from 4 to 1 postoperatively. CONCLUSION: This study showed that significant deobstruction can be demonstrated using a pressure-flow study at 3 months postoperatively.

Performance and attributes of liquid chromatography-mass spectrometry with targeted charge separation in quantitative analysis of therapeutic peptides.

Herein we describe a new method, targeted enhanced multiply charged scans (tEMC), for the quantification of therapeutic peptides in tandem mass spectrometry on the linear ion trap mass spectrometer. Therapeutic peptides with chain lengths between eight and 39 amino acid residues and charge states from 2+ to 6+ were used to evaluate and illustrate the method which relies on the ability to separate ions trapped in a linear ion trap according to their charges. In particular, interference from singly charged ions on multiply charged ions can be effectively minimized. The method requires optimization of relatively few parameters, the most important of which being the exit lens barrier (EXB) voltage, thereby offering substantial time saving in a high-throughput quantification environment that currently relies on selected reaction monitoring.

Conformation switching in gas-phase complexes of histidine with alkaline earth ions.

Infrared multiple photon dissociation spectroscopy of gas-phase doubly charged alkaline earth complexes of histidine reveals a transition from dominance of the zwitterion (salt bridge, SB) conformation with Ba2+ to substantial presence of the canonical (charge-solvated, CS) conformation with Ca2+. This result is a clear illustration of the importance of metal-ion size in governing the delicate balance between these two modes of complexation of gas-phase amino acids. The two conformational motifs are clearly distinguished by characteristic spectral features, confirmed by density functional theory simulated IR spectra of the low-energy conformers. As a further illustration of histidine complexation possibilities, the spectrum of the Na+His complex shows purely CS character and emphasizes the greater tendency toward SB character induced by the higher charge in the alkaline earth complexes. Calculation of the complete series of alkaline earth/histidine complexes confirms the increasing stability of the SB conformations relative to CS with increasing metal ion size, as well as showing that among SB conformations the most highly chelated conformation (SB3) is favored for small metals, whereas the most extended conformation (SB1) is favored for large metals. A decomposition of the binding thermochemistry shows that these thermochemical trends versus metal-ion size are due to differences in electrostatic binding energies, with relatively little contribution from the deformation and rearrangement energy costs of distorting the ligand framework.

Electrospray: from ions in solution to ions in the gas phase, what we know now.

There is an advantage for users of electrospray and nanospray mass spectrometry to have an understanding of the processes involved in the conversion of the ions present in the solution to ions in the gas phase. The following processes are considered: Creation of charge droplets at the capillary tip; Electrical potentials required and possibility of gas discharges; Evolution of charged droplets, due to solvent evaporation and Coulomb explosions, to very small droplets that are the precursors of the gas phase ions; Production of gas phase ions from these droplets via the Ion Evaporation and Charge residue models; Analytical uses of ESIMS of small ions, qualitative and quantitative analysis; Effects of the ESI mechanism on the analysis of proteins and protein complexes; Determination of stability constants of protein complexes; Role of additives such as ammonium acetate on the observed mass spectra.

1,2,4,5-Tetrakis(diazidomethyl)benzene.

The molecule of the title compound, C(10)H(6)N(24), lies on a crystallographic inversion centre located in the middle of the benzene ring. Steric overcrowding by the bulky N(3) groups is avoided by the tendency of four azide entities to be arranged parallel to the benzene ring and the other four azide groups to be arranged alternately above and below the benzene plane in a skeletal C(i) symmetry. The compound is of interest for high-energy research and as a precursor for the synthesis of carbon nanotubes, nanospheres or high-nitrogen carbon nitrides with great potential for biological and technological applications.

Gas-phase fragmentation of protonated benzodiazepines.

Protonated 1,4-benzodiazepines dissociate in the gas phase by the common pathway of CO elimination and by unique pathways dictated by the substituents; the latter typically differentiate one benzodiazepine from another. Protonated 3-dihydro-5-phenyl-1,4-benzodiazepin-2-one, the base diazepam devoid of substituents, dissociates by eliminating CO, HNCO, benzene, and benzonitrile. Mechanisms of these reactions are proposed with ionic products being resonance stabilized. The abundant [MH-CO]+ ion dissociates to secondary products via elimination of benzene, benzonitrile, the NH2 radical, and ammonia, yielding again ionic products that are stabilized by resonance.

Stable gas-phase radical cations of dimeric tryptophan and tyrosine derivatives.

