bluuebunny/crossref_metadata_2025 huggingface dataset:
Streptomycin as a selective agent to facilitate recovery and isolation of introduced and indigenous Sphingomonas from environmental samples
Authors: Vanbroekhoven Karolien , Ryngaert Annemie , Bastiaens Leen , Wattiau Pierre , Vancanneyt Marc , Swings Jean , De Mot René , Springael Dirk
Published: October 2004

Sphingomonas is an organism of major interest for the degradation of organic contaminants in soils and other environments. A medium based on the aminoglycoside antibiotic streptomycin (Sm) was developed, which, together with the yellow pigmentation of Sphingomonas, facilitated the detection, recovery and quantification of culturable Sphingomonas from soils. All 29 previously described bacterial strains belonging to 17 different Sphingomonas species were able to grow on mineral media containing 200 µg ml−1 streptomycin, showing that the capacity to resist high concentrations of Sm is a common characteristic within Sphingomonas. Incorporation of Sm into the mineral medium led to a significant reduction in the background microbial population and a concomitant 100 times more sensitive detection of Sphingomonas inoculated in non‐sterile soil matrices. The Sm‐containing medium was used to examine a variety of hydrocarbon‐contaminated soils for the presence and biodiversity of Sphingomonas. Incorporation of Sm in the medium led to a significant increase in the number of yellow‐pigmented colonies. Comparison of contaminated and non‐contaminated soils derived from the same site revealed colonization by culturable yellow‐pigmented Sm‐resistant bacteria of the polluted location solely. Both yellow and non‐yellow‐pigmented colonies were purified from plates containing glucose and Sm, and BOX‐polymerase chain reaction (PCR) was used to sort out clonally related strains. Representative strains from the major BOX‐PCR clusters were identified using FAME and partial 16S rRNA gene sequencing. Forty‐eight of 58 Sm‐resistant isolates were identified as Sphingomonas sp. Streptomycin‐resistant Sphingomonas isolates generated BOX‐PCR diversity patterns that were site dependent and represented different species mainly belonging to Sphingomonas subgroups containing species formerly designated as Sphingopyxis and Sphingobium. The ability to degrade phenanthrene was only found in a minority of the Sphingomonas isolates, which all originated from soils containing high phenanthrene concentrations.
Bacterial endosymbionts of insects: insights from comparative genomics
Authors: Gil Rosario , Latorre Amparo , Moya Andrés
Published: October 2004

The development of molecular techniques for the study of uncultured bacteria allowed the extensive study of the widespread association between insects and intracellular symbiotic bacteria. Most of the bacterial endosymbionts involved in such associations are γ‐proteobacteria, closely related toEscherichia coli. In recent years, five genomes from insect endosymbionts have been sequenced, allowing the performance of extensive genome comparative analysis that, as a complement of phylogenetic studies, and analysis on individual genes, can help to understand the different traits of this particular association, including how the symbiotic process is established, the explanation of the special features of these microbial genomes, the bases of this intimate association and the possible future that awaits the endosymbionts with extremely reduced genomes.
Effects of dietary fatty acids on insulin sensitivity and secretion
Authors: Manco Melania , Calvani Menotti , Mingrone Geltrude
Published: October 2004

Globalization and global market have contributed to increased consumption of high‐fat, energy‐dense diets, particularly rich in saturated fatty acids( SFAs). Polyunsaturated fatty acids (PUFAs) regulate fuel partitioning within the cells by inducing their own oxidation through the reduction of lipogenic gene expression and the enhancement of the expression of those genes controlling lipid oxidation and thermogenesis. Moreover, PUFAs prevent insulin resistance by increasing membrane fluidity and GLUT4 transport. In contrast, SFAs are stored in non‐adipocyte cells as triglycerides (TG) leading to cellular damage as a sequence of their lipotoxicity. Triglyceride accumulation in skeletal muscle cells (IMTG) derives from increased FA uptake coupled with deficient FA oxidation. High levels of circulating FAs enhance the expression of FA translocase the FA transport proteins within the myocites. The biochemical mechanisms responsible for lower fatty acid oxidation involve reduced carnitine palmitoyl transferase (CPT) activity, as a likely consequence of increased intracellular concentrations of malonyl‐CoA; reduced glycogen synthase activity; and impairment of insulin signalling and glucose transport. The depletion of IMTG depots is strictly associated with an improvement of insulin sensitivity, via a reduced acetyl‐CoA carboxylase (ACC) mRNA expression and an increased GLUT4 expression and pyruvate dehydrogenase (PDH) activity. In pancreatic islets, TG accumulation causes impairment of insulin secretion. In rat models, β‐cell dysfunction is related to increased triacylglycerol content in islets, increased production of nitric oxide, ceramide synthesis and β‐cell apoptosis. The decreased insulin gene promoter activity and binding of the pancreas‐duodenum homeobox‐1 (PDX‐1) transcription factor to the insulin gene seem to mediate TG effect in islets. In humans, acute and prolonged effects of FAs on glucose‐stimulated insulin secretion have been widely investigated as well as the effect of high‐fat diets on insulin sensitivity and secretion and on the development of type 2 diabetes.
Role of early insulin secretion in postglucose‐loading hyperglycaemia and postfat‐loading hyperlipidaemia: comparing nateglinide and glibenclamide for acute effects on insulin secretion in OLETF rats
Authors: Mori Y. , Kitahara Y. , Miura K. , Mine T. , Tajima N.
Published: October 2004

Aim:  The aim of this study was to clarify the role of an early insulin secretion in postprandial hyperglycaemia and hyperlipidaemia; a study using spontaneously type 2 diabetic Otsuka Long‐Evans Tokushima Fatty rats with visceral obesity was performed to investigate the acute effect of nateglinide (NAT) vs. glibenclamide (GB) on increases in glucose after glucose loading and on increases in triglyceride (TG) after fat loading.

