bluuebunny/crossref_metadata_2025 huggingface dataset:
METHYLENE BLUE INCREASES CONTRALATERAL TESTICULAR ISCHAEMIA–REPERFUSION INJURY AFTER UNILATERAL TESTICULAR TORSION
Authors: Inan Mustafa , Basaran Umit N , Dokmeci Dikmen , Yalcin Omer , Aydogdu Nurettin , Turan Nesrin
Published: August 2007

Testicular ischaemia–reperfusion injury is commonly seen in childhood. Infertility occurs in 25% of patients after unilateral testicular ischaemia. It is has been reported that methylene blue has a positive effect in the reparation of ischaemia–reperfusion injury in different tissues. Therefore, we hypothesized that methylene blue may prevent the hazardous effects of ischaemia–reperfusion injury in testicular tissue after unilateral testicular torsion.

Thirty‐two prepubertal Wistar‐albino rats were divided into four groups. Testicular torsion was created by rotating the right testis 720° in a clockwise direction for 5 h in all groups except for Group C, which was the sham control group. In Group T, bilateral orchiectomy was performed following the torsion period. In Group TD, both testes were removed 5 days after the torsion period. In Group MB, methylene blue (1 mg/kg, i.p.) was administered 40 min before detorsion and once daily over 5 days; then, both testes were harvested. Tissue levels of malondialdehyde (MDA), serum levels of creatine kinase (CK), mean testicular biopsy score (MTBS) and mean seminifer tubule diameter (MSTD) were determined.

There was a significant difference in MTBS between Groups T and TD (P < 0.05) in both ipsilateral and contralateral testes. In the contralateral testis, treatment with methylene blue decreased MTBS and MSTD (P < 0.05) and increased MDA levels (P < 0.05). In Group T, mean serum CK concentrations were higher than in any of the other groups (P < 0.05).

After 5 h of unilateral testicular torsion and a 5 day reperfusion period, serious tissue damage occurred on both the ipsilateral and contralateral sides. Serum CK concentrations may be an indicator for ischaemia, but not for ischaemia–reperfusion injury. Contrary to our hypothesis, methylene blue increased contralateral testicular damage after unilateral testicular torsion and exacerbated oxidative events.
EFFECTS OF YUNKE (TECHNETIUM‐99 CONJUGATED WITH METHYLENE DIPHOSPHONATE; 99Tc‐MDP) AND/OR COLLOIDAL CHROMIC PHOSPHATE PHOSPHONIUM‐32, ALONE AND IN COMBINATION, IN RATS WITH ADJUVANT ARTHRITIS
Authors: Wang Liming , Gu Qiangrong , Xu Yan , Li Shaohua , Gui Jianchao , Yang Jianping , Yao Qingqiang , Ji Yong
Published: August 2007

The present study investigated the therapeutic effects of both single and combination treatment with Yunke (technetium‐99 conjugated with methylene diphosphonate; 99Tc‐MDP) and colloidal chromic phosphate 32P (phosphonium‐32) in rats with adjuvant arthritis (AA).

Rats were randomly allocated to one of five groups: (i) normal control group (sham operated and treated with normal saline); (ii) AA control group (arthritis induced with adjuvant and treated with normal saline); (iii) 32P colloid group (arthritis induced with adjuvant and treated with a single intra‐articular injection of colloidal chromic phosphate phosphonium‐32 (0.02 mCi) and i.p. injections of normal saline every other day); (iv) Yunke group (arthritis induced with adjuvant and treated with i.p. Yunke (2.5 ¥ 10−3 mg/kg) every other day and single intra‐articular injection of normal saline); and (v) combination group (arthritis induced with adjuvant and treated with a combination of both therapies).

The left‐to‐right diameter (LRD) of the left hind ankle, serum levels of tumour necrosis factor (TNF) and interleukin (IL)‐1b and histological sections of the ankle joints were examined at different time points.

The LRD of the left hind ankle was smaller for the combination group compared with 32P colloid alone at Week 4 (7.11 ± 0.28 vs 7.57 ± 0.24 mm, respectively; P < 0.001). The combination treatment was more effective than 32P colloid alone in decreasing serum TNF (1.614 ± 0.368 vs 1.977 ± 0.255 ng/mL, respectively; P = 0.002 for Week 4) and IL‐1b (0.271 ± 0.027 vs 0.308 ± 0.020 ng/mL, respectively for Week 4; 0.209 ± 0.023 vs 0.255 ± 0.016 ng/mL, respectively for Week 6; both P = 0.001). Histologically, the combination group exhibited less synovium proliferation compared with Yunke treatment alone and decreased inflammatory cell infiltration compared with 32P colloid alone.

In conclusion, the combination of Yunke and 32P colloid is more effective in the treatment of AA in rats compared with Yunke or 32P colloid alone.
EFFECTS OF DIRECT HAEMOPERFUSION THROUGH FIBRES IMMOBILIZING POLYMYXIN B AND NAFAMOSTAT MESILATE ON ENDOTOXAEMIA IN CONSCIOUS GUINEA‐PIGS
Authors: Nakanowatari Yuichi , Nemoto Kayo , Hara Syunsuke , Ninomiya Norifumi , Yamamoto Yasuhiro
Published: August 2007

Direct haemoperfusion through a network of fibres immobilizing polymyxin B (PMX‐B) is used for the treatment of septic shock, but the mechanism underlying its clinical benefits remains unclear. The aims of the present study were to assess the actions of direct haemoperfusion through fibres immobilizing PMX‐B (PMX‐DHP) on the effects of exogenously administered endotoxin in conscious guinea‐pigs and to examine the difference in the effects of heparin compared with nafamostat mesilate (NM) used as an anticoagulant. Although nafamostat is widely used in Japan, the agent cannot necessarily be used elsewhere in the world. Therefore, the study aimed to investigate and elucidate the effectiveness of NM compared with heparin.

