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Biomedical subjects

Prem Puri

Publications and source records attributed to Prem Puri.

At least 91 records · Page 5Linked to original sources
PubMed2002

Acute renal damage in infants after first urinary tract infection.

Urinary tract infection (UTI) is one of the most common causes of unexplained fever in neonates. The aim of this study was to determine the incidence of urinary tract anomalies and acute renal damage in neonates who presented with first urinary tract infection in the first 8 weeks of life. We reviewed the records of 95 infants, who were hospitalised with UTI during a 6-year period (1994-1999). Patients with antenatally diagnosed hydronephrosis and incomplete radiological investigations were excluded from the study. Of the remaining 57 patients, 42 were boys and 15 girls. The mean age at diagnosis was 32 days (range 5-60 days). All patients underwent renal ultrasonography (US), voiding cystourethrogram (VCUG) and (99m)Tc-dimercaptosuccinic acid (DMSA) scan. Urinary tract abnormalities were detected in 20 (35%) patients. Vesicoureteral reflux (VUR) was found in 19 (33%) neonates, 7 girls and 12 boys. Acute cortical defects on DMSA scan were present in 19 kidneys of patients with VUR and in 25 of those without reflux. Only one-third of neonates after first symptomatic UTI had VUR. We recommend that US, VCUG, and DMSA scan should be routinely performed after the first UTI in infants younger than 8 weeks.

Acute Disease↗
PubMed2002

Demonstration of nitrergic and cholinergic innervation in whole-mount preparations of rabbit, pig, and human upper urinary tract.

To investigate the distribution of nitrergic and cholinergic innervation in rabbit, pig, and human upper urinary tract, (UUT) whole-mount preparations and frozen sections were stained with nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase and acetylcholinesterase (AChE) histochemistry. NADPH-diaphorase and AChE staining demonstrated two neuronal plexuses in the submucous and muscular layer of the UUT in all three species. The presence of nitrergic and cholinergic neuronal networks in the normal UUT suggests that autonomic innervation may play an important role in the transmission of ureteral peristalsis.

Adult↗
PubMed2002

Selective chemical ablation of the enteric plexus in mice.

Although genetically aganglionic mice such as piebald lethal and lethal spotted mice exhibit striking similarities to the human condition of Hirschsprung's disease (HD), the aganglionic segment is very short and always located in the distal part of the rectum. Topical application of benzalkonium chloride (BAC) to the rectum of rats has been reported to result in segmental aganglionosis. To induce chemical ablation of the enteric plexus in mice to produce an aperistaltic narrow segment simulating HD, 32 mice were divided into three groups: (1) abdominal (n=12), for sigmoid colon treatment; (2) rectal (n=10), for rectum treatment; and (3) controls (n=10). For groups 1 and 2, 0.1% BAC was applied to a 1-cm serosal surface of the bowel for 15 min. In the controls, isotonic saline was applied in this fashion. A detailed histologic examination was performed using hematoxylin and eosin staining and acetylcholinesterase histochemistry. Ten animals (9 in group 1 and 1 in group 2) died 1 to 9 weeks after BAC treatment. Autopsy revealed a narrow segment of bowel at the site of BAC treatment and marked dilatation of the bowel proximal to the narrow segment. The remaining animals were killed 12 weeks after BAC treatment. Histologic examination demonstrated normal myenteric and submucous plexuses in the controls, whereas there was a total lack of innervation in the BAC-treated segments.Topical application of BAC thus successfully produced a narrow aganglionic segment of bowel in normal mice. This model provides the basis for future studies to investigate the pathophysiology of HD and megacolon and for comparison with genetically aganglionic mice.

Animals↗
PubMed2002

Megacystis-microcolon-intestinal hypoperistalsis syndrome: evidence of intestinal myopathy.