Methods:  Fasting rats were given 50 mg/kg of NAT, 1 mg/kg of GB or 5% methyl cellulose (vehicle) as control and then immediately given oral glucose 1 g/kg.

Results:  An acute increase in insulin levels in portal blood peaked at 15 min in the NAT group, while insulin levels in the GB group continued to increase significantly after 60 min. Glucose levels in peripheral blood were significantly lower in the NAT group at 30 and 60 min and in the GB group at 120, 180 and 270 min after glucose loading, compared with those in the vehicle group. Subsequently, fasting rats were given NAT, GB or vehicle and then immediately given oral fat emulsion (soy oil 2 g/kg). An acute increase in insulin secretion was seen with NAT, peaking at 30 min, while TG, chylomicron and very low‐density lipoprotein levels after fat loading were shown to be significantly lower with NAT than with vehicle. However, the continued insulin secretion observed with GB led to no significant decrease in TG levels after fat loading. In addition, lipoprotein lipase mRNA expression in adipose tissue increased significantly 120 min after NAT administration in comparison with baseline. This increase was not noted with GB administration.

Conclusion:  Abnormalities in early insulin secretion are closely associated with the pathogenesis of various disease conditions that combine to characterize type 2 diabetes, suggesting that normalizing early insulin response in portal blood represents an important treatment not only for postprandial hyperglycaemia but also for postprandial hyperlipidaemia.
Gliclazide modified release*: results of a 2‐year study in patients with type 2 diabetes
Authors: Drouin P. , Standl E. ,   for the Diamicron MR Study Group
Published: October 2004

Aim:  To evaluate the efficacy and safety of gliclazide modified release (MR), alone or combined with other oral antidiabetic drug(s) over 2 years in type 2 diabetic patients.

Methods:  Two consecutive periods: (i) a 10‐month, double‐blind comparative study, where 800 type 2 diabetic patients were randomized either to gliclazide MR (30–120 mg) once daily or to gliclazide (80–320 mg) twice daily. All the patients were then treated with gliclazide MR for a 2‐month switch period; (ii) 549 patients were subsequently enrolled in a 12‐month, open‐label period on gliclazide MR alone or in combination according to glycaemic control, 507 of whom completed the study.

Results:  Glycated haemoglobin (HbA1c) significantly decreased from baseline over 2 years by −0.46 ± 1.08% in the whole cohort of 2‐year completed patients, −0.95% in the subgroup of diet‐failed patients and by −0.34% in the subgroup of patients pretreated with one oral antidiabetic drug. HbA1c was reduced by −0.43 ± 1.02% and by −0.51 ± 1.16%, when gliclazide MR was used in monotherapy and in combination therapy, respectively. The overall incidence of symptoms suggestive of hypoglycaemia was 4.8 episodes/100 patient‐year, with no severe episode. This incidence was similarly low in elderly patients and patients with impaired renal function.

Conclusion:  Gliclazide MR alone or in combination with another oral antidiabetic drug significantly improved glycaemic control in type 2 diabetic patients over 2 years with a very good safety profile, notably in the elderly and in patients with impaired renal function.
The effect of neural embryonic stem cell therapy in a rat model of cavernosal nerve injury
Authors: Bochinski Derek , Lin Gui Ting , Nunes Lora , Carrion Rafael , Rahman Nadeem , Lin Ching Shwun , Lue Tom F.
Published: October 2004

OBJECTIVE

To isolate embryonic stem cells that have differentiated along the neuronal cell line, and to assess whether injecting these neural stem cells into the corpus cavernosum influences cavernosal nerve regeneration and functional status.

MATERIALS AND METHODS

Embryonic neural stem cells were obtained; 26 male Sprague‐Dawley rats were divided into four groups: five had a sham operation; eight (controls) had a bilateral cavernosal nerve crush and injection of culture medium into the corpora cavernosa; four had an injection of neural embryonic stem (NES) cells into the major pelvic ganglion (MPG); and nine had bilateral cavernosal nerve crush and injection of NES cells into the corpora cavernosa. Erectile response was assessed by cavernosal nerve electrostimulation at 3 months, and penile tissue samples were evaluated histochemically for nitric oxide synthase (NOS)‐containing fibres, tyrosine hydroxylase and neurofilament staining.

RESULTS

The groups injected with NES cells into the MPG and corpora cavernosa had significantly higher intracavernosal pressures than the control group. Immunohistochemical staining also revealed differences in the quality of the NOS‐containing nerve fibres. Neurofilament staining was significantly better in the experimental groups injected with NES cells.

CONCLUSION

We were able to isolate embryonic stem cells that had differentiated along the neural cell line and, using these NES cells intracavernosally, showed improved erectile function in a rat model of neurogenic impotence.
Mini‐reviews. The expanding indications for laparoscopic radical nephrectomy
Authors: Fenn Neil J. , Gill Inderbir S.
Published: October 2004

In this section there are two mini‐reviews which act as updates on the modern surgical management of RCC, specifically relating to laparoscopic radical nephrectomy and partial nephrectomy. It is clear that the somewhat outdated idea of an open radical nephrectomy for all cases of RCC is no longer acceptable to patients, so it behoves us to adopt the newer treatment methods. The other mini‐reviews describe the use of three‐dimensional imaging in urology and the surgical alternatives for treating Peyronie's disease.
Upper tract tumour after radical cystectomy for transitional cell carcinoma of the bladder: incidence and risk factors
Authors: Sved Paul D. , Gomez Pablo , Nieder Alan M. , Manoharan Murugesan , Kim Sandy S. , Soloway Mark S.
Published: October 2004

The considerable experience of the University of Miami in treating TCC is reviewed in the first article in this section. The authors found that the incidence of upper tract tumour after radical cystectomy for TCC is low, but that patients with prostatic urethral involvement at cystectomy have a greater risk of developing upper tract tumours.

