Biomedical subjects

V R Marshall

Publications and source records attributed to V R Marshall.

At least 19 recordsLinked to original sources

PubMed1997

Troublesome lower urinary tract symptoms in the community: a prevalence study.

OBJECTIVE: To determine the prevalence of troublesome lower urinary tract symptoms (LUTS) in men and women in the community. DESIGN: Interview-based prevalence survey. SETTING: Metropolitan and rural communities in South Australia, September, 1995. SUBJECTS: Probability sample of 1204 men and 1686 women (aged over 18 years) weighted to reflect the age and sex distribution of the South Australian population. DATA COLLECTED: Presence of storage (irritative) and voiding (obstructive) symptoms, based on the International Prostate Symptom Score questionnaire; satisfaction with urinary condition (quality-of-life measure); and visits to a doctor for urinary symptoms in the preceding 12 months. RESULTS: The prevalence of one or more troublesome LUTS was 26% (318/1204) for men and 39% (662/1686) for women (all ages) and 48% (314/649) for men and women over 65. The most common troublesome symptoms in men and women were nocturia and frequency. Symptoms were significantly age-related in men, but less so in women, in whom symptom prevalence exceeded 30% for all age groups. Ten per cent of men (123/1204) and 15% of women (249/1686) had visited a doctor for a urinary problem in the previous 12 months. Nine per cent of men (104/1204) and 16% of women (274/1686) were substantially dissatisfied with their urinary condition. Symptom prevalence and dissatisfaction with urinary condition were significantly associated with visiting the doctor (P < 0.0001), but only 28% (88/318) of men and 27% (179/662) of women with troublesome LUTS saw a doctor, and 63% (65/104) of men and 59% (162/274) of women dissatisfied with their urinary condition did not seek medical help. CONCLUSIONS: Although the prevalence of troublesome LUTS in the community is high, the number of people whose quality of life is substantially affected is much lower. The impact of these symptoms upon quality of life is a major reason for patients to see a doctor, yet many who are "bothered" by the symptoms do not do so.

Adolescent↗

PubMed1997

Prospective study of biofeedback for treatment of constipation.

PURPOSE: This study was designed to evaluate prospectively the results of pelvic floor physiotherapy with the aid of biofeedback in a heterogeneous group of patients with intractable constipation. METHODS: Biofeedback was used to treat 19 patients (age range, 16-78 (median, 63) years) with intractable constipation. Assessment, using visual linear analog scales of symptoms, was performed prospectively by an independent researcher. Biofeedback was performed by a physiotherapist, and patients were required to attend six sessions on an outpatient basis. The cause of constipation was heterogeneous, with no specific disorder being implicated on testing with anal manometry, defecating proctography, and colonic transit time. RESULTS: At six weeks, there was a median 27 percent (range, -8-93 percent) improvement in symptom scores. At six months, there was a median 23 percent (range, -54-64 percent) improvement in symptom scores. These were statistically significant compared with the scores at outset, six weeks (P = 0.0006), and six months (P = 0.012). However, only two (12.5 percent) patients at the six-month follow-up had an improvement of greater than 50 percent in their symptoms. CONCLUSION: Biofeedback is not recommended in the management of constipation.

Adolescent↗

PubMed1997

Finasteride significantly reduces acute urinary retention and need for surgery in patients with symptomatic benign prostatic hyperplasia.

OBJECTIVES: A pooled analysis of all available randomized trials with 2-year follow-up data with finasteride and placebo was undertaken to further investigate recent observations that finasteride use may reduce the occurrence of acute urinary retention (AUR) and benign prostatic hyperplasia (BPH)-related surgical intervention. METHODS: Occurrences of AUR and surgical intervention were examined by treatment group in a pooled series of 4222 men with moderately symptomatic BPH. RESULTS: In total, 81 occurrences of AUR were reported, 24 (1.1%) of 2113 in the finasteride group and 57 (2.7%) of 2109 in the placebo group. The hazard ratio was consistent in all three studies, with a 57% decrease in the hazard rate for occurrence of AUR with finasteride compared with that for placebo present in the pooled data set over the 2-year study period (P < 0.001). Additionally, 227 surgical interventions were recorded over the 2-year study period, 89 (4.2%) of 2113 in the finasteride group and 138 (6.5%) of 2109 in the placebo group. The hazard ratio was consistent across the three studies, with a 34% reduction in the hazard rate for occurrence of surgery with finasteride compared with that for placebo (P < 0.002). Overall, there was 35% reduction in the two BPH-related end points (ie, AUR or surgery). CONCLUSIONS: Treatment with finasteride for up to 2 years more than halves the frequency of AUR and reduces surgical intervention by over one third relative to placebo in patients with moderate BPH. This is the first demonstration that long-term medical therapy can reduce clinically significant end points such as AUR or surgery, and these data have important implications for the long-term management of patients with BPH.

