Mechanisms of bladder smooth-muscle hypertrophy and decompensation: lessons from normal development and the response to outlet obstruction.
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Animals↗
Biomedical subjects
S A Zderic
Publications and source records attributed to S A Zderic.
Giant hyperplastic nephrogenic rest in a solitary kidney presenting as an angiomyolipoma in a child.
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Adolescent↗
Surgical management of the nonpalpable testis: the Children's Hospital of Philadelphia experience.
PURPOSE: The management of the nonpalpable testis permits an individualized operative approach. We analyze the results of surgical management of a large series of patients with a nonpalpable testis. MATERIALS AND METHODS: Between January 1986 and June 1994 we treated 1,866 boys with undescended testes. There were 447 testes (24%) that were not palpable at presentation. Intra-operative data on these patients were collected for age at presentation, bilateral testes position, testicular size, associated inguinal anomalies (vas, epididymis and processus vaginalis) and surgical approach. For intra-abdominal testes postoperative results of 2 surgical techniques, the Fowler-Stephens procedure and Koop orchiopexy (retroperitoneal mobilization of spermatic vessels and vas) were compared in 76 patients with at least 18 months of followup. RESULTS: Average patient age at presentation was 34 months with 63% presenting before age 48 months. Of the impalpable testes 58% were on the left side, 35% were on the right side and 7% were bilateral. At operation 181 testes (41%) were atrophic or absent, 91 (20%) were intra-abdominal with 14 (3.1%) bilateral, 136 (30%) were in the inguinal canal and 39 (9%) were in other locations, including 22 at the pubic tubercle, 2 in the upper scrotum, 13 in the superficial inguinal pouch and 2 in the perineum. Of the intra-abdominal group associated extratesticular malformations were identified in 36 cases (39%). Attachment of the vas deferens to the testis was abnormal in 23 of 64 cases (36%), including 10 that were completely detached and 13 with head or tail attachment only. Of the 91 evaluable cases in the intra-abdominal group 38 (42%) had been treated with the Fowler-Stephens repair (5 in 2 stages), 33 (36%) with inguinal orchiopexy and intraperitoneal dissection without dividing the spermatic vessels, 5 with 2-stage procedures and vessel preservation and 14 (15%) with orchiectomy. One testis was left in situ. The inguinal approach with intraperitoneal extension was successful in defining the testis location or blind-ending vas and vessels in 100% of the cases. A single operation to perform orchiopexy was successful in 92% of the cases. Overall, results were considered excellent or acceptable in 32 of 33 cases (97%) after Koop orchiopexy and 28 of 38 (74%) after the Fowler-Stephens orchiopexy. CONCLUSIONS: Nonpalpable testes accounted for 24% of the patients presenting with undescended testes. At surgical exploration 39% of impalpable testes were distal to the external inguinal ring, 41% were atrophic or absent and 20% were intra-abdominal. All cases were treated through a standard inguinal incision. These data provide evidence that the inguinal approach to orchiopexy with transperitoneal mobilization of the vas and vessels without transection is highly successful for the intra-abdominal cryptorchid testis and, to date, is the preferred technique for the management of the intra-abdominal undescended testis.
Child, Preschool↗
Lateral meningocele syndrome: three new patients and review of the literature.
One female and two male patients with multiple lateral meningoceles are presented. They do not have neurofibromatosis or Marfan syndrome and share findings with the two previously described patients with multiple lateral meningoceles. The original report by Lehman et al. [1977: J Pediatr 90:49-54] was titled "familial osteosclerosis," because osteosclerosis was present in the proposita and her mother; the patient described by Philip et al. [1995: Clin Dysmorphol 4:347-351] also had increased bone density of the skull base and the sutures. Thickened calvaria were present in one of our patients; two had a prominent metopic suture. Other shared findings include multiple lateral meningoceles, Wormian bones, malar hypoplasia, downslanted palpebral fissures, a high narrow palate, and cryptorchidism in males. In addition, our patients showed ligamentous laxity, keloid formation, hypotonia, and developmental delay. A short umbilical cord was noted in two patients. One had a hypoplastic posterior arch of the atlas and an enlarged sella, as reported by Lehman et al. [1977]. Our patients appear to have the same syndrome as previously reported. We suggest it be called "lateral meningocele syndrome," because of this unique finding.