A questionnaire‐based study in the UK attempted to assess how upper tract surveillance is carried out by British urologists in patients with urinary tract TCC. They found a wide variation in practice, which presumably is similar to that also found in other parts of the world. They recommend a follow‐up strategy and suggest that this surveillance should continue for at least 15 years.

There is an evaluation of the long‐term results of salvage cystectomy after interstitial radiotherapy and external beam radiotherapy for TCC reported from Amsterdam. They found that salvage cystectomy gives acceptable morbidity and for any type of urinary diversion.

OBJECTIVE

To review the incidence, pattern and outcome of upper tract transitional cell carcinoma (TCC) after radical cystectomy for carcinoma of the bladder, and identify risk factors for its development.

PATIENTS AND METHODS

The records of 235 consecutive patients who had a radical cystectomy and urinary diversion for TCC at the authors’ institution by one surgeon between January 1992 and August 2003 were retrospectively reviewed.

RESULTS

Five (2%) of 235 patients developed an upper tract urothelial tumour. The mean follow‐up for all patients was 42 months, and was 52.2 months for those with an upper tract tumour. Four of the five patients presented with haematuria and one was diagnosed on routine follow‐up intravenous urography. The mean time to the diagnosis of an upper tract tumour was 39.6 months. Of the potential risk factors, only the presence of TCC of the prostatic urethra had a statistically significant association with eventual upper tract tumour (P < 0.01). At the last follow‐up, four patients died from urothelial cancer and one was disease‐free.

CONCLUSIONS

The incidence of upper tract tumour after cystectomy for TCC is low; most patients present with symptoms (haematuria) and have advanced disease at diagnosis. Patients with prostatic urethral involvement at cystectomy are at greater risk of developing upper tract tumour.
The total percentage of biopsy cores with cancer improves the prediction of pathological stage after radical prostatectomy
Authors: Winkler Mathias H. , Khan Farooq A. , Kulinskaya Elena , Hoh Ivan M. , McDonald Donald , Boustead Gregory , Kaisary Amir V.
Published: October 2004

OBJECTIVE

To examine whether the simple variable ‘percentage of cancer‐positive biopsy cores’ is a significant predictor of true pathological stage after radical prostatectomy and can be used to improve pathological stage prediction by simple means.

PATIENTS AND METHODS

In all, 375 patients had a radical prostatectomy for localized prostate cancer in two UK centres; 260 had complete preoperative staging information. Logistic regression was used and predicted probability graphs constructed to assess predictors of pathological stage.

RESULTS

In this study, only PSA (P = 0.004) and percentage cancer‐positive biopsy cores (P < 0.001) were significant predictors of pathological stage. The final model was an acceptable classifier for pathological stage (area under the receiver operating characteristic curve 0.76, specificity 85%, sensitivity 47%). A patient with a PSA of 10 ng/mL and one of six cores positive for cancer would have a predicted probability of extraprostatic disease of 20%, whereas the same patient with all six biopsy cores positive would have a predicted probability of extraprostatic disease of 80%.

CONCLUSIONS

The percentage of cancer‐positive biopsy cores significantly predicts the disease stage after radical prostatectomy. This variable is easy to obtain by the clinician and avoids the need to estimate the percentage of biopsy tissue infiltrated by cancer. This readily available information can easily be computed and may help to counsel patients about realistic expectations of organ‐confined disease in relation to surgery as a treatment option.
Comparison of doxazosin with or without tolterodine in men with symptomatic bladder outlet obstruction and an overactive bladder
Authors: Lee Ji Youl , Kim Hyun Woo , Lee Seung Ju , Koh Jun Sung , Suh Hong Jin , Chancellor Michael B.
Published: October 2004

In a study of patients with BOO and an overactive bladder, authors from Seoul and Pittsburgh compared the use of doxazosin with or without tolterodine. The combination of the two drugs was helpful in most patients, but doxazosin alone was also effective.

The impact of controlled‐release delivery of drugs on patient comfort has been considerable. The paper by authors from Germany and the USA describes the effect of the leader in this field on the pharmacokinetics of oxybutynin at different dosages. They confirm that this technology facilitates the severity‐dependent treatment of the overactive bladder with flexible‐dose adaptations to patient requirements.

There are two papers on virtual cystoscopy, in one case using CT and in the other IVU. The authors report that virtual cystoscopy is valuable in investigating patients, drawing attention to its benefits and shortcomings.

OBJECTIVE

To assess the efficacy of combined treatment with doxazosin and tolterodine, as although α‐blockers are commonly used and generally effective in men with symptomatic bladder outlet obstruction (BOO), a subset of men with BOO and overactive bladder (OAB) symptoms often complain of persistent symptoms.

PATIENTS AND METHODS

In a prospective study of 144 consecutive men with BOO at one tertiary urology centre, all had a baseline pressure‐flow urodynamic study and were then subdivided into those with BOO or BOO + OAB, based on absence or presence of involuntary detrusor contractions. The Abrams–Griffiths nomogram was used to determine obstructive BOO. After the initial evaluation, all patients were treated with doxazosin 4 mg/day for 3 months. In patients with no symptomatic improvement, tolterodine 2 mg twice daily was added for an additional 3 months.

