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Biomedical subjects

C J Gilpin

Publications and source records attributed to C J Gilpin.

11 recordsLinked to original sources

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

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

Presumptive sensory axons of the human urinary bladder: a fine structural study.

The mucosa of the human urinary bladder possesses an extensive plexus of suburothelial nerve fibres which are believed to be sensory in nature. Many of these presumptive sensory nerves occur as single axons whose vesicle-packed varicose regions are totally devoid of neurilemmal cell covering and occasionally penetrate the urothelial basal lamina. The axonal vesicles are of two types, small agranular vesicles (median diameter 47 nm, range 39-54 nm) and large granulated vesicles (median diameter 105 nm, range 62.5-187.5 nm). When compared statistically with intramuscular axon varicosities the suburothelial varicosities are shown to possess a significantly greater packing density of axonal vesicles and to contain a significantly greater proportion of large granulated vesicles. The latter finding may reflect the presence of substance P, a neuropeptide known to occur in primary sensory nerves.

Adult

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

Electron microscopic investigation of the bladder urothelium and glycocalyx in patients with interstitial cystitis.

The electron microscopic appearance of the bladder urothelium and glycocalyx was investigated in ten patients with well defined interstitial cystitis and compared to the findings in ten control patients with stress incontinence as the only symptom. Ruthenium red, a polycationic dye which binds specifically to cell surface acid polysaccharides, was used to demonstrate the glycocalyx. In cases of interstitial cystitis two types of luminal cell were observed, each possessing a distinct surface glycocalyx. One type of cell possessed numerous plaques of asymmetric unit membrane associated with a relatively thin glycocalyx. The second type of cell was characterised by numerous microvilli and a relatively thick glycocalyx. In control material each type of cell and its associated glycocalyx was identified with similar frequency. Our study concludes that there are no differences in the morphologic appearances of the glycocalyx and of urothelial cells in patients with interstitial cystitis when compared with controls. Hence, the hypothesis that an important pathogenic factor in interstitial cystitis is a defective glycocalyx associated with a permeable urothelium, has not been supported.

Adult

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

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

The fine structure of autonomic neurons in the wall of the human urinary bladder.

Using fresh biopsy specimens, intramural ganglia of the human urinary bladder have been examined by electron microscopy. The fine structural features of these neurons were compatible with their classification as parasympathetic in type. In several ganglia, groups of neurons were observed lying in close apposition to one another without any intervening satellite cell cytoplasm. Apart from occasional septate junctions the apposing membranes lacked any specialisation. The majority of terminals occurring in association with these intramural neurons were axosomatic in location. The terminals contained numerous small agranular and occasional large granulated vesicles and structurally were presumptive cholinergic in type. Occasional axon varicosities packed with a heterogeneous population of small agranular vesicles, large vesicles of variable density and multivesicular bodies lay in close association with the ganglion cells. The functional significance of these morphological features in terms of ganglionic transmission has been considered.

Adult

Mast cells in interstitial cystitis.

Specific clinical criteria have been used to diagnose interstitial cystitis in 32 patients. The distribution of mast cells in biopsies of the bladder wall from these patients has been compared with that of similar cells in control specimens. A highly significant increase (P less than 0.001) in the number of mast cells within the detrusor muscle bundles has been demonstrated in 27 of these patients. This mast cell infiltration is widespread throughout the detrusor muscle and is not confined to the ulcerative lesions seen cystoscopically. Histological estimation of mast cells is of value, therefore, in establishing the diagnosis of interstitial cystitis, and may be particularly helpful in equivocal cases. The relationship between mast cell infiltration of the detrusor muscle bundles and the aetiology of the disease remains to be determined.

Cell Count