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Biomedical subjects

G H Muir

Publications and source records attributed to G H Muir.

At least 19 recordsLinked to original sources
PubMed2006

Lycopene inhibits DNA synthesis in primary prostate epithelial cells in vitro and its administration is associated with a reduced prostate-specific antigen velocity in a phase II clinical study.

Interest in lycopene has focused primarily on its use in the chemoprevention of prostate cancer (CaP); there are few clinical trials involving men with established disease. In addition, most data examining its mechanism of action have been obtained from experiments using immortal cell lines. We report the inhibitory effect(s) of lycopene in primary prostate epithelial cell (PEC) cultures, and the results of a pilot phase II clinical study investigating whole-tomato lycopene supplementation on the behavior of established CaP, demonstrating a significant and maintained effect on prostate-specific antigen velocity over 1 year. These data reinforce the justification for a large, randomized, placebo-controlled study.

Aged↗
PubMed2006

Laparoscopic partial nephrectomy using the potassium titanyl phosphate laser in a porcine model.

INTRODUCTION: To evaluate the potential and feasibility of the potassium titanyl phosphate (KTP) Greenlight laser to perform partial nephrectomy in a porcine model. TECHNICAL CONSIDERATIONS: A total of 15 laparoscopic partial nephrectomies were performed in 4 Danish land-raised pigs under anesthesia. Transperitoneal access was obtained, and using a total of four ports, the 80-W KTP laser was used to perform bilateral upper and lower pole partial nephrectomy. The procedures were done successfully without renal cooling or clamping of the vessels. The estimated blood loss for each procedure was less than 30 mL. Only in one operation, in which a secondary renal vein was transected, was any additional hemostasis required (a single Endoclip). The mean operating time was 42 minutes (range 31 to 59) for each partial nephrectomy. As demonstrated on video, smoke formation was, at times, a problem during the procedure, because it reduced visibility, making only intermittent application of laser energy possible. Histopathologic analysis of the specimens showed a zone of loss of substance (less than 1 mm) at the resection line and narrow adjacent zones on both sides of the resection line with minimal changes. CONCLUSIONS: We have shown for the first time that normally perfused laparoscopic partial nephrectomy using the KTP laser is feasible and efficacious in the porcine model. This represents a novel application for the KTP laser, which produced excellent renal parenchymal hemostatic ablation. We are currently working on ways to improve the visibility by reducing smoke formation before undertaking a clinical trial in humans.

Animals↗
PubMed2006

Use of expired breath ethanol measurements in evaluation of irrigant absorption during high-power potassium titanyl phosphate laser vaporization of prostate.

OBJECTIVES: To evaluate formally the risk and levels of irrigant absorption during high-power potassium titanyl phosphate (KTP) laser vaporization of the prostate by the Greenlight PV system using the expired breath ethanol technique. METHODS: Forty consecutive patients underwent laser vaporization of the prostate. Of these patients, 17 had a preoperative transrectal ultrasound estimation of the prostate volume (mean 97 cm3). All procedures were performed under general anesthesia, by either of two consultants or a trainee. A 1% ethanol solution was used as irrigation fluid. Throughout the operation, the expired breath was analyzed for ethanol using a standard alcometer "plumbed" into the anesthetic circuit. Venous blood samples were taken immediately before and after the procedure for measurements of serum sodium and plasma alcohol levels. RESULTS: On average, 155,000 J of laser energy was delivered in 47 minutes. In all patients and on all occasions, the expired breath ethanol remained at 0. No statistically significant change was found in the serum sodium concentration during the procedure (P = 0.42), and no patient displayed any clinical evidence of transurethral resection syndrome. CONCLUSIONS: The results of this study have confirmed, for the first time, the lack of significant absorption of irrigation fluid during high-power KTP vaporization of the prostate using a recognized sensitive technique and the safety of using sterile water as that irrigant. This was the case even in those patients with very large prostates who are usually considered at high risk of experiencing the clinical consequences of fluid absorption during transurethral resection of the prostate and regardless of the experience of the surgeon.

Absorption↗
PubMed2004

Phentolamine re-dosing during penile dynamic colour Doppler ultrasound: a practical method to abolish a false diagnosis of venous leakage in patients with erectile dysfunction.

