Biomedical subjects
Publications and source records attributed to A Elbadawi.
Inverted papilloma of the urinary bladder is not uncommon in adults. In children, only two cases had been reported to our knowledge. Another pediatric case is described herein, in which the lesion occurred in a 9-year-old boy; he is the youngest patient reported to have this condition.
Voiding dysfunctions are common in the elderly. Yet the pathogenesis and pathophysiology have remained largely unknown. To date there has been little information on structure of the aging detrusor. To gain insight into the structural basis of voiding dysfunction in the elderly, we examined detrusor biopsy specimens by electron microscopy. The specimens were obtained from 24 women and 11 men 65 to 96 years old (mean age 79 years) who were carefully selected by detailed clinical and neurological examination. Symptom-free subjects were particularly sought to identify those who might provide the structural/functional norm of aging detrusor. Comprehensive urodynamic study was performed in all subjects. A transurethral detrusor biopsy was obtained and processed to study ultrastructure of the smooth muscle, intrinsic nerves and interstitium. Subjects were segregated purely by urodynamic findings, regardless of symptoms, into detrusor overactivity, outlet obstruction, obstruction plus overactivity and neither (that is no obstruction and no overactivity) groups, each with a subgroup of normal and another of impaired contractility. Specimens were segregated blindly and independently by ultrastructural features into dysjunction, myohypertrophy, myohypertrophy plus dysjunction and dense band patterns, each with a subset with widespread degeneration of muscle cells and nerves, and another with minimal or no degeneration. When codes were broken, each structural pattern (and subset) matched with a specific urodynamic group (and subgroup)--with no overlap. The dysjunction pattern matched with overactivity, the myohypertrophy pattern with obstruction, the myohypertrophy plus dysjunction pattern with obstruction plus overactivity, and the dense band pattern with the neither group. Structural subsets of widespread degeneration matched with impaired contractility subgroups, and subsets with minimal or no degeneration matched with normal contractility subgroups. These observations identify specific structural bases of the major forms of geriatric voiding dysfunction, provide important insights into their pathogenesis, and introduce detrusor biopsy as a potentially valuable tool in their diagnosis and clinical management.
Little information on the structural norm of the aging detrusor is currently available. To gain insight into the pathophysiology of geriatric voiding dysfunction, detrusor biopsies were examined by electron microscopy to identify structural correlates of specific, urodynamically defined abnormalities of vesical function in 35 elderly subjects. Prospective urodynamic grouping of the subjects and segregation of the detrusor specimens by ultrastructural features were done independently and blindly. One structural pattern so identified, the dense band pattern, matched the urodynamic group with neither detrusor overactivity nor bladder outlet obstruction. This neither group included 11 women and 2 men 65 to 91 years old (mean age 76 years). Except for 2 patients with minimal stress incontinence, all were symptom-free. None of the patients had diabetes or a neurological deficit. Urodynamically, 10 patients had impaired and 3 had normal detrusor contractility. The dense band structural pattern was characterized by overall normal configuration of muscle cells and cell junctions, sarcolemma (muscle cell membrane) dominated by dense bands with depleted caveolae in interposed zones and slight widening of spaces between muscle cells with little-collagen content. Specimens from the 10 subjects with impaired contractility displayed, in addition, widespread degeneration of muscle cells and axons. The remaining 3 specimens, without degeneration, matched the subjects with normal contractility, who were continent and symptom-free. It is proposed that the dense band pattern represents the structural norm of aging detrusor, heralds a process of muscle cell de-differentiation in the detrusor accompanying natural aging, and may affect exchange and storage of ions involved in the excitation-contraction coupling mechanism of muscle cells through depletion of caveolae. Widespread degeneration of muscle cells and axons, superimposed on the dense band pattern, is proposed as the structural correlate of impaired detrusor contractility in the aging detrusor.
