PubMed Health⌕ Search

Biomedical subjects

D E Neal

Publications and source records attributed to D E Neal.

At least 181 records · Page 10Linked to original sources
PubMed1993

Glutathione-S-transferase pi expression in transitional cell carcinoma of the bladder.

Glutathione-S-transferase pi (GST pi) is a multifunctional protein that acts as an enzyme, involved in the detoxification of drugs and carcinogens. It has been implicated both in drug resistance and malignant transformation of epithelium. Using an indirect immunohistochemical technique, we have evaluated cytoplasmic and nuclear staining in normal urothelium, 23 superficial bladder tumours and 26 invasive tumours. All 26 invasive tumours had been treated with platinum-based chemotherapy. Cytoplasmic staining was seen in normal urothelium and all bladder tumours. Nuclear staining was seen in 1 superficial tumour and in 13 invasive tumours. There was no association between nuclear staining and response to chemotherapy. Nuclear staining was seen in 1 area of dysplasia and in 2 of 3 areas of carcinoma in situ. GST pi expression is not a predictor of response to chemotherapy. Increased intra-nuclear expression of GST pi may be associated with progression of transitional cell carcinoma of the bladder.

Carcinoma, Transitional Cell↗
PubMed1993

p53 expression and clinical outcome in prostate cancer.

Abnormally high levels of expression of p53 protein are found in many human cancers. In most cases increased expression is associated with point mutations in one allele of the p53 gene and loss of the other allele. Accumulation of the protein product can be detected by immunohistochemistry. p53 protein expression in 68 men with prostate cancer, followed up for at least 8 years or until death, was assessed by immunohistochemistry. The aim of the study was to determine the association between p53 protein expression, cell cycling and clinical outcome. Nine (13%) of 68 tumours stained positively for p53; all 9 tumours were category T3 or T4. p53 positive tumours had a significantly greater Gleason score than p53 negative tumours. Eight of the 9 p53 positive tumours had > 10% cells in G2 + mitosis, compared with 61% of p53 negative tumours. All 17 patients with p53 positive tumours available for follow-up progressed clinically, compared with 28 of 38 patients (74%) with p53 negative tumours. The median time to progression was 12 months in p53 positive tumours and 24 months in p53 negative tumours. Median survival in p53 positive tumours was 40 months, compared with 76 months in p53 negative tumours. This study demonstrates that overexpression of p53 in a small population of prostate cancers is associated with a poor prognosis in terms of progression and survival.

Aged↗
PubMed1993

Detrusor contraction strength in men undergoing prostatectomy.

Elective prostatectomy is a frequently performed operation but the outcome may not always be satisfactory. This is probably because a significant number of men, despite subjective symptoms, are not urodynamically obstructed before operation and the preoperative assessment of obstruction is not easy using conventional urodynamic criteria. We have calculated detrusor contraction strength (WF) in men before and after prostatectomy. Our aim was to determine its relationship with symptomatic and urodynamic findings before and after prostatectomy and whether it was associated with clinical outcome. One hundred and twenty nine men listed for operation because of symptoms and low urinary flow rates were studied by means of urodynamic investigation and symptom scoring both before and 6 months after prostatectomy. A significant association was found between persistent obstructive symptoms after operation and a low WF before operation (P = 0.01), suggesting that weak detrusor function before operation was the cause of persistent symptoms afterwards. A significant correlation was also found between a high pre-operative WF and a high post-operative urinary flow rate; (P = 0.003); men with high detrusor power achieving the better flow rates after operation. Despite this relationship, the overall subjective clinical outcome was not strongly associated with WF and WF was no better than simple measurement of voiding pressure in predicting outcome in a multivariate analysis. The measurement of detrusor contraction strength provides some insight into the relationship between bladder function and clinical outcome after prostatectomy, but we have found it unable to predict outcome for the individual patient.

Aged↗
PubMed1992

Prostate specific antigen and prostatitis. I. Effect of prostatitis on serum PSA in the human and nonhuman primate.

Prostate specific antigen (PSA) has become a mainstay in the diagnosis and management of patients with prostate cancer. We have found, as have others, that it may be elevated in patients with prostatic inflammation. Ten patients had clinical evidence of prostatitis and elevated PSA levels. Six of these had persistently elevated levels after antibiotic treatment. After transrectal ultrasonography and biopsy, two had findings of adenocarcinoma, and the rest had a pathologic diagnosis of acute or chronic prostatitis. We studied this process in an experimental model of prostatitis using a nonhuman primate. We infected six cynomolgus monkeys and followed their PSA levels until resolution of the infection. The PSA peaked between 5 and 7 days after inoculation and gradually returned to baseline in 8 weeks. The dramatically elevated serum PSA levels in bacterial prostatitis can cause confusion in the diagnosis of prostatic carcinoma.