Increased sympathetic tone may cause an equivocal response to a prostaglandin E1 (PGE1) penile Doppler ultrasound (US) examination interpreted as a venous leak. We evaluated the US parameters and erectile response to the addition of phentolamine to a PGE1 penile Doppler US examination to ascertain whether addition of phentolamine would abolish a suboptimal response. 32 patients (median age 29 years, range 17-70 years) with either a previous Doppler US pattern of venous leakage or a clinical suspicion of venogenic impotence, underwent Doppler US after a total dose of 20 microg of PGE1. Peak systolic velocity (PSV), end diastolic velocity (EDV) and grade of erection were documented. If erectile response was suboptimal irrespective of the EDV measurement, 2 mg-intracavernosal phentolamine was administered and measurements repeated. Six patients had a normal erectile response, the remaining 26 received phentolamine. A significant increase in PSV between baseline and 20 microg PGE1 (p<0.001) was observed in all cases. Following phentolamine there was a significant increase in grade of erection (p=0.0001) and a significant reduction in the EDV (p=0.0001). A reduction of the EDV to below 0.0 cm s(-1) was observed in 16 patients. Four patients with EDV <5.0 cm s(-1) but >0.0 cm s(-1) had improved erectile response following phentolamine while six showed persistent EDV elevation >5 cm s(-1). No priapism was documented. It is essential to ensure cavernosal relaxation using phentolamine before a Doppler US diagnosis of venous leak is made. This two-stage assessment will allow this to be done efficiently and with a low risk of priapism.

Adolescent↗
PubMed2003

Sildenafil does not improve sexual function in men without erectile dysfunction but does reduce the postorgasmic refractory time.

Sildenafil is one of two oral drugs approved for first-line treatment of erectile dysfunction (ED). Anecdotally, some young healthy men who wish to enhance their sexual performance are requesting or abusing sildenafil. In this randomized double-blind, placebo-controlled clinical study, we investigated the effect of sildenafil in young men without ED. A total of 60 young healthy men age 20-40 y with no reported ED were enrolled for this single-dose home-use study. Subjects had used no medication in the 6 months prior to the study. All had been engaged in a stable relationship for at least 3 months. After completing the IIEF-5 questionnaire, patients were randomized in a double-blind fashion to receive either one 25 mg tablet of sildenafil (group 1) taken prior to intercourse, or an identical placebo tablet (group 2). All subjects completed a questionnaire relating to their erectile quality. There were no differences between the two groups in the reported improvement of erection quality, 12/30 sildenafil vs 10/30 placebo (Fisher's test, P=0.79). Sildenafil caused a significant reduction of the postejaculatory refractory time (12/30 vs 4/30) (chi(2) test, P=0.04). Sildenafil does not improve erections in young healthy men. Sildenafil should not be given to young healthy men to improve their erections and patients should be advised against recreational abuse of the drug. In this limited single-dose home study, sildenafil appears to reduce the postorgasmic refractory time. Although controlled studies are needed to evaluate the efficacy of erection-enhancing drugs in premature ejaculation, it is possible that sildenafil might be useful for this indication.

Adult↗
PubMed2002

Penile length is normal in most men seeking penile lengthening procedures.

Concerns over penile size and a desire for a longer penis are common in the male population. The number of male patients seeking an andrological consultation for the problem of 'short penis' is increasing. We looked at the numbers of patients presenting to a University andrology clinic over a 2-y period and correlated their perceived penis size with the accepted norms. Sixty-seven patients were evaluated with a median age of 27 (range 16-55) complaining of 'short penis' and requesting surgical correction. Clinical history, including the IIEF-5 questionnaire and an accurate physical examination were obtained. Data concerning measures of penile length and circumference were recorded in both the flaccid and fully stretched states and compared to the normal reference range as previously described in the nomogram we recently published (Eur Urol 2001; 39: 183-186.). All patients were also asked to estimate the length of a normal sized penis.Fourty-four (65.7%) complained of a short penis only while flaccid, 22 patients (32.8%%) while both flaccid and erect, and only one patient (1.5%) was worried only by the erect length of the penis. Fifteen (22.4%) also complained about their penile circumference. Fifty-seven (85%) patients thought a 'normal' penile length should range from 10 to 17 cm (median value of 12 cm). Ten patients (15%) were not able to estimate 'normal' penile size. No patient was found to have a penile length under the 2.5 percentile according to our nomogram. Forty-two (62.7%) subjects recalled the problem starting in childhood, when they felt that their penis was smaller than their friends'. In 25 patients (37.3%) the problem started in the teenage years after seeing erotic images. Our data show that most men who seek penile lengthening surgery overestimate 'normal' penile length. In our series, none of the patients could be classified as having a severely short penis according to our nomogram and none had any anatomical penile abnormality. Most found the use of a nomgram to show them how they compared with other men helpful. We suggest that documentation of such a demonstration should be made for any man seeking an opinion on penile lengthening surgery.

