bluuebunny/crossref_metadata_2025 huggingface dataset:
Preclinical Profile of VX-950, a Potent, Selective, and Orally Bioavailable Inhibitor of Hepatitis C Virus NS3-4A Serine Protease
Authors: Perni Robert B. , Almquist Susan J. , Byrn Randal A. , Chandorkar Gurudatt , Chaturvedi Pravin R. , Courtney Lawrence F. , Decker Caroline J. , Dinehart Kirk , Gates Cynthia A. , Harbeson Scott L. , Heiser Angela , Kalkeri Gururaj , Kolaczkowski Elaine , Lin Kai , Luong Yu-Ping , Rao B. Govinda , Taylor William P. , Thomson John A. , Tung Roger D. , Wei Yunyi , Kwong Ann D. , Lin Chao
Published: February 2006

VX-950 is a potent, selective, peptidomimetic inhibitor of the hepatitis C virus (HCV) NS3-4A serine protease, and it demonstrated excellent antiviral activity both in genotype 1b HCV replicon cells (50% inhibitory concentration [IC
50
] = 354 nM) and in human fetal hepatocytes infected with genotype 1a HCV-positive patient sera (IC
50
= 280 nM). VX-950 forms a covalent but reversible complex with the genotype 1a HCV NS3-4A protease in a slow-on, slow-off process with a steady-state inhibition constant (

K
i

*) of 7 nM. Dissociation of the covalent enzyme-inhibitor complex of VX-950 and genotype 1a HCV protease has a half-life of almost an hour. A >4-log
10
reduction in the HCV RNA levels was observed after a 2-week incubation of replicon cells with VX-950, with no rebound of viral RNA observed after withdrawal of the inhibitor. In several animal species, VX-950 exhibits a favorable pharmacokinetic profile with high exposure in the liver. In a recently developed HCV protease mouse model, VX-950 showed excellent inhibition of HCV NS3-4A protease activity in the liver. Therefore, the overall preclinical profile of VX-950 supports its candidacy as a novel oral therapy against hepatitis C.
Rate of Elimination of
Wolbachia pipientis
by Doxycycline In Vitro Increases following Drug Withdrawal
Authors: Makepeace Benjamin L. , Rodgers Lisa , Trees Alexander J.
Published: February 2006

Wolbachia pipientis
is an obligate intracellular bacterium within the family
Anaplasmataceae
that infects many terrestrial arthropods and arthropod-transmitted nematodes (filariae). Several filarial species are major human pathogens, and antibiotics with activity against
Wolbachia
offer a promising new therapeutic approach, since the adult worms are relatively refractory to conventional anthelmintics but depend on
Wolbachia
for reproduction and viability. In a natural filarial parasite of cattle,
Onchocerca ochengi
, intermittent chemotherapy is adulticidal whereas the equivalent dose administered as a continuous treatment is not. To investigate this further and to aid the design of efficacious regimens for human therapy, we used
Wolbachia
-infected
Aedes albopictus
mosquito cells in vitro. Here, we describe for the first time the accelerated depletion of bacteria after antibiotic withdrawal relative to the rate of elimination in the continuous presence of the drug. Mosquito cells were incubated with doxycycline while changes in 16S (bacterial) and 18S (host) rRNA and rRNA genes were determined by quantitative PCR assays. In cultures treated for 7 or 14 days followed by 7 days of drug withdrawal, the
Wolbachia
-to-
Aedes
rRNA ratio declined by ∼6 log, whereas immediately after 14 or 21 days of continuous treatment, the reduction was only ∼4 log (
P
< 0.05). However, low levels of 16S rRNA remained after 21 days of treatment, irrespective of whether doxycycline was withdrawn. Application of similar methodology to related intracellular bacteria may reveal that this posttreatment effect is not restricted to
Wolbachia
and could have wider implications for the design of intermittent regimens for antibiotic chemotherapy.
Pharmacokinetic and Safety Evaluation of High-Dose Combinations of Fosamprenavir and Ritonavir
Authors: Shelton Mark J. , Wire Mary Beth , Lou Yu , Adamkiewicz Brigette , Min Sherene S.
Published: February 2006

High-dose combinations of fosamprenavir (FPV) and ritonavir (RTV) were evaluated in healthy adult subjects in order to select doses for further study in multiple protease inhibitor (PI)-experienced patients infected with human immunodeficiency virus type 1. Two high-dose regimens, FPV 1,400 mg twice a day (BID) plus RTV 100 mg BID and FPV 1,400 mg BID plus RTV 200 mg BID, were planned to be compared to the approved regimen, FPV 700 mg BID plus RTV 100 mg BID, in a randomized three-period crossover study. Forty-two healthy adult subjects were enrolled, and 39 subjects completed period 1. Due to marked hepatic transaminase elevations, predominantly with FPV 1,400 mg BID plus RTV 200 mg BID, the study was terminated prematurely. For FPV 1,400 mg BID plus RTV 100 mg BID, the values for plasma amprenavir (APV) area under the concentration-time profile over the dosing interval (τ) at steady state [AUC
(0-τ)
], maximum concentration of drug in plasma (
C
max
), and plasma concentration at the end of τ at steady state (
C
τ
) were 54, 81, and 26% higher, respectively, and the values for plasma RTV AUC
(0-τ)
,
C
max
, and
C
τ
were 49% higher, 71% higher, and 11% lower, respectively, than those for FPV 700 mg BID plus RTV 100 mg BID. For FPV 1,400 mg BID plus RTV 200 mg BID, the values for plasma APV AUC
(0-τ)
,
C
max
, and
C
τ
were 26, 48, and 32% higher, respectively, and the values for plasma RTV AUC
(0-τ)
,
C
max
, and
C
τ
increased 4.15-fold, 4.17-fold, and 3.99-fold, respectively, compared to those for FPV 700 mg BID plus RTV 100 mg BID. FPV 1,400 mg BID plus RTV 200 mg BID is not recommended due to an increased rate of marked hepatic transaminase elevations and lack of pharmacokinetic advantage. FPV 1,400 mg BID plus RTV 100 mg BID is currently under clinical evaluation in multiple PI-experienced patients.
Population Pharmacokinetics of Liposomal Amphotericin B in Pediatric Patients with Malignant Diseases
Authors: Hong Ying , Shaw Peter J. , Nath Christa E. , Yadav Satya P. , Stephen Katherine R. , Earl John W. , McLachlan Andrew J.
Published: February 2006