Stable radical cations of dimeric amino acid derivatives of tryptophan and tyrosine were generated by collision-induced dissociation of [Cu(II)(diethylenetriamine)(amino acid derivative)2]*2+. The yields of the dimer radical cations were dependent on both the auxiliary ligand and the tryptophan or tyrosine derivatives used. Amino acid derivatives with an unmodified carboxylic acid group did not generate dimer radical cations. For the amino acid derivatives Ac-Trp-OMe and Ac-Trp-NH2 (Ac is N-acetyl; OMe and NH2 are the methyl ester and amide modifications of the C-terminal carboxylic group), no auxiliary ligand was required for generating the dimer radical cations. Collision-induced dissociation of the [Cu(II)(amino acid derivative)4]*2+ precursor generated the dimer radical cation [(amino acid derivative)2]*+. Stabilizing interactions, most likely involving hydrogen bonding, between the two amino acid derivatives are proposed to account for observation of the dimer radical cations. Dissociation of these ions yields protonated or radical cationic amino acid derivatives; these observations are consistent with the expectation of proton competition between monomeric units, whose proton affinities were calculated using density functional theory.

Hydration energies in the gas phase of select (MX)mM+ ions, where M+ = Na+, K+, Rb+, Cs+, NH4+ and X- = F-, Cl-, Br-, I-, NO2-, NO3-. Observed magic numbers of (MX)mM+ ions and their possible significance.

The sequential hydration energies and entropies with up to four water molecules were obtained for MXM(+) = NaFNa(+), NaClNa(+), NaBrNa(+), NaINa(+), NaNO(2)Na(+), NaNO(3)Na(+), KFK(+), KBrK(+), KIK(+), RbIRb(+), CsICs(+), NH(4)BrNH(4)(+), and NH(4)INH(4)(+) from the hydration equilibria in the gas phase with a reaction chamber attached to a mass spectrometer. The MXM(+) ions as well as (MX)(m)M(+) and higher charged ions such as (MX)(m)M(2)(2+) were obtained with electrospray. The observed trends of the hydration energies of MXM(+) with changing positive ion M(+) or the negative ion X(-) could be rationalized on the basis of simple electrostatics. The most important contribution to the (MXM-OH(2))(+) bond is the interaction of the permanent and induced dipole of water with the positive charge of the nearest-neighbor M(+) ion. The repulsion due to the water dipole and the more distant X(-) has a much smaller effect. Therefore, the bonding in (MXM-OH(2))(+) for constant M and different X ions changes very little. Similarly, for constant X and different M, the bonding follows the hydration energy trends observed for the naked M(+) ions. The sequential hydration bond energies for MXM(H(2)O)(n)(+) decrease with n in pairs, where for n = 1 and n = 2 the values are almost equal, followed by a drop in the values for n = 3 and n = 4, that again are almost equal. The hydration energies of (MX)(m)M(+) decrease with m. The mass spectra with NaCl, obtained with electrospray and observed in the absence of water vapor, show peaks of unusually high intensities (magic numbers) at m = 4, 13, and 22. Experiments with variable electrical potentials in the mass spectrometer interface showed that some but not all of the ion intensity differentiation leading to magic numbers is due to collision-induced decomposition of higher mass M(MX)(m)(+) and M(2)(MX)(m)(2+) ions in the interface. However, considerable magic character is retained in the absence of excitation. This result indicates that the magic ions are present also in the saturated solution of the droplets produced by electrospray and are thus representative of particularly stable nanocrystals in the saturated solution. Hydration equilibrium determinations in the gas phase demonstrated weaker hydration of the magic ion (NaCl)(4)Na(+).

Prospective randomized Phase II trial of pegylated doxorubicin in the management of symptomatic hormone-refractory prostate carcinoma.

BACKGROUND: Liposomal encapsulation of doxorubicin has been shown to reduce nonspecific delivery of this agent to normal tissue and to increase specific delivery to malignant cells. On the basis of doxorubicin's demonstrated clinical efficacy against hormone-refractory prostate carcinoma (HRPCA), the authors conducted a prospective, randomized Phase II clinical trial to evaluate the feasibility, toxicity, and therapeutic efficacy associated with the pegylated form of this agent. METHODS: Forty-eight patients with symptomatic HRPCA were randomized to receive pegylated liposomal doxorubicin at either 25 mg/m2 every 2 weeks for 12 cycles (Group A) or 50 mg/m2 every 4 weeks for 6 cycles (Group B). Thirty-eight of these 48 patients (79%) presented with severe pain (corresponding to a pain score of 7.5 on a visual analog scale [VAS] ranging from 0 to 10) due to osseous metastases. Therapeutic efficacy was assessed by serial evaluation of serum prostate-specific antigen (PSA) concentrations and by serial measurement of pain levels (using a VAS ranging from 0 to 10). Toxicity data were obtained using the National Cancer Institute of Canada/Cancer and Leukemia Group B criteria and the 30-item European Organization for Research and Treatment of Cancer Quality of Life Questionnaire. RESULTS: The median patient age was 68.9 years (range, 58-79 years), and the mean follow-up duration was 42 months. The mean pretreatment PSA level was 660.4 ng/mL (mean, 8-6340 ng/mL); an objective decrease in PSA levels (i.e., a decrease of > 50%) was observed in 8 of 31 patients (25.8%) in Group B, whereas no other patient in either group experienced such a decrease. The mean time to disease progression was 6.5 months, and the mean survival duration was 13.4 months. Patients in Group B had a significantly higher rate of response with respect to pain (52.6% vs. 28.6%; P = 0.04), and the mean 1-year survival rate also was significantly higher in Group B (42% vs. 15%; P = 0.02). Severe side effects were observed, with 24 patients (50%) experiencing World Health Organization Grade 3/4 toxicity. Toxicity types differed significantly between Group A and Group B; palmar-plantar erythrodysesthesia developed in 60% of patients in the former group (P < 0.0005), whereas tachycardia was more common in the latter group (39% of patients; P < 0.0005). No dose-limiting cardiotoxicities or hematotoxicities were documented. CONCLUSIONS: Pegylated liposomal doxorubicin yielded a noteworthy objective palliative response rate and a mean survival of 13 months for patients with symptomatic HRPCA. The dosage tested in the current study should be used in future Phase II and Phase III trials of pegylated liposomal doxorubicin-containing combination regimens for patients with HRPCA.