Acute Disease↗

PubMed1997

Pelvic floor exercises as a treatment for post-micturition dribble.

OBJECTIVE: To determine the effectiveness of pelvic floor exercises and urethral milking as treatments for post-micturition dribble. PATIENTS AND METHODS: A method of measuring small amounts of urine loss during normal activity was developed; pads were worn for short periods (< 4 h) and then stored in two sealed plastic bags which were weighed within 72 h. Forty-nine men (age range 36-83 years) drawn from a hospital out-patient population, who had not undergone surgery on the bladder, urethra or prostate gland, entered the study. They were randomly assigned to one of three treatment groups; pelvic muscle exercise, urethral milking or counselling. Participants in each group followed the treatment specific to their group for 12 weeks. At 5, 9 and 13 weeks, urine loss was assessed using the method described. RESULTS: The groups were comparable for age, height, weight and pelvic muscle contraction strength and compliance of the men who completed the study was excellent. The outcome measure (improvement in pad weight gain) was strongly influenced by initial pad weight gain, or degree of urine loss at the start of the study and this was treated as a covariate in an analysis of variance model. After allowing for the effects of initial pad weight gain, the counselling group showed no improvement, the urethral milking group showed an adjusted mean improvement in urine loss of 2.9 g after 13 weeks, compared with 4.7 g in the exercise group. CONCLUSION: Both pelvic floor exercises and urethral milking are effective treatments for post-micturition dribble compared with counselling alone. Pelvic floor exercises were more effective in reducing urine loss than urethral milking in this study.

Adult↗

PubMed1997

Does evaluation with the International Prostate Symptom Score predict the outcome of transurethral resection of the prostate?

PURPOSE: We determined the reliability of the International Prostate Symptom Score (I-PSS) in predicting the outcome of transurethral prostatectomy and, therefore, how useful it can be in patient selection for surgery. MATERIALS AND METHODS: A prospective trial was done of 105 consecutive patients undergoing transurethral prostatectomy at our institution. Patients were assessed with the I-PSS before and 3 months after surgery. Flow rates and preoperative residual volumes also were measured. RESULTS: There was significant postoperative improvement in all parameters of the symptom score and a change in symptom profile. Symptoms remaining with the greatest scores at 3 months postoperatively were frequency, urgency and nocturia. A significant correlation was found between I-PSS and quality of life before and after transurethral prostatectomy, and between postoperative improvement in flow rates and change in I-PSS. Patients with a greater preoperative I-PSS gained the most symptomatic benefit. The positive predictive value of a significant postoperative improvement of at least 7 I-PSS points depended on the preoperative I-PSS criteria applied. With a preoperative I-PSS of more than 17 the positive predictive value was 87% with a corresponding negative predictive value of 71%. CONCLUSIONS: The preoperative I-PSS predicted a symptomatic improvement of more than 7 points with high sensitivity. The predictive value depends on the definition of significant improvement (magnitude of I-PSS change) and the level of I-PSS symptoms defined as sufficient to warrant transurethral prostatectomy.

Aged↗

PubMed1997

Epidemiologic survey of lower urinary tract symptoms in Asia and Australia using the international prostate symptom score.

BACKGROUND: The prevalence of lower urinary tract symptoms was determined by survey as an initial step in estimating the significance of benign prostatic hyperplasia (BPH) in Asia and Australia. METHODS: The symptom index (0 to 35) and quality-of-life (QOL) index (0 to 6) of the international prostate symptom score were measured in 7588 men in 9 Asian countries and 146 men in Australia. RESULTS: The percentages of Asian men considered to be symptomatic (symptom index > or = 8) were 18%, 29%, 40%, and 56% in the age groups of 40 to 49, 50 to 59, 60 to 69, and 70 to 79 years, respectively. For Australian men, these figures were 36%, 33%, and 37% in the 50 to 59, 60 to 69, and 70 to 79 year age groups, respectively. CONCLUSIONS: Our estimates indicate that the prevalences of symptomatic men in Asia and Australia are similar to or greater than those in Europe and America, and suggest BPH is similarly common in these areas.