Adult↗
PubMed1992

Prostate specific antigen and prostatitis. II. PSA production and release kinetics in vitro.

Elevations in serum prostate specific antigen (PSA) levels in patients with prostatitis are well known, but the pathophysiologic mechanisms involved with this phenomenon are poorly understood. We have recently evaluated the effect of prostatitis on PSA levels in primates. This data demonstrated a rapid rise in PSA, which subsequently fell along the biological decay curve. This suggested a release of sequestered PSA. We evaluated the effect of infection upon PSA production for the prostatic adenocarcinoma cell line LNCaP. The cell line was determined to produce 9.6 +/- 2.7 fg/cell/hr PSA with essentially linear kinetics. No effect was seen with dead bacteria, bacterial supernatant or complement upon the PSA production. Live E. coli had no effect for 4-8 hours at which time the cells sloughed and PSA production ceased. No release of stored PSA was seen. These data do not elucidate the reasons for increased serum PSA levels found with acute bacterial prostatitis, but indicate that it is not a storage phenomenon.

Antigens, Neoplasm↗
PubMed1992

Ambulatory monitoring of bladder pressure in low compliance neurogenic bladder dysfunction.

Upper tract dilatation is an important complication of neurogenic bladder dysfunction. Risk factors include incomplete bladder emptying with large residual volumes of urine and high tonic increases in bladder pressures during artificial filling. However, on natural bladder filling many of these patients do not have high tonic increases in detrusor pressures. We compared conventional urodynamic studies with ambulatory monitoring during natural bladder filling in 66 patients with low compliance neurogenic bladder dysfunction. There were marked differences in the tonic increase in bladder pressure during filling and in compliance during artificial bladder filling compared with ambulatory monitoring. Faster filling rates during artificial filling resulted in greater end filling pressures and lower compliance but the lowest increases in bladder pressure were found during ambulatory monitoring with natural bladder filling. During natural bladder filling significantly more patients had phasic changes in detrusor pressure; a high intensity of phasic activity during ambulatory monitoring correlated with high end filling pressures during artificial bladder filling. Upper tract dilatation was associated with large volumes of residual urine, high resting bladder pressures and low bladder compliance on filling at 100 ml. per minute. However, upper tract dilatation was most strongly associated with high intensity phasic pressure activity during natural bladder filling in combination with high residual urine volumes and high resting bladder pressures. On multivariate statistical analysis the intensity of phasic pressure activity during ambulatory monitoring was the best discriminator between patients with dilated and normal upper tracts. Our study has highlighted important differences in the results obtained by artificial filling cystometry and ambulatory monitoring during natural bladder filling. In particular, high increases in pressure did not occur during natural bladder filling, apparently being replaced by phasic activity. Within this group of patients who had the high risk factor of low bladder compliance measured during artificial bladder filling, a combination of greater residual urine volumes, greater resting pressures and greater phasic activity during natural bladder filling was found in patients with upper tract dilatation.

Adolescent↗
PubMed1992

p53, c-erbB-2 and the epidermal growth factor receptor in the benign and malignant prostate.

Expression of the p53, the epidermal growth factor receptor (c-erbB-1) and c-erbB-2 protein was studied in 34 men with benign prostatic hyperplasia and 29 men with locally advanced prostate cancer by means of an immuno-histochemical method. Strong staining for p53 was found in five of 29 prostate cancers (17%; mean 21% +/- 7% of malignant cells stained in the positive tumours), but no staining was found in benign prostatic hyperplasia (p less than 0.05). On the other hand, the epithelium in benign glands was stained positively for c-erbB-2 in 18% (6/34) and for the epidermal growth factor receptor in 88% (30/34); whereas malignant epithelium stained strongly for c-erbB-2 in 21% (6/29) and for the epidermal growth factor receptor in only 17% (5/29). Prostate cancer was associated with a significant decrease in epidermal growth factor receptor staining (p less than 0.0001) and a significant increase in p53 staining (p less than 0.05). Most of the tumours were advanced and no significant relationship was observed between tumour stage and grade and expression of p53, the epidermal growth factor receptor or c-erbB-2. These findings demonstrate that altered expression of the epidermal growth factor receptor and p53 protein occurs in prostate cancer, but were not associated with other features of prognostic importance such as stage or grade.

Aged↗
PubMed1992

Cavernous tissue antibiotic levels in penile prosthesis surgery.