Adolescent↗
PubMed2002

Primary cultures of prostate cells and their ability to activate carcinogens.

Differences in the incidence of prostate cancer (CaP) amongst different migrant populations point to causative agents of dietary and/or environmental origin. Prostate tissues were obtained following transurethral resection of the prostate (TURP) or radical retropubic prostatectomy. After surgery, TURP-derived or tumour-adjacent tissue fragments were minced in warm PFMR-4A medium (37 degrees C) and suspensions pipetted into collagen-coated petri dishes. Non-adherent material was removed by washing with fresh medium after 12 h. Adhered cells subsequently reacted positively with monoclonal antibodies to prostate specific antigen (PSA). PSA was also detected in the medium. The genotoxicities of the chemical carcinogens 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP), its N-hydroxy metabolite (N-OH-PhIP) and benzo[a]pyrene (B[a]P) in adherent cell populations from different donors (n=8) were examined. Cells were treated in suspension for 30 min at 37 degrees C in the presence of the DNA repair inhibitors hydroxyurea (HU) and cytosine arabinoside (ara-C). DNA single-strand breaks were detected in cells by the alkaline single cell-gel electrophoresis ('Comet') assay and quantified by measuring comet tail length (CTL) in microm. All three carcinogens induced dose-related increases in CTLs (P<0.0001) in cells from four donors 24 h post-seeding. However, in cells from a further two donors the genotoxic effects of PhIP, N-OH-PhIP and B[a]P were much less apparent after 48 h than after 24 h in culture. After 96 h in culture, cells from these donors appeared to be resistant to the comet-forming activity of the compounds. However, B[a]P-DNA adducts were still measurable by (32)P-postlabelling for up to 14 days following a 24-h exposure to 50 microM B[a]P in adhered cells from another two donors. This study shows that primary cultures of cells derived from the prostate can activate members of two classes of chemical carcinogens. Further development may provide a robust model system in which to investigate the aetiology of CaP.

Adult↗
PubMed2001

The genetic alterations in the oncogenic pathway of transitional cell carcinoma of the bladder and its prognostic value.

This review focuses on the main oncogenes studied in transitional cell carcinoma (TCC) in order to describe their mechanisms of action and investigate their possible prognostic value. Each oncogene family is reported following the order through which the proliferative signal is transduced from the extracellular space via a growth factor to the nucleus where transcription factors are switched on. Oncogenic activation at any level of the pathway will cause an increased transcription of genes enhancing the cell cycle, and proliferation will therefore be amplified. The main molecular or immunohistochemical studies from the literature on the aberrant expression of these genes are examined and compared with the aid of tables. Conclusions suggest that, although some may initially appear promising, no oncogene, has thus far been found to have a definite prognostic value superior to conventional grading and staging.

Carcinoma, Transitional Cell↗
PubMed2001

Validity of PSA, free/total PSA ratio and complexed/total PSA ratio measurements in men with acute urinary retention.

The reliability of serum prostate specific antigen (PSA) measurements in men with acute urinary retention is unclear. Total PSA, free and complexed PSA were measured, and the free/total (f/t) PSA and complexed/total (c/t) PSA ratios calculated, prior to catheterisation and at 48 and 72 h post-catheterisation in 39 men with acute retention. Subsequent histology showed 12 patients had prostate cancer and 27 benign prostatic hypertrophy. Serum free and total PSA fell following catheterisation, while complexed PSA rose during the first 48 h then subsequently fell. The f/t PSA and c/t PSA ratios provided the best discrimination at 48-72 h with 100% sensitivity and 75-82% specificity.Prostate Cancer and Prostatic Diseases (2001) 4, 167-172.