Adult↗

PubMed1996

Neuropeptides and neurotransmitter-synthesizing enzymes in intrinsic neurons of the human urinary bladder.

The expression of neuropeptides, and the enzymes nitric oxide synthase and tyrosine hydroxylase were examined in intramural ganglia of human urinary bladder using single label immunocytochemistry. Scattered ganglia composed of between 1-36 neurons (median 4) were observed in all layers of the lateral wall of the bladder. These contained immunoreactivity to vasoactive intestinal peptide, nitric oxide synthase, neuropeptide Y, and galanin. Neurons within the bladder were heterogeneous with regard to their content of these antigens, with the proportion of immunopositive cells ranging from 58-84%. Occasional neurons with immunoreactivity to the catecholamine-synthesizing enzyme, tyrosine hydroxylase, were also observed. No cell somata, however, were immunoreactive for enkephalin, substance P, calcitonin gene-related peptide or somatostatin. Varicose terminals entering the ganglia were seen to form pericellular baskets surrounding some of the principal ganglion cells. The most prominent pericellular varicosities were those containing calcitonin gene-related peptide- or vasoactive intestinal peptide-immunoreactivity, followed by those with immunoreactivity for enkephalin, neuropeptide Y, or galanin. Less common were pericellular varicosities with substance P-immunoreactivity, which may represent collateral processes of unmyelinated primary sensory fibres, and presumptive noradrenergic processes containing tyrosine hydroxylase. Some calcitonin gene-related peptide-immunoreactive varicosities constituted a distinct type, terminating as large pericellular boutons 2-4 microns in diameter. Fibres containing nitric oxide synthase- or somatostatin-immunoreactivity were not associated with the intramural neurons. The results demonstrate that intrinsic neurons within the human urinary bladder express a number of neuroactive chemicals, and could in principle form circuits with the potential to support integrative activity.

Aged↗

PubMed1996

Distribution of nitric oxide synthase-immunoreactive nerves and identification of the cellular targets of nitric oxide in guinea-pig and human urinary bladder by cGMP immunohistochemistry.

The distribution of nerves with the potential to synthesize nitric oxide was examined within the urinary bladder and proximal urethra of humans and guinea-pigs, using an antibody to nitric oxide synthase. Further experiments identified cells in which cGMP-immunoreactivity was induced following exposure to the nitric oxide donor, sodium nitroprusside. These cells represent the potential physiological targets of neuronally released nitric oxide, since activation of soluble guanylate cyclase, and a consequent rise in intracellular cGMP, mediate many of the effects of this transmitter. Nitric oxide synthase-immunoreactivity was widely distributed in the lower urinary tract. In guinea-pigs, 50-68% of all intrinsic vesical neurons expressed nitric oxide synthase-immunoreactivity, while in humans 72-96% of neurons in the wall of the bladder contained nitric oxide synthase. In both humans and guinea-pigs, varicose nitric oxide synthase-immunoreactive nerve terminals provided a moderate innervation to the detrusor muscle of the bladder body, and a denser innervation to the urethral muscle. Immunoreactive nerves also projected to the subepithelium and around blood vessels, but were rarely observed encircling intramural vesical ganglia. Following stimulation with sodium nitroprusside, smooth muscle cells of the urethra expressed strong cGMP-immunoreactivity, but detrusor muscle cells remained uniformly negative. Although the detrusor muscle fibres did not express cGMP, numerous interstitial cells throughout the bladder body demonstrated an intense induction of cGMP-immunoreactivity by sodium nitroprusside. These cells had long dendritic processes extending parallel to the smooth muscle fibres, and contained vimentin, an intermediate filament expressed by cells of mesenchymal origin. Other cell types in which sodium nitroprusside exposure induced cGMP-immunoreactivity were the uroepithelial cells, vascular smooth muscle cells and pericytes, and a small number of varicose nerve terminals. In the guinea-pig, a minor proportion (less than 10%) of intrinsic neurons in the wall of the bladder also expressed cGMP. No intrinsic neurons were observed in specimens of human bladder processed for cGMP immunohistochemistry. The results provide anatomical evidence that nitric oxide may function as a neurotransmitter in the lower urinary tract. Although nerves with the capacity to produce nitric oxide supply both the detrusor muscle and the urethra, distinct regional differences exist in the effects of nitric oxide on the induction of cGMP. If the nitric oxide-mediated induction of cGMP is a reliable indicator of the physiological responsiveness of a cell to nitric oxide, then smooth muscle cells appear to be the predominant targets of nitric oxide in the urethra, while in the bladder body, interstitial cells may serve this role. These findings support previous studies which have implicated nitric oxide as an inhibitory transmitter involved in the relaxation of the bladder neck. Our experiments further indicate that a number of cell types within the lower urinary tract could potentially mediate the effects of endogenously released nitric oxide.

