Megacystis microcolon intestinal hypoperistalsis syndrome with bilateral duplicated systems

A 29-year-old multigravida woman presented for her second prenatal ultrasound evaluation at 30 weeks of gestation. The study showed a female fetus, bilateral duplicated systems with severe hydronephrosis in the upper pole moieties and a massively distended bladder. Initial interpretation suggested ectopic/obstructing bilateral ureteroceles. To evaluate these findings further, a prenatal magnetic resonance imaging scan was obtained, documenting the absence of ureteroceles. The presumptive diagnosis of megacystis microcolon intestinal hypoperistalsis syndrome was made. After birth, contrast enema confirmed the presence of microcolon. This appears to be the first reported case of megacystis microcolon intestinal hypoperistalsis syndrome with bilateral duplex systems evaluated with prenatal magnetic resonance imaging.     

Autonomic innervation of the intestine from a baby with megacystis microcolon intestinal hypoperistalsis syndrome: I. Immunohistochemical study

A typical case of megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) is reported. The patient, an infant girl, was fed only by total intravenous nutrition and is now 3 years old. The distribution of several gut peptides was examined in the resected small intestine using an immunohistochemical method. Vasoactive intestinal polypeptide (VIP) and peptide histidine methionine (PHM)-containing nerve fibers were decreased; however, substance P- and leucine enkephalin (Leu-ENK)-containing fibers were increased. The imbalance between several kinds of gut peptides might be one the causes of aperistalsis in MMIHS. This is the first report about the gut peptides of MMIHS.     

Autonomic innervation of the intestine from a baby with megacystis microcolon intestinal hypoperistalsis syndrome: II. Electrophysiological study

The pattern of spontaneous activity and innervation of the stomach, small intestine, and bladder obtained from a patient with megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) was studied in vitro, using tension recording and microelectrode techniques. We found that, compared with findings in the controls, autonomic inhibitory input to the smooth muscle cells of the small intestine was significantly decreased.     

Alterations in smooth muscle contractile and cytoskeleton proteins and interstitial cells of Cajal in megacystis microcolon intestinal hypoperistalsis syndrome

Background/Purpose: Megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) is characterized by decreased or absent peristalsis. Gastrointestinal motility depends on the enteric nervous system, smooth muscle cells (SMCs), and the interstitial cells of Cajal (ICCs). Contractile and cytoskeleton proteinase are important structural and functional components of SMCs. The aim of study was to examine the expression of contractile and cytoskeleton proteins in SMCs and distribution of ICCs in MMIHS bowel. Methods: Full-thickness bowel specimens were obtained from 4 infants with MMIHS and 4 controls. Specimens were processed as whole-mount preparations and frozen and paraffin sections. Combined staining of NADPH-d histochemistry/c-kit immunohistochemistry, single and double immunohistochemistry using [alpha ]-smooth muscle actin ([alpha ]-SMA), calponin (CALP), caldesmon (CALD), desmin (DES), protein gene product 9.5 (PGP 9.5) and c-kit antibodies were performed and examined using light and confocal scanning microscopy. Results: [alpha ]-SMA, CALP, CALD, and DES immunoreactivity were reduced markedly in MMIHS bowel compared with controls. Combined NADPH/c-kit staining showed dense network of ICCs around myenteric plexus in MMIHS bowel. In contrast, the intramuscular ICCs either were absent or reduced in MMIHS bowel. Conclusions: Marked reduction of contractile and cytoskeleton proteins in SMCs combined with reduced expression of intramuscular ICCs in the gut may be responsible for the motility dysfunction in MMIHS. J Pedriatr Surg 38:749-755. [copy ] 2003 Elsevier Inc. All rights reserved.     

Contents and effects of substance P and vasoactive intestinal polypeptide in the bladder of rats with and without infravesical outflow obstruction

The concentrations of substance P and vasoactive intestinal polypeptide (VIP) were determined in the upper, middle, and lower part of the bladder of rats with and without infravesical outflow obstruction. In the obstructed animals there was a significant increase in bladder weight and the total amounts of substance P and VIP were increased. However, the concentrations of substance P were significantly lower than in the control bladders. The concentrations of VIP, on the other hand, were significantly higher in the middle and lower parts of obstructed bladders than in the controls. In isolated strips of the normal and obstructed bladders VIP had neither contractile nor relaxant effects. The peptide had no effect on electrically induced contractions. Substance P produced concentration-dependent contractions in both normal and obstructed bladders. However, obstructed bladders were significantly less sensitive than controls. It is concluded that the bladder instability seen in rats with infravesical outflow obstruction cannot be explained only in terms of changes in the bladder content of substance P or VIP.     