A population pharmacokinetic model of liposomal amphotericin B (L-AmB) in pediatric patients with malignant diseases was developed and evaluated. Blood samples were collected from 39 pediatric oncology patients who received multiple doses of L-AmB with a dose range from 0.8 to 5.9 mg/kg of body weight/day. The patient cohort had an average age of 7 years (range, 0.2 to 17 years) and weighed an average of 28.8 ± 19.8 kg. Population pharmacokinetic analyses were performed with NONMEM software. Pharmacokinetic parameters, interindividual variability (IIV), between-occasion variability (BOV), and intraindividual variability were estimated. The influence of patient characteristics on the pharmacokinetics of L-AmB was explored. The final population pharmacokinetic model was evaluated by using a bootstrap sampling technique. The L-AmB plasma concentration-time data was described by a two-compartment pharmacokinetic model with zero-order input and first-order elimination. The population mean estimates of clearance (CL) and volume of distribution in the central compartment (
V
1
) were 0.44 liters/h and 3.12 liters, respectively, and exhibited IIV (CL, 10%) and significant BOV (CL, 46% and
V
1
, 56%). The covariate models were CL (liters/h) = 0.44 ·
e
0.0152
·
(WT
−
21
)
and
V
1
(liters) = 3.12 ·
e
0.0241
 · 
(WT
 
−
 
21)
, where WT is the patient's body weight (kg) centered on the study population cohort median of 21 kg. Model evaluation by the bootstrap procedure indicated that the full pharmacokinetic model was robust and parameter estimates were accurate. In conclusion, the pharmacokinetics of L-AmB in pediatric oncology patients were adequately described by the developed population model. The model has been evaluated and can be used in the design of rational dosing strategies for L-AmB antifungal therapy in this special population.
Biochemical and Molecular Characterization of Three New Variants of AmpC β-Lactamases from
Morganella morganii
Authors: Power Pablo , Galleni Moreno , Ayala Juan A. , Gutkind Gabriel
Published: February 2006

Morganella morganii
produces an inducible, chromosomally encoded AmpC β-lactamase. We describe in this study three new variants of AmpC within this species with apparent pIs of 6.6 (M19 from
M. morganii
strain PP19), 7.4 (M29 from
M. morganii
strain PP29), and 7.8 (M37 from
M. morganii
strain PP37). After gene sequencing, deduced amino acid sequences displayed one to six substitutions when compared to the available
Morganella
AmpC sequences. An AmpR-encoding gene was also found upstream of
ampC
, including the LysR regulators' helix-turn-helix DNA-binding domain and the putative T-N
11
-A-protected region in the
ampR-ampC
intercistronic sequence. All three AmpC variants were purified from in vitro-generated derepressed mutants and showed overall similar kinetic parameters. None of the observed amino acid changes, occurring at the surface of the protein, appear to have a major influence in their catalytic properties.
Morganella
AmpCs exhibit the highest catalytic efficiencies (

k
cat

/

K
m

) on classical penicillins, cefoxitin, narrow-spectrum cephalosporins, and cefotaxime. Cefotaxime was more effectively hydrolyzed than other oxyimino-cephalosporins, whereas cefepime was 3 log-fold less efficiently hydrolyzed than other cephalosporins such as cephalothin. Several differences with other AmpC β-lactamases were found. Ampicillin was more efficiently hydrolyzed than benzylpenicillin. High

k
cat

/K
m

values were observed for oxacillin and piperacillin, which are usually poor substrates for AmpC. A fairly efficient hydrolysis of imipenem was detected as well. Aztreonam, carbenicillin, and tazobactam were effective transient inactivators of these variants.
VP35 Knockdown Inhibits Ebola Virus Amplification and Protects against Lethal Infection in Mice
Authors: Enterlein Sven , Warfield Kelly L. , Swenson Dana L. , Stein David A. , Smith Jeffery L. , Gamble C. Scott , Kroeker Andrew D. , Iversen Patrick L. , Bavari Sina , Mühlberger Elke
Published: February 2006

