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Biomedical subjects

D E Neal

Publications and source records attributed to D E Neal.

At least 91 records · Page 5Linked to original sources
PubMed1998

The management of men with acute urinary retention. National Prostatectomy Audit Steering Group.

OBJECTIVES: To determine the outcome of men with acute urinary retention undergoing prostatectomy and to assess whether discharge with a catheter before subsequent planned re-admission for prostatectomy had an adverse effect on outcome. PATIENTS AND METHODS: A prospective cohort study was conducted of all men undergoing prostatectomy in five health care regions over a 6-month period in 56 hospitals where prostatectomies were performed under the care of 103 surgeons. The study included 3966 men undergoing prostatectomy, of whom 1242 presented with acute urinary retention; the complication rates and symptomatic outcome were assessed. RESULTS: Compared with those who underwent elective prostatectomy for symptoms alone, men presenting with acute retention had an excess risk of death at 30 days (relative risk [RR], 26.6, 95% confidence interval [CI], 3.5-204.5) and at 90 days after operation (RR 4.4, 95% CI 2.5-7.6), and an increased risk of perioperative complications. Although men with retention were older, had larger glands and had more comorbidity, these factors did not totally explain the excess risk. The final symptomatic outcome of men with acute retention was no different from that of men presenting for elective treatment. Men with retention who were managed by initial catheterization, sent home and subsequently re-admitted for planned operation had similar pretreatment characteristics, post-operative complications and outcomes to those who were kept in hospital throughout, although the men kept in hospital had a total increased length of stay. CONCLUSIONS: Men with acute retention have a high risk of developing complications after undergoing prostatectomy. We were unable to confirm that a short-term period of catheter drainage at home before re-admission for planned surgery carried increased risks of peri-operative complications.

Acute Disease↗
PubMed1998

Neuromodulation in bladder dysfunction.

Neuromodulation is one option for the management of a wide variety of lower urinary tract disorders, including non-neuropathic and neuropathic bladder dysfunctions. The mechanisms of action of the reported techniques remain unclear; urodynamic changes are minimal, but symptomatic improvements are common. Although the treatment is relatively free from side-effects compared with more aggressive surgical options, the placebo effect is likely to be significant. Its exact cost effectiveness is unclear, but the technology is a welcome addition to the range of treatment options for lower urinary tract dysfunctions, such as urgency and urge incontinence.

Electric Stimulation Therapy↗
PubMed1998

Bowel dysfunction after bladder reconstruction.

PURPOSE: Bowel function may be disturbed after intestinal segments are used in urinary reconstruction. The etiology of this condition and its incidence in different patient groups is unclear. We studied the incidence of bowel disturbance in patients who underwent bladder replacement, continent diversion, enterocystoplasty for idiopathic detrusor instability and ileal conduit diversion. MATERIALS AND METHODS: We evaluated 71 patients after ileal conduit diversion and 82 after bladder reconstruction, including clam enterocystoplasty for detrusor instability in 28, neurogenic bladder dysfunction in 26 and nonneuropathic conditions in 28. We noted the severity of symptoms, such as frequency of defecation, nocturnal diarrhea, flatus leakage, fecal urgency, fecal incontinence and explosive diarrhea, as well as quality of life. RESULTS: Of the patients who underwent bladder reconstruction 24% had symptoms of bowel dysfunction preoperatively and 42% of those who were asymptomatic preoperatively described new bowel symptoms postoperatively. These symptoms were most common and severe in 54% of patients after clam enterocystoplasty for detrusor instability compared to 26% with neuropathy, 14% with a nonneuropathic condition and 15% with an ileal conduit. Compared to those in other groups patients who underwent enterocystoplasty for detrusor instability had a significantly higher incidence of nocturnal bowel movements (18 versus less than 4%, p <0.01), flatus leakage (29 versus less than 8%, p <0.01), fecal urgency (39 versus less than 12%, p <0.001) and fecal incontinence (32 versus less than 16%, p <0.001). The length of ileum used for clam enterocystoplasty was only slightly greater than that used for ileal conduit operations (25 versus 18 cm.). Of the patients who underwent enterocystoplasty for detrusor instability 29% regretted undergoing the procedure due to subsequent bowel symptoms. CONCLUSIONS: After enterocystoplasty for detrusor instability patients are at risk of significant bowel symptoms. The development of new bowel symptoms was associated with poor patient satisfaction.

Adult↗
PubMed1998

Molecular biological changes in bladder cancer.