Abnormalities, Multiple↗
Compliance of the obstructed fetal rabbit bladder.
We evaluated compliance in the developing bladder using a newly developed animal model of posterior urethral valves: partial infravesical obstruction in the fetal rabbit bladder. Partial bladder outlet obstruction was created in fetal rabbits at day 23 of a 31 to 32-day gestation period. An in vitro whole bladder preparation provided data on compliance and an isolated bladder strip preparation provided data on the mechanical properties of the bladder wall. In addition, the influence of calcium on both preparations was evaluated. Partial bladder outlet obstruction in the fetal rabbit resulted in a markedly larger bladder weight (246.4 +/- 22.3 mg, n = 14) than control bladders (90.2 +/- 5.7 mg, n = 13). Isolated smooth muscle strips from obstructed and normal bladders revealed identical stretch-stress patterns. In contrast, obstructed bladders had significantly increased compliance in the whole bladder preparation. Since the increase in compliance was not correlated to mechanical properties of the isolated bladder strips, it must therefore result from the pattern of mass increase of the whole bladder wall. During filling, both the control and obstructed bladders had the same slow, large amplitude spontaneous contractions. In addition, both had rapid contractions: those in the obstructed bladders had significantly lower frequency and higher amplitude than the ones in the control bladders. Removing the calcium from the organ bath eliminated the spontaneous contractions but did not change the baseline pressure or force values, indicating that the compliance of these fetal rabbit bladders is a function of the passive properties of the bladder wall. Three main patterns occur in cystometrograms of patients with posterior urethral valves: myogenic failure, hyperreflexic bladders, and low compliance bladders. Using our model of partial outlet obstruction in the fetal rabbit bladder, we could not imitate the group with low compliance. We therefore hypothesize that the different patterns of bladder dysfunction associated with posterior urethral valves are due to infravesical obstruction occurring with different severities or at different ages of gestation.
Animals↗
Skin flap closure by dermal laser soldering: a wound healing model for sutureless hypospadias repair.
OBJECTIVES: Laser tissue soldering (LTS) with the diode laser and human albumin-hyaluronate-indocyanine green solder is a safe and effective method of providing an immediate leak-free closure during hypospadias repair. In this report, we compare the physiology, histology, and immunohistochemistry of wound healing following LTS and suturing in a rat skin flap model. METHODS: A 4 x 5-cm skin flap was raised and bisected (4 cm) on the dorsum of 48 Sprague-Dawley rats. The central wound was either closed from a dermal approach by suturing or LTS or left open, and studied at 0, 3, 5, 7, 10, 14, and 21 days postoperatively. An intraoperative comparison was made between suturing and LTS with respect to operative time. Postoperatively, flaps were excised for tensiometric analysis, and sections were stained with hematoxylin-eosin to define wound architecture. Resting skin temperature, laser exposed temperature without solder, and maximum temperature with solder (one drop) were measured at the level of the deep dermis, superficial striated muscle layer, and within the solder. Mean peak temperatures were recorded during a 1-minute laser activation time. RESULTS: Mean continuous suturing time (4.9 +/- 1.1 minutes) was significantly (P < 0.001) faster than either LTS (7.7 +/- 0.77 minutes) or discontinuous suturing (8.2 +/- 0.62 minutes). Two seromas (sutured) and two instances of partial wound dehiscence (1 sutured, 1 LTS) were noted. Tensile strength was increased significantly (P < 0.001) for up to 5 days in the LTS group, but was equal to suturing at 7 and 10 days. Immediate tensile strength after LTS was equivalent to a 7-day healed wound. At 14 days, wounds initially left open and those closed by LTS were stronger than sutured wounds (P < 0.05). There was no evidence of thermal injury or foreign body reaction in the LTS group. Solder was incorporated within the dermis in all wounds at 21 days. Laser activation of solder resulted in significant increases in temperature at all three tissue levels: 65.0 +/- 5.2 and 69.9 +/- 6.8 degrees C in the deep and superficial skin (no significant difference between the two), and 101 +/- 15.6 degrees C within the solder (P < 0.001 versus superficial and deep skin). CONCLUSIONS: Our results indicate that sutureless dermal LTS of skin flaps provides increased tensile strength for up to 7 days, with relatively greater tensile strength provided within the first 3 days. Our laser technique does not appear to alter the normal wound healing process. Rather, solder-tissue interaction initially, and extracellular matrix infiltration of solder later, provide the basis for improved wound strength. For hypospadias repair using skin flaps, these wound attributes may permit sutureless surgery.