Phosphorodiamidate morpholino oligomers (PMO) are a class of uncharged single-stranded DNA analogs modified such that each subunit includes a phosphorodiamidate linkage and morpholine ring. PMO antisense agents have been reported to effectively interfere with the replication of several positive-strand RNA viruses in cell culture. The filoviruses, Marburg virus and Ebola virus (EBOV), are negative-strand RNA viruses that cause up to 90% lethality in human outbreaks. There is currently no commercially available vaccine or efficacious therapeutic for any filovirus. In this study, PMO conjugated to arginine-rich cell-penetrating peptide (P-PMO) and nonconjugated PMO were assayed for the ability to inhibit EBOV infection in cell culture and in a mouse model of lethal EBOV infection. A 22-mer P-PMO designed to base pair with the translation start site region of EBOV VP35 positive-sense RNA generated sequence-specific and time- and dose-dependent inhibition of EBOV amplification in cell culture. The same oligomer provided complete protection to mice when administered before or after an otherwise lethal infection of EBOV. A corresponding nonconjugated PMO, as well as nonconjugated truncated versions of 16 and 19 base residues, provided length-dependent protection to mice when administered prophylactically. Together, these data suggest that antisense PMO and P-PMO have the potential to control EBOV infection and are promising therapeutic candidates.
A NEURAL NETWORK CONTROLLER FOR THE PATH TRACKING CONTROL OF A HOPPING ROBOT INVOLVING TIME DELAYS
Authors: CHAITANYA V. SREE KRISHNA , REDDY M. SRINIVAS
Published: February 2006

In this paper a hopping robot motion with offset mass is discussed. A mathematical model has been considered and an efficient single layered neural network has been developed to suit to the dynamics of the hopping robot, which ensures guaranteed tracking performance leading to the stability of the otherwise unstable system. The neural network takes advantage of the robot regressor dynamics that expresses the highly nonlinear robot dynamics in a linear form in terms of the known and unknown robot parameters. Time delays in the control mechanism play a vital role in the motion of hopping robots. The present work also enables us to estimate the maximum time delay admissible with out losing the guaranteed tracking performance. Further this neural network does not require offline training procedures. The salient features are highlighted by appropriate simulations.
NEURO-FUZZY DECISION TREES
Authors: BHATT RAJEN B. , GOPAL M.
Published: February 2006

Fuzzy decision trees are powerful, top-down, hierarchical search methodology to extract human interpretable classification rules. However, they are often criticized to result in poor learning accuracy. In this paper, we propose Neuro-Fuzzy Decision Trees (N-FDTs); a fuzzy decision tree structure with neural like parameter adaptation strategy. In the forward cycle, we construct fuzzy decision trees using any of the standard induction algorithms like fuzzy ID3. In the feedback cycle, parameters of fuzzy decision trees have been adapted using stochastic gradient descent algorithm by traversing back from leaf to root nodes. With this strategy, during the parameter adaptation stage, we keep the hierarchical structure of fuzzy decision trees intact. The proposed approach of applying backpropagation algorithm directly on the structure of fuzzy decision trees improves its learning accuracy without compromising the comprehensibility (interpretability). The proposed methodology has been validated using computational experiments on real-world datasets.
Chromatin Modifications by Methylation and Ubiquitination: Implications in the Regulation of Gene Expression
Authors: Shilatifard Ali
Published: February 2006

It is more evident now than ever that nucleosomes can transmit epigenetic information from one cell generation to the next. It has been demonstrated during the past decade that the posttranslational modifications of histone proteins within the chromosome impact chromatin structure, gene transcription, and epigenetic information. Multiple modifications decorate each histone tail within the nucleosome, including some amino acids that can be modified in several different ways. Covalent modifications of histone tails known thus far include acetylation, phosphorylation, sumoylation, ubiquitination, and methylation. A large body of experimental evidence compiled during the past several years has demonstrated the impact of histone acetylation on transcriptional control. Although histone modification by methylation and ubiquitination was discovered long ago, it was only recently that functional roles for these modifications in transcriptional regulation began to surface. Highlighted in this review are the recent biochemical, molecular, cellular, and physiological functions of histone methylation and ubiquitination involved in the regulation of gene expression as determined by a combination of enzymological, structural, and genetic methodologies.
Estrogen and progestagens differentially modulate vascular proinflammatory factors
Authors: Sunday Lorraine , Tran Minh Minh , Krause Diana N. , Duckles Sue P.
Published: February 2006

The potential benefit of ovarian hormone replacement therapy in cerebrovascular disease is well supported by experimental observations but not by recent large, randomized clinical trials. This discrepancy points out the need for better understanding of the vascular actions of ovarian hormones as well as medroxyprogesterone acetate (MPA), a synthetic analog of progesterone (P) widely prescribed in combination with estrogens. Therefore, we investigated whether in vivo exposure to 17β-estradiol (E) and/or P or MPA modifies inflammation in the cerebral vasculature, a key process in the evolution of ischemic brain injury. Female rats were injected (ip) with LPS to induce inflammation, and 6 h later brains were taken for blood vessel isolation and Western blot analysis of the inflammatory enzymes inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2). In ovariectomized (O) females, LPS induced cerebrovascular iNOS and COX-2; however, this effect was significantly decreased when O animals were treated for 3 wk with E. In contrast, treatment of O females with either MPA or P exacerbated the cerebrovascular inflammatory response to LPS. In intact females, LPS induction of iNOS and COX-2 in cerebral vessels was found to vary with the stage of the estrous cycle: LPS had the greatest effect during estrus, when circulating estrogen is low and progesterone is high. Thus exposure to endogenous or exogenous ovarian hormones appears to modulate cerebrovascular inflammation. Anti-inflammatory effects of estrogen would attenuate ischemic brain injury; however, this vasoprotective benefit may be diminished in the presence of progestagens.
Serotonergic Modulation of Inspiratory Hypoglossal Motoneurons in Decerebrate Dogs
Authors: Brandes Ivo F. , Zuperku Edward J. , Stucke Astrid G. , Jakovcevic Danica , Hopp Francis A. , Stuth Eckehard A. E.
Published: February 2006