We investigated small- and large-bowel specimens of three newborn infants presenting with the clinical and radiological symptoms of megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS). Conventional histological staining revealed marked thinning of the longitudinal muscle layer. Electron-microscopic investigations showed typical "central core" vacuolic degeneration of smooth-muscle-cells combined with proliferation of col lagen fibres. The expression of alpha-smooth-muscle actin was absent or markedly reduced in the circular and longitudinal muscle layers and muscularis mucosae compared to the normal controls. These findings suggest that the intestinal obstruction in MMIHS is due to an abnormality of the smooth-muscle cells.

Abnormalities, Multiple↗
PubMed2002

Angiotensin II type 2 receptor gene is not responsible for familial vesicoureteral reflux.

PURPOSE: The renin-angiotensin system has an important role in the development of the kidney and ureter. It has been reported that disruption of the angiotensin II type 2 receptor (AT2) gene leads to congenital anomalies of the kidney and ureter in mice, including vesicoureteral reflux. In humans a single base A to G transition at position -1332 in intron 1 (A-1332G) of the AT2 gene has been reported to occur significantly more often in patients with ureteropelvic junction obstruction and primary obstructive megaureter than in controls. We investigate the incidence of A-1332G transition in patients with primary familial vesicoureteral reflux to determine if AT2 gene is involved in pathogenesis of this disease. MATERIALS AND METHODS: We evaluated the incidence of A-1332G transition in 82 male and 110 female patients, 111 male and 124 female nonaffected family members from 88 families in which 2 or more members had primary vesicoureteral reflux, and 106 male and 107 female controls with no unselected for reflux status. Genomic DNA was extracted from whole blood samples. Polymerase chain reaction method modified for fluorescent detection was used to type all samples for the A-1332G variant. Furthermore, to identify mutations in the coding sequence of the AT2 gene, we selected 61 patients from different families as well as 15 controls with no vesicoureteral reflux status. RESULTS: The incidence of A-1332G transition in male patients with primary familial vesicoureteral reflux and controls was 33% (27 of 82 patients) and 38% (41 of 106 controls), respectively, and, the incidence of A-1332G substituted allele in female patients and controls was 47% (104 of 220 total alleles) and 50% (107 of 214 total alleles), respectively. Moreover, the transmission/disequilibrium test revealed no significant skewing of genotype transmission from mother to children. None of the 61 patients or 15 controls carried by mutations or polymorphisms in the coding sequence of the AT2 gene. CONCLUSIONS: Although the AT2 gene has been reported to have a role in developmental anomalies of the kidney and ureter, our data indicate that it is not involved in the pathogenesis of primary familial vesicoureteral reflux.

Angiotensin II↗
PubMed2002

Endoscopic treatment of vesicoureteral reflux: 11 to 17 years of followup.

PURPOSE: We review our 17-experience with endoscopic subureteral polytetrafluoroethylene injection for the treatment of primary vesicoureteral reflux in children. MATERIALS AND METHODS: We retrospectively reviewed the charts of 258 patients with primary vesicoureteral reflux who were treated with subureteral polytetrafluoroethylene injection from 1984 to 1990. RESULTS: The study included 205 girls and 53 boys between 3 months and 14 years old (median age 6 years). Of the patients 92 had unilateral vesicoureteral reflux, 129 had bilateral reflux and 37 had a refluxing duplex system including 6 with bilateral duplex systems. Endoscopic treatment by subureteral polytetrafluoroethylene injection was performed in 393 ureters. Reflux was corrected in 302 ureters (76.8%) after a single injection. Injection failed to stop reflux in 7 ureters (7 patients) and reimplantation was required. Patients were followed from 11 to 17 years with a mean followup plus or minus standard deviation of 13.5 +/- 3.4 years. Four patients were either lost to followup or parents refused to let them undergo voiding cystourethrography. Voiding cystourethrography in 247 patients with 379 ureters revealed that 360 ureters (95%) remain free of reflux whereas reflux recurred in 19 ureters (5%). Of these 19 ureters reflux was grade I or II in 13 for which no treatment was given and reflux was grade III or IV in 6, which required repeat injection. No untoward effects were seen in any of these patients with use of polytetrafluoroethylene as an injectable biomaterial. CONCLUSIONS: Endoscopic subureteral polytetrafluoroethylene injection is a simple and effective outpatient procedure for in the treatment of vesicoureteral reflux. No long-term morbidity was observed in our patients with small amounts of injectable polytetrafluoroethylene.