Colonic motion was monitored continuously via telemetry using a force transducer attached to the taenia caecum, whereas blood pressure was monitored using a carotid artery catheter. To establish a haemoperfusion circuit in each freely moving and conscious guinea‐pig, catheters were implanted in the carotid artery and the jugular vein, tunnelled subcutaneously, exteriorized at the back of the neck in contact with a lightweight tethering spring and attached to a swivel device at the top of the cage. On the day after the operation, lipopolysaccharide (LPS; Escherichia coli, O111:B4; 1 mg/kg) was administered i.v. and PMX‐DHP was conducted for 2 h. Heparin (50 IU/h) or NM (0.4 mg/h) was used as the anticoagulant. Furthermore, guinea‐pigs were administered a lethal dose of LPS (10 mg/kg) and the survival rate was examined for animals undergoing PMX‐DHP compared with control animals.

In guinea‐pigs treated with PMX‐DHP, relaxation of colonic longitudinal muscle caused by LPS was significantly suppressed, as were decreases in blood pressure. Of the two anticoagulants used, NM was more effective than heparin. In addition, PMX‐DHP significantly increased the survival rate of guinea‐pigs that received potentially lethal doses of LPS.

In ca onscious and unrestrained guinea‐pig endotoxaemia model, PMX‐DHP significantly improved intestinal paralysis and decreases in blood pressure. These effects were augmented more by NM than by heparin when an anticoagulant was used in the perfusion process. These findings suggest that haemoperfusion using PMX and NM performed in the early stage of endotoxaemia is an effective treatment.
PRESERVATION OF MECHANICAL AND ENERGETIC FUNCTION AFTER ADENOVIRAL GENE TRANSFER IN NORMAL RAT HEARTS
Authors: Sakata Susumu , Liang Lifan , Sakata Naoya , Sakata Yuri , Chemaly Elie R , Lebeche Djamel , Takewa Yoshiaki , Chen Jiqiu , Park Woo Jin , Kawase Yoshiaki , Hajjar Roger J
Published: August 2007

The aim of the present study was to examine the acute and chronic effects of adenoviral gene transfer on cardiac function in terms of left ventricular (LV) mechanoenergetic function. Recombinant adenoviral vector carrying β‐galactosidase and green fluorescent protein genes (Ad.βgal‐GFP) was used. Cardiac function was examined in cross‐circulated rat heart preparations, where end‐systolic/diastolic pressure–volume relationships (ESPVR/EDPVR), systolic pressure–volume area (PVA), LV relaxation rate, equivalent maximal elastance at mid‐range LV volume (eEmax at mLVV), coronary blood flow, coronary vascular resistance and myocardial oxygen consumption (VO2) were also measured.

To examine the ex vivo acute effects of the adenoviral vector, data were obtained before and 30–90 min after intracoronary infusion of Ad.βgal‐GFP in the excised, cross‐circulated hearts that underwent serotonin pretreatment. To examine the in vivo chronic effects of adenoviral gene transfer, normal rat hearts received Ad.βgal‐GFP or saline by a catheter‐based technique and data were obtained 3 days after the injection of Ad.βgal‐GFP or saline.

The ESPVR, EDPVR, LV relaxation rate, eEmax at mLVV, coronary blood flow and coronary vascular resistance remained unchanged in Ad.βgal‐GFP‐transfected hearts in both ex vivo acute and in vivo chronic experiments. Moreover, the ex vivo and in vivo transfection caused no change in the slope and VO2 intercept of the VO2–PVA relationship, VO2 for basal metabolism and for Ca2+ handling in excitation–contraction coupling and O2 costs of LV contractility.

These results indicate that adenoviral gene transfer has neither acute nor chronic toxic effects on LV mechanical and energetic function. A special combination of in vivo adenoviral gene transfer and a cross‐circulation experimental system may provide a useful novel strategy to explore the functional and mechanoenergetic role of specifically targeted genes in the diseased heart.
Comparative cost‐effectiveness of antiviral therapies in patients with chronic hepatitis B: A systematic review of economic evidence
Authors: Sun Xin , Qin Wen‐Xia , Li You‐Ping , Jiang Xu‐Hua
Published: August 2007

Background and Aim:  Economic efficiency of the alternative antiviral therapies for chronic hepatitis B has not been systematically investigated and their quality remains unknown. The aim of the present study was to systematically overview economic evidence of antiviral therapies for chronic hepatitis B.

Methods:  We searched six databases and eight major journals supplemented with screening references of eligible studies. Full economic evaluations comparing alternative antiviral therapies in patients with chronic hepatitis B virus infection were included. Two investigators assessed the study quality and transferability, independently. Data were analyzed qualitatively with adjustment when appropriate.

Results:  Fourteen studies (six modeling vs eight trials and database analyses) were included. Quality was high in five studies, moderate in one US and five Chinese studies, and low in three Chinese studies. The major problems of quality are costing methods and analysis and the presentation of results. In Australia and Poland, lamivudine‐preferred strategies dominated interferon (IFN)‐α and its related strategy from the health‐care sector perspective. In the US, adefovir salvage produced US$8446 per additional quality‐adjusted life years (QALY) compared with IFN‐α. In Spain, the cost of adefovir was US$34 840 for additional virological response. In Taiwan, the use of pegylated IFN‐α (pegIFN‐α) produced US$11 711.4 per additional QALY, compared with lamivudine. In China, the incremental cost‐effectiveness ratios of combination therapy lamivudine ranged from US$2860 to US$22 160 per additional loss of hepatitis B e antigen (HBeAg), and IFN‐α versus lamivudine ranged from US$2490 to US$8890 per additional loss of HBeAg.

