Yellow Fever Vaccine YF-VAX ¨ Caution: Federal (USA) law prohibits dispensing without prescription. DESCRIPTION YF-VAX¨, Yellow Fever Vaccine, for subcutaneous use, is prepared by culturing the 17D strain of yellow fever virus in living avian leukosis virus-free (ALV-free) chicken embryos. The vaccine, containing sorbitol and gelatin as a stabilizer, is lyophilized, and hermetically seal
Advantag of ingestion administration way is its easiness even when applied at home. But with their help necessary treatment concentration in blood cannot be always quickly achieve amoxil online transaction is carried out on anonymity and mutual profit principles, and in addition customers will be positively surprised with quality and speed of service.
Bju_4798-4801.fmBlackwell Science, LtdOxford, UKBJUBJU International1464-4096BJU InternationalMay 2004937 A little more than 10 years has passed since TRAINING AND MENTORING IN UROLOGY: THE ‘LAP’ GENERATION
Clayman and Kavoussi performed the first S.V. BARIOL and D.A. TOLLEY – Scottish Lithotriptor Centre, Western General Hospital,
techniques have flourished in the few units dedicated to laparoscopic endeavour, the Accepted for publication 10 February 2004 problem of training a generation of urologists in laparoscopy, a technique that is rapidly becoming the standard of care, remains.
achieving operative competence is the use of simulators or tools to select applicants, based The wide use of laparoscopy in many other on aptitude. At present, those who train surgical specialities means the junior trainee The pathway described above is more suited further in laparoscopy are those who have has often had considerable previous exposure to speciality registrars, who are able to chosen to do so. Tools such as the Advanced to laparoscopy with associated development incorporate the programme into their period Dundee Endoscopic Psychomotor Tester  of spatial awareness and appropriate motor of training. Mentoring trained urologists and Minimally Invasive Surgical Trainer – skills. Nevertheless an integrated programme requires the cooperation of the mentor and trainee, as well as their respective hospital adequately validated to justify their expense competency is essential. To this end BAUS and . The testing of airline pilots, often used the Specialist Advisory Committee in urology as a model for surgical training, has used simulators for selection and training for pathway to facilitate the acquisition of decades. There is little doubt that similar tests laparoscopic skills, like most endo-urological will play a role for laparoscopists of the future modular training and mentoring. Once the competence as an endpoint. The programme minimum of skills have been acquired for safe Consideration of future service provision also tissue handling, the trainee can be guided by needs to be considered in selecting urologists complemented by assisting and observing at a mentor and video feedback used to facilitate for further training in laparoscopy. The various laparoscopic urological procedures, number of urologists offering laparoscopy in and independent practice on bench models, a geographical area should be limited to followed by an advanced skills course that Videotape recording can be a double-edged maintain the highest technical standards. This might otherwise be compromised by dilution laparoscopic surgeon is placed is intense and follows until independent practice appears far exceeds that of conventional ‘scalpel’ The laparoscopic approach is of proven benefit in laparoscopic nephrectomy and However, the number of cases required to nephroureterectomy, in terms of blood loss achieve satisfactory performance varies and techniques should not be under-emphasized as a method of improving laparoscopic skills, affecting oncological control (Bariol SV, independent of mentor or apprentice, and although it is recognized that laparoscopy is a Stewart G, MacNeil SA, Tolley DA, Oncological technique that applies across the breadth of urology rather than to a subspeciality. Wide certification. However, the Endourological experience with endoscopic surgery facilitates unpublished), but its role in radical pelvic Society, among other criteria, requires at least the development of spatial awareness and the surgery has yet to be firmly established. 40 laparoscopic procedures to be undertaken However, as laparoscopy in urology increases or assisted in a 1-year period for a fellowship to be recognized. The European Society of maintain a system for training in laparoscopic Urotechnology, a full participant in the There is as yet no recognized way to select those suitable for laparoscopic training. A their early experience with new techniques. has espoused the British model, also wishes conspicuous omission from the pathway to This can easily be incorporated into current 2 0 0 4 B J U I N T E R N A T I O N A L | 9 3 , 9 1 3 – 9 1 8 | doi:10.1111/j.1464-410X.2004.04798–04801.x training programmes for speciality registrars, Macmillan AI, Cuschieri A. Assessment
of innate ability and skills for endoscopic Therapy Trial compared doxazosin, finasteride and combination therapy with placebo . Results from both trials (each at 1-year) with open surgery must submit themselves Predictive and concurrent validity. Am J showed no benefit in the use of combined Surg 1999; 177: 274–7
Failure to do so risks a decrease in the Wilson MS, Middlebrook A, Sutton C,
standard of care offered to patients with Stone R, McCloy RF. MIST-VR: a virtual
urological conditions, or at the very least reality trainer for laparoscopic surgery to the possibility of the patient being treated by assess performance. Ann R Coll Surg Eng effect of medical therapy on the clinical the non-urologist with appropriate technical 1997; 79: 403–4
Paisley AM, Baldwin PJ, Paterson-
Brown S. Validity of surgical simulation
for the assessment of operative skill. Br J
Surg 2001; 88: 1525–32
The recently published Medical Therapy of REFERENCES
McDougall EM, Clayman RV, Elashry
OM. Laparoscopic radical nephrectomy
5 years has the longest follow-up of any Clayman RV, Kavoussi LR, Soper NJ et al.