A large number of potential molecular markers of bladder cancer have been identified, although only a few are truly independent prognostic factors. A number of markers may need to be measured in a single tumour and used as a combination for use in the diagnosis and prognosis of transitional cell carcinoma (TCC). Epidermal growth factor receptor immunoreactivity has been shown to be an independent predictor of survival and stage progression. TP53 may be an independent predictor of recurrence and overall survival in TCC confined to the bladder, and TP53 alterations may predict chemosensitivity in patients who have had TCC treated by radical cystectomy. At present molecular techniques such as fluorescence in situ hybridization and the polymerase chain reaction are restricted to the laboratory, but immunohistochemical methods are available in most hospital pathology departments. There are some discrepancies and conflicting reports of the usefulness of molecular markers in different studies, and these need to be addressed in large, prospective, multi-institutional studies using standardized molecular techniques.

Animals↗
PubMed1998

Treatment of hypospadias: an update of current practice.

Hypospadias is a commonly occurring congenital deformity of the urethra in young boys, which is a cause of concern and psychological trauma for the child and his parents. Although there are numerous procedures for correcting hypospadias, the principles of hypospadias surgery are well defined. Adherence to sound surgical practice can yield good results with low complication rates.

Child, Preschool↗
PubMed1997

Testicular "tumor" of the adrenogenital syndrome: a case report of an unusual association with myelolipoma and seminoma in cryptorchidism.

BACKGROUND: Males with congenital adrenal hyperplasia may develop bilateral testicular masses in early adult life. These are not malignant and generally regress with corticosteroid therapy. The authors report a case occurring in a 44-year-old man with associated seminoma and myelolipoma in an undescended testis. METHODS: The testicular tumors were analyzed by histologic, flow cytometric, and ultrastructural techniques. RESULTS: The tumors in both testes were comprised of polygonal cells with abundant granular eosinophilic cytoplasm, occasionally with brown (lipochrome) pigment and round nuclei of various sizes with prominent nucleoli. These cells were grouped into nodules by dense and sometimes thick fibrous trabeculae in the right testis. The areas corresponding to the fibrous trabeculae in the left (intraabdominal) testis were replaced by mixture of hematopoietic (myeloid) and fatty tissue in various proportions characteristic of myelolipoma. The left testis also had a well demarcated tumor that was diagnostic of seminoma. Electron microscopy demonstrated abundant smooth endoplasmic reticulum, a moderate number of mitochondria with tubulovesicular cristae, lipid droplets, and lipofuscin granules in the polygonal cells. No Reinke's crystals were observed. The patient received corticosteroids for his adrenocorticoid deficiency and also underwent external beam irradiation to the retroperitoneum for seminoma. CONCLUSIONS: This case illustrates an unusual presentation of a testicular tumor in a patient with the adrenogenital syndrome as well as with myelolipoma and seminoma in a cryptorchid testis. The possibility of an associated neoplasm that could be potentially fatal should be considered whenever a testicular tumor of the adrenogenital syndrome continues to grow despite adequate hormonal treatment.

Adrenal Gland Neoplasms↗
PubMed1997

Immunolocalization and messenger RNA expression of bone morphogenetic protein-6 in human benign and malignant prostatic tissue.

Skeletal metastases are common in advanced prostate cancer, causing considerable morbidity, and they are usually osteoblastic in nature with no clear explanation for this phenomenon. Bone morphogenetic proteins (BMPs) induce bone formation in vivo, and preliminary work showed a possible association between BMPs and prostatic skeletal metastases; differential expression favors BMP-6 as a potential new marker and mediator of osteosclerotic deposit formation. We investigated BMP-6 mRNA and protein expression by in situ hybridization and immunohistochemistry in malignant and benign prostates from 40 men. BMP-6 mRNA expression was detected exclusively in malignant epithelial cells in 20 of 21 patients (95%) with metastases and in 2 of 11 patients (18%) with localized cancer, and it was absent in 8 benign samples. Immunostaining for BMP-6 was predominantly cytoplasmic and was present in all primary tumors with established metastases and in 4 of 11 (36%) organ-confined cancers. In benign prostatic hyperplasia, basal cells and areas of basal cell hyperplasia were positive for BMP-6 by immunohistochemistry. The results suggest a close association between BMP-6 expression in primary malignant prostatic tissue and skeletal metastases. BMP-6 may be responsible, in part, for the osteoblastic changes in metastatic lesions secondary to prostate cancer.

Adenocarcinoma↗
PubMed1997

Effects of a new 5 alpha reductase inhibitor (epristeride) on human prostate cell cultures.