Animals↗
Partial bladder outlet obstruction in the fetal rabbit.
PURPOSE: We developed and tested an animal model of bladder dysfunction due to posterior urethral valves using partial outlet obstruction of the fetal rabbit bladder. MATERIALS AND METHODS: Partial bladder outlet obstruction of fetal rabbit bladders was created on day 23 of gestation. Of the litter of 8 to 10 fetuses half was obstructed and the remainder served as controls. The doe and fetuses were sacrificed on day 30 of gestation (full term 31 to 32 days) and the fetal bladders were removed. Bladders that had doubled in weight from the average bladder weight of the control littermates were deemed sufficiently obstructed. Hematoxylin and eosin staining was performed and bladder strip response to 32 Hz. field stimulation, 200 microM. bethanechol and 200 mM. potassium chloride was measured. RESULTS: Average body weight did not differ between the control and obstructed fetuses, indicating that surgery did not hinder fetal development. Hematoxylin and eosin staining confirmed smooth muscle cell hypertrophy and increased connective tissue in the obstructed bladders. Obstructed bladder strips responded significantly less to field stimulation, and significantly more to bethanechol and potassium chloride (mean plus or minus standard deviation 5.18 +/- 1.52, 6.29 +/- 1.3 and 10.15 +/- 2.18 x force per/100 mg. tissue, respectively)than control bladder strips (9.0 +/- 1.19, 3.5 +/- 0.46 and 6.16 +/- 1.33 x force per/100 mg. tissue, respectively) suggesting that denervation supersensitivity may have resulted from obstruction. CONCLUSIONS: Partial outlet obstruction of the fetal rabbit bladder results in bladder hypertrophy and dysfunction but these changes are markedly different from those in the adult rabbit. Since rabbit fetal development is delayed compared to human fetal development, this model can be used to assess the consequences of posterior urethral valves.
Animals↗
The operative management of recurrent ureteropelvic junction obstruction.
PURPOSE: Surgical repair of ureteropelvic junction obstruction is successful in 98% of cases. We evaluated children undergoing repeat pyeloplasty and discuss the etiology of recurrent ureteropelvic junction obstruction, surgical approach and outcome. MATERIALS AND METHODS: Between 1982 and 1996, 366 children with ureteropelvic junction obstruction were surgically treated at our institution, including 16 who presented with recurrent ureteropelvic junction obstruction and required surgery. RESULTS: Repeat repair was successful in all 16 patients, including ureterocalicostomy in 3 and dismembered pyeloplasty in the remainder. No nephrectomy was necessary. Anteriorly elongated flank incisions were made in all cases. Dense scar tissue around and obstructing the ureteropelvic junction was noted in the majority of cases. In 7 patients a redundant pelvis resulted in a kink at the ureteropelvic junction. A nephrostomy tube was placed in all cases and an additional transanastomotic stent was used in all but 2. Obstruction was relieved with 1 operation. CONCLUSIONS: A redundant pelvis resulting in a kink at the ureteropelvic junction may contribute to a higher change of urinary leakage and subsequent obstructive scar formation in cases of failed pyeloplasty. Before repeat surgery anatomy should be precisely identified by antegrade and retrograde studies. The surgical approach usually involves identifying the ureter below the area of the previous surgery and then ensuring a tension-free anastomosis. If inadequate ureteral length or an intrarenal pelvis precludes direct anastomosis, ureterocalicostomy is an alternative. A nephrostomy tube and transanastomotic stent are advisable. Nephrectomy is rarely necessary and a good functional result can be anticipated.