University experience. J Urol 1999; 155:
blockers, and investigated >3000 men. report. J Urol 1991; 146: 278–82
Shalhav AL, Dabagia MD, Wagner TT,
McDougall EM, Clayman RV, Elashry O.
Koch MO, Lingeman JE. Training
finasteride, or as combination, would delay or upper tract transitional cell cancer: The surgery: the current challenge. J Urol Washington University experience. J Urol (defined primarily as either a significant 2002; 167: 2135–7
1995; 154: 975–80
worsening of symptoms, recurring UTI, AUR, as surgery). The trial had the same four and its aim was to evaluate BPH progression. TWO-DRUG THERAPY IS BEST FOR SYMPTOMATIC PROSTATE
Analysis of the results at 1 year showed similarities to both the Veterans Affairs and ENLARGEMENT: COULD A COMBINATION OF DOXAZOSIN AND
the PREDICT study. However, by 5 years the FINASTERIDE CHANGE CLINICAL PRACTICE? J.M. FITZPATRICK and
risks of AUR and the need for invasive surgery R.S. KIRBY* – Department of Surgery, Mater Hospital, Eire, and *St George’s Hospital, London,
were significantly lower with combined therapy.
Accepted for publication 10 February 2004 Over a mean follow-up of 4.5 years the rate of overall clinical progression (the primary endpoint) among men in the placebo group standard surgical treatment for symptomatic was 4.5 per 100 person years. Compared with placebo, doxazosin significantly reduced the was related to the normal ageing process risk of progression by 39% (P < 0.001) and finasteride reduced it by 34% (P = 0.002). 1895 bilateral orchidectomy was proposed Therefore the reduction in risk between the drugs, used as a single agent, did not differ completely effective it is not surprising significantly. For combined therapy the risk of overall clinical progression was reduced by commonplace, and their value has been well 66% (P < 0.001), a significantly greater documented. Short-to-moderate clinical trials showed the effectiveness of a-blockers for amongst older men, and which fundamentally relieving symptoms and improving urinary flow rate [2–5]. Until recently, trials reduced the need for invasive therapy, with urinary symptoms. While a small proportion combining the two classes of drugs showed the magnitude of the reduction similar to that little superiority in alleviating symptoms and in previous trials with 5a-reductase inhibitors absolute indications, e.g. acute urinary improving urinary flow rate. The Veterans retention (AUR) or UTI, most have traditionally Affairs Cooperative Studies Benign Prostatic had surgery to relieve the bothersome urinary symptoms and improve their quality of life finasteride and combination therapy with slightly, but over the duration of the trial 2 0 0 4 B J U I N T E R N A T I O N A L failed to reduce the risk of AUR and invasive Trial study: a one-year study of terazosin Therapy (PREDICT) trial. Urology 2003; 61:
growth of the prostate eventually overcame McConnell JD, Roehrborn CG, Bautista
the reduction in the urethral obstruction hyperplasia. Urology 1996; 47: 159–68
OM et al. The long-term effect of
achieved by relaxing the smooth muscle in the Roehrborn CG, Siegel RL. Safety and
efficacy of doxazosin in benign prostatic benign prostatic hyperplasia. N Engl J Med double-blind, placebo-controlled studies. 2003; 349: 2387–98
provides long-lasting relief from symptoms Urology 1996; 48: 406–15
Roehrborn CG, Boyle P, Nickel JC
Kawabe K. Efficacy and safety of
et al. Efficacy and safety of a dual inhibitor been widely used singly, but the increased prostatic hyperplasia. Br J Urol 1995; 76:
benefits of combined therapy show for the prostatic hyperplasia. Urology, 2002; 60:
first time that there is almost certainly a Roehrborn CG. Efficacy and safety of
medical alternative to surgery for patients 10 Andersen JT, Nickel JC, Marshall VR
et al. Finasteride significantly reduces clinical benign prostatic hyperplasia: a Consequently, the advent of effective medical therapies has offered the possibilities for Urology 2001; 58: 953–9
benign prostatic hyperplasia. Urology Lepor H, Williford WO, Barry MJ et al.