Journal Article↗
PubMed2001

Acute segmental testicular infarction: differentiation from tumour using high frequency colour Doppler ultrasound.

Segmental testicular infarction is rare, of variable aetiology but usually idiopathic. B-mode ultrasound may demonstrate a focal mass indistinguishable from a testicular tumour, with confirmation only achieved following surgery. We report a case of segmental testicular infarction presenting as a heterogeneous mass on B-mode ultrasound, confidently diagnosed as an area of infarction on high frequency colour Doppler ultrasound and proven on histology. The pre-operative differentiation of tumour from segmental infarction allows testis-sparing surgery.

Acute Disease↗
PubMed2000

An appraisal of telomerase activity in benign prostatic hyperplasia.

BACKGROUND: Prostate cancer is one of the commonest neoplasms in elderly males in developed countries. It is not clear which individuals are at high risk of developing aggressive adenocarcinoma of the prostate. Biomarkers are therefore urgently needed to identify such individuals. It had been suggested both by ourselves and others that prostatic telomerase activity may represent a valuable marker in this respect, particularly if applied to BPH, as tissue is readily available from both transurethral resection of prostates and transrectal ultrasound biopsy. METHODS: Tissue was collected prospectively from 46 patients with BPH who underwent TURP for clinically benign prostatic disease, and who were examined using the telomeric repeat amplification protocol (TRAP assay). RESULTS: Telomerase activity was not detected in any of 46 BPH samples, using TRAP assay conditions of 0.12, 1.2, and 12.0 microg protein. CONCLUSIONS: The study confirms that telomerase is not detectable in BPH samples. This would suggest that absence of telomerase activity may be a strong indicator of a lack of cancer. However further studies are necessary to confirm this.

Adenocarcinoma↗
PubMed2000

Penile fracture repair: assessment of early results and complications using color Doppler ultrasound.

The aim of this study was to determine early results and complications of penile fracture treated with immediate surgical repair by means of color Doppler ultrasound study. Four patients with the clinical features of penile fracture were submitted to immediate surgical exploration via a subcoronal incision with repair of the torn cavernosal albuginea (unilateral in three cases, bilateral in one case) and anastomosis of the transected urethra (one case). Color Doppler ultrasound (CDUS) was performed by means of an Acuson 128XP/10 using a 7-10 MHz extended frequency linear array transducer. Erectile function at five months follow-up was reported as normal by two patients (age 59 and 55 y), slightly decreased in one case (bilateral partial cavernous fracture + total urethral transection in a 32 y old) and weak in one case (51 y old). In the latter two, the investigation included a dynamic phase following a 10 mcg PGE injection. B-mode ultrasound showed no fibrotic changes in relation to the long-term absorbable suture material. Baseline CDUS demonstrated full length integrity of the cavernous arteries in all patients. The CDUS dynamic study was entirely normal in the patient with weak erection while showed a continuous venous leak in the patient with bilateral cavernosal rupture and transected urethra. We conclude that despite the onset of erectile failure in two out of four patients, there was no evidence of arteriogenic impotence in any patients with major penile fracture and thus we advocate early simple repair without any microsurgical exploration of the cavernosal arteries.

Adult↗
PubMed2000

The influence of dietary and environmental factors on prostate cancer risk.

Prostate cancer is the most common malignancy found in males and one of the most common causes of cancer death. The epidemiology implicates environmental and nutritional factors in the initiation and progression of the disease. Identification of these factors would allow chemoprevention strategies to be tested. Potent mutagenic and carcinogenic heterocyclic amines and polycyclic aromatic hydrocarbons are produced in cooked meat, and following metabolic activation some of them are strongly associated with prostate carcinogenesis in rodents. Primary cell cultures of human prostate epithelial cells were obtained from patients undergoing transurethral resection of the prostate. Metabolic activation of the cooked food carcinogens 2-amino-1-methyl-6-phenylimidazo- [4,5-b]pyridine (PhIP) and benzo[a]pyrene (B[a]P) was examined and resultant DNA damage (single strand breaks) measured using the Comet assay. Increased concentrations of carcinogen were associated with increased DNA damage and comet tail length compared to controls. Prostate Cancer and Prostatic Diseases (2000) 3, 256-258

Journal Article↗
PubMed2000

Metabolic activation of carcinogens and expression of various cytochromes P450 in human prostate tissue.