A comparison of the delivery of several antibiotics (vancomycin, gentamicin and aztreonam) to the tissue site of prosthesis implantation was studied using cavernous tissue levels for each antibiotic. A total of 32 patients underwent penile prosthesis implantation. Intravenous antibiotics were administered 1 to 2 hours preoperatively, with vancomycin and aztreonam given to patients at the Tulane University Medical Center, and vancomycin and gentamicin given to patients at the New Orleans Veterans Administration Hospital. At operation the urine, serum and cavernous tissue were concurrently sampled and later analyzed for antibiotic concentration. The mean cavernous tissue level for vancomycin was 55.5 +/- 5.5 ng./mg. (standard deviation) for 20 patients, while the mean cavernous tissue levels for aztreonam and gentamicin were 8.9 +/- 2.1 ng./mg. for 10 patients and 4.7 +/- 1.2 ng./mg. for 12 patients, respectively. When the delivery of antibiotic to cavernous tissue was compared (quantitated as ng. antibiotic per mg. tissue per mg. drug administered), a statistically significant value (p less than 0.01) was observed with vancomycin (0.11 ng./mg./mg.) greater than gentamicin (0.06 ng./mg./mg.) or aztreonam (0.01 ng./mg./mg.), and with no significant difference observed between aztreonam or gentamicin. These findings suggest that cavernous tissue levels may be used as a method to determine optimal antibiotic prophylaxis against penile prosthesis infection.

Aztreonam↗
PubMed1992

A self-administered patient questionnaire in the assessment of symptoms before and after prostatectomy.

A self-administered patient questionnaire was developed to assess the severity of key symptoms before and after transurethral prostatectomy (TURP). This questionnaire was validated by comparison with a standard assessment performed by the doctor. Complete data were obtained on 39 men studied before and 3 months after prostatectomy. Close associations were found between the scores resulting from the assessments performed by the patient and those carried out by the doctor. These associations were found for individual scores and for aggregate scores for obstructive and irritative symptoms before and after operation. Symptom scores after operation were significantly related to the patients' overall assessment of whether the operation had been a success--a low score being associated with a satisfactory outcome. It is suggested that self-administered symptom questionnaires can give a reliable picture of the outcome of prostatectomy and might be useful in developing audit systems.

Humans↗
PubMed1992

P53 and Ki-67 immunoreactivity in human prostate cancer and benign hyperplasia.

Mutation of the p53 gene is one of the commonest genetic abnormalities found in solid human tumours. This gene is probably concerned with the control of cellular proliferation and in view of this we carried out a study of human prostate cancer and benign prostatic hyperplasia, comparing the expression of mutated p53 with measurement of growth fractions as assessed by staining with Ki-67. A series of 29 patients with prostate cancer (CaP) were compared with 34 men with benign hyperplasia (BPH); 22 of 29 prostate cancers (76%) contained Ki-67 immunoreactivity compared with 10 of 34 (29%) BPH. With respect to p53 staining, significantly more prostate cancers (17%) were stained than BPH (0%). The mean Ki-67 score in cancers positive for p53 (4.3%) was greater than that found in cancers negative for p53 (1.2%), but no statistically significant relationship was found between tumour grade and Ki-67 staining. The use of Ki-67 and p53 staining may allow identification of tumours with a higher rate of cell growth and may permit development of prognostic factors.

Aged↗
PubMed1992

Electromyographic abnormalities in the urethral and anal sphincters of women with idiopathic retention of urine.

Previous concentric needle studies of the urethral sphincter in women with idiopathic urinary retention have found evidence of denervation and reinnervation as well as abnormal patterns of muscle fibre discharge--complex repetitive discharges (CRDs). In order to test the hypothesis that these abnormalities represented a more widespread disease process of pelvic floor function, we carried out an electromyographic (EMG) study of both anal and urethral sphincters in 18 women with idiopathic urinary retention. The urethral sphincter EMG was abnormal in 15 patients. These abnormalities included polyphasic and long duration potentials. Complex repetitive discharges were identified in 8 women. However, abnormalities of the anal sphincter were found in 14 of the 15 patients with abnormal urethral sphincter EMGs, polyphasic and abnormally long duration potentials being found in the anal sphincters of all 14 patients. In addition, 7 of the 8 women who had complex repetitive discharges in the urethral sphincters had similar complex repetitive discharges in their anal sphincters. Women with complex repetitive discharges had a significantly greater proportion of abnormal potentials than women with no such repetitive discharges. These results support the previous findings of electromyographic urethral sphincter abnormalities in women with idiopathic urinary retention, but also suggest that these abnormalities reflect a widespread disease process involving the pelvic floor in such patients.