Conclusion:  The cost‐effectiveness frontiers of treatment alternatives vary and are influenced by the comparators and socioeconomic conditions of countries. Lamivudine‐containing therapy is cost‐effective when newer antiviral agents (e.g. adefovir/pegIFN‐α) were not available. Economic methods should be further improved in studies, particularly in China.
Finite‐element analysis and experimental study on tensile fatigue behaviour of bitumen–stone adhesion
Authors: MO L. T. , HUURMAN M. , WU S. P. , MOLENAAR A. A. A.
Published: August 2007

Tensile fatigue behaviours of bitumen–stone adhesion were investigated using a dynamic mechanics analyser under stress‐controlled mode at two temperatures of 5 and 25°C and various controlled‐stress levels. Failure characteristics including interfacial failure and cohesive failure were examined using image analysis of fracture surfaces. Finite‐element analysis on stress distributions was conducted under different temperatures, film thickness and interfacial bonding conditions. A Coulomb–Mohr like criterion in combination with shear and normal stresses is proposed to deal with the extreme thin adhesive layer, which can be further simplified into an adhesive zone without significant loss of accuracy for stress analysis.
Experimental and numerical studies on dynamic crack growth in layered slate rock under wedge impact loads: part I—plane strain problem
Authors: ALAM M. R. , SWAMIDAS A. S. J. , MUNASWAMY K.
Published: August 2007

The experimental and numerical investigations presented in this paper were carried out to determine the splitting forces and crack propagation scenarios of naturally bedded layered slate rock. Splitting loads were determined by impact splitting of regular‐sized slate blocks under plane strain test loading conditions, using a hydraulic actuator with a wedge‐shaped indenter. The mechanical properties of slate blocks required for numerical analyses were obtained from detailed experimental testing. The velocity of dynamic crack propagation in slate blocks under indenting wedge impact loading was determined using a series of strain gauge sensors. Numerical studies were carried out using ABAQUS, a general purpose, finite element analysis (FEA) program. Mode I dynamic crack propagation was simulated numerically by the gradual releasing of the restrained node on the symmetric plane of the specimens. Mode I stress intensity factors were computed for different crack lengths and the results were compared with the plane strain material fracture toughness obtained from earlier experiments/FEA. Very good agreement was obtained between analysis results and the measured fracture toughness value of slate, for the applied impact splitting load. Using the equation derived from a parametric study, of results obtained from the numerical analysis of different sizes of slate blocks, the maximum theoretical impact splitting force was determined using the plane strain fracture toughness value obtained from FEA. The difference between the loads obtained from the experimental studies and the derived empirical equation, varied between + 4.96% and −32.34%.
Docosahexaenoic acid stimulates non‐amyloidogenic APP processing resulting in reduced Aβ levels in cellular models of Alzheimer's disease
Authors: Sahlin Charlotte , Pettersson Frida Ekholm , Nilsson Lars N. G. , Lannfelt Lars , Johansson Ann‐Sofi
Published: August 2007

Epidemiological studies suggest that a high intake of polyunsaturated fatty acids, such as docosahexaenoic acid (DHA), is associated with a reduced risk of Alzheimer's disease. Here, we examined the effects of DHA on amyloid precursor protein (APP) processing in cellular models of Alzheimer's disease by analysing levels of different APP fragments, including amyloid‐β (Aβ). DHA administration stimulated non‐amyloidogenic APP processing and reduced levels of Aβ, providing a mechanism for the reported beneficial effects of DHA in vivo. However, an increased level of APP intracellular domain was also observed, highlighting the need to increase our knowledge about the relevance of this fragment in Alzheimer's disease pathogenesis. In conclusion, our results suggest that the proposed protective role of DHA in Alzheimer's disease pathogenesis might be mediated by altered APP processing and Aβ production.
Isolation, purification and expansion of myelination‐competent, neonatal mouse Schwann cells
Authors: Honkanen Henrika , Lahti Outi , Nissinen Marja , Myllylä Riina M. , Kangas Salla , Päiväläinen Satu , Alanne Maria H. , Peltonen Sirkku , Peltonen Juha , Heape Anthony M.
Published: August 2007

Most studies of peripheral nerve myelination using culture models are performed with dorsal root ganglion neurons and Schwann cells pre‐purified from the rat. The potential of this model is severely compromised by the lack of rat myelin mutants and the published protocols work poorly with mouse cells, for which numerous myelin mutants are available. This is partly due to difficulties in obtaining sufficient quantities of myelination‐competent mouse Schwann cells. Here, we describe the isolation, purification and expansion of wild‐type, myelination‐competent Schwann cells from the sciatic nerves of 4‐day‐old mouse pups. The method consistently yields 1.9–3.3 × 106 of ∼95% pure Schwann cells from the sciatic nerves of 12–15 4‐day‐old mouse pups, within 14–20 days. The Schwann cell proliferation rate ranges from 2.7‐ to 4.30‐fold growth/week. Proliferation ceases within 4 weeks, when the cells become quiescent. Growth is reinduced by the presence of neurons; neuregulin is not sufficient for this effect. The Schwann cells isolated by this protocol are able to form compact myelin in culture, as judged by the segregated expression patterns of early (myelin‐associated glycoprotein) and late (myelin basic protein) myelination markers in a three‐dimensional neuron/Schwann cell coculture model. The Schwann cell batch yields are sufficient to perform 100–150 individual myelinating coculture assays. Employing mixed phenotype/genotype mouse neuron/Schwann cell cocultures, it will be possible to analyse the cell specificity of a mutation, and the cumulative effects of different mutations, without having to cross‐breed the animals.
Oxidative stress‐induced phosphorylation, degradation and aggregation of α‐synuclein are linked to upregulated CK2 and cathepsin D
Authors: Takahashi Makio , Ko Li‐wen , Kulathingal Jayanarayan , Jiang Peizhou , Sevlever Daniel , Yen Shu‐Hui C.
Published: August 2007

