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Biomedical subjects

S A Gilpin

Publications and source records attributed to S A Gilpin.

At least 19 recordsLinked to original sources

Histological and histochemical study of the vesicoureteric junction in infancy and childhood.

The morphology of the vesicoureteric junction was compared using 19 post mortem specimens obtained from male and female Afro-American and Caucasian children with an age range of 1 to 72 months (mean 4). All specimens were serially sectioned and the tissues processed using standard histological and histochemical techniques (acetylcholinesterase ¿AChE¿ and pseudocholinesterase ¿PChE¿). The results failed to reveal any differences in the structure of the vesicoureteric junction with respect to age, sex and ethnic origins. The vesicoureteric junction comprised 3 histologically and histochemically distinct smooth muscle components. Ureteric muscle formed a complete inner layer rich in PChE which continued beyond the ureteric orifices to merge distally with the superficial trigone. An intermediate layer of muscle was also demonstrated whose constituent muscle cells possessed specific histological features and which was rich in both AChE and PChE, which is distinct from that derived from the ureter and detrusor. The presence of detrusor muscle on the outer aspect of the juxtavesical segment of ureter rich in AChE was also confirmed. While this study, using histochemical studies in infants and children, did not reveal any differences in the structure of the vesicoureteric junction with respect to age, sex or ethnic origin, an intermediate layer of muscle was identified with histochemical characteristics more like that of the male genital tract than that derived from the ureter or detrusor muscle.

Acetylcholinesterase

Increase in presumptive sensory nerves of the urinary bladder in idiopathic detrusor instability.

The density of subepithelial, presumptive sensory nerves in the bladder wall was assessed in 21 women with idiopathic detrusor instability and compared with the density of these nerves in 21 asymptomatic women, using a point-counting technique on sections of bladder biopsies stained for acetylcholinesterase activity. The mean value (+/- S.E.) for the amount of such nerves in patients with detrusor instability (91 +/- 13/mm2) was significantly greater than that from the control group (61 +/- 7/mm2). This suggests that a relative abundance of subepithelial sensory nerves may serve to increase the appreciation of bladder filling, giving rise to the frequency and urgency of micturition which are characteristic of patients with detrusor instability.

Adult

The innervation of the human prostate gland--the changes associated with benign enlargement.

Different regions of the prostate gland, namely prostatic capsule, peripheral prostate and central prostate (subdivided into proximal (near the bladder neck), distal (near the verumontanum) and midway between these areas) were obtained from 32 obstructed (stable obstructed, n = 8; unstable obstructed, n = 13; acute retention, n = 11) and five control patients. The innervation of these tissues was studied both histochemically to localise acetylcholinesterase activity and immunohistochemically for dopamine-beta-hydroxylase, 5-hydroxytryptamine, vasoactive intestinal polypeptide, neuropeptide Y, leu- and met-enkephalin, calcitonin gene-related peptide, substance P and somatostatin. In control patients the greatest density of nerves was found in the proximal central prostate, followed by the anterior capsule and distal central prostate, with the least density in the peripheral prostate. The greatest density of nerves were acetylcholinesterase positive and immunoreactive to neuropeptide Y followed (in decreasing order) by nerves immunoreactive to: vasoactive intestinal polypeptide and dopamine beta-hydroxylase; leu-enkephalin and 5-hydroxytryptamine; calcitonin gene-related peptide; met-enkephalin; substance P; somatostatin. In addition a group of periacinar 5-hydroxytryptamine-immunoreactive cells and ganglia containing acetylcholinesterase, dopamine beta-hydroxylase and all of the peptides studied except somatostatin were identified. In the prostate gland from obstructed patients there was a significant reduction in the density of acetylcholinesterase-positive nerves (p less than 0.001) when compared with the controls. A similar trend was found for dopamine beta-hydroxylase, 5-hydroxytryptamine and all of the putative neuropeptides in most areas of the prostate, the most notable exceptions being in the peripheral prostate, with an increase in dopamine beta-hydroxylase- and leu-enkephalin-immunoreactive nerves in all three groups of obstructed patients an an increase in vasoactive intestinal polypeptide- and calcitonin gene-related peptide-immunoreactive nerves in those presenting in urinary retention. The functional significance of these findings is discussed.