Adolescent↗
PubMed2002

Endoscopic management of vesicoureteral reflux: does it stand the test of time?

Endoscopic subureteral injection of tissue-augmenting substances, a 15-minute outpatient procedure has become an alternative to long-term antibiotic prophylaxis and surgical intervention in the treatment of vesicoureteral reflux (VUR) in children. This paper reviews the long-term results of endoscopic treatment of reflux using various tissue-augmenting substances presently available. In terms of effectiveness and long-term successful results, polytetrafluoroethylene is still the most reliable injectable material for the endoscopic treatment of VUR.

Biocompatible Materials↗
PubMed2002

Nitric oxide, enhanced by macrophage-colony stimulating factor, mediates renal damage in reflux nephropathy.

BACKGROUND: Reflux nephropathy (RN) is a major cause of end-stage renal failure in children and young adults. Nitric oxide (NO) is an important mediator of tissue injury and inflammation. NO production is enhanced by hematopoietic growth factor including macrophage colony stimulating factor (M-CSF). M-CSF plays a pivotal role in the development of nephritis via macrophage activation. The aim of this study was to investigate the expression of inducible NO synthase (iNOS) and M-CSF in the refluxing kidney, in order to further understand the pathogenesis of RN. METHODS: The kidney specimens from 6 patients with severe RN and 6 controls were examined by NADPH-diaphorase histochemistry and immunohistochemistry using ABC method with anti-M-CSF antibody. Double staining using NADPH-diaphorase histochemistry/M-CSF immunohistochemistry and M-CSF/iNOS fluorescence immunohistochemistry also was performed. In situ hybridization was performed using digoxigenin labeled M-CSF specific probe. RT-PCR was performed to evaluate the relative amount of iNOS mRNA expression. Apoptosis was determined using the in situ end-labeling technique. RESULTS: The most striking difference between tissues from RN patients and controls was the marked increase in NADPH-d activity, iNOS immunoreactivity and mRNA and M-CSF immunoreactivity and mRNA expression in the kidneys of RN patients, particularly in the distal tubules, collecting system. Apoptotic cells were markedly increased in RN compared to controls. CONCLUSIONS: Our findings suggest that the increase in M-CSF-stimulated local production of nitric oxide may be a major mediator in the development of reflux nephropathy.

Adolescent↗
PubMed2002

Upregulation of angiotensin II receptors in reflux nephropathy.

BACKGROUND/PURPOSE: Reflux nephropathy (RN) is the cause of end-stage renal failure in 3% to 25% of children and in 10% to 15% of adults. Angiotensin II (Ang II) is a biologically active peptide of the renin-angiotensin system (RAS), which has a profound role not only in the urinary tract-development, but also in the response of the urinary tract to injury. The actions of Ang II are mediated through 2 receptors, angiotensin type 1 receptor (AT(1)R) and angiotensin type 2 receptor (AT(2)R). The aim of this study was to examine the expression of AT(1)R and AT(2)R in severe reflux nephropathy. METHODS: The kidney specimens from 8 patients (age range, 6 months to 14 years) with severe reflux nephropathy secondary to primary high-grade vesicoureteral reflux (VUR) were obtained at the time of nephrectomy. Control material included normal kidney specimens obtained from 3 adult patients during partial nephrectomy for an incidentaloma. Soluble enzyme immunohistochemistry was carried out using polyclonal antibodies to AT(1)R and AT(2)R. Reverse transcriptase polymerase chain reaction (RT-PCR) was performed to evaluate the relative amount of AT(1)R and AT(2)R mRNA. RESULTS: In the refluxing kidney there was strong AT(1)R immunoreactivity in the glomerulus and proximal tubules and moderate to weak immunoreactivity in the distal tubules. There was strong AT(2)R immunoreactivity in the distal tubules with absent or weak staining in the glomerulus and proximal tubules. In the control kidneys, homogeneous weak AT(1)R immunoreactivity was shown in the proximal and AT(2)R in the distal tubules, respectively. RT-PCR showed strong AT(1)R and AT(2)R expression in the refluxing kidneys compared with controls. CONCLUSIONS: Upregulation of angiotensin II receptors in reflux nephropathy suggests that Ang II is involved in the pathogenesis of the renal parenchymal damage in patients with RN. Pharmacologic blockade of angiotensin II receptors may be helpful in preventing renal fibrosis associated with reflux nephropathy.