Inspiratory hypoglossal motoneurons (IHMNs) maintain upper airway patency. However, this may be compromised during sleep and by sedatives, potent analgesics, and volatile anesthetics by either depression of excitatory or enhancement of inhibitory inputs. In vitro data suggest that serotonin (5-HT), through the 5-HT2A receptor subtype, plays a key role in controlling the excitability of IHMNs. We hypothesized that in vivo 5-HT modulates IHMNs activity through the 5-HT2A receptor subtype. To test this hypothesis, we used multibarrel micropipettes for extracellular single neuron recording and pressure picoejection of 5-HT or ketanserin, a selective 5-HT2A receptor subtype antagonist, onto single IHMNs in decerebrate, vagotomized, paralyzed, and mechanically ventilated dogs. Drug-induced changes in neuronal discharge frequency ( Fn) and neuronal discharge pattern were analyzed using cycle-triggered histograms. 5-HT increased the control peak Fn to 256% and the time-averaged Fn to 340%. 5-HT increased the gain of the discharge pattern by 61% and the offset by 34 Hz. Ketanserin reduced the control peak Fn by 68%, the time-averaged Fn by 80%, and the gain by 63%. These results confirm our hypothesis that in vivo 5-HT is a potent modulator of IHMN activity through the 5-HT2A receptor subtype. Application of exogenous 5-HT shows that this mechanism is not saturated during hypercapnic hyperoxia. The two different mechanisms, gain modulation and offset change, indicate that 5-HT affects the excitability as well as the excitation of IHMNs in vivo.
Biphosphonates in Advanced Prostate and Renal Cell Cancer – Current Status and Potential Applications
Authors: Hoesl C.E. , Altwein J.E.
Published: February 2006

Objective:This review summarizes recent findings on the therapeutic benefits of biphosphonates in patients with advanced prostate or renal cell carcinoma (RCC). The role of biphosphonates in ADT-induced osteoporosis and delay of skeletal-related events (SREs) in metastatic bone disease is discussed. A brief overview on the proposed modes of action is given. Methods: Literature search of PubMed documented publications and abstracts from meetings. Results: Among the biphosphonates currently available, zoledronic acid is the only one known to be capable of delaying SREs in RCC and prostate cancer patients. Zoledronic acid counteracts cancer treatment-induced osteoporosis in men with prostate malignancies. The antitumor activity of biphosphonates found in vitro and in vivo is intriguing and has to be further assessed in clinical studies. Conclusion: Due to its unique properties, zoledronic acid is a breakthrough in the management of metastatic bone disease in patients with advanced prostate cancer and RCC. It significantly improves the patients’ quality of life, drastically prolongs time to first SRE, and showed a positive but not significant effect on survival.
Intravesical Gemcitabine in BCG-Refractory T1G3 Transitional Cell Carcinoma of the Bladder: A Pilot Study
Authors: Gacci Mauro , Bartoletti Riccardo , Cai Tommaso , Nerozzi Stefano , Pinzi Novello , Repetti Fabrizio , Viggiani Fabrizio , Ghezzi Paolo , Nesi Gabriella , Carini Marco
Published: February 2006

Objective: The aim of this pilot study is to analyze the safety and short-term efficacy of gemcitabine (GEM) as salvage intravesical therapy in a very selected population of bacille Calmette-Guérin (BCG)-resistant T1G3 patients. Methods: 9 recurrent BCG-refractory pT1G3 patients, unsuitable for radical treatment, were treated with GEM, and compared with 10 pT1G3 patients previously treated with at least two courses of transurethral resection plus BGC, with further conservative endovesical BCG administration. Results: Both intravesical administrations of GEM and BCG were generally well tolerated: no severe adverse events were reported. Of the 9 patients treated with GEM, 3 were recurrence-free after 13, 17 and 21 months and 7 kept an intact bladder, with an overall survival rate of 9 of 9. Among 10 patients treated with BCG instillation, 1 was recurrence-free after 27 months and 6 kept their bladders, with a survival rate of 8 of 10. Conclusions:Our experience confirms the high risk of tumor recurrence and progression of BCG-refractory pT1G3 transitional cell carcinoma. In this case, further BCG courses seem to be unsuitable, resulting in a high risk of tumor progression and mortality. The use of GEM in BCG-refractory pT1G3 patients has to be considered experimental until multicentric randomized studies with adequate follow-up are able to confirm the preliminary results of this pilot study.
Evaluation of a Contralateral Biopsy Specimen in Prostate Cancer Patients with Unilateral Suspicious Lesions
Authors: Sakamoto Naotaka , Ohtsubo Satoshi , Masaki Takurou , Iguchi Atsushi , Takeshita Morishige
Published: February 2006