Intracellular accumulation of α‐synuclein (α‐Syn) as filamentous aggregates is a pathological feature shared by Parkinson's disease, dementia with Lewy bodies and multiple system atrophy, referred to as synucleinopathies. To understand the mechanisms underlying α‐Syn aggregation, we established a tetracycline‐off inducible transfectant (3D5) of neuronal lineage overexpressing human wild‐type α‐Syn. α‐Syn aggregation was initiated by exposure of 3D5 cells to FeCl2. The exposure led to formation of α‐Syn inclusions and oligomers of 34, 54, 68 kDa and higher molecular weights. The oligomers displayed immunoreactivity with antibodies to the amino‐, but not to the carboxyl(C)‐, terminus of α‐Syn, indicating that C‐terminally truncated α‐Syn is a major component of oligomers. FeCl2 exposure also promoted accumulation of S129 phosphorylated monomeric α‐Syn (Pα‐Syn) and casein kinase 2 (CK2); however, G‐protein‐coupled receptor kinase 2 was reduced. Treatment of FeCl2‐exposed cells with CK2 inhibitors (DRB or TBB) led to decreased formation of α‐Syn inclusions, oligomers and Pα‐Syn. FeCl2 exposure also enhanced the activity/level of cathepsin D. Treatment of the FeCl2‐exposed cells with pepstatin A or NH4Cl led to reduced formation of oligomers/inclusions as well as of ∼ 10 and 12 kDa truncated α‐Syn. Our results indicate that α‐Syn phosphorylation caused by FeCl2 is due to CK2 upregulation, and that lysosomal proteases may have a role in producing truncated α‐Syn for oligomer assembly.
Integrated bioinformatic and phenotypic analysis of RpoN‐dependent traits in the plant growth‐promoting bacterium Pseudomonas fluorescens SBW25
Authors: Jones Jacob , Studholme David J. , Knight Christopher G. , Preston Gail M.
Published: August 2007

The alternative sigma factor RpoN is a key regulator in the acclimation of Pseudomonas to complex natural environments. In this study we show that RpoN is required for efficient colonization of sugar beet seedlings by the plant growth‐promoting bacterium Pseudomonas fluorescens SBW25, and use phenotypic and bioinformatic approaches to profile the RpoN‐dependent traits and genes of P. fluorescens SBW25. RpoN is required for flagellar biosynthesis and for assimilation of a wide variety of nutrient sources including inorganic nitrogen, amino acids, sugar alcohols and dicarboxylic acids. Chemosensitivity assays indicate that RpoN‐regulated genes contribute to acid tolerance and resistance to some antibiotics, including tetracyclines and aminoglycosides. Gain of function changes associated with loss of RpoN included increased tolerance to hydroxyurea and Guanazole. Bioinformatic predictions of RpoN‐regulated genes show a close correspondence with phenotypic analyses of RpoN‐regulated traits and suggest novel functions for RpoN in P. fluorescens, including regulation of poly(A) polymerase. The reduced plant colonization ability observed for an rpoN mutant of P. fluorescens is therefore likely to be due to defects in multiple traits including nutrient assimilation, protein secretion and stress tolerance.
Epidermal growth factor receptor in colorectal carcinoma: correlation with clinico‐pathological prognostic factors
Authors: Abd El All H. S. , Mishriky A. M. , Mohamed F. A.
Published: August 2007

Objective  This study was undertaken to determine the relationship between epidermal growth factor receptor (EGFR) status in primary colorectal cancer (CRC) to different clinico‐pathological prognostic factors.

Method  Seventy‐nine primary CRC were studied using four scoring systems: 1‐ EGFR pharmDx score, 2‐ score modified from the Hercept test [J Histo cytochem, 52 (2004) 893], 3‐ two additive scores with different cutoff points [Mod Pathol, 11 (1998) 155], 4‐ two multiplicative scores with different cutoff points [Ann Oncol, 16 (2005) 102].

Results  More than 10% membranous EGFR reactivity was identified in 46.8% (37/79) of the tumours. The intensity was classified as mild, moderate and strong representing 8.9%, 20.3% and 17.7% respectively. Strong correlation was found between the EGFR pharmDx and the proposed scores, at different cutoff points (P < 0.01). A strong correlation was found between EGFR expression, advanced clinical stage (P < 0.01), nodal involvement (P < 0.01) and lympho‐vascular invasion (LV) (P < 0.05) in category I factors, poorly differentiated tumours in IIA (P < 0.05), infiltrative border configuration in IIB (P < 0.01), perineural invasion (PN) in III (P < 0.01), and larger tumours in IV (P < 0.01). Heterogenous staining was present in 46.3% of tumours and was associated with an increased score, LV and PN invasion and advanced clinical stage (P < 0.05).

Conclusion  Using a cut‐off point of 10%, similar results with different scoring systems were obtained, representing standardization for EGFR interpretation. EGFR expression is correlated with conventional clinico‐pathological prognostic factors.
Prospective, case‐matched study of heated and humidified carbon dioxide insufflation in laparoscopic colorectal surgery
Authors: Yeh C. H. , Kwok S. Y. , Chan M. K. Y. , Tjandra J. J.
Published: August 2007

Purpose  Laparoscopic colorectal surgery is often prolonged and may cause hypothermia. It is uncertain if heated and humidified carbon dioxide (CO2) in laparoscopic colorectal surgery is beneficial. This is a prospective case‐matched study on the use of heated and humidified CO2 in patients undergoing laparoscopic colorectal surgery.

Method  Twenty consecutive patients undergoing laparoscopic colorectal surgery with heated (36°C) and humidified (95%) CO2 were compared with 20 consecutive patients using standard CO2 (30.2°C). All procedures were performed by a single surgeon in an institution. The changes in core temperature during surgery, visual quality of images and the short‐term clinical outcome were documented.