Interstitial cells of Cajal in the human normal urinary bladder and in the bladder of patients with megacystis-microcolon intestinal hypoperistalsis syndrome

OBJECTIVE: To investigate the distribution of c-kit-positive interstitial cells of Cajal (ICCs) in normal bladder and bladders from patients with megacystis-microcolon-intestinal peristalsis syndrome (MMIHS, a rare congenital and generally fatal cause of functional intestinal obstruction in the newborn), the most characteristic feature of which is abdominal distension caused by a distended unobstructed urinary bladder. PATIENTS AND METHODS: Full-thickness bladder specimens were obtained from four infants with MMIHS and four controls, and processed as paraffin-wax and frozen sections. Sections were assessed using single immunohistochemistry with monoclonal and polyclonal anti-c-kit antibodies. Anti-alpha-smooth muscle actin (SMA) antibody was used to investigate the contractile apparatus in smooth muscle cells of the urinary bladder. Specimens were examined using light and confocal scanning microscopy. RESULTS: There were many c-kit positive ICCs in the normal urinary bladder, appearing as small, long, bipolar cells with only two long and several short processes. In contrast, ICCs were absent in the MMIHS bladder. alpha-SMA immunoreactivity was lower in MMIHS urinary bladder than in control sections. CONCLUSION: This study shows for the first time the presence of c-kit-positive ICCs in the normal human urinary bladder. The lack of ICCs in the MMIHS bladder may contribute to the voiding dysfunction in this disease.     

Indoramin in the treatment of prostatic bladder outflow obstruction.

A series of 40 patients took part in a double-blind, placebo-controlled trial of indoramin in prostatic bladder outflow obstruction. Patients were assessed clinically and urodynamically before and after 4 weeks' treatment. Significant improvement was seen in nocturia, volume voided, flow rates and residual urine. The drug was well tolerated, although 7 patients on treatment and 7 on placebo noted side effects. These results suggest that indoramin may be a useful agent in the symptomatic management of bladder outflow obstruction.     

Sphincterometry in the diagnosis of male bladder outflow obstruction.

Pressure patterns recorded during urethral sphincterometry in 281 male patients have been analyzed and measurements of prostatic length, peak, plateau height and pressure area have been made. These parameters show significant correlations with the established pressure-flow index of urethral resistance. Sphincterometry is a useful adjunct to the established urodynamic techniques for the diagnosis of bladder outflow obstruction in the male patient.     

Bladder instability and denervation in patients with bladder outflow obstruction

In vitro pharmacological studies were performed on endoscopic detrusor biopsies from patients with bladder outflow obstruction. Urodynamic studies had been undertaken to detect the presence of bladder instability. Muscle strips from patients with instability demonstrated supersensitivity to acetylcholine and reduction in nerve mediated responses, as compared with strips from stable bladders. These changes are interpreted as suggesting the presence of cholinergic denervation in obstructed patients with bladder instability.     

Indoramin--an effective new drug in the management of bladder outflow obstruction

There is a need for symptomatic relief in some patients with bladder outflow obstruction. The alpha blocker indoramin was tested in a prospective, double-blind, placebo-controlled trial. Thirty men were given indoramin or placebo. Flow rates and cystometrograms were performed before inclusion and at the end of 8 weeks' treatment. Indoramin gave significant relief of symptoms and dramatically improved peak flow rates. There were three withdrawals because of adverse effects and two withdrawals in the placebo group because of retention. Other side effects were either minor or transient.     

Effects of long-term partial outflow obstruction on bladder function in the rat

The effects of chronic partial outflow obstruction in rats were investigated. The urethra of male rats was partially obstructed for 3 or 6 months and bladder function was compared with that of age-matched controls. Bladder function was studied in vivo by infusion cystometry and in vitro by measuring the response of bladder muscle strips to stimulation. Cystometrograms of outflow-obstructed bladders were categorized into three types: type 1 was equivalent to a normal bladder; type 2 was characterized by large capacity, enhanced voiding pressure, and some residual urine; type 3 had the largest capacity, an impaired voiding pressure, and considerable residual volume (overflow-type of incontinence). The type 3 bladder was the most frequently observed type in rats obstructed for 6 months. Bladder weight increased significantly in rats with outflow obstruction. When five in vivo cystometric parameters (pressure at which micturition was induced, capacity, maximum voiding pressure, voided urine volume, and residual urine volume) were analyzed according to duration of obstruction, only two parameters (capacity and residual urine volume) in rats obstructed for 6 months differed significantly from those in age-matched controls. Evaluation of these values according to cystometric type showed a significant deterioration in four of five parameters in type 3 bladders. Contractile responses of the bladder in vitro to field stimulation, bethanechol, ATP, and KCI were significantly impaired in those obstructed for 3 or 6 months. When in vitro responses were analyzed according to the classification of cystometric type, deterioration of contractility was confirmed in both types 2 and 3 bladders. The present animal model of outflow obstruction can serve as a model of benign prostatic hyperplasia in humans. © 1996 Wiley-Liss, Inc.     