Introduction: In patients with a clinically unilateral palpable and/or visible lesion confined to the prostate on digital rectal examination and transrectal ultrasonography, the findings of biopsy specimens of a clinically unsuspicious lobe do not reflect TNM staging results (2002 classification). In patients with such a unilateral lesion, we compared the biopsy results of a clinically unsuspicious lobe with the pathological assessment of the radical prostatectomy specimen and evaluated the importance of the results of biopsy specimens in an unsuspi cious lobe. Patients and Methods: Between April 2000 and August 2004, 97 prostatic cancer patients without neoadjuvant therapy underwent a radical retropubic prostatectomy. In the patients with a unilateral lesion on digital rectal examination and/or transrectal ultrasound, the preoperative prostate-specific antigen levels, the results of contralateral biopsy specimens, and contralateral cancer foci in radical prostatectomy specimens were examined. Results: Of 39 patients with a unilateral palpable and/or visible lesion, 15 had contralateral positive biopsy findings, while 24 had contralateral negative biopsy findings. In a pathological analysis of prostatectomy specimens, a significantly higher rate of clinically significant cancer foci and a larger cancer volume in a clinically unsuspicious lobe have been observed in patients with contralateral positive biopsy findings than in patients with contralateral negative biopsy findings (p < 0.001). Moreover, contralateral cancer foci in patients with a contralateral positive biopsy specimen exhibited a more ominous state, such as seminal vesicle invasion, extraprostatic extension, and a positive surgical margin, than those in patients with a contralateral negative biopsy specimen (40.0 vs. 8.3%, p = 0.017). However, in a pathological analysis of both ipsilateral and contralateral cancer foci, the proportion of ominous pathological findings did not differ between the patients with a contralateral positive biopsy and those with a contralateral negative biopsy. Conclusions: In patients with clinically unilateral palpable and/or visible tumors confined to the prostate, the results of a bilateral biopsy need not be used to determine the clinical stage. However, in patients with positive biopsy results for an unsuspicious lobe, urologists should perform an extended surgical resection.
Clinical Diagnosis in Men Undergoing Infertility Investigation in a University Hospital
Authors: Firmbach Pasqualotto Fabio , Bedin Pasqualotto Eleonora , Passos Sobreiro Bernardo , Hallak Jorge , Medeiros Fernanda , Marmo Lucon Antônio
Published: February 2006

Introduction: It was the aim of this study to assess whether the changes in the diagnostic techniques and treatment modalities have altered the epidemiology of male factor infertility in the last decade. Material and Methods: From September 1999 to July 2003, 822 patients were evaluated for infertility in a University Hospital. We divided our infertility patients according to the clinical diagnosis. Results: Most of the patients presented with varicocele (n = 282, 34.3%), idiopathic infertility (n = 260, 31.6%), or had had seminal tract obstruction (n = 85, 10.34%). Least common but equally important causes found were mumps (n = 43, 5.23%), pyospermia (n = 37, 4.5%), systemic diseases (n = 36, 4.37%), testicular failure (n = 34, 4.13%), cryptorchidism (n = 14, 1.7%), ejaculatory dysfunction (n = 11, 1.3%), genetics (n = 9, 1.1%), endocrinopathies (n = 4, 0.5%), testicular cancer (n = 4, 0.5%), and testicular torsion (n = 3, 0.36%). Conclusions: Even with the changes in reproductive healthcare in the last years, varicocele and seminal tract obstruction remain the leading causes of male infertility. However, clinicians should not forget other treatable causes of male infertility such as pyospermia, systemic diseases, or testicular cancer.
Videolaparoscopic Orchiectomy and Nephrectomy: Training Model in Rats
Authors: Matheus Wagner Eduardo , Leitão Victor Augusto , Thiel Marcelo , Rodrigues Palma Paulo César , Carvalho Fernandes Roni , Rodrigues Netto Jr. Nelson
Published: February 2006

Objective: Videolaparoscopic surgery conducted on small animals has proved to be of great importance for the improvement of surgical skills. This is a report utilizing an experimental model for laparoscopic orchiectomy and nephrectomy in training courses for urologists. Material and Methods: Of 350 American Wistar rats enrolled, 319 animals underwent laparoscopic orchiectomy and nephrectomy under intraperitoneal general anesthesia. Graspers, dissectors, and a 0-degree telescope were introduced into the peritoneal cavity by two trocars of 5 mm and one of 10 mm, respectively. Results: Of 350 rats enrolled, 15 (4.2%) died due to anesthetic complications and 16 (4.5%) due to cannibalism and stress during transport. A total of 319 rats were operated on, 178 underwent bilateral orchiectomy, two per model (356 operations), and in 141 animals one nephrectomy per model (141 operations) was performed. A total of 497 operations were performed involving 140 urologists. The animals were easy to handle providing adequate practice without the occurrence of any major intraperitoneal lesion and hemorrhage. Conclusion: Ne- phrectomy and orchiectomy are feasible in rats, and this model can be utilized for training videolaparoscopic surgeries.
Transurethral Electrovapor Resection versus Standard Transurethral Resection Treatment for a Large Prostate: A 2-Year Follow-Up Study Conducted in Taiwan
Authors: Liu Chih-Kuang , Lee Wen-Kai , Ko Ming-Chung , Chiang Han-Sun , Wan Kong-Sang
Published: February 2006

Introduction: Those patients featuring a large prostate and undergoing transurethral resection typically face a longer duration of surgery, they have a higher degree of hemorrhage and a higher irrigant volume required for the procedure, and they tend to reflect a higher incidence of morbidity than is the case for a small prostate. We report on the relative safety and efficacy of transurethral electrovapor resection of the prostate (TUVRP) as compared with standard transurethral resection of the prostate (TURP) for Taiwanese patients having a prostate size >50 ml. Patients and Methods: Seventy-six symptomatic benign prostatic hyperplasia patients featuring a prostate size >50 ml were randomized and underwent either TUVRP using wedge loop or standard TURP. Perioperative parameters, treatment outcome, and adverse events associated with the surgical procedure are assessed herein. Results: Mean operation time, changes in hemoglobin levels, resected prostate weight, perioperative irrigant volume needed, and incidences of recatheterizations and readmissions, all differed significantly when the two surgical procedures were compared. The average expense differences for the two procedures were impressive (p < 0.0001). No postoperative intergroup sexual dysfunction differences were noted. Clinical improvements following either TUVRP or TURP were significant and sustained for at least a period of 2 years. Intergroup comparison of International Prostate Symptom Score, quality of life, peak flow rate, and postvoid residual volume revealed no significant differences at 2 years (p = 0.45, 0.48, 0.12, and 0.29, respectively). The need for postoperative medical retreatment and/or reoperation did not differ significantly between the two groups (p = 0.62 and p = 0.56, respectively, at 6 months and p = 0.47 and p = 0.48, respectively, at 2 years). Conclusions: The TUVRP procedure offers advantages as regards a number of perioperative parameters when compared with the TURP procedure, and it seems that TUVRP might provide at least an equivalent treatment outcome as is the case for TURP.
Obstructive Primary Bladder Neck Disease: Evaluation of the Efficacy and Safety of α1-Blockers
Authors: Cisternino A. , Zeccolini G. , Calpista A. , De Marco V. , Prayer Galetti T. , Iafrate M. , Artibani W.
Published: February 2006