RESULTS

Of the 144 patients, 76 (53%) were diagnosed as having BOO and 68 (47%) BOO + OAB. The patients with BOO + OAB were older (P < 0.05) and had a higher International Prostate Symptom Score. After 3 months of treatment with doxazosin, 60 (79%) with BOO and 24 (35%) BOO + OAB reported a symptomatic improvement. In those patients with no improvement, six of 16 with BOO and 32 of 44 (73%) with BOO + OAB improved after adding tolterodine. Acute urinary retention developed in only two of 60 men (3.3%) treated with the combined therapy.

CONCLUSIONS

About half of men with symptomatic BOO had an OAB; while about three‐quarters of men with symptomatic BOO and no OAB improved with doxazosin, only a third with BOO + OAB were helped with doxazosin alone. Combining tolterodine with doxazosin was effective in three‐quarters of men with BOO + OAB. Overall, most men with BOO with or with no OAB were helped with doxazosin alone or with the addition of tolterodine.
Effect of controlled‐release delivery on the pharmacokinetics of oxybutynin at different dosages: severity‐dependent treatment of the overactive bladder
Authors: Preik Michael , Albrecht Detlef , O'Connell Martin , Hampel Christian , Anderson Rodney
Published: October 2004

OBJECTIVE

To assess the pharmacokinetics of a controlled‐release formulation of oxybutynin (OROS®‐O, ALZA Corp., Mountain View, CA) at different dosages, compared with immediate‐release oxybutynin (IR‐O), and to determine the pharmacodynamic properties in the severity‐dependent reduction of urge urinary incontinence (UUI).

PATIENTS AND METHODS

In all, 105 patients were enrolled in this multicentre, randomized, double‐blind study. Individual dose titration was used to assess the minimum effective, maximum tolerated or maximum allowed dose of either OROS‐O or IR‐O. Blood samples were collected during maintenance therapy with frequent sampling to analyse for R‐oxybutynin and R‐desethyloxybutynin concentrations. Pre‐dose plasma levels before dosing were obtained as the minimum concentrations achieved at steady state during the dosing regimen. In parallel, UUI episodes were assessed at baseline and during maintenance therapy at the final dose level.

RESULTS

For both IR‐O and OROS‐O, initial R‐oxybutynin plasma concentrations increased in a dose‐dependent fashion. For comparable dosages pre‐dose plasma levels were higher for OROS‐O than IR‐O. After one dose of IR‐O plasma concentrations peaked at ≈ 27‐fold after 1 h and decreased to baseline levels within 4–8 h. In contrast, plasma concentrations of R‐oxybutynin remained constant for up to 24 h after taking OROS‐O at all doses. The overall percentage reduction in weekly UUI episodes was 84% (to 4.8 episodes) and 88% (to 3.1 episodes) for OROS‐O and IR‐O, respectively (P < 0.05). Patients who titrated to final dose levels of 10, 15 and 20 mg OROS‐O differed in their weekly UUI episodes at baseline (14.5, 30.3 and 42.0). Because of individual dose titration, UUI episodes/week were profoundly reduced at all applied doses (1.9–2.0, respectively). Fewer patients reported moderate to severe dry mouth with OROS‐O than with IR‐O (25% vs 46%, P < 0.05).

CONCLUSION

The pharmacokinetics of OROS‐O are proportional to dose, with minimal fluctuations between peak and trough concentrations, as associated with IR‐O. In clinical practice OROS‐O may thus facilitate the highly effective severity‐dependent treatment of UUI with flexible dose adaptations based on the patients’ needs.
Virtual cystoscopy from computed tomography: a pilot study
Authors: Nambirajan Thiagarajan , Aslam Sohaib Syed , Muller‐Pollard Christopher , Reznek Rodney , Chinegwundoh Frank I.
Published: October 2004

OBJECTIVE

To assess the feasibility of virtual cystoscopy reconstructed from helical computed tomography (CT) obtained using an intravenous contrast agent, and to correlate the findings with flexible (FC) and rigid cystoscopy (RC) in patients with bladder tumours.

PATIENTS AND METHODS

Eighteen patients (16 men and two women, mean age 72 years, range 59–80) with haematuria and found to have a bladder tumour on FC were included in a pilot study. Contrast‐enhanced helical CT scans were taken and based on these datasets, virtual cystoscopy (VC) images were reconstructed by a radiologist unaware of the findings at cystoscopy. All patients had RC and a biopsy taken. The VC images were compared with the findings from FC and RC.

RESULTS

At FC, VC and RC, 32, 34 and 36 lesions were identified, respectively; 33 (92%) of the abnormal lesions at RC were correctly identified at VC. At VC, all lesions of >4 mm were identified but only one of three <4 mm was seen. There were two false‐positive finding at VC; VC correctly identified 17 (94%) of 18 abnormal bladders. Only 25% of the ureteric orifices were seen. Carcinoma in situ and urethral tumours were not visualized.

CONCLUSION

CT‐based VC has a high sensitivity for detecting bladder lesions and is comparable with FC; it may have a potential role as a single imaging tool for haematuria. Further larger studies are required to assess its clinical role.
The management of haemorrhagic cystitis with sodium pentosan polysulphate
Authors: Sandhu Sarbjinder S. , Goldstraw Miles , Woodhouse Christopher R.J.
Published: October 2004

OBJECTIVE

To assess the use of sodium pentosan polysulphate (SPP) for haemorrhagic cystitis (HC), a potentially life‐threatening side‐effect in patients treated with pelvic radiotherapy or cyclophosphamide, and which can be difficult to manage as patients often have significant comorbidity.

PATIENTS AND METHODS

Between September 1991 and December 2000, 60 consecutive patients (24 women and 36 men) with haemorrhagic cystitis were primarily treated with SPP; 53 patients had had radical radiotherapy for pelvic malignancy and seven systemic cyclophosphamide. All patients were screened for blood dyscrasia and residual/primary urothelial malignancy with imaging, urine cytology and cystoscopy.