Results  The core temperature fell during surgery in both groups. Although the fall of core temperature was more in the control group, it was not statistically significant (P > 0.05). The passage of flatus was more delayed in heated and humidified group (P = 0.004), but it did not affect the hospital discharge. All the other parameters, including the quality of visual images and the postoperative pain, were similar in both groups.

Conclusions  Despite better temperature maintenance (nonsignificant), pneumoperitoneum using heated and humidified CO2 gas did not appear to have any clinical benefits in laparoscopic colorectal surgery.
Laparoscopy in the management of closed loop sigmoid volvulus
Authors: Cartwright‐Terry T. , Phillips S. , Greenslade G. L. , Dixon A. R.
Published: August 2007

Objective  To investigate the feasibility and surgical outcome of elective laparoscopic surgery for acute closed loop sigmoid volvulus.

Method  A prospectively electronic database of colorectal laparoscopic procedures identified nine consecutive patients with sigmoid volvulus managed by colonoscopic decompression followed by same admission laparoscopic recto‐sigmoidectomy.

Results  Between January 2001 and February 2007, nine patients, ASA I (one), II (four), III (four) with sigmoid volvulus were treated: seven were women. Their age distribution was 37–87 years (median 64). The volvulus was the first episode in one patient, the second episode for four and the third (or more) for the remainder. The median operation time was 115 min (45–145). No anastomosis was de‐functioned. Postoperative analgesia was parenteral paracetamol (eight) supplemented by 10 mg oral morphine in one case; a ninth patient received patient controlled parenteral morphine for 36 h. Complications included: ileus (one), myocardial infarct (one) and wound infection (one). There was one death on day 32 from a brainstem infarct. Seven had an uncomplicated recovery. The median postoperative stay was 4 days (2–32).

Conclusion  Laparoscopic recto‐sigmoidectomy postcolonoscopic decompression is a good option for patients with sigmoid volvulus. Surgical complications are minimal and recovery is quick.
A prospective, single‐blind, randomized crossover trial of sacral vs pudendal nerve stimulation for interstitial cystitis
Authors: Peters Kenneth M. , Feber Kevin M. , Bennett Richard C.
Published: August 2007

OBJECTIVE

To compare sacral nerve stimulation (SNS) with pudendal nerve stimulation (PNS) for interstitial cystitis (IC).

PATIENTS AND METHODS

Twenty‐two patients with well‐documented, refractory IC had a tined lead placed at S3 and a second electrode implanted at the pudendal nerve via a posterior approach. In a blinded, randomized design, each lead was tested for 7 days. The best lead was implanted to a pulse generator and patients were followed at 1, 3 and 6 months.

RESULTS

The time required to place a sacral lead was 27.4 min, and a pudendal lead 19.6 min (P = 0.039). Of the 22 patients, 17 (77%) responded and had a permanent implant placed. PNS was chosen as the better lead in 77% and SNS in 24%. The order in which the lead was stimulated had no effect on the final lead implanted and there was no ‘carry‐over’ effect. The overall reduction in symptoms was 59% for PNS and 44% for SNS (P = 0.05). At 6 months after implantation, voids improved by 41% (PNS) and 33% (SNS), and mean voided volume increased 95% and 21%, respectively; validated IC questionnaires improved markedly and complications were minimal.

CONCLUSIONS

This is the first ‘blinded’ study of SNS vs PNS for IC. A pudendal lead was implanted successfully in all patients, and most chose PNS as better than SNS; the improvement was sustained over time.
Inhibitory roles of peripheral nitrergic mechanisms in capsaicin‐induced detrusor overactivity in the rat
Authors: Masuda Hitoshi , Kim Jang H. , Kihara Kazunori , Chancellor Michael B. , De Groat William C. , Yoshimura Naoki
Published: August 2007

OBJECTIVES

To investigate the peripheral role of nitric oxide (NO) in capsaicin‐induced detrusor overactivity (DO), as exogenously applied vanilloids can evoke NO release in urothelial cells but its functional role has not yet been reported.

MATERIALS AND METHODS

The effects of NG‐nitro‐l‐arginine methyl ester (L‐NAME), an inhibitor of NO synthase (NOS), on bladder activity during intravesical capsaicin (30 µm) instillation were examined by using continuous infusion cystometry in urethane‐anaesthetized rats. L‐NAME was administered intravenously (i.v., 20 mg/kg), intrathecally (i.t., 270 µg/rat), intracerebroventricularly (i.c.v., 270 µg/rat) or intravesically (10 mg/mL) before or during capsaicin instillation.

RESULTS

During cystometry with intravesical saline infusion, L‐NAME injected i.v., i.t. and i.c.v., but not intravesically, significantly increased the intercontraction intervals (ICI) and L‐NAME injected i.v., but not i.t., i.c.v. or intravesically, increased the maximum voiding pressure (MVP) without affecting the baseline pressure. Capsaicin instillation induced DO evidenced by a significant reduction in the ICI. L‐NAME administered i.v. further decreased the ICI and increased the MVP and the baseline pressure during capsaicin instillation. Co‐intravesical application of capsaicin and L‐NAME also similarly enhanced capsaicin‐induced DO. However, L‐NAME injected i.t. or i.c.v. had no effect on capsaicin‐induced DO. The excitatory effects of i.v and intravesical L‐NAME on the ICI, MVP and baseline pressure during capsaicin infusion were significantly suppressed by desensitization of C‐fibre afferent pathways by capsaicin pretreatment (125 mg/kg s.c., 4 days before cystometry).