Detrusor overactivity in the absence of outlet obstruction is common in the elderly. The few available studies on structure of the overactive detrusor generally have dealt only with its innervation. We conducted a prospective study to examine the ultrastructure of muscle cells, interstitium and nerves of the detrusor in biopsies from 35 elderly subjects to identify structural correlates of various urodynamically defined forms of voiding dysfunction. A distinctive dysjunction structural pattern was identified blindly in 15 detrusor biopsies. These patterns matched 12 women and 3 men 66 to 96 years old (mean age 79 years) who were segregated independently as a detrusor overactivity group by prospective urodynamic evaluation. All but 1 patient had incontinence and/or other symptoms, and none had diabetes or a significant neurological deficit. The dysjunction pattern was characterized by moderately widened intercellular spaces, scarce intermediate muscle cell junctions, abundant distinctive protrusion junctions and ultra-close cell abutments, and absence of profiles characteristic of enlarged hypertrophic cells. There was superimposed widespread degeneration of muscle cells and axons in 8 specimens, which matched the subgroup of patients with impaired detrusor contractility. The remaining 7 specimens with no degeneration matched the patients with normal contractility. Protrusion junctions and abutments are proposed as a possible manifestation of a process of muscle cell de-differentiation associated with natural aging, as well as the mediator in overactive detrusor of electrical coupling of muscle cells, in lieu of their normal mechanical coupling curtailed by marked reduction of intermediate cell junctions. On this basis, a bipartite myogenic mechanism is proposed to account for the involuntary contractions yet allow neurally triggered unitary voiding contractions in the overactive detrusor. Superimposed degeneration is proposed as the structural basis of impaired detrusor contractility, when also present.
Several aspects of the pathogenesis of voiding dysfunction in bladder outlet obstruction remain unresolved. The structural basis of obstructive versus nonobstructive dysfunction was investigated in a prospective ultrastructural/urodynamic study of 35 elderly subjects of comparable age. Detrusor structure was examined by electron microscopy, with blinded clinical and urodynamic information. Seven detrusor specimens were segregated by a distinctive myohypertrophy, structural pattern, which matched with 6 male and 1 female subjects 72 to 96 years old (mean age 83) who had urodynamically proved outlet obstruction. This pattern was characterized by widely separated muscle cells with reduction of intermediate cell junctions, collagenosis, that is abundant collagen plus some elastic fibers, in the markedly widened spaces between individual muscle cells and abundant profiles characteristic of enlarged, hypertrophic muscle cells. Superimposed degeneration of muscle cells and axons in 6 specimens matched those of 5 men and 1 woman who had impaired detrusor contractility. In 3 specimens there were also abundant protrusion junctions and ultra-close abutments; these matched those of 2 men and 1 woman with obstruction plus detrusor overactivity. Observations on the degree of bladder trabeculation in the entire population of 35 subjects are presented. It is concluded that bladder outlet obstruction is associated with changes in detrusor structure that can account for the resultant voiding dysfunction. Features of the myohypertrophy pattern, with or without superimposed degeneration, can explain overall weakness of the obstructed detrusor despite hypertrophy of its cells. Protrusion junctions and abutments probably mediate electrical coupling of muscle cells leading to involuntary contractions in the overactive (unstable) obstructed detrusor. Excessive deposits of elastic fibers (hyperelastosis) between widely separated muscle cells and in interstitium are suggested as the probable structural basis for increased bladder distensibility and chronic retention.
Disorders of micturition (voiding dysfunction), the essence of urinary bladder function, are unknown to the discipline of pathology, despite their prevalence and profound socioeconomic impact. Their pathogenesis has remained largely unknown, their diagnosis often difficult or uncertain, and the outcome of their management generally unpredictable. A new approach to morphologic study of the bladder has been developed to identify microstructural correlates of its function. Application of this approach to endoscopic biopsies culminated in the concept of functional pathology of urinary bladder muscularis. The basis, elements, current status, and diagnostic potential of this new concept are presented in relation to the major forms of clinical voiding dysfunction.