Animals↗

PubMed1995

Calcium oxalate crystal matrix extract: the most potent macromolecular inhibitor of crystal growth and aggregation yet tested in undiluted human urine in vitro.

Demineralization of calcium oxalate (CaOx) crystals precipitated from human urine in vitro yields an organic crystal matrix extract (CME) consisting predominantly of a single protein which we originally named crystal matrix protein but have subsequently shown to be a urinary form of prothrombin activation peptide fragment 1 (F1). The aim of this study was to determine whether CME is a promoter or inhibitor of CaOx crystallization. The effect of CME on CaOx crystal growth and aggregation was tested using a standard seeded crystallization system, and its effect quantified by use of particle size analysis and a computer model. In addition, the effect of CME on the crystallization of CaOx was tested in undiluted, ultrafiltered human urine using Coulter Counter analysis and scanning electron microscopy. It was shown that CME is a potent inhibitor of CaOx crystal growth and aggregation in a seeded metastable solution. However, of greater significance is that at a concentration of 10 mg/l it completely reversed the formation of large crystalline aggregates that form upon the removal of urinary macromolecules from undiluted urine. It was concluded that CME is the most potent macromolecular urinary inhibitor yet to be tested in urine in vitro. By preventing the aggregation of newly formed crystals, the components of CME may significantly reduce the probability of particle retention in vivo and therefore the occurrence of urolithiasis.

Calcium Oxalate↗

PubMed1995

Differential expression of apolipoprotein-D and prostate specific antigen in benign and malignant prostate tissues.

PURPOSE: To investigate Apolipoprotein-D (Apo-D) and prostate specific antigen (PSA) immunohistochemical staining of nonmalignant and malignant human prostate tissues. MATERIALS AND METHODS: Apolipoprotein-D and PSA immunoreactivity were evaluated by video image analysis in nonmalignant prostates and in 30 stage D2 prostate cancers. RESULTS: Apolipoprotein-D was detected in all 30 tumors, and the level of staining was elevated in comparison to age-matched nonmalignant prostates (p < 0.05). In contrast, the level of PSA staining in tumors was less than that detected in nonmalignant prostates. CONCLUSIONS: Apolipoprotein-D is expressed in normal human prostate. Elevated Apo-D staining is associated with advanced prostate cancer.

Adolescent↗

PubMed1995

Ploidy and Tn-antigen expression in the detection of transitional cell neoplasia in non-tumour-bearing patients.

OBJECTIVE: To study the effectiveness of combining DNA ploidy and the blood-group related membrane antigen Tn as bladder tumour markers which have been individually associated with high tumour grade and poor prognosis. In particular to (i) determine whether use of these two markers would improve tumour detection compared with either alone, particularly of high grade disease and (ii) determine whether intermediate rates of marker expression would occur in bladder cancer patients with no current tumour compared with those with a tumour and a control group with benign prostatic hypertrophy. PATIENTS AND METHODS: A total of 102 patients undergoing cystoscopic monitoring for either benign prostatic hyperplasia (BPH) or for transitional cell carcinoma (TCC) at the Repatriation Hospital and Flinders Medical Centre were included in the study. The patients comprised three study groups, those with BPH (n = 37), with TCC but no tumour present (n = 38) and those with TCC and a tumour present at cystoscopy (n = 27). Exfoliated cells obtained from bladder washings at cystoscopy were double-labelled using a monoclonal antibody to the Tn antigen and a DNA stain, propidium iodide and examined by flow cytometry. RESULTS: Rates of marker expression in 27 patients with tumours were 30% for Tn antigen, 30% for aneuploidy and 48% for either marker. Marker expression was strongly associated with tumour grade, with no expression at grade 1, 38% (3/8) tumours at grade 2 and 90% (9/10) at grade 3. In patients with a history of bladder tumours but no current tumour, rates were intermediate (30%) compared with patients with current transitional cell carcinoma (42%) and control patients (19%). CONCLUSION: The use of Tn antigen combined with DNA flow cytometry can increase tumour detection, particularly of high grade, aggressive disease. Gradation of expression of these markers across patient groups at increasing risk of a tumour, with intermediate expression in patients with no current tumour, suggests that marker expression may be detecting a preneoplastic stage of the disease, which is not possible with cytology. Given two parallel disease processes for superficial papillary and for high grade disease with invasive potential, the expression of high grade tumour markers in cells from cystoscopically normal bladders may represent a pre-clinical stage of aggressive disease. The identification of patients at risk of invasive disease using combinations of tumour markers may offer advantages in clinical management, particularly when no tumour is present and therefore no histopathological assessment is made.