1997; 49: 839–45
The efficacy of terazosin, finasteride or 11 Roehrborn CG. The Agency for
immediate urological referral. Treatment both in benign prostatic hyperplasia. N Healthcare Policy and Research. Clinical guidelines for urologists are available but Engl J Med 1996; 335: 533–9
they are not aimed at GPs . The BAUS Kirby RS, Roehrborn C, Boyle P et al.
treatment of benign prostatic hyperplasia. Efficacy and tolerability of doxazosin and Urol Clin North Am 1995; 22: 445–53
finasteride, alone or in combination, in 12 Speakman MJ, Kirby RS, Joyce A
et al. Guideline for the primary care is published in this issue of the BJU International . The new guideline places symptoms. BJU Int 2004; 93: in press
GPs firmly in the front rank for the initial The new guideline is for both GPs and patients, and reflects the high degree COGNITIVE EFFECTS OF HORMONAL TREATMENT FOR PROSTATE
CANCER A. KOUPPARIS, A. RAMSDEN and R. PERSAD – Department of
implementation. This guideline will hopefully Urology, Bristol Royal Infirmary, Bristol, UK offer real practical advice to both doctors and other healthcare professionals, and the many Accepted for publication 10 February 2004 patients suffering from symptomatic BPH.
Hormonal manipulation is a well established were subjectively apparent to individuals. Fortunately, these adverse effects appear to be reversible with oestrogen-replacement primary-care level with the BAUS guidelines troublesome side-effects. Recently, interest may reduce the number of patients requiring has turned to the possible adverse effects It would be reasonable to assume that LHRH agonists have similar effects in men. Substantial declines in testosterone levels REFERENCES
and neuropsychological function are well acknowledged in the ageing male population Mebust WK, Holtgrewe HL, Cockett
. Interestingly, in addition to the adverse ATK, Peters PC. Transurethral
populations, falling androgen levels have been shown to have a negative effect on visual memory and the capacity for new learning memory and visual-spatial performance in men. Once again, treatment with exogenous J Urol 1989; 141: 243.
androgens can reverse these changes, and has Roehrborn CG, Oesterling JE, Auerbach
impairment of daily activities they were S et al. The Hytrin Community Assessment
statistically significant, and in many cases 2 0 0 4 B J U I N T E R N A T I O N A L Although hormone manipulation for prostate REFERENCES
to some of the inconsistencies reported. Newton C, Slota D, Yuzpe AA, Tummon
cognitive functions are selectively affected Furthermore, the role of learning bias, which IS. Memory-complaints associated with
remains outstanding. Cherrier et al.  is inherent to such cognitive tests, cannot be reported minor effects arising from combined androgen blockade. Although testosterone Fertil Steril 1996; 65: 1253–5
levels were lower in all patients than at In conclusion, the adverse effects of hormonal Moffat SD, Zonderman AB, Metter EJ,
baseline, only a decline in spatial ability was Blackman MR, Harman SM, Resnick
detected. Surprisingly, they found that verbal to be appreciated. Because of their age, SM. Longitudinal assessment of serum
comorbidities and polypharmacy this group free testosterone concentration predicts of patients is particularly susceptible to cognitive impairment. This has implications status in elderly men. J Clin Endocrinol In the light of findings in women, Green both for patients’ quality of life and treatment Metab 2002; 87: 5001–7
et al.  postulated that men receiving compliance. By acknowledging the effects Cherrier M, Rose A, Higano C. The
deterioration in their cognitive function suppression we can provide patients with than controls or those receiving cyproterone more information about hormone treatment. acetate. Furthermore, they suggested that As a result they will be able to make informed decisions when faced with the prospect of cancer. J Urol 2003; 170: 1703–8
Green H, Pakenham KI, Headley BC et al.
this field are obviously required, both to Altered cognitive function in men treated in all patients, and this was associated formulate a standardized and reproducible with a wide range of effects on cognitive memory, attention and executive functions control trial. BJU Int 2002; 90: 427–32
at our centre are examining the possible Sherwin B, Tulandi T. ‘Add-back’
addition to these effects, patients receiving cyproterone acetate also had an impairment results will be of interest, as bicalutamide competes with testosterone at a receptor leiomyomata uteri. J Clin Endocrinol Metab 1996; 81: 2545–9
Several possibilities exist for the differences between male and female study populations. The duration of androgen suppression was shorter in patients with prostate cancer than EARLY REHABILITATION OF ERECTILE FUNCTION AFTER
in women, particularly in those after bilateral NERVE-SPARING RADICAL PROSTATECTOMY: WHAT IS
salpingo-oophorectomy. The possibility arises THE EVIDENCE?