The cat and the rabbit have both been utilized extensively in the study of lower urinary tract function. Previous studies have demonstrated that although both the cat and rabbit bladder are approximately the same weight, the in-vitro cat bladder can generate over 6 times the intravesical pressure of the rabbit bladder. The current study was designed to compare the ability of the isolated bladder to generate pressure with the pressures required to maintain flow through the isolated urethra for both the cat and the rabbit. The results can be summarized as follows. 1) The cat bladder is visibly much thicker than the rabbit bladder, and in vitro cystometry demonstrates that it is far less compliant than the rabbit bladder. 2) Over 20 cm.H2O pressure is required to begin flow through the isolated cat urethra preparation, whereas 5 cm.H2O begins flow through the rabbit urethra. 3) Increasing the flow rate (up to 7-fold) through both the isolated cat and rabbit urethra increases intraurethral pressure only slightly. 4) Both the isolated cat and rabbit urethra respond strongly to field stimulation and alpha-adrenergic stimulation (relative to the opening pressure required to begin flow), but not to cholinergic stimulation. 5) Field stimulation following pre-stimulation by methoxamine induces a strong relaxation of the pre-stimulated cat urethra, but an additive contraction in the pre-stimulated rabbit urethra. These studies demonstrate that in order for the cat to empty its bladder, it must generate a comparatively high intravesical pressure, whereas the rabbit is required to generate a relatively low intravesical pressure.
Experimental bladder outlet obstruction in cats induces a significant increase in the in vivo leakage pressure. The effects of obstruction on the detrusor function were analyzed, using control, 3, 6 and 12 month obstructed cats. The in vivo leakage pressures were substantially increased in all obstructed groups. From a previous study on the short-term effects of obstruction in the cat; although there was an immediate increase in pressure, there were no significant differences between control bladders and two week obstructed bladders in: bladder weight, peak pressure response to field stimulation and bethanechol, and emptying of the in vitro whole bladder model. In this current study, although there was no direct relationship between duration of obstruction and severity of the impaired pharmacological response of the isolated whole bladder, there was a direct relationship between the magnitude of the increase in bladder weight, leakage pressure, and impaired functional response of the in vitro whole bladder. In this regard the cats were separated into four groups: controls and shams (average bladder weight 2.95 gm.), obstructed group 1 with bladder weights less than 6.0 gm. obstructed group 2 with bladder weights between 6 and 10 gm., and obstructed group 3 with bladder weights greater than 10 gm. The results can be summarized as follows: A) In vivo leakage pressures were significantly increased in all obstructed groups, and progressively higher in proportion to the bladder weights. B) Bladder capacity significantly increased in all, being greatest in obstructed group 3. C) The magnitude of the response to field stimulation of obstructed groups 1 and 2 were significantly greater than the response of control bladders at virtually all frequencies. The frequency response curve of obstructed group 3 was similar to control. D) The ability of the bladder to empty in response to field stimulation was significantly reduced in all obstructed groups. The magnitude of the decrease was proportional to the increase in bladder weight. E) There were no differences between control and obstructed bladders in the pressure response to bethanechol or KCl; the ability of both bethanechol and KCl to empty the bladder was reduced in the obstructed groups. In general, the presence of bladder enlargement was accompanied by significant alterations in the ability of the in vitro bladder to empty in response to field stimulation, bethanechol, and KCl.(ABSTRACT TRUNCATED AT 400 WORDS)
The aim of this project was to create a reproducible, quantifiable feline model of obstructive uropathy. Seventy-three adult female cats of comparable age were evaluated to obtain the normal control urodynamic data base. Twenty-four cats had a silastic cuff installed around the urethra to induce bladder outlet obstruction, and eight underwent a sham operation. Repeated urodynamic evaluations were performed at predetermined postoperative intervals. The obstructed and normal cats inhibited detrusor contractility by reflex striated urethral sphincter activity. Measurements of voiding pressure to verify the presence, and to assess the degree of induced outlet obstruction, required paralysis of the sphincter by curare. Following cuff implantation, voiding pressure increased from a mean normal of 17.2 cm./H2O to 31.6 to 42.5 cm./H2O in animals designated as moderately obstructed, and to 101.7-125.0 cm./H2O in animals designated as severely obstructed. 84.6% of the high pressure bladders developed vesicoureteral reflux. Analysis of resting, low bladder volume, urethral pressure profile (UPP) data and voiding pressures indicate a compensatory sphincteric response to filling in non-curarized animals, and a lack of that response in curarized animals. It appears that implantation of a silastic cuff to prevent full opening of the urethra during voiding, without actually compressing it, is a reasonable model of obstructive uropathy. The observation that the relationship between striated urethral sphincter activity and inhibition of detrusor contractility is influenced by administration of curare was unexpected, and may have clinical implications.
