The helminth parasite community of European badgers (Meles meles) in Ireland.

The European badger (Meles meles) is Ireland's largest terrestrial carnivore. Since first being identified as a wildlife reservoir of bovine tuberculosis in 1974 there has been an increased research focus into the behaviour of these ecologically important mammals in the Republic of Ireland (ROI). However, to date there has never been an assessment of the helminth parasite community of Irish badgers. This study of 289 badgers found helminth infection to be endemic within the sample population and we report for the first time the prevalence, abundance, intensity and aggregation of helminth infection in ROI. Eight distinct helminth taxa were recorded: Aelurostrongylus falciformis, Crenosoma melesi, Eucoleus aerophilus, Species A, Strongyloides spp., Uncinaria criniformis, and two unidentifiable but morphologically distinct nematodes. All helminths belong to the taxon Nematoda, and this is the first report of an exclusively nematode community across the badger's Eurasian distribution. Infection was not significantly influenced by the host sex, region of origin or season of sampling.

A prospective audit of hypospadias correction in a regional paediatric surgery centre.

AIM: To prospectively review the management and treatment of hypospadias in a single regional centre, and in particular, to assess the spectrum of cases treated, techniques used and to determine the nature of the complications. METHODS: One hundred and fifty-three consecutive boys undergoing hypospadias repair during a 36-month period were included in the study. Information was collected prospectively and included the site of the urethral meatus, presence of chordee, surgical technique employed, use of urinary diversion, and the prescription of postoperative antibiotics and analgesics. Patients were assessed in the clinic following surgery at which time information on outcome and complications was obtained. RESULTS: One hundred and fifty-seven procedures for hypospadias were performed. Single-stage reconstruction was performed in 145 boys. GRAP (glanular reconstruction and preputioplasty) repair was the most common operation employed (n=112). The overall fistula rate was 11.7 % with the majority of patients having a satisfactory functional and cosmetic outcome following surgery. CONCLUSION: A variety of techniques can be employed to provide satisfactory correction of hypospadias with an increasing emphasis on single-stage day case procedures. GRAP repair is the favoured option for distal hypospadias and incorporates preservation of the prepuce.

Transforming growth factor-beta1 up-regulates p15, p21 and p27 and blocks cell cycling in G1 in human prostate epithelium.

Transforming growth factor-beta1 (TGFbeta1) is inhibitory to most epithelia, but its role in the control of proliferation of prostatic epithelium is unclear. In some cells, TGFbeta1 inhibition is achieved by up-regulation of cyclin-dependent kinase (cdk) inhibitors including p15, p21 and p27. Our aims were to determine whether the effects of TGFbeta1 on human prostatic epithelial cell cycle kinetics were mediated by alterations in the levels of the cdk inhibitors p15, p16, p21 and p27 and hypo-phosphorylated retinoblastoma protein (Rb). Human prostatic epithelial cells in primary culture were grown in the presence of TGFbeta1 (0-10 ng/ml) for up to 4 days and proliferation assessed using a [3H]thymidine uptake assay. Levels of p15, p16, p21 and p27 were measured at both mRNA and protein level by means of a reverse transcriptase PCR-based assay and Western analysis. Rb and cdk2 levels were measured. Exogenous TGFbeta1 (0-5 ng/ml) inhibited proliferation. This was associated with blocking of the cell cycle at G1, and up to 4-fold increases in p15, p21 and p27 mRNA levels, but no change was observed in p16 mRNA levels; these changes were not blocked by cycloheximide. Increased levels of p15, p21 and p27 protein were also accompanied by increased levels of hypo-phosphorylated Rb and decreased cdk2 kinase activity. TGFbeta1 has mainly inhibitory effects on benign human prostatic epithelium, which are caused by up-regulation of cdk inhibitors, hypo-phosphorylation of Rb and delaying of the cell cycle in G1.

The immunohistochemical detection of cripto-1 in benign and malignant human bladder.