Adolescent↗
PubMed2002

Abnormalities of C-Kit-positive cellular network in isolated hypoganglionosis.

BACKGROUND/PURPOSE: C-Kit-positive interstitial cells of Cajal (ICCs) have a key role in the normal motility function and development of the bowel. They are pacemaker cells, which facilitate active propagation of electrical events and neurotransmission in the bowel wall. ICCs are present in the bowel as myenteric ICCs (ICC(my)S) and muscular ICCs (ICC(mus)S). The aim of this study was to examine the distribution of c-Kit-positive ICCs and their relationship to the autonomic intrinsic innervation in bowel specimens from patients with isolated hypoganglionosis. METHODS: Full-thickness large bowel specimens were obtained from 6 patients with hypoganglionosis and from 4 patients during bladder augmentation (controls). Frozen sections and whole-mount preparations were stained using c-Kit immunohistochemistry, nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase, and acetylcholinesterase (AChE) histochemistry and evaluated using normal brightfield and confocal laser scanning microscopy. RESULTS: NADPH-diaphorase and AChE histochemistry findings showed characteristic histologic features of hypoganglionosis, eg, sparse and small myenteric ganglia and low or absent AChE activity in the lamina propria. Myenteric plexus in the normal bowel was surrounded by a dense network of c-Kit-positive ICC(my)S, whereas in hypoganglionosis sparse isolated ICC(my)S were found. C-Kit-positive ICC(mus)S were reduced markedly in the longitudinal and circular muscle layer and at the innermost part of the circular muscle in hypoganglionosis. CONCLUSION: Deficient expression of c-Kit-positive myenteric and muscular ICCs in the hypoganglionic colon may contribute to the motility dysfunction in the affected bowel.

Acetylcholinesterase↗
PubMed2002

Glucocorticoid receptor gene expression in the hypoplastic lung of newborns with congenital diaphragmatic hernia.

BACKGROUND/PURPOSE: In experimentally produced congenital diaphragmatic hernia (CDH), antenatal glucocorticoids have been shown to improve morphologic and biochemical lung immaturity and normalize the thickened pulmonary vascular wall. The action of glucocorticoids on a target tissue is mediated by glucocorticoid receptors (GRs), which have 2 isoforms; GRalpha binds glucocorticoids and acts as a ligand-dependent transcription factor, and GRbeta does not bind glucocorticoids and acts as an inhibitor of GRalpha. The aim of this study was to examine the expression of GR gene and its isoforms in the CDH lung. METHODS: RNA was extracted from archival lung tissue of 11 patients (mean age, 3.5 days) with CDH. Five age-matched newborns (mean age, 13.5 days) with sudden death syndrome served as control. Reverse transcription (RT) and polymerase chain reaction (PCR) was performed using primers specific to the common region of GR, GRalpha, and GRbeta. Soluble enzyme immunohistochemistry was carried out using polyclonal antibodies to GRalpha. RESULTS: Relative mRNA levels of GR, GRalpha, and GRbeta as detected by RT-PCR were increased significantly in CDH lung compared with controls. GRalpha immunoreactivity confined only to the cytoplasm of the cells was markedly increased in the epithelium and interstitial cells in the CDH lung compared with controls. CONCLUSION: The findings of increased mRNA expression of GR and particularly of its isoform GRalpha in the CDH lung suggests that GR may play an important role in regulating target cell responsiveness to glucocorticoids in the hypoplastic lung.