Epidemiological evidence suggests a link between meat consumption and prostate cancer. In this study, benign prostatic hyperplasia tissues, obtained by transurethral resection or radical retropubic prostatectomy from UK-resident individuals (n = 18), were examined for CYP1 expression and for their ability, in short-term organ culture, to metabolically activate carcinogens found in cooked meat. Semi-quantitative RT-PCR analysis of CYP1 expression detected CYP1A2 mRNA transcripts in the prostates of four individuals, as well as mRNA transcripts from CYP1A1 and CYP1B1. The compounds tested for metabolic activation were 2-amino-1-methyl-6-phenylimidazo[4, 5-b]pyridine (PhIP; 500 microM, n = 9) and its metabolite N:-hydroxy PhIP (20 microM, n = 8), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ; 500 microM, n = 6) and benzo[a]pyrene (B[a]P; 50 microM, n = 5). After incubation (PFMR medium, 22 h, 37 degrees C), DNA was isolated from tissue fragments and DNA adducts were detected and quantified by (32)P-postlabelling analysis. DNA adduct formation was detected in all samples incubated with PhIP (mean, adducts per 10(8) nucleotides), N:-hydroxy-PhIP (2736/10(8)) or B[a]P (1/10(8)). IQ-DNA adducts were detected in 5/6 tissues (mean, 1/10(8)). The CYP1 inhibitor alpha-naphthoflavone (10 microM) reduced B[a]P-DNA adduct formation in tissues from two individuals by 96 and 64%, respectively. This pilot study shows that human prostate tissue can metabolically activate 'cooked meat' carcinogens, a process that could contribute to prostate cancer development.

Adult↗
PubMed2000

Evaluation of P53 protein overexpression, Ki67 proliferative activity and mitotic index as markers of tumour recurrence in superficial transitional cell carcinoma of the bladder.

OBJECTIVES: To confirm the interrelationship between p53, ki67, mitotic index with others known prognostic factors such us stage, grade, multifocality, tumour size, history of recurrence in transitional cell carcinoma (TCC) of the bladder and to determine the prognostic impact of p53, Ki67 and mitotic index in predicting recurrence in superficial bladder cancer. METHODS: Two hundred and fourteen patients with apparently superficial TCC of the bladder underwent TURBT and the 192 histologically Ta-T1 were divided into 104 primary lesions (group 1, mean follow-up 26 months) and 88 recurrent tumours (group 2, mean follow-up 28 months). Data concerning focality, tumour size, number of recurrences and recurrence-free survival were considered in each patients. All samples were immunohistochemically stained with p53 and Ki67 monoclonal antibodies. Mitotic index (MI) was calculated on haematoxylin and eosin stained sections. RESULTS: Recurrence-free survival was significantly lower in superficial recurrent tumours (group 2) compared with primary tumours (group 1). P53 staining was correlated with grade and stage for both 5 and 20% positivity thresholds. Ki67 and MI were significantly different over strata defined by stage, grade and focality in both patients groups but only Ki67 showed a correlation with p53 status. Recurrence-free survival could not be predicted either by p53 status or MI. A 20% cut-off level of Ki67 staining resulted a good predictor of recurrence in group 1 Ta-T1/G1-G2 tumours (p = 0.03). Only Ki67 and multifocality were found to be independent prognostic factors of recurrence in multivariate analysis. Stratifying Ta-T1/G1-G2 patients according to these variables, Ki67 provided a useful tool to predict early recurrence in monofocal lesions from both groups. CONCLUSIONS: P53 and MI despite a fairly good correlation with traditional prognostic factors in bladder TCC seem to play no role in the prediction of tumoural recurrence. A Ki67 index over 20% predicts those single well-differentiated (Ta-T1/G1-G2) tumours which are likely to recur within one year of treatment.

Aged↗