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Biomedical subjects

D E Neal

Publications and source records attributed to D E Neal.

At least 199 records · Page 11Linked to original sources
PubMed1991

Renin production after experimental extracorporeal shock wave lithotripsy: a primate model.

Since the advent of extracorporeal shock wave lithotripsy (ESWL) concern has surfaced as to the long-term risk of the development of hypertension, as well as risk to the developing kidney. To study this concern 8 infant and 3 adult rhesus monkeys (Macaca mulatta) underwent treatment with the XL1 experimental lithotriptor to 1 kidney varying the amount of voltage and shocks. Followup consisted of measurement of renin levels and quantitative renal scans, using 131iodine hippurate to calculate effective renal plasma flow. In the infants a slight change was noted in the absolute effective renal plasma flow of the treated kidney versus the untreated side but it was not statistically different. When indexed to body surface area in the growing animal, there was a statistically significant decrease in renal function. However, peripheral renin levels were markedly elevated in the infants at 3 weeks, and they gradually declined during the 6-month period, although levels remained elevated over baseline. The adults also had central renin levels drawn from the renal vein on the treated side, and there was a close correlation with the peripheral levels, which peaked at 3 weeks and returned to normal. Thus, it seems that at least in the short term renin production is increased in infants more than adults. This finding may be an indicator as to renal damage and is a possible explanation for hypertension occurring after ESWL.

Animals↗
PubMed1991

Filling and voiding pressures measured by ambulatory monitoring and conventional studies during natural and artificial bladder filling.

A total of 20 men awaiting elective prostatectomy for bladder outflow obstruction underwent conventional medium filling cystometry and ambulatory monitoring of bladder pressures during natural bladder filling. Total bladder capacity was similar during both tests (medium filling cystometry 256 +/- 138 ml. and ambulatory monitoring 248 +/- 120 ml., p not significant) as was the voided volume (medium filling cystometry 180 +/- 100 ml. and ambulatory monitoring 179 +/- 88 ml., p not significant). However, the peak urinary flow rate at the end of medium filling cystometry (4 +/- 6 ml. per second) was significantly lower than during ambulatory monitoring (9 +/- 4 ml. per second, p less than 0.05). The bladder contraction pressure during medium filling cystometry (79 +/- 44 cm. water) was significantly lower than during ambulatory monitoring (107 +/- 39 cm. water, p less than 0.005). Bladder pressures during voiding recorded after natural filling were significantly greater than after artificial filling. This finding may have significant implications for the use of conventional cystometry to study conditions such as outflow obstruction.

Aged↗
PubMed1991

The outcome of prostatectomy on chronic retention of urine.

A total of 68 men with bladder outflow obstruction and chronic retention (residual urine greater than 300 ml.) underwent investigation before and after prostatectomy with medium fill cystometry and natural fill long-term bladder pressure monitoring. Postoperatively, upper tract dilatation (present in 28 men preoperatively) resolved in all but 2 men and serum creatinine levels improved significantly. Irritative and obstructive symptom scores improved postoperatively (p less than 0.00006), although 17% of the men still had significant symptoms. Residual urine volumes decreased and flow rates improved (p less than 0.00006) but 32% of the men still had a residual urine of greater than 200 ml. Urodynamic parameters improved during medium fill cystometry and long-term monitoring. The main risk factors for upper tract dilatation are a pressure increase during bladder filling on conventional cystometry and the frequency of phasic detrusor activity during long-term monitoring, and they decreased postoperatively.

Aged↗
PubMed1991

Tamm-Horsfall autoantibodies in interstitial cystitis.

Interstitial cystitis presents a diagnostic and therapeutic challenge. Although many etiologies, including autoimmunity, have been proposed its pathogenesis remains obscure. Tamm-Horsfall protein has been identified in the superficial urothelium of patients with interstitial cystitis demonstrating abnormal urothelial permeability. Eight patients with a clinical diagnosis of interstitial cystitis underwent cystoscopy and bladder biopsy. Characteristic cystoscopic findings were present, and each patient had chronic inflammation and mast cells by histopathological analysis. Preoperative anti-Tamm-Horsfall protein serum antibody (IgG) titers were determined by enzyme-linked immunosorbent assay (range 500 to 8,000, mean 2,750). A control group of 8 patients with a negative urological history also had titers of 0 to 500 (p = 0.02). The humoral response to Tamm-Horsfall protein in these patients suggests a role for Tamm-Horsfall protein in interstitial cystitis. Measurement of serum Tamm-Horsfall protein antibody may prove to be useful as a noninvasive diagnostic test in patients with this disease.