Management of chronic testalgia by microsurgical testicular denervation.

OBJECTIVES: Chronic testicular pain (CTP) is defined as uni- or bilateral, intermittent or continuous testicular discomfort of at least 3 months duration that interferes with the patient's daily activities and prompts him to seek medical advice is a rather common urological manifestation of chronic pain syndrome. Diagnosis and treatment of CTP has been a difficult and often unrewarding clinical situation. Success rates of conservative and surgical measures including epididymectomy and orchiectomy rarely exceed 55-73% and 10-40%, respectively. We report our experience on microsurgical testicular denervation as therapeutic option in CTP. PATIENTS AND METHODS: Following an extensive preoperative work-up (urine/semen cultures, transrectal ultrasound, testicular sonography, pain and orthopedic consultation) not revealing any pathologic abnormalities and a positive response to spermatic cord block, 35 patients underwent microsurgical testicular denervation. In brief, spermatic cord was dissected, vas deferens, cremasteric muscle and testicular vessels were separated. After identification of the testicular artery by application of vasodilatating agents using magnifying loops or the operating microscope, all structures besides the testicular artery, vas deferens and 1-2 lymphatic vessels were coagulated and transsected using bipolar diathermy. RESULTS: After a mean follow-up of 31.5 months 34/35 (96%) patients are completely pain-free; no intra- or postoperative complications were encountered. No case of testicular atrophy or hydrocele formation was observed during postoperative follow-up. CONCLUSIONS: Microsurgical testicular denervation results in reliable and reproducible excellent therapeutic success rates of 96% and should be integrated in the management of CTP at an early stage. High success rates require adequate and meticulous diagnostic work-up of the patients by spermatic cord block using saline as placebo and different local anaesthetics as an initial therapeutic armentarium predicting postoperative outcome.

[Analyses of work-relatedness of health problems among truck drivers by questionnaire survey].

In order to estimate occupational risk factors for health problems among truck drivers, a questionnaire survey of working conditions, job content in truck transportation, subjective symptoms and present illnesses was carried out among 541 truck transportation workers in 1997. The valid response rate was 85.7%, and 134 local truck drivers, 199 long-distance truck drivers and 71 clerical workers were analyzed. First, to examine occupational risk factors and health problems among the three groups, the authors analyzed working conditions, job content in truck transportation, subjective symptoms and present illnesses. Second, to estimate the work-relatedness of health problems among local truck drivers and long-distance truck drivers, logistic regression analyses were conducted, and odds ratios and 95% confidence intervals were computed. The prevalence rates of working factors affecting health problems of truck drivers were significantly higher than those of clerical workers in the items on irregular shift work, working environment, working posture, handling heavy materials, job stress due to overloading and long working time and limited time off. The prevalence rates for subjective symptoms (ringing in the ears, neck pain and low back pain) and present illnesses (hypertension, ulcers in the digestive tract, back injuries, whiplash injuries and hemorrhoids) among truck drivers were significantly higher than those of clerical workers. In logistic regression analyses, many work-related items except age, BMI and smoking habit showed significantly higher odds ratios for subjective symptoms and present illnesses of truck drivers. Odds ratios for hypertension, heart diseases and related subjective symptoms among local truck drivers were significantly increased by job career, twisting posture, vibration and driving stress. Odds ratios for gastro-duodenal diseases and related subjective symptoms were significantly increased by narrow working space, sleeping in the truck, driving distance, squatting posture and driving stress. Odds ratios for ringing in the ears among local truck drivers were significantly increased by job career, long working time, narrow working space, sleeping in the truck and driving stress. Odds ratios for musculo-skeletal diseases and related subjective symptoms were significantly increased by overwork, vibration, narrow working space, sitting posture and shortage of recess. Odds ratios for fatigue symptoms were significantly increased by the shortage of recess, vibration and driving stress. In order to cope with the health problems of truck drivers, it is recommended that working conditions and work loads for among truck drivers as described above be improved.