RESULTS

In all, 51 patients were available for follow‐up; the median (range) interval between completing treatment and developing haematuria was 4.5 (0.08–39.4) years, the duration of treatment 180 (21–1745) days and patients were followed for 450 (19–4526) days from the onset of haematuria. All patients were started on SPP at an initial dose of 100 mg three times daily. In 21 patients the dose was gradually reduced to a maintenance dose of 100 mg and in 10 further patients SPP was stopped because the haematuria stopped completely. Twenty patients died while on treatment from causes not directly related to their haematuria.

CONCLUSION

We recommend the use of SPP as the primary method of managing haemorrhagic cystitis associated with pelvic radiotherapy or systemic chemotherapy.
Upper pole access for complex lower pole renal calculi
Authors: Aron Monish , Goel Rajiv , Kesarwani Pawan K. , Seth Amlesh , Gupta Narmada P.
Published: October 2004

Authors from New Delhi assessed the efficacy of superior pole access for complex lower pole calyceal calculi; they found this to be the best way of approaching such complex stones, allowing faster and better clearance with a single puncture.

The second paper in this section is from authors from the UK who set out to describe the frequency of renal symptoms and complications in patients with tuberous sclerosis complex, and to relate the history of renal haemorrhage with renal lesions identified on renal scan.

OBJECTIVES

To assess the efficacy of superior pole access for complex lower pole calyceal calculi.

PATIENTS AND METHODS

In all, 102 patients with complex inferior calyceal calculi were included in a prospective unrandomized study. Complex inferior calyceal calculi were defined as multiple calculi in two or more inferior calyces of the lower polar group, with each calyx draining through a separate infundibulum and at an acute angle to each other. In 33 patients (32%; group 1) an inferior calyceal puncture was made and in 69 (68%; group 2) access was obtained through a superior calyceal puncture. The stone‐free rates, decrease in haemoglobin, operative duration, requirement for additional tracts and second procedures in the two groups were compared.

RESULTS

Stone clearance rates and blood loss values were better in group 2, although they were not significantly different. The mean operative duration, number of tracts required and the re‐look procedure rate was significantly less in group 2. Two patients (3%) in group 2 had hydrothorax related to supracostal puncture and required chest tube insertion.

CONCLUSIONS

Superior calyceal puncture (supracostal or infracostal) affords optimum access to complex inferior calyceal stones, providing faster and better clearance with a single puncture, and less requirement for second‐look procedures.
Efficacy and safety of tadalafil in a Western European population of men with erectile dysfunction
Authors: Eardley Ian , Gentile Vincenzo , Austoni Edoardo , Hackett Geoff , Lembo Danilo , Wang Christine , Beardsworth Anthony
Published: October 2004

Section Editor

Michael G. Wyllie

Panel of Advisors

Ian Eardley, UK

Jean Fourcroy, USA

Sidney Glina, Brazil

Julia Heiman, USA

Chris McMahon, Australia

Bob Millar, UK

Alvaro Morales, Canada

Michael Perelman, USA

OBJECTIVE

To evaluate, in a randomized, double‐blind, placebo‐controlled, multicentre trial, the safety and efficacy of on‐demand tadalafil (an oral phosphodiesterase type‐5 inhibitor approved in many countries for treating erectile dysfunction, ED) in a Western European population of men with mild‐to‐severe ED.

PATIENTS AND METHODS

Patients were randomized according to baseline severity of ED in a ratio of 3 : 1 to receive either tadalafil 20 mg or placebo for 12 weeks. Primary efficacy endpoints were mean changes from baseline to endpoint (12 weeks) in the erectile function (EF) domain of the International Index of Erectile Function (IIEF) and percentages of ‘Yes’ responses to Sexual Encounter Profile (SEP) diary Question 2 (‘Were you able to insert your penis into your partner's vagina?’) and Question 3 (‘Did your erection last long enough for you to have successful intercourse?’). Secondary endpoints included mean changes from baseline to endpoint in IIEF Intercourse Satisfaction and Overall Satisfaction domains, selected questions of the IIEF, and the percentage of ‘Yes’ responses to Global Assessment Questions (GAQ) at the last visit. Other analyses included the percentage of patients in each treatment group at endpoint with IIEF EF domain scores in the normal range (>26), the frequency of intercourse attempts and mean per‐patient intercourse success rate at various times after dosing.

RESULTS

The mean age of the patients was 53 years and 80% had a history of ED of ≥ 1 year. The mean baseline EF domain score was 13.5, with 40.5% of patients in the severe category. Tadalafil improved mean EF domain scores by 11.1, vs 0.4 for placebo (P < 0.001). In addition, 73.9% of sexual intercourse attempts were successful (SEP‐Q3) in tadalafil‐treated patients, compared with 29.9% in placebo‐treated patients during the period after baseline (P < 0.001). Tadalafil significantly improved the mean IIEF intercourse satisfaction (5.1, tadalafil; 1.1, placebo) and overall satisfaction domain scores (3.9, tadalafil; 0.5, placebo), P < 0.001. GAQs used to assess the overall effect of the treatment indicated that tadalafil was superior to placebo (P < 0.001) in improving erections (82.1%, tadalafil; 23.1%, placebo) and sexual activity (78.6% and 17.3%). The most common treatment‐emergent adverse events more frequent (>2%) with tadalafil than placebo were headache, dyspepsia, flushing, back pain, pain in limb and myalgia. These adverse events were mostly mild to moderate.