Adult↗
PubMed1991

Expression of mutant p53, c-erbB-2 and the epidermal growth factor receptor in transitional cell carcinoma of the human urinary bladder.

Expression of the p53, the epidermal growth factor receptor (EGFr; c-erbB-1) and c-erbB-2 proteins was studied in 82 patients with primary transitional cell carcinoma of the bladder using an immuno-histochemical method. Strong or moderate staining was found in 18% of tumours for p53 with weaker staining in a further 36% giving a total of 54% of tumours stained for p53. Strong staining was found in 15% of tumours for c-erbB-2 and in 31% for the EGFr. Tumours invading the bladder muscle were significantly more likely to be strongly stained positively for p53 and/or EGFr compared with superficial tumours: only 15% of invasive tumours were stained negatively for both p53 and EGFr. No statistical association was found between p53 and EGFr expression. Weakly positive associations were found between the expression of c-erbB-2 and p53 and between muscle invasive tumours and increased expression of c-erbB-2. Alterations in the expression of p53, c-erbB-1 and c-erbB-2 were found frequently in human transitional cell carcinoma of the urinary bladder and may be of clinical use in defining patient sub-groups of differing prognosis.

Aged↗
PubMed1991

Is voided urine suitable for flow cytometric DNA analysis?

Samples of bladder washings are frequently used to provide cellular material for flow cytometric DNA analysis. Since voided urine is a potential source of similar material, the aim of this study was to determine whether voided urine yields satisfactory specimens. We compared the qualitative results of flow cytometric DNA analysis of the cells in 53 specimens of voided urine and 109 samples of bladder washings; 45% (24/53) of urine specimens gave satisfactory DNA histograms compared with 93% (101/109) of bladder washings. This difference was apparent regardless of whether the bladder contained a tumour. It was concluded that bladder washings provide superior material for flow cytometric DNA analysis and that flow cytometric DNA analysis of freshly voided urine may have deficiencies which preclude its use in routine clinical practice.

DNA, Neoplasm↗
PubMed1991

Systemic chemotherapy for urothelial cancer in patients with ureteric obstruction.

The aims of this study were to document the toxicity of systemic chemotherapy and response rates in patients with ureteric obstruction caused by urothelial cancer. The study group included 91 patients who received cisplatin and methotrexate; 36 (40%) had upper tract dilatation, 9 of whom had drainage by stenting or nephrostomy and 55 (60%) had normal upper tracts. The response rate was documented in 65 patients (71%) who had measurable primary or metastatic disease. No significant differences were found between the dilated/drained group, the dilated/undrained group and the normal group in biochemical measurements of renal function during or after the courses of chemotherapy. Serious haematological toxicity occurred in 10% (10/104 cycles) of the dilated/undrained group and in 6% (12/200 cycles) of the normal group. The complete response rate in the dilated group was 15% compared with 41% in the normal group. No increased chemotherapy toxicity was observed in patients with upper tract dilatation and a significant complete response rate was found in patients with upper tract dilatation without renal impairment.

Acute Kidney Injury↗
PubMed1991

Urodynamic study of ileocystoplasty in the treatment of idiopathic detrusor instability.

Enterocystoplasty is being used with increasing frequency in the treatment of patients with idiopathic detrusor instability. We have performed a prospective clinical and urodynamic study of this procedure in 11 patients using both conventional (CMG) and ambulatory monitoring techniques (AM). Nine of 11 patients were satisfied with the symptomatic outcome, but 7 relied on clean intermittent self-catheterisation (CISC) to achieve a good result. Urodynamic studies demonstrated a significant increase in residual urine volume from 48 +/- 72 ml before to 347 +/- 298 ml after operation, but there was only a small and statistically insignificant increase in cystometric capacity. Detrusor instability, present before operation in all patients, could still be demonstrated in over half of them after operation. However, a significant decrease in the severity of instability was found after operation as assessed by an increased volume at first unstable contraction. The bladder volume before operation at which the first unstable contraction occurred was smaller in those who still had persistent instability after enterocystoplasty compared with those in whom instability could not be identified after operation. These results suggest that all patients about to undergo ileocystoplasty should be trained in the use of CISC. In selected patients with idiopathic detrusor instability refractory to other treatment, this procedure can yield satisfactory results.