Child↗
Contractile protein changes in urinary bladder smooth muscle during obstruction-induced hypertrophy.
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Animals↗
Laser soldering technique for sutureless urethral surgery.
Investigators have attempted sutureless surgery to decrease operative time, lessen the inflammatory response, maintain luminal continuity, and increase the ease of performing technically difficult surgery. Only recently has laser-tissue welding (LTW) been used for urologic reconstruction in humans. Herein, we present our technique of laser soldering with the half-watt diode laser and wavelength matched albumin-based solder. Our methodology of LTW relies on bonding between the outer surface of the wound edges and the solder. The 808-nm diode wavelength does not penetrate deep tissue, and thus relies on indocyanine green dye to localize photon absorption. Since 1994, we have performed LTW, as an adjunct to suturing (N = 25) and as a primary means of tissue closure (N = 11). Preoperative diagnoses included hypospadias, urethral stricture, urethral diverticulum, and urethral fistulae. Follow-up ranged between 3 months and 3 years to identify complications of wound healing, stricture, and fistula formation. In the 37 patients undergoing urethral surgery, no strictures or diverticula have resulted. None of the patients have had wound infections or poor wound healing. Overall, five patients have developed fistulas between 2 weeks and 6 months postoperatively. The location of the hypospadiac meatus was scrotal or penoscrotal in four of these patients. Two fistulas developed following sutureless urethroplasty (reoperative) after traumatic catheterization for urinary retention (one case for inadvertent catheter removal). In our initial experience, the overall complication rate using laser soldering was 19% compared to 24% in an historical control group. Half of the complications occurred in a reoperative situation. More recently, the overall fistula rate was 14%; however, for primary cases, the current fistula rate is only 6%. LTW is safe and easy to perform. The application of protein solders (+/-chromophores) have permitted far greater tensile strengths to be achieved than laser alone. Temperature-control and chromophore-control have permitted safety and efficacy to be achieved. Solder application site and technique are equally important in the success of the LTW process. A randomized, prospective study comparing LTW to suturing is ongoing.
Adolescent↗
Properties of Ca2(+)-Mg2+ ATP-ase in rabbit bladder muscle and mucosa: effect of urinary outlet obstruction.
The contractile response of the smooth muscle of the urinary bladder is dependent upon both the entrance of extracellular calcium through receptor-operated calcium channels and the stimulated release of calcium from the sarcoplasmic reticulum. In addition, partial outlet obstruction induces marked alterations in the utilization of intracellular calcium. Although calcium ATP-ase provides the energy for the translocation of intracellular free calcium into storage sites within the sarcoplasmic reticulum, very little is known about the properties of this enzyme in bladder muscle and mucosa. As an initial study, divalent ion specific ATP-ase activity was measured in extracts of rabbit bladder muscle and mucosa from control animals and from rabbits following partial urinary outlet obstruction. In both normal bladder muscle and mucosa, magnesium and calcium ions were equally effective in activating the enzyme. Seven days following partial urinary outlet obstruction, the ATP-ase activity in both bladder muscle and mucosa was significantly depressed by over 70%. The degree of the decreased enzyme activities observed within the muscularis and mucosa would indicate that specific membrane functions supported by divalent-ion-ATP-ase are dysfunctional. This hypothesis is supported by marked alterations in the utilization of intracellular calcium following partial outlet obstruction and the marked dysfunctions in both mucosal permeability and bacterial adherence to mucosa observed following partial outlet obstruction.
Animals↗
Effect of thapsigargin on the contractile response of the normal and obstructed rabbit urinary bladder.