The recently identified epidermal growth factor-related peptide cripto-1 has been previously implicated in the development of the malignant phenotype. The identification of gene products that can act as prognostic markers in bladder cancer would be value in determining the management of this heterogeneous group of patients. This study examines cripto-1 expression in benign and malignant bladder using immunohistochemical techniques. The expression of cripto-1 protein in benign and malignant bladder was examined in 45 bladder tumours (Ta/T1 n = 26, T2 n = 5, T3/T4 n = 14) and six benign controls. All 45 tumours showed positive cytoplasmic staining for cripto-1, including areas of carcinoma in situ. None of the six benign controls showed any evidence of positive cripto-1 staining. Twenty-three (60 per cent) bladder tumours had areas of papillary tumour that showed strong positive staining for cripto-1 as opposed to six (29 per cent) sections of histologically normal urothelium adjacent to tumour (P < 0.05). There was no association between cripto-1 staining and tumour grade, stage, or clinical outcome. Cripto-1 protein appears to be specifically expressed in malignant and benign adjacent urothelium of patients with bladder cancer. Its clinical significance, however, remains to be determined.

The expression of waf-1, p53 and bcl-2 in prostatic adenocarcinoma.

OBJECTIVE: To determine the associations between the expression of waf-1 (a cyclin-dependent kinase inhibitor regulated by p53), p53, bcl-2 and tumour progression in prostate cancer. PATIENTS AND METHODS: Samples of prostatic tissue were obtained by biopsy or at prostatectomy from 40 men (mean age 73 years, range 55-88) with histologically confirmed prostate cancer, examined using immunohistochemical staining for the three gene products, and the expression related to the stage, grade, disease progression and survival of the patients. RESULTS: Fifteen of 18 patients whose tumours were positive for waf-1, 10 of 12 positive for bcl-2 and 17 of 19 positive for p53 had disease progression. Fifteen of 19 patients positive for p53 had poorly differentiated tumours compared with 11 of 21 negative for p53 (P < 0.05). A significant number of patients positive for p53 progressed and had a shorter time to progression compared to those negative for p53 (P < 0.05). There was no correlation between either waf-1 and/or bcl-2 staining and clinical grade, stage or tumour progression. CONCLUSIONS: This study confirmed the association of p53 protein accumulation with aggressive behaviour in prostate cancer and identified waf-1 protein in prostatic tumours. There was no evidence that the upregulation of waf-1 was associated with a better outcome in patients with prostate cancer.

Surgery for chronic pancreatitis: a review of 12 years experience.

The surgical management of chronic pancreatitis remains controversial. We have practised a selective approach to surgery using symptoms and endoscopic retrograde cholangiopancreatography (ERCP) as the indications for operation and the procedure performed. A total of 76 patients who underwent surgery for chronic pancreatitis over a 12 year period were reviewed. Of the patients, 24 (32%) had a Whipple's resection (WR), 41 (54%) distal pancreatectomy (DP) with drainage, and 11 (14%) had other procedures. Eleven patients had died. Hospital records were reviewed and of the 65 patients alive at follow-up, 51 (79%) were interviewed. Twenty-three patients (74%) who underwent DP reported either excellent or good general health compared with 7 (44%) who had WR (P = 0.04). However, there was no difference in general health between operative groups using visual analogue scales. There was no difference in pain at follow-up between DP and WR. Of patients interviewed, 88% felt that their pain was better than before operation and 25 (49%) had no pain at all. Diabetes developed more frequently after DP (P = 0.005) than after WR. Good results can be achieved by pancreatic resection when careful selection is exercised.

Peptide growth factors in the prostate as mediators of stromal epithelial interaction.