CONCLUSIONS

Tadalafil improved erectile function and was well tolerated when taken by men from Western Europe with mild‐to‐severe ED.
Sacral ratio and fecal continence in children with anorectal malformations
Authors: Macedo Mauricio , Martins José L. , Freitas Filho Luiz G.
Published: October 2004

OBJECTIVE

To evaluate the sacral ratio (SR) in patients with an anorectal malformation (ARM) and verify whether it has predictive value for fecal continence.

PATIENT AND METHODS

From January 1990 to April 2002, 42 patients (aged 3–14 years) with an ARM and having already been operated on were reassessed and enrolled in the study. Patients with solid or paste‐like stools but no soiling were deemed continent, those with similar stool and episodes of soiling partially continent, and those with no sphincter control, incontinent. The fecal continence was always analysed by the same observer. Sacral radiographic images were reviewed and the SR calculated from anteroposterior and images in the lateral position. All images were obtained before surgery and analysed by the same observer, while a third analysed the results. Results were considered statistically significant at P < 0.001.

RESULTS

Seventeen patients were deemed continent, seven partially continent and 18 incontinent; there was no significant difference in SR among the three groups. When fecal continence was analysed in relation to changes in the findings on computed tomography of the lumbosacral spine, patients with sacral agenesis had a significantly higher frequency of fecal incontinence than the others, and all had a SR below ‘normal’.

CONCLUSION

Although the SR was different in patients with sacral agenesis it was no different in continent, partially continent or incontinent patients, and thus it is of no practical value in identifying patients likely to have fecal incontinence.
Measurement of bladder compliance can be standardized by a dimensionless number: theoretical perspective
Authors: Wahl Edward F. , Lerman Steven E. , Lahdes‐Vasama Tuija T. , Churchill Bernard M.
Published: October 2004

OBJECTIVES

To: (i) calculate traditional compliance (CTrad) for a normal bladder by ΔV/ΔPdet, where ΔV is the mean volumetric capacity and ΔPdet is the detrusor pressure rise; (ii) assess its usefulness; (iii) identify the variables that are necessary for correctly assessing bladder compliance; and (iv) using these variables, report a method that, because it includes the effect of patient age, sex and size, correctly assesses compliance for management strategies.

METHODS

We obtained the mean volumetric capacity of a normal bladder (Vcap,NL) and the mean detrusor pressure rise (Pcap,NL) on filling a normal bladder to its volumetric capacity from our and other published work; (ii) calculated CTrad for a normal bladder; (ii) showed that the variables necessary for assessing compliance correctly are ΔV, ΔPdet, Vcap,NL, and Pcap,NL; and (iii) showed that the relationship among these is the dimensionless number, NWahl−1, calculated as (ΔV/Vcap,NL)/(ΔPdet/Pcap,NL). This value for individuals with a normal bladder was calculated, tabulated and graphed.

RESULTS

Because a normal individual's bladder capacity increases with age while the detrusor pressure increase does not, CTrad increases with age and therefore cannot be used for assessing compliance. Published data substantiate our result that CTrad for an individual with a normal bladder varies from 6.3 at 0.5 years old to 90 mL/cmH2O at 18 years old. NWahl−1 correctly assesses bladder compliance because it is the same for all normal cases; consequently NWahl−1 is more practical for clinical use.

CONCLUSIONS

Bladder compliance is standardized using ΔV, ΔPdet, Vcap,NL, and Pcap,NL to give NWahl−1, and bladder compliance is usefully reported using this value.
Measurement of bladder compliance can be standardized by a dimensionless number: clinical perspective
Authors: Wahl Edward F. , Lerman Steven E. , Lahdes‐Vasama Tuija T. , Churchill Bernard M.
Published: October 2004

OBJECTIVE

To devise a new, practical and more accurate method for measuring bladder compliance, and to show that traditional estimates of compliance are impractical.

MATERIALS AND METHODS

Childhood bladder capacity varies greatly with age while detrusor pressure in a normal bladder does not. Consequently, traditional bladder compliance (ΔV/ΔP) increases with age, i.e. maturation. Therefore we devised a standard method that includes normal values of pressures and volumes to calculate and report bladder compliance in children, and that also applies to adults. A dimensionless number (NWahl−1) was computed for standardizing bladder compliance, comparing the normalized capacity to normalized pressure by the ratio (ΔV/Vcap,NL)/(ΔP/Pcap,NL), where ΔP is the pressure at bladder capacity, ΔV the volume at bladder capacity, Vcap,NL the volume at mean expected bladder capacity and Pcap,NL the pressure at mean expected bladder capacity. Vcap,NL is obtained from nomograms of published data.

RESULTS

The bladder compliance of patients undergoing urodynamic testing was calculated using NWahl−1 and the traditional equation (ΔV/ΔP). NWahl−1 provided a more accurate diagnosis and therefore was of more practical use.

CONCLUSIONS

Bladder compliance depends on patient age, sex and size; the new estimate used to standardize bladder compliance is based on these factors and is a dimensionless number. This may help when comparing patients and assessing outcomes.
Detrusor pressure rise in a normal bladder
Authors: Wahl Edward F. , Churchill Bernard M.
Published: October 2004

OBJECTIVE

To determine the detrusor pressure rise of a normal bladder (Pcap,NL) when filled to capacity.

PATIENTS AND METHODS

Twenty‐four patients with an apparently normal bladder, i.e. with symptoms but whose cystometrogram (CMG) showed no pathology of any kind and a near‐normal pressure vs volume plot, were selected from 218 clinical CMGs. A straight line was fitted to the PV plot of these CMGs and then the Pcap,NL calculated, e.g. by a straight line extending to the point of the normal expected cystometric bladder capacity (Vcap.NL). Published data relative to Pcap,NL were evaluated and compared with the values obtained.