Isolated detrusor muscle from control cats and cats parasympathetically decentralized for 3 and 10 weeks responded to electrical field stimulation by tetrodotoxin-sensitive, frequency-dependent contractions. There were no significant differences in the frequencies producing 50% response. However, the amplitude of the scopolamine-resistant contraction was distinctly lower in decentralized bladder preparations than in controls. Decentralized detrusor muscle (10 weeks) showed no increased response to alpha-adrenoceptor stimulation (phenylephrine, clonidine, noradrenaline), but the sensitivity to carbachol (at 3 and 10 weeks) was significantly decreased compared with controls. The release of [3H]noradrenaline was decreased by carbachol 10(-7) to 10(-5) M both in controls and in decentralized (10 weeks) detrusor muscle, the decrease being significantly more pronounced in the decentralized group at carbachol concentrations of 10(-7) and 10(-6) M. There were no differences between controls and decentralized bladders of muscarinic receptor concentration, but decentralization significantly reduced the affinity for the radioligand used to label the receptors. Thus, the main changes caused by parasympathetic decentralization of the feline bladder seem to be a reduced post-junctional, but an increased prejunctional response to muscarinic receptor stimulation.
The cat and the rabbit are two of the most popular models for the study of lower urinary bladder function. The cat has been used extensively for in-vivo studies of spinal and supra-spinal micturition reflexes. In contrast, the rabbit has been used extensively for the in-vitro study of bladder function. In order to determine if the results obtained using one species can be applied to another, we have compared the in-vitro physiology and pharmacology of the cat and rabbit bladder using isolated strips and whole bladder preparations. The results can be summarized as follows: 1) The cat displays significant spontaneous activity during in-vitro cystometry, but the rabbit shows no such activity (whole bladder studies). 2) Although the bladder weights of the cat and rabbit are similar, the rabbit bladder has a capacity three times that of the cat. 3) The maximal response to field stimulation was obtained at one gram of passive tension for the rabbit isolated strips, whereas five grams of passive tension was required for the cat strips. 4) Atropine inhibited the response of isolated strips of cat bladder to field stimulation by approximately 13% whereas the response of rabbit bladder strips was inhibited by approximately 45%. 5) The magnitude of the response of rabbit bladder strips to ATP was similar to the response to field stimulation in the presence of atropine; the response of cat bladder strips to ATP was only 20% of the response of that of the rabbit bladder strips, and approximately 10% of the response of the cat strips to field stimulation in the presence of atropine. 6) Field stimulation produced a 10fold greater rise in intravesical pressure in the cat isolated bladder than in the isolated rabbit bladder; in response to bethanechol, the cat bladder generated a 6-fold greater response than the rabbit bladder. It is clear that the in-vitro pharmacological responses of the cat urinary bladder are qualitatively and quantitatively different from that of the rabbit bladder.
Experimental bladder outlet obstruction in cats was produced by surgical placement of a silastic cuff around the urethra. Two sizes of cuff were used to produce either moderate or severe obstruction. The following is a summary of the short-term effects on bladder function. Obstruction induced a significant increase in the in vivo voiding pressure, in proportion to severity of the obstruction. There were no significant differences between control and obstructed cats in bladder mass, response of the isolated whole bladder to field stimulation or bethanechol, response of isolated bladder strips to field stimulation, bethanechol and ATP, or muscarinic receptor density in the bladder body. Although there were no differences in bladder mass between control and obstructed bladders, the hydroxyproline concentration of the severely obstructed bladders was significantly reduced. Creatine phosphate concentration was also significantly reduced in obstructed bladders. Although all whole cat bladder preparations displayed spontaneous contractile activity during in vitro cystometry, the obstructed bladders had a greater amplitude and frequency of spontaneous contractions with a lower volume threshold. In addition, the obstructed bladders had a greater tetrodotoxin-resistant contractile response to field stimulation. These results suggest that the obstructed cat bladder can compensate for increased outlet resistance without induction of bladder hypertrophy or significant functional changes, as seen in both rat and rabbit.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The influence of muscarinic receptor stimulation (carbachol) and blockade (scopolamine) on the release of 3H-labelled noradrenaline from adrenergic neurons was investigated in isolated detrusor preparations from rabbit, cat and man. A significant influence on the release of 3H from adrenergic nerve terminals was found in the three species with a concentration-dependent decrease and increase induced by carbachol and scopolamine, respectively. Using the alpha 2-adrenoceptor stimulating and blocking agents clonidine and rauwolscine in rabbit and human detrusor preparations, the presence of prejunctionally located inhibitory alpha 2-adrenoceptors could also be demonstrated. The findings indicate the possibility of a functionally important interaction between cholinergic and adrenergic nerves in the urinary bladder mediated via inhibitory muscarinic receptors on adrenergic nerve terminals.