Objective: The efficacy and safety of using α1-adrenergic blockers for treating primary bladder neck obstruction in young and middle-aged men was assessed as the first therapeutic step, before surgery, in a symptomatic non-neurogenic selected group of patients. Materials and Methods: From January 1995 to December 2001, primary bladder neck obstruction was diagnosed in 41 men whose average age was 43 years. All of them were evaluated by a complete clinical history, American Urological Association (AUA) symptom score index, physical examination, uroflowmetry, transabdominal ultrasound prostatic volume determination, ultrasound post-void residual determination, videourodynamics including pressure-flow analysis and upper urinary tract screening with renal ultrasound or an excretory urogram. A full daily dose of α1-adrenergic blockers (alfuzosin or tamsulosin) was administered for at least 6 months. Successful treatment was defined as improved symptoms, voiding diary, maximum flow rate and pressure-flow parameters. Patients who did not gain improvement of symptoms with pharmacological treatment were offered surgery. Results: Overall, pharmacological treatment was successful in 29/41 patients (70.7%) whereas bladder neck endoscopic incision was mandatory in 12/41 (29.3%). Conclusions: α1-Blockers were effective and safe for treating young and middle-aged men with symptomatic bladder neck obstruction.
Valsalva Leak Point Pressure to Determine Internal Sphincter Deficiency in Stress Urinary Incontinence
Authors: Rodrigues Paulo , Afonso Yuri , Hering Flavio O. , Campagnari João C. , Azoubel Alberto
Published: February 2006

Introduction: Valsalva leak point pressure (VLPP) represents the global competence of the conjunctive forces around the urethra to support increased pressure from the abdominal cavity with transmission to the bladder. Assessment of VLPP has prognostic meaning, but measurement techniques are still subject to controversy. Patients and Methods: One hundred and eight consecutive women with no genital prolapse or bladder hyperactivity exclusively presenting with urinary stress incontinence were submitted to VLPP determination during urodynamic evaluation using a rectal and urethral catheter. Rectal pressure measurement served as the landmark in the determination of Valsalva’s maneuver. After determining the rectal pressure, the urethral probe was pulled out and the maneuver repeated. Results: Eighty-four cases (group I) presented leakage during Valsalva’s maneuver with the urethral catheter being in place. Group Ia (66.6%) had a reduction of 44.5 cm H2O in the rectal pressure after catheter removal. In group Ib, rectal leakage pressure increased after catheter removal from 76.5 ± 18.7 to 79.5 ± 24.7 cm H2O. Eight patients did not demonstrate urine leakage after catheter removal. In group II, 24 cases showed a rise in rectal leakage pressure to 76.2 ± 22 cm H2O, but urinary leakage was only observed after catheter removal. In group IIa (19 cases), the VLPP decreased by 12.6 ± 15 cm H2O, while in group IIb (5 cases) leakage occurred only in patients showing an increase of 22.2 ± 7 cm H2O in the rectal pressure after the second maneuver with the urethral catheter in position. Conclusions: Precise determination of the abdominal leak point pressure through Valsalva’s maneuver may be critical. The different techniques used for VLPP determination may render comparisons difficult. Rectal pressure measurement with no urethral catheter in place to monitor abdominal leak pressure seems to be more appropriate because it resembles clinical practice. Although lower abdominal leakage pressures may be found, this is not a uniform finding, and a higher incidence of type III incontinence may be expected, and critical analysis or painstaking repetition may be required in the case of lack of demonstration of urinary loss.
Efficacy of Dretler Stone Cone in the Treatment of Ureteral Stones with Pneumatic Lithotripsy
Authors: Gonen M. , Cenker A. , Istanbulluoglu O. , Ozkardes H.
Published: February 2006