CONCLUSION

These results indicate that locally released NO can suppress DO induced by capsaicin‐mediated C‐fibre activation and that central NO pathways are not involved in capsaicin‐induced DO.
Effect of the abnormal bladder when full on upper tract drainage using a combined cystometrogram‐99mTc‐mercapto‐acetyltriglycine renogram: a prospective study
Authors: Hoh Ivan M.Y. , Bomanji Jamshed B. , Nagabhushan Nagesh , Chu Andrew , Ell Peter J. , Neild Guy H. , Woodhouse Christopher R.J.
Published: August 2007

Authors from the UK present a prospective study into the effect of the full abnormal bladder on upper tract drainage, using a combined cystometrography procedure.

A new transportable ESWL machine for managing urinary stones is presented by authors from Italy, and its use in 233 patients is described. Its merits and demerits are outlined.

OBJECTIVE

To examine the relevance of bladder volume in patients with chronic hydronephrosis and abnormal bladder function who lose renal function even though the bladder or reservoir pressure is normal (<40 cmH20).

PATIENTS AND METHODS

In all, 20 patients (16 male; age range 17–67 years) were studied prospectively; 12 had a reconstructed bladder. All had progressive loss of renal function with a glomerular filtration rate (GFR) of >15 mL/min. The study was in three parts: a baseline 99mTc‐mercapto‐acetyltriglycine (MAG3) scan was performed with an empty bladder, then a combined full bladder cystometrogram (CMG) with 99mTc‐MAG3 study was done supine, and finally repeated in the sitting position. The pressure and volume changes together with the 99mTc‐MAG3 scintigraphic variables with and without a full bladder were compared.

RESULTS

Of the 17 patients with normotensive bladders, 13 (77%) had functional obstruction of the kidneys with a full bladder. In seven this was threshold dependent and occurred at a total mean (range) bladder volume of 348 (135–720) mL for both positions. In the other six patients there was minimal drainage of isotope from the kidneys even with the bladder empty. When the sitting position was compared with supine, gravity was more important for upper tract drainage in the reconstructed bladders. In five patients the detrusor pressure at which drainage began was close to zero.

CONCLUSIONS

In 13 of 17 patients (77%) the kidneys failed to drain with a full bladder despite ‘normal’ detrusor pressures. It remains to be seen whether bladder emptying designed to keep the urine volume below the obstructing threshold volume will prevent further loss of renal function.
Robotic abdominal sacrocolpopexy/sacrouteropexy repair of advanced female pelvic organ prolaspe (POP): utilizing POP‐quantification‐based staging and outcomes
Authors: Daneshgari Firouz , Kefer John C. , Moore Courtenay , Kaouk Jihad
Published: August 2007

Associate Editor

Ash Tewari

Editorial Board

Ralph Clayman, USA

Inderbir Gill, USA

Roger Kirby, UK

Mani Menon, USA

OBJECTIVES

To assess the management of advanced pelvic organ prolapse (POP) with robotic‐assisted abdominal sacrocolpopexy (RASC) and evaluate outcomes using the POP quantification scale (POP‐Q).

PATIENTS AND METHODS

Women with symptomatic stages III and IV POP were evaluated at our institution. After complete clinical assessment, including POP‐Q‐based physical examination and urodynamic studies, the patients underwent RASC with or without anti‐incontinence surgery in the presence (sacrouteropexy) or absence of uterus (sacrocolpopexy). Follow‐up examinations at 3 and 6 months included a POP‐Q‐based examination.

RESULTS

Fifteen women were consented for RASC; 12 underwent successful RASC, one required conversion to laparoscopic ASC, one to open ASC, and one to transvaginal repair. The mean (range) patient age was 64 (50–79) years. Before surgery, the mean POP‐Q stage was 3.1 (3–4) and the POP‐Q values for the anterior (Aa, Ba), posterior (Ap, Bp) and apex (C) of the vagina were: Aa − 0.9, Ba + 1.0, Ap − 1.0, Bp + 1.3, and C +2.1. After surgery, the mean POP‐Q stage was 0 and the POP‐Q values had improved to Aa − 2.29, Ba − 2.29, Ap − 2.65, Bp − 2.65, and C − 8.28. The mean (range) estimated blood loss during surgery was 81 (50–150) mL. The mean hospital stay was 2.4 (1–7) days. Seven patients had concurrent placement of a mid‐urethral sling and one patient had a concurrent Burch colposuspension.

CONCLUSIONS

These early results show that RASC is safe and efficacious, and that its anatomical outcomes compare favourably to the reported results for open or laparoscopic ASC.
Effect of age on the response to short‐term partial bladder outlet obstruction in the rabbit
Authors: Guven Ahmet , Mannikarottu Anita , Whitbeck Catherine , Chichester Paul , Leggett Robert E. , Kogan Barry A. , Levin Robert M.
Published: August 2007

OBJECTIVE

To compare the physiological and structural changes after short‐term partial bladder outlet obstruction (PBOO) in young and old rabbits, as PBOO results in marked contractile and histological alterations in the bladder.

MATERIALS AND METHODS

In all, 20 young (7–8‐week‐old) and 20 old (2 years old) male rabbits were divided into four subgroups of five each (four obstructed and one sham control rabbit). The rabbits in the groups were evaluated after 1, 3, 7 and 14 days of PBOO, respectively. At the end of the respective periods, cystometry and contractile responses to field stimulation (FS), ATP, carbachol and potassium chloride were determined. Full‐thickness sections of the bladder body and base were used to determine the vascular density, nerve density and smooth muscle/collagen ratios.