P. GONTERO and R. KIRBY – St George’s Hospital, London, UK
that the degree and type of cognitive effects are related to the period of treatment.
Accepted for publication 10 February 2004 There are inherent differences in neuropsychological function between men INTRODUCTION
and women; the latter excel in verbal abilities abilities . This observation seems to be prophylaxis for erectile function after nerve- Comparing sexual function after normal (no related to the influences that different sparing radical prostatectomy (NSRP) was nerve sparing) and NSRP, Gralnek et al.  androgen levels in the sexes have on brain recently stressed by Montorsi and Burnett . reported that the latter had significantly organization during prenatal development. Despite that the patient compliance with better quality-of-life scores for both sexual Oestrogen and testosterone continue to be erectile rehabilitation protocols may be and physical function. The negative effect of suboptimal, as documented by the relatively sexual bother on quality of life may become areas of the brain which subserve verbal even more marked with a longer time after and visual-spatial functions, respectively. discontinue treatment for sexual dysfunction the procedure. In the study by Penson et al.  Therefore, their suppression during hormonal . It seems appropriate therefore to attempt manipulation could result in the selective determinant of worse general health-related currently proposed rehabilitative protocols in terms of cost-efficiency and quality of life.
2 0 0 4 B J U I N T E R N A T I O N A L treatment (27%) also had better nocturnal between sexual dysfunction and quality of erections recorded a year after surgery. Unfortunately that study did not address the recovery of sexual function an important prevalence of nocturnal erections over the issue for patients surgically treated for Spontaneous erectile function is absent for 9 months for all the patients in the treatment most patients soon after NSRP, but there is a arm compared with those in the placebo arm. progressive return over 2 years in a variable It is possible that sildenafil and the other proportion of them. This observation led to currently available PDE-5 inhibitors, e.g. the hypothesis of the so-called ‘neuropraxia’ effective in the early phase of nerve healing, cavernosal nerves which would abolish any as documented by the lack of clinical efficacy The proportion of men who have a complete form of erection. The low oxygen tensions in a of sildenafil in the first 9 months after NSRP recovery of erectile function after bilateral constantly flaccid penis may initiate severe anatomical preservation of neurovascular fibrotic changes in the cavernosal tissue. In a recent experimental model, penile tissue from reported to be up to 20% for patients under debate, but probably is less than half overall. rats which had undergone bilateral incision of Differences in surgical technique, patient cavernosal nerves 3 months earlier showed a significant overexpression of hypoxia-related Three-monthly intracavernosal injections substances like TGF-b and collagen I and III with prostaglandin E1 starting in the first compared with the same tissue from a control month after surgery significantly enhanced almost all the reported studies there is no compared with sildenafil alone started after 4 undergone specific erectile rehabilitation trabecular smooth muscles is replaced by months. At the 6-month follow-up, 82% of treatment during the follow-up. However, collagen, the caverno-occlusive mechanism is patients in the combination arm responded to lost, with subsequent venogenic erectile subsequent sildenafil, vs only 52% in the sildenafil-only arm . Intracavernosal therapy produces a high erectile response in patients after standard (not nerve-sparing) RP surgery gave the best results of potency and therefore it may be the treatment of recovery at 2 years . By contrast, in the support in the initial year after surgery choice in soon after NSRP. Similarly, the use of study of Katz et al.  patients were revealed a progressive incidence of venous the vacuum constrictor device may facilitate deliberately asked not to use any erectile leakage, varying from 14% at 4 months to early sexual intercourse and potentially an rehabilitation after laparoscopic RP, and 50% at >12 months . Similarly, in the early return of natural erections, although no study of Montorsi et al. , eight of 15 controlled study has been carried out to test alprostadil in the first 4 months after surgery had a colour Doppler diagnosis of venous postoperative erectile treatment rely on very leakage, compared with only two of 12 of the CONCLUSIONS
treatment group. These findings corroborate Montorsi et al.  recovery of spontaneous the hypothesis that erectile rehabilitation Erectile dysfunction may significantly affect the quality of life of patients who have had erectile dysfunction during the process of NSRP, and every effort should be made to improve sexual outcomes of these procedures. The current scientific evidence supporting the patients taking sildenafil at bedtime for early postoperative use of erectile aids is at present based mainly on indirect proof of The ideal treatment designed to promote the temporary postoperative ‘erectile silence’.