Gene Expression↗
PubMed2002

Effect of mechanical ventilation on the pulmonary expression and production of elastin in nitrofen-induced diaphragmatic hernia in rats.

BACKGROUND/PURPOSE: Hypolastic lung in congenital diaphragmatic hernia (CDH) shows markedly thickened alveolar walls, increased interstitial tissue, and markedly diminished alveolar air space, showing morphologic immaturity. Decrease in lung compliance and distensibility often is seen in human CDH as well as experimentally produced CDH. Collagen and elastin, critical components of the lung connective tissue, have been suggested to have important influence on lung compliance and maximal expansion. The barotrauma caused by mechanical ventilation is known to produce structural changes in the pulmonary architecture. The aim of this study was to investigate the expression and production of elastin in the lung in newborn rats with CDH during mechanical ventilation. METHODS: CDH was induced in rat embryos after administration of nitrofen to pregnant dams on day 9.5 of gestation. Cesarean section was performed on day 21 of gestation. The newborn rats were intubated using a 24-gauge Teflon catheter. After ligation of the umbilical cord, the intubated animals were transferred immediately to a warm plate and connected to a modified ventilator. Ventilation was continued for a maximum of 6 hours. The relative amount of soluble elastin in the lung was assessed using an enzyme-linked immunosorbent assay (ELISA) technique. Reverse transcription polymerase chain reaction (RT-PCR) was performed to evaluate the relative amount of tropoelastin mRNA expression in the lung. RESULTS: Elastin mRNA in the CDH lung was increased significantly (P <.01) at one hour after ventilation compared with ventilated controls. Elastin protein significantly increased in the CDH lung at one hour (P <.01) and 6 hours (P <.01) after starting ventilation compared with controls. CONCLUSION: The data show that during mechanical ventilation, elastin production is increased significantly in the CDH lung, and this may further affect lung compliance.

Animals↗
PubMed2002

Antenatal dexamethasone enhances endothelin-1 synthesis and gene expression in the heart in congenital diaphragmatic hernia in rats.

BACKGROUND/PURPOSE: Although high levels of endothelin-1 (ET-1) in plasma may be relevant in certain pathophysiologic states, such as pulmonary hypertension accompanying congenital diaphragmatic hernia (CDH), experimental evidence favors a local, paracrine, or autocrine role for ET-1 in most tissues. Evidence of ET-1 production has been documented in fetal heart tissue where it exerts growth-enhancing and mitogenic effects. ET-1 also has a potent positive inotrope action on cardiac muscle. ET-1 -/- homozygous mice display a wide variety of cardiac anomalies, which also are features of the human and of the experimental CDH. Autopsy reports have shown that total heart weight is reduced significantly in the presence of CDH, and animal models have documented the presence of cardiac hypoplasia associated with CDH. Experimental and clinical studies have shown that prenatal exposure to corticosteroids improves cardiovascular function in the immediate newborn period. The aim of this study was to determine cardiac gene expression of ET-1 and of its receptor ET(A) and the cardiac ET-1 content in the heart of nitrofen-induced CDH in rats and to evaluate the effect of antenatal Dexamethasone (Dex) treatment. METHODS: A CDH model was induced in pregnant rats after administration of 100 mg of nitrofen on day 9.5 of gestation (term, 22 days). Dex (0.25 mg/kg) was given by intraperitoneal injection on days 18.5 and 19.5 of gestation. Cesarean section was performed on day 21 of gestation. The fetuses were divided into 3 groups: group I, control (n = 8); group II, nitrofen-induced CDH (n = 8); group III, nitrofen-induced CDH with antenatal Dex treatment (n = 8). ET-1 protein was measured using ELISA. RT-PCR was performed to evaluate the relative amount of ET-1 and ET(A) mRNA expression. RESULTS: There was a reduction in ET-1 mRNA (P <.05) and in ET(A) mRNA (P <.01) in the heart of CDH group compared with controls. ET-1 protein level also was reduced in heart of CDH compared with controls. Antenatal Dex treatment increased significantly both ET-1 mRNA and protein levels in the heart of CDH animals (P <.05 and P <.01, respectively). CONCLUSIONS: The reduced cardiac ET-1 gene expression and ET-1 synthesis may be responsible for the heart hypoplasia associated with CDH. Prenatal corticosteroids increase the cardiac production of ET-1, and this may enhance heart growth and cardiac inotropism at birth.