The case is presented of a 15-year-old boy with a mixed nongerminomatous germ-cell tumor of the pineal region associated with elevated cerebrospinal fluid and serum levels of the beta subunit of human chorionic gonadotropin. Treatment consisted of initial subtotal resection followed by radiotherapy and systemic chemotherapy with cisplatin, vinblastine, and bleomycin. The patient is alive without evidence of tumor 37 months after his initial diagnosis. A literature review of intracranial embryonal carcinoma and choriocarcinoma provided the rationale for a combined-modality approach to this otherwise lethal neoplasm.
Rapid structural and functional alterations have been noted in several models of partial outlet obstruction. To better characterize the rapid progression of alterations, the partially obstructed urinary bladders of mature NZW male rabbits were studied at 1, 3, 5, 7 and 14 days of outlet obstruction with respect to muscarinic receptor density, DNA, RNA, lipid and hydroxyproline content. Functional characteristics were assessed by measuring the in vitro response of the whole bladder to cholinergic and field stimulation. Wet weight increased eight-fold by day 7, decreasing to four-fold at day 14. Receptor density decreased by 50% by day 1 and remained low throughout. Although DNA concentration varied only slightly from controls, RNA increased four-fold by day 7. Hydroxyproline concentration per mg. tissue decreased in the obstructed bladder, yet total hydroxyproline content of the obstructed bladder significantly increased. Total lipids increased significantly during day 3 through 7 and decreased by day 14. Cystometry revealed a large capacity low pressure system at day 1 which rapidly changed to a low compliance system of lesser volume by day 14. Bladder emptying was significantly impaired in all obstructed specimens. Additionally, electrical field stimulation was significantly less effective than cholinergic stimulation in effecting bladder emptying. The above findings suggest that rapid changes in biochemical parameters occur during the early stage of acute obstruction which may in part be secondary to metabolic or inflammatory alterations in the detrusor. It additionally suggests that the myogenic alterations in partial outlet obstruction are rapid and partially adaptive, while neurogenic alterations appear degenerative and display a lesser degree of short term adaptation.
Partial bladder outlet obstruction is a commonly encountered pathophysiologic state. Recently we have reported on the rapid nature of the contractile and functional changes that occur in the rabbit urinary bladder within one week of chronic partial obstruction. The purpose of this present study is to investigate the ability of the bladder to recover from one week of partial obstruction. Twenty-six mature male white New Zealand rabbits were separated into 3 groups. Each rabbit was anesthetized with ketamine-xylazine and a partial obstruction of the bladder established by gently securing a 2.0 silk suture around the temporarily catheterized bladder neck. The rabbits in group 1 were sacrificed following one week of partial obstruction. For groups 2 and 3, the obstructing suture was surgically removed after one week of obstruction adn the rabbit was allowed to recover for either two or four weeks. At the end of one week of obstruction the bladder displayed a 9-fold increase in tissue mass, 50 per cent reduction in contractile response to bethanechol and a 76 per cent reduction in the ability of the bladder to expel saline. After the two week recovery period, the bladder mass was reduced to approximately twice the control mass, the contractile and pressure responses to bethanechol were returned to control levels, and the ability of the bladder to expel saline recovered to approximately 75 per cent of control levels. No further improvements were observed following the four week recovery period. It appears that although the contractile response recovers completely following the one week obstruction period, the ability of the bladder to empty remains partially impaired.