Aged↗

PubMed1995

Regional differences in the innervation of the human ureterovesical junction by tyrosine hydroxylase-, vasoactive intestinal peptide- and neuropeptide Y-like immunoreactive nerves.

We have used double-label immunohistochemistry to examine the presence and pattern of colocalization of vasoactive intestinal peptide (VIP), neuropeptide Y (NPY), tyrosine hydroxylase (TH) and protein gene product (PGP) in nerve fibers supplying the human ureterovesical junction (UVJ). Several populations of nerve fibers within the UVJ region were identified according to their expression of potential transmitter substances. Presumptive noradrenergic axons containing TH- and NPY-like immunoreactivity (LIR) and non-noradrenergic fibers containing VIP- and NPY-LIR accounted for most of the total (PGP-LIR) innervation and supplied all regions of the UVJ. The distal ureter, Waldeyer's sheath and the trigone were supplied by predominantly noradrenergic TH/NPY-LIR nerve fibers, whereas the majority of fibers supplying the detrusor muscle were non-noradrenergic VIP/NPY-LIR axons. The similarity in innervation of Waldeyer's sheath, ureter and trigone is consistent with the notion that these structures are all derived from a common mesodermal origin. Regional differences in innervation were also noted within the musculature of the distal ureter: TH/NPY-LIR fibers were localized to the outer part of the ureter, while VIP/NPY-LIR fibers supplied the inner part. This finding suggests that the different layers of the ureter may be independently controlled by different populations of nerves. The findings of this study support the view that noradrenergic nerves are important in maintaining the tone of the UVJ, but indicate that other neurotransmitters or neuromodulators may also be involved in the control of this region.

Aged↗

PubMed1994

Detection of discrete androgen receptor epitopes in prostate cancer by immunostaining: measurement by color video image analysis.

To determine whether multiple features of immunohistochemical staining of the androgen receptor (AR) in prostate cancer could reliably predict androgen dependence, tumor biopsy specimens from 30 patients (stages A-D2) were stained using anti-peptide antibodies to the amino- and carboxyl-terminal of the AR. Measurements were made of the mean area and total amount (i.e., integrated optical density) of AR staining in at least 20 fields per section using a color video image analysis system, and the mean intensity of AR staining per cell and the percentage of AR positive tumor cells were derived. Video image analysis measurement identified quantitative differences in AR staining between the two antibodies, suggesting that this approach may provide a means of identifying receptor variants in prostate tumors. The AR staining measurements were analyzed by discriminant function analysis to assign individual cases to good and poor clinical outcome groups. AR staining features measured with a single antibody (e.g., amino-terminal) were sufficient to predict outcome following hormonal therapy in stage D2 patients (predictive value, 1.0), whereas all features of AR staining measured with both antibodies were required for the entire patient group (predictive value, 0.97). The principal discriminant in both patient groups contributing to the correct assignment of outcome was the mean intensity of AR staining per cell. These findings suggest that AR staining features measured by video image analysis have the potential to predict outcome in prostate cancer.

Aged↗

PubMed1994

Nuclear shape and prognosis following orchiectomy in stage D2 prostate cancer.