Collagen content in the rat urinary bladder subjected to infravesical outflow obstruction

Collagen content was determined in the detrusor muscle from control rats and rats subjected to infravesical outflow obstruction for periods of 3 days to 4 months. During the 1st 6 weeks of obstruction the detrusor weight increased 12-fold. The total amount of detrusor collagen increased by a factor of 4, while the concentration of collagen decreased to 1/3 of the initial concentration. A longer period of obstruction, 4 months, did not further affect detrusor weight or collagen content or concentration. Ultrastructurally, both normal and hypertrophic detrusor showed a great number of collagen fibrils (probably synthetized by fibrocytes) between the smooth muscle bundles. Collagen fibrils (probably synthesized by the smooth muscle cells) could also, although less frequently, be found within the bundles. The decreased collagen concentration in the hypertrophic detrusor could largely be explained by a coalescence of the smooth muscle bundles resulting in a relative increase of this tissue component.     

P－Q图及A－G图诊断前列腺增生性膀胱出口梗阻

对１０８例临床拟诊为前列腺增生症患者进行压力－流率测定，应用Ｐ－Ｑ图诊断膀胱出口梗阻（ＢＯＯ），着重阐述诊断方法及价值，并与Ａ－Ｇ图诊断结果相比较．表明Ｐ－Ｑ图在ＢＯＯ诊断及其疗效评价等方面均具有重要价值，值得临床推广应用。     

Differential expression of bladder neurotrophic factor mRNA in male and female rats after bladder outflow obstruction

PURPOSE: We validated a male rat model of bladder outflow obstruction and compared the expression of bladder neurotrophic factor mRNA in male and female rats 6 weeks after bladder outlet obstruction. MATERIALS AND METHODS: We examined the proximal urethra in male Wistar rats. Urethral lumen reducing ligatures were placed in 15 females and 19 males, while 10 male and 10 female controls underwent sham surgery. Awake cystometry was performed 6 weeks after surgery. Ribonuclease protection assay was used to measure changes in bladder neurotrophic factor mRNA expression in the 2 sexes. RESULTS: Average bladder capacity in rats with bladder outlet obstruction increased 3-fold in males and 4.4-fold in females compared with controls, while bladder weight increased 2.2 and 4.3-fold, respectively. Filling and threshold pressure increased significantly and nonvoiding bladder contractions were recorded in 100% of female and 80% of male rats with bladder outlet obstruction. An 8-fold increase in bladder brain derived neurotrophic factor mRNA was noted in each sex after obstruction. A 2-fold increase in bladder nerve growth factor mRNA after obstruction was only observed in females. CONCLUSIONS: This male rat model of bladder outlet obstruction was created by placing lumen reducing ligatures at the urethrovesical junction. The dramatic increase in bladder brain derived neurotrophic factor mRNA expression and differential expression of nerve growth factor mRNA in male and female rats with bladder outlet obstruction suggest that additional neurotrophic factors may contribute to the lower urinary tract neuroplasticity associated with bladder outlet obstruction and this contribution may be gender dependent.     

Changes in the nervous control of the rat urinary bladder induced by outflow obstruction

The influence of bladder outflow obstruction on the peripheral nervous control of the detrusor was investigated in female rats. The obstruction was performed by means of partial urethral ligation. The influence of exogenously applied drugs and electrical field stimulation was investigated after obstruction for 6 weeks. The content of noradrenaline and choline acetyltransferase was also determined as well as the density of alpha-adrenoceptors. A significant decrease of the contractile response to alpha-adrenoceptor stimulation was found in the obstructed bladders when compared to normal controls. Also the density of alpha-adrenoceptors decreased in the obstructed bladders. The concentrationresponse relationship to carbachol remained unchanged, and neither were any changes seen in the relation between the cholinergic and noncholinergic components of the electrically induced, nerve-mediated contractile response. A rightward shift of the frequencyresponse curve for the obstructed bladders was found with 50% of the maximum response occurring at 13 Hz compared to 4 Hz in the control preparations. The total amount of both noradrenaline and choline acetyltransferase had increased after 6 weeks of obstruction, but owing to the pronounced degree of hypertrophy of the bladder wall the concentrations were only approximately 30% of those in the control bladders, which also was the case after 1 and 3 weeks of obstruction. It is concluded that changes in the peripheral nervous control of the rat bladder seem to occur secondary to outflow obstruction, but also that some of the changes observed might be due to factors unrelated to innervation and receptor-mediated functions. Whether the decreased alpha-adrenoceptor mediated influence seen in the presence of obstruction might reflect a generally decreased adrenergic influence in the obstructed bladder remains to be established.