RESULTS

The mean (range) Pcap,NL was 6 (4.5–7) cmH2O for patients with apparently normal bladders infused at the maximum physiological diuresis (MPD). This value was substantiated by three other studies of published values. The Pcap,NL was 6 cmH2O at infusion rates of 10% of glomerular filtration rate (GFR), 10 cmH2O at 20% of GFR and 7–15 cmH2O for 3–10 times the infusion rate of 10% of GFR.

CONCLUSION

Pcap,NL is independent of age, size and sex and, at constant infusion rates of ≈ MPD, will be 6. For infusion rates up to 35 mL/min, it is in the range of 6–15 cmH2O.
Transmitters contributing to the voiding contraction in female rats
Authors: Streng Tomi , Talo Antti , Andersson Karl‐Erik
Published: October 2004

OBJECTIVES

To assess in detail the contribution of acetylcholine and ATP to the different phases of the voiding contraction, urine flow and rhabdosphincter electromyographic (RB‐EMG) activity in rats, using α,β‐methylene‐ATP (desensitizing purinoceptors) and atropine (blocking muscarinic receptors). These agents and possibly other transmitters contribute to bladder emptying in rats, but how they contribute to the different phases of the micturition cycle, including the intraluminal pressure high‐frequency oscillations (IPHFOs) is unclear.

MATERIALS AND METHODS

Adult anaesthetized female Sprague‐Dawley rats were used; intravesical pressure, RB‐EMG and urine flow from the distal urethra were recorded. After baseline recordings, α,β‐methylene‐ATP (0.5 mg/kg), atropine (1 mg/kg), or both, were injected intravenously.

RESULTS

α,β‐Methylene‐ATP significantly decreased the maximum bladder pressure during the first micturition phase, whereas atropine had little effect; the maximum bladder pressure during the second phase was also reduced. IPHFOs were apparent after both treatments. Atropine significantly reduced the maximum bladder pressure during the third phase. The maximum urinary flow rate was reduced by both α,β‐methylene‐ATP and atropine; after exposure to both agents together, urinary flow was markedly reduced or stopped, and overflow incontinence developed.

CONCLUSIONS

ATP contributes mainly to the initial and acetylcholine to the later phases of the voiding cycle in the rat. Neither agent abolished the IPHFOs; even after blocking the receptors for one transmitter and in the presence of IPHFOs, the bladder can still empty. However, if both receptors are blocked, overflow incontinence develops, suggesting that even if further transmitters are taking part in the voiding contraction, their physiological significance is questionable.
Induction of proliferation and differentiation of cultured urothelial cells on acellular biomaterials
Authors: Ram‐Liebig Gouya , Meye Axel , Hakenberg Oliver W. , Haase Michael , Baretton Gustavo , Wirth Manfred P.
Published: October 2004

OBJECTIVE

To determine the optimum conditions for the proliferation of urothelial cells, leading to the confluent coverage of large surfaces of biocompatible membranes, and for their terminal differentiation.

MATERIALS AND METHODS

Porcine and human urothelial cells were cultured on different matrices under different growth conditions. Proliferative activity and the viability of cells were evaluated using fluorescent markers for nuclei and cytoplasm. Growth and differentiation were assessed by histological, histochemical and immunohistochemical methods.

RESULTS

Under fibroblastic induction and supplementation of 5% fetal calf serum (FCS), urothelial cells showed more proliferation than in other conditions tested. Terminal differentiation of superficial cells was achieved by lowering the concentration of FCS to 1% at the air–liquid interface.

CONCLUSIONS

The mitogenic effects of the extracellular matrix content of biological membranes and fibroblastic inductive factors are synergistic with each other, and can compensate for a low FCS concentration and the absence of other additives. Lowering the FCS concentration to 1% inhibits the proliferation of urothelial cells and permits their terminal differentiation.
Metamorphic evolution of calcsilicate granulites near Battye Glacier, northern Prince Charles Mountains, East Antarctica
Authors: STEPHENSON N. C. N. , COOK* N. D. J.
Published: October 2004

Calcsilicate granulites of probable Middle Proterozoic age (c.1000–1100 Ma) in the vicinity of Battye Glacier, northern Prince Charles Mountains, East Antarctica, contain prograde metamorphic assemblages comprising various combinations of wollastonite, scapolite, clinopyroxene, An‐rich plagioclase, calcite, quartz, titanite and, rarely, orthoclase, ilmenite, phlogopite and graphite. Comparison of the prograde assemblages with calculated and experimentally determined phase relations in the simple CaO–Al2O3–SiO2–CO2–H2O system suggests peak metamorphism at ≥835 °C in the presence (in wollastonite‐bearing assemblages at least) of a CO2‐bearing fluid (XCO≥0.3) at a probable pressure of 6–7 kbar.

Well‐preserved retrograde reaction textures represent: (1) breakdown of scapolite to anorthite+calcite±quartz; (2) formation of grossular–andradite garnet and, locally, (3) epidote, both principally by reactions involving scapolite breakdown products and clinopyroxene; (4) local coupled replacement of clinopyroxene and ilmenite by hornblende and titanite, respectively; and finally (5) local sericitization of prograde and retrograde plagioclase. These retrograde reactions are interpreted to be the result of cooling and variable infiltration by H2O‐rich fluids, possibly derived from crystallizing pegmatitic intrusions and segregations that may be partial melts, which are common throughout the area.
Geotectonic subdivision and areal extent of the Sangun belt, Inner Zone of Southwest Japan
Authors: NISHIMURA Y.
Published: October 2004