In this study, we have examined whether tumor grade and morphometric nuclear features can predict the outcome of treatment by orchiectomy in patients with stage D2 prostate cancer. Two outcome groups based on duration of survival postorchiectomy were examined, a bad outcome group of 63 patients who died from prostate cancer within 12 months and a good outcome group of 34 patients who survived beyond 5 years. Tumors were histologically classified as well (17%), moderate (17%), or poorly differentiated (66%). Tumor grade and patient outcome were significantly associated (Mann-Whitney test; P < 0.005), with 76% of poorly differentiated tumors in the bad outcome group, and 65% of well-differentiated tumors in the good outcome group. Using discriminant function analysis, tumor grade correctly predicted outcome in 70% of cases. A statistically significant difference was also detected in nuclear shape values between the two outcome groups (P < 0.05) and histological grades (P < 0.05). Using discriminant function analysis, 51% of cases were correctly classified into outcome groups using nuclear shape factors, a figure which rose to 65% when all nuclear morphometric features were used. This demonstrates that nuclear morphometric features are of no clinical value in predicting the outcome of treatment in stage D2 disease. Furthermore, these evaluations cannot select patients who might be spared orchiectomy on the basis of a predicted poor response. However, nuclear shape and variance measurements of benign glandular epithelial cells within cancerous prostates were significantly different from those of malignant cells (P < 0.005). We conclude that, while video image analysis of prostatic nuclear shape can reliably discriminate between benign and malignant cells, nuclear morphometric features are of minimal prognostic value in men with stage D2 prostate cancer treated by androgen ablation.

Aged↗

PubMed1994

Glycosaminoglycans of guinea pig prostate fibromuscular stroma: influence of estrogen and androgen on levels and location of chondroitin sulfate.

The effects of aging and hormone manipulation on the glycosaminoglycan (GAG) content of prostatic stroma in guinea pigs were investigated. Total GAG and individual GAG classes (chondroitin, dermatan, and heparan sulfates, and hyaluronic acid) were measured biochemically in stromal extracts. Chondroitin sulfate was also measured and localized by video image analysis of immunocytochemically-stained tissue sections. The weight and total GAG (uronic acid) content of prostatic stroma increased between the ages of 2 weeks and 2 years by 7-8-fold and 4-5-fold respectively. GAG concentration per unit weight of stroma declined 4-fold during puberty and remained essentially unchanged thereafter. Similar results were obtained for each of the GAG classes. The decreases in GAG concentration were associated with a 3-fold increase in the size of the smooth muscle cells of the prostatic stroma during puberty. Hormonal control of GAG deposition in the prostatic stroma was investigated by steroid replacement in prepubertally-castrated animals. Administration of dihydrotestosterone (DHT) to castrate animals for 6 weeks resulted in significantly reduced concentrations of stromal uronic acid, compared with untreated castrate animals (P < 0.05). The GAG levels post-DHT treatment were similar to those observed after pubertal development in sham-operated control animals. Estradiol treatment had the opposite effect to that of DHT, resulting in a significantly increased concentration of uronic acid compared with castrate animals (P < 0.05). These steroid-induced changes in stromal GAG deposition were mostly contributed to by chondroitin and dermatan sulfates. Combined treatment with DHT and estradiol resulted in stromal uronic acid concentrations similar to those of animals receiving DHT alone, indicating that the effect of DHT on stromal GAG deposition is dominant over the effects of estradiol. Morphometric measurement, using computer-assisted video image analysis of a chondroitin sulfate epitope in prostatic sections stained with a monoclonal antibody (6C3), supported the biochemical data. Stereometric profiles across several sectioned glands demonstrated that chondroitin sulfate was confined to the periacinar basement membranes of the prostatic stroma in all groups except the estradiol-treated castrate animals, where the immunostaining extended from the periacinar basement membrane throughout the fibromuscular stroma. Treatment of castrate animals with estradiol alone also induced a physicochemical change in the chondroitin sulfate molecule, resulting in reduced electrophoretic mobility. In summary, this study identifies changes in the quantity, structure, and localization of chondroitin sulfate in the prostatic stroma of estradiol-treated guinea pigs. Furthermore, estradiol and DHT have opposing effects on the level of chondroitin and dermatan sulfate expression in the prostatic stroma.

Aging↗

PubMed1994

Patterns of neuronal colocalisation of tyrosine hydroxylase, neuropeptide Y, vasoactive intestinal polypeptide, calcitonin gene-related peptide and substance P in human ureter.