Peptide growth factors play a role in the maintenance of normal prostatic growth and differentiation (Fig. 2). It seems likely that the androgen sensitivity of human prostate is mediated by the production of peptide growth factors from stromal cells which act as the direct intermediate of androgen action on epithelial cells. TGF-beta 1 inhibition of epithelial cells is opposed by the stimulatory action of EGF, IGF and FGFs to maintain an equilibrium of epithelial cell numbers. The indirect mitogenic action of androgens appear to act by down-regulation of TGF-beta 1 and possibly EGF receptors. There is also interaction with the effects of IGF-II, produced by prostatic stromal cells and acting on epithelial cells to increase proliferation. The growth of normal prostatic fibroblasts is under the control of bFGF and TGF-beta 1. However, although our understanding of the actions of these growth factors in the normal prostate has improved over the last decade, their role in the development and maintenance of prostate cancer is less clearly defined. TGF-beta 1, classically considered to be inhibitory for epithelial cells, may be up-regulated in prostatic tumours, stimulating growth. Alternatively, autocrine production of such growth factors by tumour cells may lead to loss of inhibitory effects from exogenous TGF-beta 1, a mechanism also witnessed with TGF-alpha and bFGF. The role of EGF in the development of prostate cancer is confusing because results from the use of different cell types and experimental conditions is contradictory. It may be that a switch in the production of the predominant EGFr ligand from EGF to TGF-alpha is an important feature in the development and maintenance of the malignant phenotype. The presence of TGF-alpha autocrine loops has been shown clearly in some tumour cell lines. This switch in the production of a particular ligand may also be a feature of IGFs in prostate cancer. IGF-II may be replaced by IGF-I during malignant progression, both of which are able to act via the type 1 receptor. This change in IGF expression appears to be accompanied by altered expression of the IGF-BP2, with less detectable within prostatic tissues but elevated serum levels [58]. Basic FGF is normally produced by prostatic fibroblasts but is also produced by some prostatic cancer cell lines [64]. However, as with all growth factors, the expression of the bFGF protein and its receptor is dependent on the cell line examined. The autocrine and paracrine control of normal and abnormal prostatic growth by growth factors is important in determining their role in the development and maintenance of prostate cancer. Better understanding of such mechanisms is essential for the development of novel therapeutic strategies in the control and treatment of prostate cancer.

Predictive value of bruits and Doppler pressure measurements in detecting lower limb arterial stenosis.

The value of bruits and Doppler ankle pressure measurements as indicators of arterial stenosis was studied in 50 patients with symptoms of lower limb ischaemia. The iliac and femoropopliteal arteries were examined for bruits, ankle systolic pressures were measured before and after an exercise stress test and the results were compared to the findings of digital subtraction angiography (DSA). Patients with occlusive lesions in the iliac and femoropopliteal arteries were not analysed. This left a group of 37 symptomatic legs in which the popliteal pulse was palpable. In this sub-group, DSA demonstrated 25 limbs with arterial stenoses and 12 limbs without evidence of a stenosis. The presence of a bruit had a sensitivity of 80%, a specificity of 75%, a positive predictive value of 87%, a negative predictive value of 64% and an accuracy of 78%. A fall in Doppler ankle pressure of > or = 20 mmHg had a sensitivity of 92%, a specificity of 75%, a positive predictive value of 88%, a negative predictive value of 82% and an accuracy of 86%. When used selectively, clinical examination for bruits has good accuracy and may be of clinical value in the early identification of patients who are suitable for percutaneous transluminal angioplasty.

Factors influencing the healing of distal amputations performed for lower limb ischaemia.

A total of 235 toes were amputated during 125 operations on 100 consecutive patients with lower limb ischaemia. The overall amputation wound healing rate for the series was 58.4 per cent and limb salvage was achieved in 66 patients. Toe amputation was performed under local anaesthesia in 57 cases and 32 (56 per cent) of these healed primarily, not significantly different from the healing rate of 41 (60 per cent) of 68 under general anaesthesia. Reconstructive arterial surgery was performed in conjunction with toe amputation in 39 patients; the healing rate with reconstruction was 32 (82 per cent) of 39, significantly better than the 41 (48 per cent) of 86 patients not undergoing bypass surgery (P less than 0.001). There was no difference in healing rates when comparing diabetic and non-diabetic patients. Multiple regression analysis demonstrated that reconstructive arterial surgery was the only factor which had an independent and significant influence on toe amputation healing. The use of local anaesthesia for distal amputation has no deleterious effects on wound healing.