restoration of erectile function after NSRP it is possible that the erectile rehabilitation acceptable tolerability. Nocturnal penile intracavernosal injections or a vacuum device should be offered as a first-line option for the ‘healing’ time of potency rather than 8 months after NSRP . The early intake of first few months after the procedure, as their mechanism of action does not require intact failure. Larger randomized trials with at inhibitor sildenafil at bedtime has been sildenafil, or equivalent PDE-inhibitor therapy, before a definite conclusion can be drawn nocturnal erections. In the preliminary study may be a reasonable choice for those patients on the true efficacy of rehabilitative sexual from Padma-Nathan et al.  patients who who can achieve at least a partial erection. A regained sexual function after 9 months of PDE-5 inhibitor may not be effective when 2 0 0 4 B J U I N T E R N A T I O N A L spontaneous erections are absent. Possibly, as Penson DF, Feng Z, Kuniyuri A et al.
prostatectomy. J Urol 2003; 169:
the rehabilitation of sexual function aims General quality of life 2 years following McCullough AR. Prevention and
providing oxygenation to the erectile tissue, prostate cancer outcome study. J Clin following radical prostatectomy. Urol Clin treatment may jeopardize the longer term Oncol 2003; 21: 1147–54
North Am 2001; 28: 613–27
results of a successful NSRP. Ultimately, while Walsh PC. Radical prostatectomy for
10 Leungwattanakij S, Bivilacqua TJ, Usta
a rehabilitative treatment should probably be localised prostate cancer provides durable MF et al. Cavernous neurotomy causes
offered to all patients undergoing NSRP, cancer control with excellent quality of patient counselling should reflect honestly life: a structured debate. J Urol 2000; 163:
cavernosum. J Androl 2003; 24: 239–45
the current level of knowledge about the 11 Mulhall JP, Slovick R, Hotaling J
potential efficacy of rehabilitative protocols.
Katz R, Salomon L, Hoznek A et al.
et al. Erectile dysfunction after radical REFERENCES
prostatectomy. J Urol 2002; 168: 2078–82
erectile function. J Urol 2002; 167: 1371–5
Montorsi F, Guazzoni G, Ferini Strambi
12 Fraiman MC, Lepor H, McCullough AR.
Montorsi F, Burnett AL. Erectile
L et al. Recovery of spontaneous erectile
dysfunction after radical prostatectomy. BJU Int 2004; 93: 1–2
Raina R, Lakin MM, Thukral M et al.
without early intracavernous injections of radical prostatectomy. J Urol 1999; 161:
intracorporeal (IC) injection for erectile randomized trial. J Urol 1997; 158: 1408–
13 Zagaja GP, Mhoon DA, Aikens JE,
Brendler CB. Sildenafil in the treatment
prostatectomy. SHIM (IIEF-5). Anal Int J Padma-Nathan H, McCullough AR,
Impot Res 2003; 15: 318–22
Giuliano F, Toler S, Wohlhuter C,
prostatectomy. Urology 2000; 56: 631–4
Gralnek D, Wessells H, Cui H, Dalkin BL.
Shpilsky A. Postoperative nightly
14 Montorsi F, Salonia A, Barbieri L et al.
Differences in sexual function and quality The subsequent use of IC alprostadil and of life after nerve sparing and nonnerve oral sildenafil is more efficacious than sparing radical retropubic prostatectomy. sildenafil alone in nerve sparing radical J Urol 2000; 163: 1166–70
prostatectomy. J Urol 2002; 167: 279
2 0 0 4 B J U I N T E R N A T I O N A L
Publications (Dr. Gijs H. Goossens) Top 5 publications 1. Goossens GH, Petersen L, Blaak EE, Hul G, Arner P, Astrup A, Froguel P, Patel K, Pedersen O, Polak J, Oppert J-M, Martinez A, Sørensen TIA, Saris WHM, and the NUGENOB Consortium. Several gene polymorphisms but not FTO variants modulate resting energy expenditure and fat-induced thermogenesis in obese subjects: The NUGENOB Study