The Sangun belt has long been considered to be a major coherent glaucophanitic terrane of Permian to Triassic age, and to be paired with the low‐P/T  Hida belt to the north. However, recent progress in geochronology, metamorphic geology, and tectonics has revealed that the belt is in fact comprised of two geologic units of different ages and with contrasting conditions of formation. The older unit is named the Renge belt and the younger the Suo belt. The Renge belt is the oldest of the high‐P/T  metamorphic belts in the Japanese Islands and extends from northern Kyushu, through the San‐in coastal regions, to the Hida marginal belt. It is characterized by 330–280 Ma ages and the association of glaucophane–schist to epidote–amphibolite facies schists. The Renge belt is also typically associated with meta–ophiolite sequences (470–340 Ma) including serpentinite. The Suo belt is characterized by 230–160 Ma high‐P/T  schists closely related to weakly metamorphosed Permian accretionary rocks of the Akiyoshi belt. Metamorphic facies series is from the prehnite–pumpellyite facies through the pumpellyite–actinolite and glaucophane–schist facies to the epidote–amphibolite facies. The belt is widespread in west Kinki to north and central Kyushu via Chugoku, but also stretches further to the southwest and is present in the Ishigaki‐Iriomote Islands of the southern Ryukyu Arc. Throughout this belt, there are scattered small blocks or lenses of meta–ophiolite, whose K–Ar ages of relict hornblendes are 590 to 220 Ma. Bounded by low‐angle faults and thrusts, both belts define subhorizontal nappes dipping gently north. The geotectonic framework in the Inner Zone of Southwest Japan is made up of, from north to south, the Hida‐Oki, Renge, Akiyoshi, Suo, Maizuru plus ultra‐Tamba, Mino‐Tamba, and Ryoke belts, with a tectonically downward‐younging polarity. This has resulted from stepwise accretions during Palaeozoic to Mesozoic time.
Unpairing metamorphic belts: P–T paths and a tectonic model for the Ryoke Belt, southwest Japan
Authors: BROWN MICHAEL
Published: October 2004

Southwest Japan is divided into Outer and Inner Zones by the Median Tectonic Line (MTL), a major transcurrent fault. The Outer Zone is composed of the Sambagawa (high‐pressure intermediate or high P/T  type metamorphism), Chichibu and Shimanto Belts. In the Inner Zone, the Ryoke Belt (andalusite– sillimanite or low P/T  type metamorphism) was developed mainly within a Jurassic accretionary complex. This spatial relationship between high P/T  type and low P/T  type metamorphic belts led Miyashiro to the idea that metamorphic belts were developed as ‘paired’ systems. Textural relationships and petrogenetically significant mineral assemblages in pelites from the Ryoke Belt imply peak P–T  conditions of ≈5 kbar and up to 850 °C in migmatitic garnet–cordierite rocks from the highest‐grade metamorphic zone. It is likely that the thermal anomaly responsible for metamorphism of the Ryoke Belt was related to a segment of the Farallon–Izanagi Ridge as it subducted under the eastern margin of the Asian continent during the Cretaceous. The sequence of mineral assemblages developed in pelites implies a metamorphic field gradient with shallow dP/dT  slope, inferred to have been generated by a nested set of hairpin‐like ‘clockwise’P–T  paths. These P–T  paths are characterized by limited prograde thickening, minor decompression at peak‐T , and near‐isobaric cooling, features that may be typical of P–T  paths in low P/T  type metamorphic belts caused by ridge subduction. A ridge subduction model for the Ryoke Belt implies that juxtaposition of the high‐P/T  metamorphic rocks of the Sambagawa Belt against it was a result of terrane amalgamation. Belt‐parallel ductile stretching, recorded as syn‐metamorphic, predominantly constrictional strain in both Ryoke and Sambagawa Belt rocks, and substantial sinistral displacement on the MTL are consistent with left‐lateral oblique convergence. Diachroneity in fast cooling of the Ryoke Belt is implied by extant thermochronological data, and is inferred to relate to progressive SW to NE docking of the Sambagawa Belt. Thus, an alternative interpretation of ‘paired’ metamorphic belts in Japan is that they represent laterally contemporaneous terranes, rather than outboard and inboard components of a trench/arc ‘paired’ system. Amalgamation of laterally contemporaneous terranes during large translations of forearcs along continental margins may explain other examples of ‘paired’ metamorphic belts in the geological record.
Cretaceous high‐temperature rapid loading and unloading in the Abukuma metamorphic terrane, Japan
Authors: HIROI Y. , KISHI S. , NOHARA T. , SATO K. , GOTO J.
Published: October 2004

The Cretaceous Abukuma metamorphic terrane consists of the oceanic Gosaisyo Series overthrust onto the terrigenous Takanuki Series. Although the dominant mineralogy defines one of the classic areas of andalusite–sillimanite type progressive metamorphism, there are several lines of evidence suggesting an earlier higher‐pressure (up to c. 12 kbar) history of the Takanuki Series and the nearby Gosaisyo Series. These are: (1) the occurrence of rare although widespread relic kyanite in sillimanite+K‐feldspar zone‐grade pelitic rocks; (2) the high grossular content of garnet interiors (up to c. 30 mol %) overgrown by Ca‐poor rims (c. 2 mol % grossular) in pelitic rocks containing Al2SiO5 minerals (sillimanite±relic kyanite±retrograde andalusite), plagioclase and quartz; (3) the occurrence of rutile as inclusions in garnet in pelitic rocks; and (4) the occurrence of relic corundum+almandine association in silica‐poor and Al–Fe‐rich rocks. Garnet in the Takanuki Series pelitic rocks commonly shows textural sector zoning and preserves growth zoning despite the high metamorphic grade, suggesting rapid changes in P–T  conditions and a relatively short duration of high‐temperature conditions. Combined with radiometric dating, these observations suggest that the Abukuma sillimanite+K‐feldspar zone‐grade rocks underwent a clockwise P–T  path with very fast (>4 mm y−1) average burial and exhumation rates.