Adult↗
PubMed1992

Screening for bacteriuria in urological patients using reagent strips.

A rapid and accurate ward-based method of diagnosing urinary infection would be of value in determining the prescription of antibiotics in pre-operative urological patients. This study describes the sensitivity and specificity of a screening technique based on commercially available reagent strips in the diagnosis of urinary infection. A total of 222 pre-operative samples and 83 post-operative samples was studied to compare the results of formal urine culture and reagent strips. Using a definition of a positive nitrite or a positive leucocyte esterase on the reagent strips as being suggestive of infection, it was found that the strips had a sensitivity of 91% and a specificity of 85% compared with formal culture in pre-operative samples. The results from post-operative samples were less satisfactory, the strips having a sensitivity of only 71% and specificity of 55%. The strips were insensitive but specific in the identification of pyuria in pre-operative specimens. These results suggest that reagent strips can be used as a ward-based method to identify men at risk of infection before urological procedures, and may allow selectivity in the use of peri-operative antibiotics.

Adolescent↗
PubMed1992

Epidermal growth factor receptor and bladder cancer: a review.

Recently, expectations have been raised that molecular biological studies of human tumours may be of value in helping to predict future clinical behaviour, in terms of therapeutic response and long-term survival. The epidermal growth factor receptor (EGFr) is a cell surface receptor for EGF and transforming growth factor-alpha which is overexpressed by a number of human tumours. This article principally reviews previous investigations of the role of the epidermal growth factor receptor in bladder cancer and examines methods of detection, the correlation between EGFr status and known prognostic indicators and the value of assessing EGFr status in predicting clinical outcome in patients with bladder cancer. Recent studies of the c-erbB-2 proto-oncogene in bladder cancer and of cell cycling using Ki-67 are included.

Biomarkers, Tumor↗
PubMed1992

Noradrenergic innervation of the human adrenal cortex as revealed by dopamine-beta-hydroxylase immunohistochemistry.

Noradrenergic innervation of the human adrenal cortex was investigated using immunohistochemistry directed at dopamine-beta-hydroxylase. Nerves were present as slender trunks and individual varicose fibres in the capsule and all cortical zones except the inner zona reticularis. Some fibres were located adjacent to blood vessels and in the muscular tunics of arterioles; others were apparently adjacent to parenchymal cells. These results in the human confirm and extend previous animal studies and suggest a possible anatomical substrate for regulation of adrenal blood flow, and also for the direct action of noradrenaline on zona fasciculata cells to stimulate glucocorticoid secretion via beta-1-adrenoceptors.

Adrenal Cortex↗
PubMed1991

Immunohistochemical detection of the epidermal growth factor receptor in paraffin-embedded human tissues.

Expression of the epidermal growth factor (EGF) receptor was evaluated by immunohistochemical staining of formalin-fixed, paraffin-embedded tumour tissues employing two antibodies raised to short synthetic peptides from the cytoplasmic domain of the molecule. Both antibodies gave concordant staining of a series of bladder cancers known to express or lack EGF receptors. There was no cross-reaction with the related c-erbB-2 protein, which was also over-expressed in some cases. Cancers with EGF receptor expression also expressed high levels of TGF-alpha, a receptor agonist.

Antibodies, Monoclonal↗
PubMed1991

Ciprofloxacin versus gentamicin in prophylaxis against bacteremia in transrectal prostate needle biopsy.

Consecutive patients with abnormal rectal examinations underwent transrectal needle prostate biopsy at VA Medical Center, New Orleans. Each patient was randomized to receive either gentamicin 1.5 mg/kg intravenously (IV) or 500 mg ciprofloxacin (Cipro-Miles) p.o., before and after the biopsy. Serum and prostate tissue levels of ciprofloxacin and gentamicin were measured by high-pressure liquid chromatography and by competitive binding immunoassay, respectively. Blood cultures were obtained, and the patients were observed for twenty-four hours after biopsy. After discharge the patients were followed up by telephone. The incidence of bacteremia and postbiopsy symptoms were less with ciprofloxacin. Prostate tissue levels of this drug were higher than gentamicin, while serum levels were roughly equivalent. Ciprofloxacin is less nephrotoxic, can be given orally, and has a better antimicrobial spectrum. We, therefore, recommend it as prophylaxis against bacteremia in transrectal prostate needle biopsy. Furthermore, it appears that prostatic drug levels are more important than serum levels in preventing bacteremia.

Aged↗