RESULTS

The bladder weight of young rabbits increased at 1–7 days of PBOO and returned toward control levels at 14 days of PBOO, while in old rabbits it was higher than the control during the entire experiment. For the young rabbits, the responses to field stimulation decreased progressively for 1, 3 and 7 days, and increased significantly at 14 days. For old rabbits there was a progressive decrease to a minimal response by 3 days of PBOO and the response remained at this level over 14 days. The contractile response to ATP, carbachol and KCl were similar to the responses to FS. The vascular density in both groups increased to a maximum at 7 days and then decreased toward control values at 14 days. For the young rabbits, nerve density decreased more than in old rabbits. In the old group, the smooth muscle/collagen ratio was increased throughout PBOO and was higher than in young rabbits. The connective tissue compartment was markedly greater than in the young rabbits and the basal mucosa had vacuoles which were not apparent in the young bladders.

CONCLUSIONS

This study shows that the adaptive changes to PBOO are faster in young rabbit bladders than in older rabbits.
Unclassified renal cell carcinoma: an analysis of 85 cases
Authors: Karakiewicz Pierre I. , Hutterer Georg C. , Trinh Quoc‐Dien , Pantuck Allan J. , Klatte Tobias , Lam John S. , Guille Francois , De La Taille Alexandre , Novara Giacomo , Tostain Jacques , Cindolo Luca , Ficarra Vincenzo , Schips Luigi , Zigeuner Richard , Mulders Peter F. , Chautard Denis , Lechevallier Eric , Valeri Antoine , Descotes Jean‐Luc , Lang Herve , Soulie Michel , Ferriere Jean‐Marie , Pfister Christian , Mejean Arnaud , Belldegrun Arie S. , Patard Jean‐Jacques
Published: August 2007

OBJECTIVES

To compare cancer‐specific mortality in patients with unclassified renal cell carcinoma (URCC) vs clear cell RCC (CRCC) after nephrectomy, as URCC is a rare but very aggressive histological subtype.

PATIENTS AND METHODS

Eighty‐five patients with URCC and 4322 with CRCC were identified within 6530 patients treated with either radical or partial nephrectomy at 18 institutions. Of 85 patients with URCC, 55 were matched with 166 of 4322 for grade, tumour size, and Tumour, Node and Metastasis stages. Kaplan‐Meier and life‐table analyses were used to address RCC‐specific survival. Subsequently, multivariate Cox regression analyses were used to test for differences in RCC‐specific survival in unmatched samples.

RESULTS

Of patients with URCC, 80% had Fuhrman grades III or IV, vs 37.8% for CRCC. Moreover, 36.5% of patients with URCC had pathologically confirmed nodal metastases, vs 8.6% with CRCC. Finally, 54.1% of patients with URCC had distant metastases at the time of nephrectomy, vs 16.8% with CRCC. Despite these differences in the overall analyses, after matching for tumour characteristics, the URCC‐specific mortality rate was 1.6 times higher (P = 0.04) in matched analyses and 1.7 times higher (P = 0.001) in multivariate analyses.

CONCLUSIONS

These findings indicate that URCC presents with a higher stage and grade, and even after controlling for the stage and grade differences, predisposes patients to 1.6–1.7 times the mortality of CRCC.
Cryoablation of small renal masses: assessment of the outcome at one institution
Authors: Bandi Gaurav , Wen Charles C. , Hedican Sean P. , Moon Timothy D. , Lee Fred T. , Nakada Stephen Y.
Published: August 2007

OBJECTIVE

To report our 5‐year experience with laparoscopic and percutaneous cryoablation (LCA and PCA) for managing small renal masses.

PATIENTS AND METHODS

We retrospectively analysed patients undergoing LCA and PCA between October 2000 and March 2006 at our institution. After approval from the Institutional Review Board, charts were reviewed retrospectively for variables during and after CA, and for clinical outcomes, the latter including the efficacy of the procedure in achieving overall, cancer‐specific and recurrence‐free survival.

RESULTS

In all, 78 patients had CA of 88 small renal masses, by LCA in 58 and PCA in 20. The median American Society of Anesthesiology score was 3 and the mean body mass index was 30 kg/m2. All procedures were done under general anaesthesia, with a mean anaesthesia time of 220 min. The mean tumour size was 2.6 cm and the mean hospital stay was 2.1 days. At a mean follow‐up of 19 months, the overall, cancer‐specific and recurrence‐free survival rates were 88.5%, 100% and 98.7%, respectively. Four patients required a repeat treatment due to persistent disease and one had progression to locally advanced disease. Five patients had complications during CA and seven had complications afterward.

CONCLUSION

This study suggests that CA is a safe, minimally invasive treatment option for patients with small renal masses, at the intermediate‐term follow‐up.
A pilot study on the early use of the vacuum erection device after radical retropubic prostatectomy
Authors: Köhler Tobias S. , Pedro Renato , Hendlin Kari , Utz William , Ugarte Roland , Reddy Pratap , Makhlouf Antoine , Ryndin Igor , Canales Benjamin K. , Weiland Derek , Nakib Nissrine , Ramani Anup , Anderson J. Kyle , Monga Manoj
Published: August 2007

OBJECTIVE

To evaluate the effect of the early use of the vacuum erection device (VED) on erectile dysfunction (ED) and penile shortening after radical retropubic prostatectomy (RP), as these are important concerns for men choosing among treatment alternatives for localized prostate cancer.

PATIENTS AND METHODS

Twenty‐eight men undergoing RP were randomized to early intervention (1 month after RP, group 1) or a control group (6 months after RP, group 2) using a traditional VED protocol. An International Index of Erectile Function (IIEF) score of >11 (no, mild or mild to moderate ED) was required as a baseline criterion for inclusion in the study. Only patients in whom unilateral or bilateral nerves were spared were subsequently randomized. Patients in group 1 followed a daily rehabilitation protocol consisting of 10 min/day using the VED with no constriction ring, for 5 months. Patients were evaluated with the IIEF‐5 questionnaire and measurements of penile flaccid length, stretched length, prepubic fat pad, and midshaft circumference before and at 1, 3, 6, 9 and 12 months after RP; the mean (range) last follow‐up visit was 9.5 (6–12) months after RP.