Acetylcholinesterase

Relationship between bladder morphology and long-term outcome of treatment in patients with high pressure chronic retention of urine.

A group of 32 men undergoing bladder outflow surgery for high pressure chronic retention (HPCR) of urine were studied prospectively. At the time of treatment marked morphological changes in the bladder wall were demonstrated histologically, but after a mean follow-up of 42.9 months residual urine had decreased significantly and renal function had improved or stabilised in 28 patients (84%). Four patients deteriorated but in 3 of these another potential cause for loss of renal function was present. The majority of patients have a good long-term prognosis following treatment for HPCR.

Adult

Cystometric, physiological and morphological studies after relief of bladder outflow obstruction in the pig.

Experimental bladder outflow obstruction was relieved in 18 pigs between 2 and 15 months after the creation of partial urethral obstruction. Cystometric, physiological and morphological studies were performed 2 to 6 months after relief of the obstruction. An increase in average voiding flow rates from 2.8 +/- 1.0 ml/s to 6.8 +/- 1.2 ml/s was recorded in the Landrace pigs and from 2.2 +/- 0.9 ml/s to 7.4 +/- 1.4 ml/s in the Göttingen mini-pigs. There was a concomitant decrease in the voiding detrusor pressures from 52 +/- 11 cm H2O to 32 +/- 8 cm H2O and from 78 +/- 12 cm H2O to 33 +/- 6 cm H2O respectively. A return towards control values of the physiological responses to exogenously applied agonists (acetylcholine and potassium) and to electrical field stimulation was observed. There was an increase in neuronal innervation in the morphological studies which was more marked in the animals with a shorter period of obstruction. The implications for patient care are discussed.

Acetylcholine

Sequential morphological changes in the pig detrusor in response to chronic partial urethral obstruction.

The sequential morphological changes which occur in the wall of the porcine urinary bladder in response to experimentally induced partial outflow obstruction have been determined using morphometric light and electron microscope techniques. The initial morphological response to urethral obstruction was a reduction of approximately 50% in the density of autonomic nerves in the bladder wall which occurred within the first 3 months. During this period the morphology of smooth muscle cells and the distribution of connective tissue were unaltered. Longer periods of obstruction produced a gradual further reduction in the density of innervation. However, from 3 months onwards the detrusor muscle bundles became infiltrated by connective tissue, although significant change in muscle cell size was not detected after obstruction for 12 months. Using electron microscopy, smooth muscle cells were observed to possess extensive amounts of perinuclear granular reticulum, this feature being particularly marked in bladders subjected to longer periods of obstruction. The underlying mechanisms responsible for these structural changes remain to be determined.

Animals

The pathogenesis of genitourinary prolapse and stress incontinence of urine. A histological and histochemical study.

Histological and histochemical analysis of biopsy samples of pubococcygeus muscle obtained from asymptomatic women and from women with stress incontinence of urine, with or without genitourinary prolapse, have been compared. In the asymptomatic women both age and parity appeared to be related to the morphological features of the samples and in particular those obtained from the posterior part of the pubococcygeus. In the symptomatic women there was a significant increase in the number of muscle fibres showing pathological damage which were obtained from the posterior part of the pelvic floor. The range of diameters of both Type I and Type II fibres obtained from this region was significantly different between symptomatic and asymptomatic women. These findings may be attributable to partial denervation of the pelvic floor in patients with urinary stress incontinence with or without genital tract prolapse.

Adult

Bladder outflow obstruction--a cause of denervation supersensitivity.