Excitation-contraction coupling is achieved by translocation of calcium from the extracellular space as well as by the release of calcium from intracellular stores. Thapsigargin has been shown to selectively block the sarcoplasmic Ca-ATPase, thereby preventing the reuptake of calcium into intracellular stores and the participation of these calcium storage sites in the contractile response to stimulation. The current study determined the effect of thapsigargin on the contractile response to field stimulation, bethanechol, and KCl in control rabbit bladders and bladders obtained from rabbits subjected to partial outlet obstruction. Partial bladder outlet obstruction resulted in a marked increase in bladder mass and in significant decreases in the contractile response to field stimulation, bethanechol, and KCl. Thapsigargin (5-40 microM) had no effect on the contractile responses of bladder strips isolated from control rabbits to field stimulation, bethanechol, or KCl. However, bladder strips isolated from obstructed rabbits showed a significant concentration-dependent decrease in the contractile response to field stimulation in the presence of thapsigargin. Thapsigargin had no effect on the contractile responses of bladder strips isolated from obstructed rabbits to either bethanechol or KCl. In general, the data described in this study support our current hypothesis: as smooth muscle cells enlarge (hypertrophy) and the cell volume increases, there is an increased dependence on the release of intracellular calcium from the sarcoplasmic reticulum to mediate the contractile response to field stimulation.
Animals↗
The decompensated detrusor I: the effects of bladder outlet obstruction on the use of intracellular calcium stores.
PURPOSE: As in other smooth muscle groups, extracellular calcium influx as well as the release of calcium from intracellular storage sites or sarcoplasmic reticulum occur in response to receptor stimulation. The relative participation of extracellular influx versus intracellular release has recently been shown to be influenced by developmental stage and obstruction. Partial bladder outlet obstruction results in marked hypertrophy of the bladder and produces alterations in contractile function. To understand better how this contractile dysfunction after outlet obstruction is influenced by intracellular calcium handling we tested the effects of 2 drugs with known effects on the sarcoplasmic reticulum. MATERIALS AND METHODS: We evaluated ryanodine, which blocks the release of calcium from the sarcoplasmic reticulum, and thapsigargin, which blocks the ability of the sarcoplasmic reticulum to pump cytosolic calcium back into the storage sites. Rabbit bladders were obstructed for different periods, after which detrusor muscle strips were harvested and contractile performance was evaluated in the absence and presence of ryanodine and thapsigargin. RESULTS: In the early phases of outlet obstruction the release of intracellular calcium increased significantly. With prolonged obstruction and detrusor decompensation the intracellular storage sites lost the ability to contribute to the generation of contractile force. CONCLUSIONS: Alterations in the calcium handling ability of the smooth muscle cell appear to have an important role in the process of decompensation of bladder function in infravesical obstruction.
Animals↗
The decompensated detrusor II: evidence for loss of sarcoplasmic reticulum function after bladder outlet obstruction in the rabbit.
PURPOSE: While it may lack the classic morphological pattern in striated muscle systems, there is ample evidence that smooth muscle also contains sarcoplasmic reticulum. These intracellular storage sites release calcium into the cytosol to generate contractile force in response to various stimuli. A major component of the sarcoplasmic reticulum is an adenosine triphosphate dependent ion pump, which serves to drive free calcium out of the cytosol back into this intracellular reservoir. This ion pump serves to maintain the intracellular calcium storage sites, and also as a marker of the sarcoplasmic reticulum. MATERIALS AND METHODS: Muscle strip studies were performed to stratify the data into 3 major groups (controls, and compensated and decompensated obstructions) based on physiological performance. These were correlated with biochemical and molecular determinations of sarcoplasmic endoplasmic reticulum calcium, magnesium-adenosinetriphosphatase expression. RESULTS: Our results demonstrate a remarkable loss of sarcoplasmic endoplasmic reticulum calcium-adenosinetriphosphatase activity in the decompensated group and a moderate loss in the compensated group. CONCLUSIONS: These data provide molecular support for our previous physiological studies in which we demonstrated an important role for intracellular calcium storage and release with normal bladder smooth muscle function. These data strongly support our contention that contractile dysfunction in bladder smooth muscle following outlet obstruction is partially mediated by changes in the mechanisms of intracellular calcium homeostasis.
Animals↗
10-year experience with prenatal intervention for hydronephrosis.