BACKGROUND: Inhibitors of 5 alpha reductase (5 alpha R), the enzyme that converts testosterone to dihydrotestosterone (DHT), have been shown to retard the growth of hyperplastic prostates. This study evaluates the effects of the 5 alpha R inhibitor, epristeride, on cultured stromal and epithelial cells from benign, hyperplastic adult prostates. METHODS: [3H]-thymidine incorporation was used as a measure of proliferation. Prostate-specific antigen (PSA) was quantified by ELISA and reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: Stromal cell proliferation in response to testosterone was dose-dependently inhibited by epristeride (1 x 10(-9) -3 x 10(-7) M, P < 0.05). However, epristeride had no effect on DHT-induced growth or the growth of androgen-unresponsive stroma. Upregulation of PSA secretion from epithelial cells by androgens was downregulated by epristeride (3 x 10(-9) M, P < 0.05) in testosterone-treated cells. Transforming growth factor beta-1 (TGF beta-1) secretion was downregulated by testosterone treatment and increased following treatment with epristeride (3 x 10(-9) M, P < 0.05). CONCLUSIONS: This demonstrates that epristeride specifically blocks testosterone-induced effects on prostatic cultures. TGF beta-1 may be a marker of 5 alpha reductase activity.

5-alpha Reductase Inhibitors↗
PubMed1997

Keratinocyte growth factor expression in hormone insensitive prostate cancer.

Cellular interactions between stroma and epithelium are important in the growth and proliferation of prostate cancer. Peptide growth factors may facilitate the progression of prostate cancer as autocrine and/or paracrine factors. Keratinocyte Growth Factor (KGF or FGF7) has a differentiative and proliferative effect on the epithelium of the developing rat prostate. We investigated if KGF may act as a paracrine agent in human prostate cancer and examined the expression of KGF and Fibroblast Growth Factor Receptors (FGFRs) (IIIb and IIIc isoforms of the FGFR1 and FGFR2 genes). Sixty-five percent (11 out of 17 informative cases) of prostate cancers (CaP) expressed KGF mRNA by RT-PCR, while KGF expression was not detected in benign prostatic hyperplasia (BPH) (n = 6). Upregulation of KGF expression was related to hormone insensitive tumours (P<0.05). Tumour grade and stage were not associated with KGF expression. The source of KGF expression was further characterised using an in vitro primary culture model, showing its restriction to the prostatic stroma. The FGFR1IIIb isoform was expressed in all cases of prostate cancer (n = 17), and FGFR1IIIc mRNA was not detected. In the BPH group, FGFR1IIIb transcripts were detected in four out of six cases. FGFR2IIIb expression was detected in five of six cases of BPH and twelve out of seventeen (71%) cases of prostate cancer. In CaP, though not reaching statistical significance, the persistence of FGFR2IIIb expression appeared to be associated with hormone insensitive tumours (P=0.052). FGFR2IIIc expression was present in eleven of seventeen tumours but was absent in all six cases of BPH. Functional assessment of recombinant KGF in a proliferation assay demonstrated a mitogenic effect of up to 100% on cultured prostatic epithelial cells.

Androgens↗
PubMed1997

Androgen regulation of ornithine decarboxylase in human prostatic cells identified using differential display.

Androgens are essential for normal prostate physiology and have a permissive role in the development and progression of prostate cancer. Using the mRNA differential display technique, ornithine decarboxylase (ODC) was identified to be up-regulated by androgens in human prostatic LNCaP cells. On Northern analysis, the induction of ODC expression by 10 nM androgen was rapid and continued up to 48 h exposure with a maximum 6.3-fold up-regulation. The anti-androgen Casodex inhibited the androgen-induced up-regulation of ODC, whereas the protein synthesis inhibitor cycloheximide did not. Together these data suggest that regulation is mediated through the androgen receptor protein and does require secondary protein synthesis, respectively. The kinetics of induction of ODC were almost identical to those of prostate specific antigen. Taken together these data suggest that ODC is directly regulated by androgens in LNCaP cells.

Base Sequence↗
PubMed1997

The molecular pathology of urological malignancies.