Adult↗
PubMed1991

Ambulatory monitoring and electronic measurement of urinary leakage in the diagnosis of detrusor instability and incontinence.

The ability of conventional artificial filling urodynamic studies (CMG) and ambulatory monitoring during natural bladder filling (AM) to detect phasic detrusor activity (detrusor instability) and incontinence was studied in 52 patients suspected on clinical grounds of having bladder dysfunction, but in whom a CMG had not provided an adequate explanation of their symptoms. Detrusor instability (DI) was found on AM in 31 patients who were not unstable on conventional CMG using the criteria of the International Continence Society: DI was diagnosed on filling in 20 patients and on provocation in a further 11. Incontinence was demonstrated by electronic nappy testing in 23 patients: 13 had urge incontinence due to DI, 7 had genuine stress incontinence alone and 3 had both genuine stress incontinence and detrusor instability. Thus DI was diagnosed significantly more frequently by AM than by CMG. Ambulatory monitoring was more sensitive in the diagnosis of instability and incontinence and it may prove to be a valuable aid in the diagnosis of bladder dysfunction not detected during conventional cystometry.

Adult↗
PubMed1991

Bladder augmentation and replacement. Urodynamic and clinical review of 25 patients.

Bladder augmentation has a role in the management of patients with neuropathic bladder dysfunction and in urinary undiversion. Several reports attest to its clinical value, but there have been few detailed urodynamic studies of its effects. We have carried out a prospective review over a 4-year period of 25 patients undergoing bladder augmentation or substitution assessed by conventional and ambulatory urodynamic studies. All patients had a detubularised reservoir made of ileum in 6, and of the ileocaecal segment in the remainder. Six patients also had an artificial sphincter fitted and 2 underwent colposuspension. There was no mortality. After operation, bladder capacity increased from 122 +/- 91 ml to 659 +/- 431 ml and there were significant decreases in the pressure rise during filling and increases in bladder compliance. Hyper-reflexia was present in 74% before operation and 23% after operation. Regular phasic activity was observed in 77% of patients at the end of filling after operation, probably due to bowel activity despite detubularisation. Four patients described urge incontinence associated with this activity. After operation, one man had persistent major stress incontinence. He has since undergone insertion of an artificial urinary sphincter (AUS) and is now completely dry. Of the remainder, 10 patients had minor, infrequent defects in continence, 9 patients with leakage when the bladder was full and 4 with occasional leakage at night. With the exception of the patient with major stress incontinence, all but one felt the operation had been worthwhile--40% reporting complete success and 52% excellent improvement. Reconstruction of the neuropathic lower urinary tract is a major surgical procedure, but the final clinical outcome is very satisfactory.

Adolescent↗
PubMed1991

Attenuation of antibody response to acute pyelonephritis by treatment with antibiotics.

While acute pyelonephritis is known to elicit an antibody response, it is also known that a patient who has had pyelonephritis once is susceptible to recurrent renal infection. Using our experimental model of pyelonephritis in the monkey, we tested whether antibiotic therapy of the acute disease would affect the antibody response. We found that it did, because antibiotic therapy beginning 72 h after bacterial inoculation attenuated the antibody response so that rechallenge 3 months later produced acute pyelonephritis and prolonged bacteriuria. The animals with untreated infection had an antibody response that lasted a sufficient period of time to prevent acute pyelonephritis after renal challenge. We have confirmed that antibody titers against P fimbriae are protective, and to a degree, this protective effect may be abrogated by antibiotic therapy.

Acute Disease↗
PubMed1991

A preliminary study of acetylcholinesterase-positive innervation in the human adrenal cortex.