Introduction: Ureteroscopic pneumatic lithotripsy has been used to treat ureteral calculi for more than 10 years. Owing to its low price and high degree of effectiveness, it has become the most popular ureteroscopic lithotripsy device in use worldwide. The major limitation of the technique is the occurrence of proximal fragment migration during intracorporeal lithotripsy. The Dretler Stone Cone is a new device developed to prevent stone migration during ureteroscopic lithotripsy. The aim of this study was to assess the efficacy and safety of this device during ureteroscopic pneumatic lithotripsy. Patients and Methods: Twenty-three consecutive patients having ureteral stones were treated with a 10-Fr semirigid ureteroscope, a Stone Cone™ Nitinol Retrieval Device, and a pneumatic lithotriptor. In all patients Stone Cones were placed under visual guidance through the working channel of the ureteroscope. Outcomes of this device were then compared with the outcomes of 23 previous patients with stones of similar sizes and locations who had undergone ureteroscopic pneumatic lithotripsy prior to the Stone Cone being available at our clinic. Results: All patients in the study group were stone-free after the procedure. No stone fragments were noted to migrate to proximal segments. Conclusions: The Dretler Stone Cone effectively prevents proximal stone migration and facilitates stone fragmentation during pneumatic lithotripsy with no risk of ureteral injury. It has only a small extra cost.
Comparison of Urinary Proteins in Calcium Stone Formers and Healthy Individuals: A Case-Control Study
Authors: Pourmand Gholamreza , Nasseh Hamidreza , Sarrafnejad Abdolfattah , Mojtahedi Alireza , Mehrsai Abdolrasoul , Hamidi Alamdari Darioush , Nourijelyani Keramat
Published: February 2006

Objective: This study aimed at comparing the urinary protein levels in calcium stone formers with those of healthy individuals. Patients and Methods: From January 2002 until June 2004, 100 calcium stone formers (mean age 38.6 ± 10.3 years), who had at least two episodes of calcium stone formation, were compared with 100 healthy individuals (mean age 33.8 ± 9.7 years). Their 24-hour urinary protein levels, using SDS-PAGE, were measured. Results: The mean 24-hour urinary Tamm-Horsfall protein (THP) levels were 3.3 ± 0.8 mg in the case group and 4.6 ± 1.9 mg in the controls, and the difference was not statistically significant (p = 0.53). However, the THP levels in individuals with and without bacteriuria were significantly different (15.8 ± 3.3 mg vs. 2.6 ± 1.0 mg, p = 0.0001). The mean 24-hour urinary albumin concentrations were 163.31 ± 15.1 mg in the case group and 74.26 ± 4.6 mg in the controls. The mean 24-hour urinary transferrin levels were 8.09 ± 2.7 mg in the case group and 0.40 ± 0.3 mg in the controls. The differences were statistically significant for both albumin and transferrin (p < 0.0001 and p = 0.0063, respectively). There were no significant differences in any other mean urinary protein concentrations between cases and controls. Conclusions: The THP level in the urine of stone formers is not quantitatively different from that of healthy individuals, but it increases in association with bacteriuria. Albumin and transferrin may play a presumptive role in stone formation.
Aqueous Garlic Extract Inhibits Protamine Sulfate-Induced Bladder Damage
Authors: Zeybek Ali , Çikler Esra , Saglam Beyhan , Ercan Feriha , Çetinel Şule , Sener Göksel
Published: February 2006

This morphological and biochemical study aims to investigate the antioxidant effects of chronic administration of aqueous garlic extract (AGE) on protamine sulfate (PS)-induced bladder injury. Wistar albino female rats were catheterized and intravesically infused with phosphate-buffered solution (control group) or PS (PS group) dissolved in phosphate-buffered solution. In the PS + AGE group after the PS instillation, AGE (1 ml/kg, i.p., corresponding to 250 mg/kg) was injected intraperitoneally for 3 days. Bladder morphology was investigated by light and scanning electron microscopy. Tissue samples were also obtained to determine bladder malondialdehyde (MDA) and glutathione levels. In the PS group, ulcerated areas, an irregular mucus layer, inflammatory cell infiltration and an increased number of mast cells were observed. In the PS + AGE group a relatively normal urothelial topography, glycosaminoglycan layer and a decreased number of mucosal mast cells and inflammatory cells were observed. Increased MDA levels as a result of PS induction led us to propose that free radicals may have a critical role in this injury. The significant decrease in MDA and increase in glutathione levels in the PS + AGE group was in accordance with morphological findings. Based on the results, AGE treatment significantly prevented PS-induced degenerative morphological and biochemical changes of urinary bladder mucosa.
Transitional Cell Carcinoma of the Fossa Navicularis in a Man with Preexisting Adenocarcinoma of the Prostate
Authors: Resnick M.J. , Wein A.J.
Published: February 2006

In this report we present a patient with a history of prostatic adenocarcinoma who was found to have a low-grade/low-stage transitional cell carcinoma of the fossa navicularis. The patient underwent transurethral resection and at approximately 2 years of follow-up he has no evidence of tumor recurrence. Very limited follow-up data exist on which to base management decisions, and this report lends support to the use of transurethral resection alone as a means to treat low-grade/low-stage lesions.
An Unusual Inguino-Scrotal Presentation of Disseminated Peritoneal Adenomucinosis
Authors: Novara Giacomo , Ficarra Vincenzo , Al Rabi Najati , Baldassarre Roberto , Artibani Walter
Published: February 2006

We report a rare case of disseminated peritoneal adenomucinosis presenting as an inguino-scrotal mass. Imaging studies showed the presence of a mass, with liquid content, expanding from right colon into the retrovesical space and downward into the right inguinal canal. Intraoperatively, we observed and removed an appendiceal gelatinous mass. The inguinal-scrotal mass consisted of a hernial sac filled with mucinous material. Histological examination allowed the diagnosis of peritoneal adenomucinosis.
Lesions in the Suprachiasmatic Nuclei Suppress Inflammatory Mediators in Sensitized Rats
Authors: Irie Masahiro , Endo Yutaka
Published: February 2006