Eighteen Landrace pigs and 12 Göttingen mini-pigs were evaluated in a study of experimental bladder outflow obstruction. Twenty-two of the animals underwent partial bladder outflow obstruction for periods up to 12 months. The subsequent changes were assessed using cystometric, physiological and morphological means. There was a consistent increase in the voiding pressures and a concomitant reduction in the flow rates in all the obstructed animals. Seventy-seven per cent of the obstructed animals showed cystometric evidence of bladder instability. In vitro studies showed an increase in sensitivity to exogenously applied agonists and a reduction in sensitivity to intramural nerve stimulation. Morphological studies showed an inverse correlation between neuronal density and the duration of obstruction. These changes are typical of post-junctional supersensitivity secondary to partial denervation. These results suggest that agents capable of stabilising the bladder smooth muscle membrane may be useful in the treatment of detrusor instability secondary to bladder outflow obstruction.

Animals

The effects of vasectomy on the autonomic innervation of the human vas deferens.

Neurohistochemical and fine structural techniques have been employed to examine the intramural autonomic innervation of the human vas deferens following surgical division of the duct one to 15 years previously. Samples from sites on the distal (testicular) and proximal (urethral) aspects of the original vasectomy have been compared with control specimens obtained at vasectomy as to the arrangement and distribution of autonomic nerves. In contrast with tissue from the proximal part and from controls, the distal samples revealed a marked reduction in the noradrenergic innervation of the muscle coat. In addition acetylcholinesterase-containing nerves associated with the basal aspect of the epithelium were usually absent from the distal portion of the vas deferens. These findings have been considered in relation to the contractile and secretory activities of the organ following vasovasostomy and may be of importance to the maturation and fertility of spermatozoa.

Adult

Quantitative study of phenol as a neurolytic agent in the urinary bladder.

The endoscopic subtrigonal injection of a 6% aqueous phenol solution is an effective technique for denervating the bladder but its clinical usefulness is limited by unpredictable side effects. This study explored the possibility of making this procedure safer by comparing the neurolytic effects of different concentrations and carriers of phenol. Phenol in 2.5 and 5% solutions in three different carriers (water, glycerine and oil) was injected into the rectovesical pouch in 35 rats. After 3 weeks the bladders were excised and the effects on the density of acetylcholinesterase-positive nerves were assessed in each animal using morphometric techniques. The density of enzyme-containing nerves was reduced by 20% in the phenolised animals when compared with controls. This reduction was maximum when water was used as the carrier for either 2.5 or 5% phenol solutions.

Administration, Intravesical

Decrease in the autonomic innervation of human detrusor muscle in outflow obstruction.

In a group of patients in whom bladder outflow obstruction had been confirmed urodynamically, quantitative assessment of the amount of autonomic nerve in detrusor biopsy samples has been carried out using light and electron microscope techniques. In each specimen allowance was made for muscle cell hypertrophy and increases in connective tissue, both of which occurred in response to bladder outflow obstruction. Similar quantitative assessment was performed on bladder biopsy samples from a group of unobstructed 'control' patients. When the results from the two groups were compared a statistically significant reduction in the amount of autonomic nerve supplying detrusor muscle was demonstrated in the obstructed group. This finding provides additional evidence that functional impairment of the urinary bladder occurs in response to outflow obstruction and emphasizes the need for prompt relief of the condition.

Aged

The effect of age on the autonomic innervation of the urinary bladder.

Quantitative methods have been used to assess the amount of autonomic nerve in bladder biopsy samples from a group of "control" patients ranging in age from 20 to 79 years. Each patient included in the study was urodynamically normal and showed no subjective evidence of bladder trabeculation at cystoscopy. Using light microscopy, a significant linear reduction in the amount of acetylcholinesterase-positive nerve was observed with increasing age. Counts of axon profiles and measurement of smooth muscle cell cross-sectional areas in the electron microscope revealed a similar reduction in the amount of nerve per mm2 of detrusor muscle tissue. These findings thus confirm that a real reduction in the number of nerve axons occurs with age and the light microscope results are not due merely to a reduction in the amount of nerve-associated acetylcholinesterase. The present study provides baseline data for future comparisons of the density of autonomic innervation in bladders which are functionally impaired.

Adult

Bladder muscle biopsy and urethral sphincter EMG in patients with bladder dysfunction after pelvic surgery.