RESULTS

The mean (sd) baseline IIEF scores were similar in groups 1 and 2, at 21.1 (4.6) and 22.3 (3.3), respectively (P = 0.54). The IIEF scores were significantly higher in group 1 than group 2 at 3 months, at 11.5 (9.4) vs 1.8 (1.4) (P = 0.008) and at 6 months, at 12.4 (8.7) vs 3.0 (1.9) (P = 0.012) after RP. There were no significant changes in penile flaccid length, prepubic fat pad, or mid‐shaft circumference in either group. Stretched penile length was significantly decreased at both 3 and 6 months, by ≈ 2 cm (P = 0.013) in group 2. By contrast, stretched penile length was preserved in group 1 at all sample times. At the last follow‐up, the proportion of men with a mean loss of penile length of ≥ 2 cm was significantly lower in group 1 than group 2 (two/17, 12%, vs five/11, P = 0.044).

CONCLUSIONS

Initiating the use of a VED protocol at 1 month after RP improves early sexual function and helps to preserve penile length.
A randomized double‐blind placebo‐controlled multicentre study to explore the efficacy and safety of tamsulosin and tolterodine in women with overactive bladder syndrome
Authors: Robinson Dudley , Cardozo Linda , Terpstra Gerben , Bolodeoku John ,   the Tamsulosin Study Group
Published: August 2007

OBJECTIVES

To evaluate the efficacy of tamsulosin oral‐controlled absorption system (OCAS) vs placebo in overactive bladder (OAB), to evaluate the safety and tolerability of once‐daily dosing with tamsulosin OCAS, and to compare the efficacy and safety with tolterodine extended‐release (ER).

PATIENTS AND METHODS

A parallel‐group, multicentre, multinational study was conducted with a single‐blind placebo run‐in period of 2 weeks, followed by a randomized, double‐blind, double‐dummy active and placebo‐controlled treatment period of 6 weeks; women (aged 18–70 years) with symptoms of OAB for ≥ 3 months were recruited. Women were randomized to receive one of four doses of tamsulosin OCAS (0.25, 0.5, 1.0 or 1.5 mg), 4 mg of tolterodine ER, or placebo once daily for 6 weeks. The primary efficacy variable was the change in the mean number of voids/24 h. Secondary efficacy variables included change from baseline in; mean volume voided per void, mean number of incontinence episodes/24 h, mean number of urgency episodes/24 h and in quality of life (QoL), as assessed using the Kings Health Questionnaire (KHQ).

RESULTS

Overall, 364 women were randomized; the primary efficacy analysis showed that the difference from placebo in the mean number of voids/24 h was not statistically significant for tamsulosin OCAS 1.5 mg (P = 0.189). There was no statistically significant difference for tolterodine ER 4 mg vs placebo in the mean number of voids/24 h (P = 0.353). Similarly, for the secondary outcome variables there was no statistically significant difference between tamsulosin and placebo. Although women taking tolterodine ER 4 mg had a consistently greater increase in mean voided volume/void and consistent decreases in incontinence episodes/24 h, urgency episodes/24 h and episodes of nocturia/24 h, this was not statistically significant. There was no significant improvement in QoL scores across the treatment groups. Tamsulosin OCAS was well tolerated and the proportion of women discontinuing because of adverse events was low (4.7%).

CONCLUSION

Tamsulosin is not effective for treating OAB in women and the evidence from this study does not support its use on an empirical basis.
Around the world in 10 million years: biogeography of the nearly cosmopolitan true toads (Anura: Bufonidae)
Authors: Pramuk Jennifer B. , Robertson Tasia , Sites Jack W. , Noonan Brice P.
Published: August 2007

Aim  The species‐rich family of true toads (Anura: Bufonidae) has been the focus of several earlier studies investigating the biogeography of geographically widespread taxa. Herein, we employ newly developed Bayesian divergence estimate methods to investigate the biogeographical history of this group. Resulting age estimates are used to test several key temporal hypotheses including that the origin of the bufonid clade pre‐dates Gondwanan vicariance (~105 million years ago, Ma). Area cladograms are also invoked to investigate the geographical origin of the family.

Location  Worldwide, except the Australia–New Guinea plate, Madagascar and the Antarctic.

Methods  A phylogenetic hypothesis of the relationships among true toads was derived from analysis of 2521 bp of DNA data including fragments from three mitochondrial (12S, tRNAval, 16S) and two nuclear (RAG‐1, CXCR‐4) genes. Analysis of multiple, unlinked loci with a Bayesian method for estimating divergence times allowed us to address the timing and biogeographical history of Bufonidae. Resulting divergence estimates permitted the investigation of alternative vicariance/dispersal scenarios that have been proposed for true toads.

Results  Our area cladogram resulting from phylogenetic analysis of DNA data supports a South American origin for Bufonidae. Divergence estimates indicate that the family originated earlier than had been suggested previously (78–99 Ma). The age of the enigmatic Caribbean clade was dated to the late Palaeocene–early Eocene. A return of bufonids to the New World in the Eocene was followed by rapid diversification and secondary expansion into South America by the early Oligocene (Rupelian).

Main conclusions  The South American origin of Bufonidae in the Upper Cretaceous was followed by relatively rapid expansion and radiation around the globe, ending with a return to the Americas via a Eurasian/North American land bridge in the Eocene. Though the exact route of this dispersal (Beringia or North Atlantic) remains unclear, an argument is made for the less frequently invoked North Atlantic connection. The origin of the enigmatic Caribbean lineage was found to be consistent with colonization following the bolide impact at the K/T boundary. These findings provide the first, firm foundation for understanding true toad divergence times and their truly remarkable and global radiation.