We have examined the distribution of probable cholinergic nerves in the human adrenal cortex using acetylcholinesterase (AChE) histochemistry. Adrenal tissue was obtained from three subjects during therapeutic radical nephrectomy for renal neoplastic disease. Light microscopy revealed a heterogeneous pattern of cortical innervation, with nerves most abundant in the head and body and largely absent from the tail. There was frequently a subcapsular plexus of interwoven AChE + ve nerve trunks in close relationship to densely stained (ganglion) cells. Nerves also traversed the zona fasciculata in radial trunks and a further plexus with ganglion cells was observed in the zona reticularis. Nerve trunks were seen to penetrate the medulla. Some nerve trunks appeared to terminate or branch or form individual nerve fibres (often with varicosities) which ramified through the cortical parenchyma. In the medulla, a generalised granular staining was superimposed on nerve trunks which were branched and interwoven to form a plexus around ganglion cells. The presence and distribution of AChE + ve nerve plexuses and varicose nerve fibres is suggestive of a functional intrinsic, probably cholinergic, innervation to the human adrenal cortex, perhaps derived from the splanchnic nerves.

Acetylcholinesterase↗
PubMed1991

125I-vasoactive intestinal peptide binding in human kidney.

The hypothesis that effects of vasoactive intestinal peptide (VIP) on human renal function are mediated via a specific intrarenal VIP receptor was investigated by measuring 125I-VIP binding in plasma membranes isolated from human kidney tissue excised for therapeutic reasons (transitional cell carcinoma, hypernephroma). Equilibrium binding of 125I-VIP was determined by a rapid filtration technique. Specific binding was saturable and showed evidence of both a high affinity binding site (K0.5 range 1.3-12.7 nM; Bmax range 4-56 fmol/mg) and another site of lower affinity. 125VIP binding was partially displaced by homologous peptides and by the VIP antagonist (4CL-D-Phe6,Leu17)-VIP. Distribution of 125I-VIP binding was established using autoradiography: specific binding was confined to the cortex. Such evidence of specific VIP binding, together with our previous report showing VIP stimulation of renal cortical plasma membrane adenylate cyclase, is consistent with a role for VIP in regulation of urine electrolyte composition in the human.

Autoradiography↗
PubMed1990

The epidermal growth factor receptor and the prognosis of bladder cancer.

Epidermal growth factor is found in high concentrations in urine, and its receptor (EGFr) has been identified in certain bladder tumors. This study was performed to determine whether receptor positivity in the tumor was associated with a poor clinical outcome. One hundred one patients with newly diagnosed bladder cancer were studied prospectively by immunohistochemical staining for the EGFr. There were 76 men and 25 women, with a mean follow-up of 30 months; 49 had tumors invading muscle: 18 were pTl (tumor invading lamina propia) and 34 were pTa (tumor confined to urothelium). Strong staining for the EGFr was found in 48% of tumors and was associated with high stage (P less than 0.001). Death of bladder cancer (40 of 101) was associated independently with high stage (P less than 0.0001) and EGFr positivity (P less than 0.001). In patients with pTa and pTl tumors, EGFr positivity was associated with multiplicity (P less than 0.01), time to recurrence (P less than 0.03), and recurrence rate (P less than 0.004). Tumor progression was associated with EGFr positivity (P less than 0.0001) and multiplicity (P less than 0.05). EGFr were found on a significant proportion of bladder tumors: such tumors were more likely to result in death, recurrence, and progression.

Aged↗
PubMed1990

Experimental prostatitis in nonhuman primates: I. Bacterial adherence in the urethra.

Both man and monkey possess urothelial (transitional cell) receptors for P-fimbriae of Escherichia coli; however, the male urethra has pseudostratified columnar cells. We studied adherence using scanning electron microscopy and found that P-fimbriae were the principal mediators of adherence to these cells as well. The monkey, therefore, should be a good model for the study of the ascending route of infection in prostatitis, the route thought to occur in man.

Animals↗
PubMed1990

Experimental prostatitis in nonhuman primates: II. Ascending acute prostatitis.

Bacterial prostatitis is a common cause of urinary tract infection in males, but little is known of its pathophysiology. To study this, we developed a nonhuman primate model using a wild-type clinical isolate of Escherichia coli. Primates have a prostatic anatomy that is similar to humans, which makes them ideal as an animal model of this disease. The monkeys had a urethral inoculation of this organism and were then followed with urine, blood, and semen cultures, white blood counts, and renal scans. They were sacrificed at from 10 days to 4 weeks, and their genitourinary tracts histologically examined. The prostatitis paralleled that reported in humans, and we conclude that the infection occurs by the ascending route. The organisms causing the infection in man do so in our primate model, and the histologic change is also the same. Thus, the primate model holds promise for studies to help us understand this disease.

Acute Disease↗