Background: Although bronchial asthma is well known as an inflammatory disease that shows obvious circadian rhythms of airway narrowing, it remains to be elucidated whether the suprachiasmatic nucleus (SCN), a major circadian pacemaker, regulates inflammatory mediators relevant to asthma. Thus, we investigated the effects of electrolytic lesioning of the SCN on the antigen-induced immediate allergic response and the late allergic response (LAR) in male Brown Norway rats, i.e. in a model of allergic inflammation. Methods: The immediate allergic response, assessed by the histamine levels in plasma and bronchoalveolar lavage fluid (BALF), and the LAR, assessed by the eosinophilic infiltration into BALF and the lamina propria mucosae of the left main bronchus, were examined in three groups of 18 rats each, including (1) an unoperated control group, (2) a sham SCN-lesioned group, and (3) an SCN-lesioned group. Results: Both the plasma histamine levels and the number of eosinophils in bronchial tissues in the SCN-lesioned group were significantly lower than those in the other groups. The concentration of histamine and the number of eosinophils in the right BALF showed a similar pattern; however, no significant differences were found. Both plasma adrenaline and noradrenaline levels were highest during the LAR, whereas the corticosterone level was lowest in the SCN-lesioned group; again, no significant differences were obtained. Conclusions: These findings indicate that the SCN has a significant effect on the inflammatory mediators relevant to bronchial asthma.
Prevalence of FMR1 Repeat Expansions in Movement Disorders
Authors: Hall D.A. , Hagerman R.J. , Hagerman P.J. , Jacquemont S. , Leehey M.A.
Published: February 2006

We reviewed prevalence rates of fragile X mental retardation gene (FMR1) repeat expansions in movement disorder populations. Inclusion criteria included published epidemiological studies from systematic searches of Medline, Pubmed, Cochrane Databases and Web Science. Thirteen cross-sectional studies were carried out between 2003 and 2005. Subjects with ataxia showed higher than expected rates while those with essential tremor and parkinsonism showed lower rates. The heterogeneous design of the studies, inclusion criteria and mean age of subjects may have led to underestimation of FMR1 repeat expansion prevalence rates.
The Prevalence of Parkinson’s Disease in an Area of North Tyneside in the North-East of England
Authors: Porter Bob , Macfarlane Rob , Unwin Nigel , Walker Richard
Published: February 2006

Objectives: UK prevalence studies have demonstrated prevalence rates for Parkinson’s disease (PD) of 108 to 164 cases per 100,000. We aimed to calculate the prevalence of PD in an area of the North-East of England. Material and Methods: A case finding methodology was used to identify cases in North Tyneside with a population of 108,597 at the 2001 UK census. Results: 161 cases were identified giving crude and age-adjusted prevalence estimates of 148 cases (95% CI 124–174) and 139 cases (95% CI 116–162) per 100,000, respectively. The mean age was 74.1 years (range 44–96 years) with mean disease duration of 5.6 years. Conclusions: The prevalence of PD in North Tyneside is comparable with that of the rest of the UK. The prevalence of PD in the UK appears not to have changed greatly over the last 30 years.
The Social Composition of Homicide in Finland, 1960–2000
Authors: Kivivuori Janne , Lehti Martti
Published: February 2006

This article examines the social composition of homicide offenders and victims in Finland between 1960 and 2000. While many prior analyses have been based on victim-based cause-of-death statistics or aggregated rates of geographical units, the present data allowed the analysis of offender and victim populations at individual level. Both the rates and patterns of homicidal behaviour were analysed from the point of view of participants’ social characteristics. It was discovered that the social anchoring of homicide remained stable in the relative sense that the typical victims and offenders were males from the lowest stratum. However, the absolute societal position of the lowest stratum male transformed as he was made economically redundant, a change that was reflected in homicide populations. The article concludes with a discussion of the paradox between the rise of the welfare state and the expected but unrealized pacification of the lowest stratum male. Four suppressing mechanisms are suggested: alcohol availability, social selection effects, cultural factors and the unintended consequences of social policy measures. The last category refers to changes in social patterns of homicide, which made the reduction of homicide rates more difficult, meaning that the present homicide situation is particularly resistant to efforts of situational crime prevention.
Youth Problem: What's the Problem?
Authors: Halleröd Björn , Westberg Annika
Published: February 2006

The questions addressed in this study are: first, what factors determine the economic situation among the young, and, second, what aspects in youth have a long-term impact on their economic situation as adults? The empirical analysis builds on a three-wave panel covering a period of 16 years. Growth curve modelling is used to estimate changes over time. The main results are: Young people's incomes say little about their current standard of living or future earnings ability. Economic deprivation during youth is unrelated to the development of deprivation over time. Hence, the finding that young people in general face economic difficulties does not mean a problem with lasting implications. Labour market situation and household characteristics during youth are relativelyl unrelated to development later in life. However, long-term unemployment hampers young people's economy in the long run. Most importantly, the results of this analysis emphasize the importance of the reproduction of class and gender relations. It is these two fundamental aspects, more than anything else, that affect young people on their way into adulthood and in their future life as adults.
Bringing the ‘Community’ Back
Authors: Blanton Robert G.
Published: February 2006

Though a great deal of scholarship has been devoted to the relationship between economic interdependence and conflict — the ‘liberal peace’ — the conceptual and analytic focus of this body of literature remains quite narrow. Seeking to improve upon extant literature, I incorporate Deutsch's concept of the ‘security community’ to provide a broader theoretical foundation for the impact of economic interdependence upon interstate relations. Next, I empirically explore where trade, the key independent variable in this body of literature, fits within the broader web of interactions and transactions that contribute towards the integrative process. I then employ events data to assess the impact of integration upon four different measures of interstate interactions — two types of interactions (conflict and cooperation) across two issue areas (economic and military).