Animals↗
PubMed2002

Fate of the retained ureteral stump after upper pole heminephrectomy in duplex kidneys.

PURPOSE: We review the long-term outcome of retained ureteral stumps in children undergoing heminephrectomy for nonfunctioning upper pole moieties in duplex kidneys. MATERIALS AND METHODS: The medical records of 50 patients who underwent 50 upper pole heminephrectomies for a nonfunctioning upper pole moiety of a duplex kidney between January 1990 and December 2000 were reviewed retrospectively. RESULTS: Median patient age at heminephrectomy was 2.5 years (range 3 weeks to 16.5 years) and median followup was 6 years (range 1 to 11). Indications for heminephrectomy in the 50 renal units were obstructive ureterocele in 25 (50%) cases, ectopic ureter in 15 (30%), obstructive megaloureter in 5 (10%) and reflux nephropathy in 5 (10%). A total of 48 (96%) of the corresponding ureters were taken down as low as possible and transfixed through the heminephrectomy incision. Residual stump excision was required in 5 (10%) of the 50 units for recurrent urinary tract infection due to vesicoureteral reflux. CONCLUSIONS: Our long-term followup suggests that the majority of patients with residual ureteral stumps after upper pole heminephrectomy do not require stump resection.

Adolescent↗
PubMed2002

Long-term results of primary avulsion of posterior urethral valves using a Fogarty balloon catheter.

PURPOSE: Posterior urethral valves are the most common cause of bladder outlet obstruction in infancy and cause renal failure in 25% to 30% of these children before adolescence. Transurethral ablation under direct vision is the most commonly used method of treatment for posterior urethral valves. Since 1987 we have used a Fogarty balloon catheter for primary avulsion of the posterior urethral valves in our patients. We evaluate the long-term results of this technique. MATERIALS AND METHODS: During 14 years (1987 to 2001) 35 consecutive patients with posterior urethral valves underwent primary valve avulsion using a Fogarty balloon catheter. In 21 patients diagnosis was made prenatally, while the remaining 14 patients (6 newborns and 8 children with median age of 6 months) presented with urinary tract infection and renal failure. Vesicoureteral reflux was present in 22 (63%) of the 35 patients involving 34 renal units. Primary valve avulsion was performed using a 4Fr Fogarty balloon catheter under fluoroscopic control in all patients. Postoperative voiding cystourethrography was done 2 weeks after valve avulsion. RESULTS: None of the patients demonstrated any evidence of periurethral extravasation during the procedure. Postoperative voiding cystourethrography showed effective relief of valvular obstruction and good urethral drainage in 34 patients. In the remaining patient residual valve required transurethral ablation under direct vision. Vesicoureteral reflux resolved spontaneously in 12 of the 22 (54%) patients (20 renal units) and after an antireflux procedure in 4 (7 units). Two patients (3 renal units) are on antibiotic prophylaxis and 4 underwent nephroureterectomy for nonfunctioning dysplastic kidneys. At followup (1 to 14 years) all patients demonstrated a good urinary stream with no evidence of urethral stricture. Renal function did not improve in 5 (14%) of the 35 patients, 1 of whom has already undergone renal transplantation and another is awaiting transplantation. CONCLUSIONS: Fogarty balloon catheter technique is a simple, safe and effective alternative to primary endoscopic transurethral ablation of posterior urethral valves.