PURPOSE: We evaluated clinical outcomes after attempted prenatal intervention in fetuses with hydronephrosis. MATERIALS AND METHODS: We retrospectively reviewed the histories of 10 fetuses considered for prenatal intervention between 1984 and 1993. One female and 8 male fetuses had bilateral hydroureteronephrosis and profound or progressive oligohydramnios, and 1 male fetus had massive progressive unilateral hydronephrosis. RESULTS: Shunt placement was not recommended and it was refused by the parents in 1 case each. Amniotic shunting was attempted in 8 fetuses between 22 and 28 weeks of gestation. Shunts were successfully placed with decreased hydronephrosis and increased amniotic fluid volume in 4 cases, while shunt placement was not technically possible in the remainder. Two shunts that retracted intra-abdominally at birth required laparotomy for retrieval. Postnatally all patients with shunts had compromised renal function. Of the 4 patients in whom attempts were unsuccessful 3 had mildly diminished renal function and 1 died of nonrenal causes (intraabdominal sepsis) on day 16 of life. No patient with a functioning shunt had postnatal pulmonary problems, whereas 3 without successful intervention had mild respiratory compromise. CONCLUSIONS: No definite advantage was noted in the small number of fetuses that underwent successful shunting. Successful shunt placement did not prevent renal insufficiency. The relief of oligohydraminos may benefit pulmonary function in some patients. The high technical failure and complication rates of in utero intervention should be considered before proceeding.
Female↗
Use of injectable fat to obstruct the urethra in rabbits.
Bulking agents have been injected to correct urinary incontinence for at least 15 years. The injection seeks to increase bladder outlet resistance by partially obstructing the urethra and thereby reduce urinary leakage in patients with stress urinary incontinence. Although the implant is effective and requires a shorter in-hospital stay than more traditional procedures, no ideal implant substance has been discovered. To assess the effectiveness of injected fat as a bulking agent, we injected small volumes of perivesical fat into the bladder neck in New Zealand White (NZW) rabbits and tested the effect on the bladder. In eight rabbits, we harvested perivesical fat and partially closed the urethral lumen with an initial injection. A second injection 1 month later completely closed the urethral lumen. We injected six other rabbits with similar volumes of saline as controls. Two weeks after the second injection, we measured micturition frequency, bladder weight, response to electrical field stimulation, and response to bethanecol in each group. Fat implants were present at the injection site in each case 4 weeks after the first injection. Rabbits receiving fat implants had increased micturition frequency, increased bladder weight, and increased response to bethanecol and field stimulation. Previous studies have demonstrated that these changes are characteristic of mild outlet obstruction in rabbits. Injected fat can be made to close the urethra and create bladder outlet obstruction in rabbits. The short-term success of fat as a bulking agent in this experiment is encouraging and suggests the need for longer term studies.
Adipose Tissue↗
Developmental aspects of excitation contraction coupling in urinary bladder smooth muscle.
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Animals↗
Developmental factors in the contractile response of rabbit urinary bladder: effect of anoxia and extracellular acidosis.
Previous studies have demonstrated that the mechanism of excitation contraction coupling changes with normal development in rabbit urinary bladder smooth muscle. The present study was designed to determine whether there were any differences in the effects of anoxia and extracellular acidosis in response to field stimulation, bethanechol and KCl between mature (8 weeks) and neonatal (3 days) rabbit bladder smooth muscle. Bladder smooth muscle strips from mature and neonatal New Zealand White rabbits were mounted in organ baths and bathed in oxygenated Tyrode's solution. Anoxia was produced by changing the gas mixture to 95% nitrogen/5% CO2 and the effects on contractility were determined at different times after initiation of anoxia. The extracellular acidosis was produced by decreasing the buffer's NaHCO3 concentration. We conclude that bladder smooth muscle does not exhibit an age-specific ability to counteract the effects of anoxia or acidosis as is seen in the developing rabbit myocardium. Instead it appears that the purinergic mechanisms of contraction are much more sensitive to the effects of anoxia or acidosis. Neonatal bladder smooth muscle exhibits a greater drop in contractility with anoxia or acidosis at low frequency (2 Hz) field stimulation; we attribute this to the fact that neonatal bladder smooth muscle has a greater purinergic component in its response to field stimulation. These differences in the responses to anoxia and pH reflect alternate mechanisms of pharmacologic activation, and not inherent differences in the biochemistry of the maturing smooth muscle.
Acidosis↗