Urological malignancies kill over 16,000 people annually in England and Wales. There have been exciting recent developments in our understanding of the molecular pathogenesis of these diseases, although many questions remain unanswered. Three separate genes (WT1, WT2, and WT3) have been implicated in Wilms' tumour development. Patients with von Hippel-Lindau (VHL) syndrome develop renal cell carcinoma and it has been shown that VHL protein inhibits elongin, a cellular transcription factor which controls RNA elongation. Use of molecular markers to identify superficial bladder tumours likely to progress to muscle invasive disease has met with some success. Increased epidermal growth factor receptor (EGFR) and p53 expression, and decreased E-cadherin expression all correlate with tumour progression. Tumours in patients with carcinoma in situ have distinct molecular features. Androgen ablation delays disease progression in men with prostate cancer, but relapse is inevitable. Research has been directed towards elucidating the mechanisms by which prostate cancer 'escapes' hormonal control. Mutations in the androgen receptor have been identified. It is apparent that locally produced growth factors mediate androgen-dependent processes and these too have been implicated in prostate carcinogenesis.

Carcinoma, Renal Cell↗
PubMed1997

Basic science aspects of prostate cancer.

Prostate cancer carries significant morbidity and mortality, but its outcome is difficult to predict in the individual. Androgen ablation delays progression in men, but hormone resistance soon develops and much basic science research has focused on how prostate cancer 'escapes' hormonal control. Stem cell models of prostate development and homeostasis have been proposed, but have not yet been fully characterized. Some androgen-regulated signalling pathways and abnormalities that affect them have been defined recently. It is apparent that locally produced growth factors, often regulated by androgens, exert an effect both physiologically and pathologically and these too will be discussed.

Androgens↗
PubMed1997

Urodynamic and clinical effects of noninvasive and minimally invasive treatments in elderly men with lower urinary tract symptoms stratified according to the grade of obstruction.

OBJECTIVES: We investigated the symptomatic and urodynamic effects of several noninvasive and minimally invasive treatment modalities to quantify these effects and to compare subjective and objective results within groups with various degrees of obstruction. METHODS: In a prospective study at one center, 487 patients who completed a full screening program including urodynamic investigation started treatment with watchful waiting, terazosin, transurethral microwave thermotherapy, or laser treatment of the prostate; they were re-evaluated symptomatically and urodynamically after 6 months of therapy. The symptomatic and urodynamic results of 87 patients from another center who underwent transurethral resection of the prostate and who had their second urodynamic evaluation 6 months after surgery were also included. RESULTS: In patients without bladder outlet obstruction (BOO), improvement in maximum flow and symptom scores with little change in the degree of obstruction was most apparent, whereas a decrease of detrusor pressure at maximum flow was observed mainly in patients with BOO. The urodynamic effect but not the symptomatic effect of treatments depended on the initial grade of BOO. Urodynamic changes were more marked in the minimally invasive treatment groups compared with the noninvasive treatment groups. CONCLUSIONS: In symptomatic patients with benign prostatic hyperplasia, symptomatic improvement in the short term does not seem to depend on changes in urodynamic parameters. Future well-controlled studies focusing on the durability of symptomatic and urodynamic effects will be needed to illustrate the relative potential of urodynamic and other clinical parameters to predict a favorable response to current and innovative treatments.

Adrenergic alpha-Antagonists↗
PubMed1997

Serum free prostate-specific antigen in the diagnosis of prostate cancer.

OBJECTIVE: To determine the value of the ratio of free prostate-specific antigen (fPSA) to total PSA (tPSA) in the diagnosis of benign prostatic hyperplasia (BPH) and prostate cancer in a cohort of patients undergoing prostatic transrectal ultrasonography (TRUS). PATIENTS AND METHODS: The study comprised 153 patients (99 with BPH and 54 with prostate cancer) undergoing diagnostic TRUS of the prostate. Patients with a tPSA of > 30 ng/mL were excluded from analysis. Free PSA was assayed using an immunoassay specific for unbound PSA (CanAg Diagnostics, Sweden). Total PSA was measured using the HybriTech Tandem-R PSA immunoradiometric assay in routine clinical use and this estimate was validated using the CanAg tPSA assay. RESULTS: The measurements of tPSA from both assay systems correlated closely. The f/tPSA ratios in patients with prostate cancer were significantly lower than in those with BPH (median values 0.152 and 0.2, respectively, P<0.01). In patients with prostate cancer, the median f/t PSA levels apparently declined with increasing tPSA levels but in those with BPH, the levels of tPSA were not significantly associated with the f/tPSA ratio; the ratios did not vary significantly with age in either group. A f/tPSA ratio at a threshold of 0.16 had positive and negative predictive values of 44% and 74%, respectively; the corresponding values for a tPSA of > 4 ng/mL were 30% and 52%. CONCLUSION: The f/tPSA ratio differs significantly between patients with BPH and cancer but because there is a considerable overlap of f/tPSA ratios between the groups, f/tPSA values alone were not sufficiently specific to be used as a single diagnostic test.

Biopsy↗