Adolescent↗
PubMed2002

Risk factors for the development of renal parenchymal damage in familial vesicoureteral reflux.

PURPOSE: The association of vesicoureteral reflux, urinary tract infection and renal parenchymal damage is well known. Recently, it was reported that the angiotensin converting enzyme (ACE) DD gene polymorphism is a risk factor for renal damage in patients with congenital uropathies and high grade vesicoureteral reflux. We determine risk factors associated with renal damage in patients with primary familial vesicoureteral reflux. MATERIALS AND METHODS: We reviewed the medical and radiological records of 188 siblings with primary vesicoureteral reflux comprising 88 families. We excluded from study 26 patients because of insufficient clinical information. Mean age at diagnosis of the remaining 92 girls and 70 boys was 2.3 years. Reflux was diagnosed by voiding cystourethrography and dimercapto-succinic acid scan was performed to evaluate renal scarring. The ACE I/D polymorphism was detected by polymerase chain reaction. For multivariate analysis risk factors, such as gender, age at diagnosis, history of urinary tract infection, reflux grade and ACE genotype, were analyzed in logistic regression model. RESULTS: Renal parenchymal damage was detected in 45 (28%) of the 162 siblings. Multivariate analysis revealed that reflux grade (p <0.0001), history of urinary tract infection (p = 0.010) and age at diagnosis (p = 0.044) were the most significant independent risk factors for renal parenchymal damage. Angiotensin converting enzyme genotype and gender were not significant. In univariate analysis ACE DD genotype significantly linked to grades IV and V reflux (p = 0.007) rather than renal parenchymal damage (p = 0.284). CONCLUSIONS: In primary familial vesicoureteral reflux, history of urinary tract infection, reflux grade, and age at diagnosis are the most important risk factors for renal parenchymal damage. ACE DD genotype is not associated with renal damage in familial vesicoureteral reflux.

Child↗
PubMed2002

Altered cytoskeleton in smooth muscle of aganglionic bowel.

CONTEXT: Intestinal motility is under the control of smooth muscle cells, enteric plexus, and hormonal factors. In Hirschsprung disease (HD), the aganglionic colon remains spastic or tonically enhanced and unable to relax. The smooth muscle cell's cytoskeleton consists of proteins or structures whose primary function is to link or connect protein filaments to each other or to the anchoring sites. Dystrophin is a subsarcolemmal protein with a double adhesion property, one between the membrane elements and the contractile filaments of the cytoskeleton and the other between the cytoskeletal proteins and the extracellular matrix. Desmin and vinculin are functionally related proteins that are present in the membrane-associated dense bodies in the sarcolemma of the smooth muscle cells. OBJECTIVE: To examine the distribution of the cytoskeletal proteins in the smooth muscle of the aganglionic bowel. DESIGN: Bowel specimens from ganglionic and aganglionic sections of the colon were collected at the time of pull-through surgery from 8 patients with HD. Colon specimens collected from 4 patients at the time of bladder augmentation acted as controls. Anti-dystrophin, anti-desmin, and anti-vinculin antibodies were used for fluorescein immunostaining using confocal laser scanning microscopy. RESULTS: Moderate to strong dystrophin immunoreactivity was observed at the periphery of smooth muscle fibers in normal bowel and ganglionic bowel from patients with HD, whereas dystrophin immunoreactivity was either absent or weak in the smooth muscle of aganglionic colon. Moderate to strong cytoplasmic immunostaining for vinculin and desmin was seen in the smooth muscle of normal bowel and ganglionic bowel from patients with HD, whereas vinculin and desmin staining in the aganglionic colon was absent or weak. CONCLUSION: This study demonstrates that the cytoskeletal proteins are abundant in the smooth muscle of normal bowel, but are absent or markedly reduced in the aganglionic bowel of HD. As cytoskeletal proteins are required for the coordinated contraction of muscle cells, their absence may be responsible for the motility dysfunction in the aganglionic segment.

Cytoskeletal Proteins↗