The patterns of colocalisation of neuropeptides, tyrosine hydroxylase (TH), and protein gene product 9.5 (PGP), were studied in nerve fibres supplying the upper and lower human ureter using a double labelling immunofluorescence technique. The majority (85%-95%) of nerve fibres within the ureter contained neuropeptide Y-like immunoreactivity (NPY-LIR), in combination with other peptides. Approximately 52%-63% of the total ureteral innervation was made up of NPY-LIR fibres also expressing TH-LIR, while 21%-42% of fibres contained NPY-LIR in combination with vasoactive intestinal polypeptide (VIP)-LIR. These two immunochemically defined classes did not overlap, since TH- and VIP-LIR were never present within the same nerve fibre. Other minor populations of neurones included those containing calcitonin gene-related peptide (CGRP)-LIR in combination with substance P (SP)-LIR (4%-17%) and those without SP (5%). Rare coexistences were also noted between CGRP- and VIP-LIR (1%-2%), CGRP- and NPY-LIR (< or = 1%), and CGRP- and TH-LIR (< 1%). Regional differences in innervation were found. There were fewer of each class of nerve fibres in the upper ureter compared to the lower ureter. In addition, the proportion of VIP/NPY-LIR fibres of the total innervation was less in the upper ureter, where they were very sparse. Differences in the distribution to various tissue targets were also observed. In the lower ureter, TH/NPY-LIR fibres were localised predominantly to the outer muscle fascicles and adventitia, while VIP/NPY immunoreactive nerves supplied the submucosa and inner smooth muscle fascicles. Both of these populations were also found around blood vessels. A population of presumptive sensory fibres expressing CGRP/SP-LIR were typically present immediately beneath the urinary epithelium and around blood vessels, and only very rarely within muscle fascicles. The finding that TH/NPY- and VIP/NPY-LIR fibres innervate different layers of the ureter raises the possibility that the muscle layers of the ureter may be independently controlled.

Aged↗

PubMed1994

Distribution of NADPH-diaphorase-positive nerves supplying the human urinary bladder.

Nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd) histochemistry was used as a marker for neuronal nitric oxide synthase in human bladder tissue. A plexus of NADPHd-containing nerve fibres was observed in bladder biopsies taken from both the lateral wall and trigone regions. Varicose terminals were present in smooth muscle bundles of the detrusor and trigone, and more commonly within the submucosal layer. Reactive fibres were seen running immediately beneath and along the urothelium, and additional nerves formed perivascular plexi around some blood vessels. Fewer positive nerve processes were observed in the trigone region in comparison to the bladder wall. NADPHd-reactive neuronal perikarya were present within intramural ganglia, some of which were in close proximity to NADPHd-stained varicosities. The results indicate that nitric oxide may be involved in the regulation of bladder function in humans.

Aged↗

PubMed1994

Colocalization of nitric oxide synthase with vasoactive intestinal peptide, neuropeptide Y, and tyrosine hydroxylase in nerves supplying the human ureter.

The distribution and patterns of colocalization of nitric oxide synthase (NOS), vasoactive intestinal peptide (VIP), neuropeptide Y (NPY) and the catecholamine-synthesizing enzyme tyrosine hydroxylase (TH) were examined in nerve fibers supplying the human lower ureter using double label immunofluorescence. Many nerve fibers immunoreactive for NOS were observed within the ureter. Positive varicose fibers were seen running longitudinally within the smooth muscle bundles, particularly those of the inner layers of the ureter. Immunoreactive axons were also prominent within the subepithelium, and as plexi surrounding many blood vessels. The colocalization studies indicated that NOS was never present in presumptive sympathetic nerve fibers expressing TH. All fibers containing VIP, however, were also immunoreactive for NOS. In addition, a minor population of NOS fibers did not contain VIP. Neuropeptide Y coexisted with NOS in a significant number of nerve terminals, although fibers expressing only NPY were equally common. Several immunochemically distinct nerve populations can therefore be distinguished in the human ureter: (1) nerves containing NOS either with or without VIP; (2) NOS-immunoreactive fibers with NPY; and (3) those fibers expressing TH or NPY which do not contain NOS. The results indicate that some non-noradrenergic peptide-containing nerves in the human ureter have the capacity to synthesize nitric oxide (NO), and that NO may be involved in the regulation of ureteric motility.

Aged↗