Eleven patients who suffered persistent bladder dysfunction after pelvic surgery have been investigated by needle urethral sphincter electromyography (EMG) and bladder muscle biopsy, and the results compared with those obtained in a series of controls. Individual motor units recorded from the urethral sphincter in patients who had undergone pelvic surgery were strikingly abnormal, suggesting the presence of reinnervation, and the density of detrusor innervation was significantly reduced. However, since reduction in the density of detrusor innervation may occur in circumstances other than peripheral nerve injury, we conclude that urethral sphincter EMG provides the most effective means of assessing damage to vesico-urethral innervation as a result of previous pelvic surgery.

Aged

Morphological and morphometric studies of the human obstructed, trabeculated urinary bladder.

As part of an ongoing study on trabeculation of the human urinary bladder, morphological and morphometric techniques have been employed on biopsy samples of detrusor muscle removed from control and urodynamically obstructed patients. In control material the mean profile area, profile diameter and nucleated profile percentage of bladder smooth muscle cells were determined. The values of the same parameters were obtained for smooth muscle cells in samples from urodynamically obstructed and endoscopically trabeculated patients. Comparison of the results obtained from the two groups showed that smooth muscle cells undergo compensatory hypertrophy in response to outflow obstruction. Furthermore, connective tissue infiltration of detrusor muscle bundles is a characteristic of those bladders which possess cells showing the largest increase in cell size.

Adult

A comparison of diuresis renography, the Whitaker test and renal pelvic morphology in idiopathic hydronephrosis.

Diuresis renography and the Whitaker test are established methods of diagnosing obstruction in dilated renal pelves. These techniques have been compared in 36 patients with radiologically demonstrated idiopathic hydronephrosis and evaluated, where possible, against renal pelvic morphological features. The agreement between the results of the tests was as follows: diuresis renography/Whitaker test 67%; diuresis renography/renal pelvic morphology 74%; Whitaker test/renal pelvic morphology 58%. Both diuresis renography and the Whitaker test are indicated in some cases of idiopathic hydronephrosis.

Diuresis

A comparison between the physiological and histochemical characterisation of urethral striated muscle in the guinea pig.

In this in vitro study comparison has been made between the actomyosin ATPase activity and the contractile properties of the external urethral sphincter in the guinea pig. Histochemical analysis showed the external urethral sphincter to contain a mixture of alkali and acid stable actomyosin ATPase positive fibres in the ratio of 3:1. External urethral sphincter isometric contraction measurements were undertaken using specimens mounted transversely or longitudinally with respect to the urethral lumen. These contraction parameters have shown that the majority of fibres which constitute the external urethral sphincter correspond to the fast twitch type. In order to determine whether the relatively small fibre diameter of urethral striated muscle influenced the contraction results, when compared with controls, corrections for different volume ratios of slow and fast fibres were applied to the results. These modified values revealed close correlation between muscle fibre actomyosin ATPase content and isometric contraction responses.

Adenosine Triphosphatases

Non-obstructive detrusor failure. A urodynamic, electromyographic, neurohistochemical and autonomic study.

Twenty-eight patients presenting with persistent loss of the voiding reflex have been evaluated. Those with cauda equina lesions or pelvic nerve injury were distinguished from a group with idiopathic detrusor failure by their abnormal urethral behaviour during filling, and by urethral sphincter electromyography (EMG). Bladder muscle biopsies revealed the presence of presumptive cholinergic fibres in all three groups, indistinguishable in quantity and distribution from normal controls. The implications of these findings for the diagnosis and management of these patients is discussed.

Adult

Intramural ganglia of the human urinary bladder.

The arrangement and distribution of intramural autonomic ganglion cells have been examined in samples of the dome and lateral walls of the human urinary bladder. Ganglia were frequently observed in samples removed from either site and possessed histochemical characteristics to support their classification as presumptive cholinergic neurons. Unlike pelvic autonomic neurons, intramural bladder ganglion cells are not associated with noradrenergic (possibly inhibitory) preganglionic nerve terminals. The widespread distribution of ganglion cells within the bladder wall serves to frustrate surgical attempts to denervate detrusor smooth muscle. The outcome of such operative procedures is likely to result in decentralisation rather than denervation of the urinary bladder.

Acetylcholinesterase