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Biomedical subjects

J Mandell

Publications and source records attributed to J Mandell.

At least 55 records · Page 3Linked to original sources
PubMed1993

Fetal compensatory renal growth due to unilateral ureteral obstruction.

To determine whether fetal compensatory renal growth occurs in response to early gestational unilateral renal obstruction and to help elucidate the characteristics of this response, a fetal lamb model was developed in which unilateral ureteral obstruction was created at 60 days of gestation (term 135 to 140 days) and the effects of the obstruction were studied at varying periods thereafter. Kidneys were retrieved at 2 weeks (75 days in 3 cases), 5 weeks (95 days in 4) and 10 weeks (135 days in 9) after obstruction, weighed and preserved for histology and biochemical studies. Deoxyribonucleic acid (DNA), ribonucleic acid and protein were quantitated using standard assays. Morphometric studies to estimate glomerular number were performed using standard stereological methods. Contralateral kidney weight was increased compared to normals in 55 cases at all ages. The relative difference increased from 75 to 95 days. The fractional increase at 135 days (49.5%, p < 0.001 versus normal) was not different from 95 days (46.4%, p = 0.87), indicating that growth rate acceleration occurred predominantly before 95 days. Total renal DNA was increased above normal at each time point, with an ultimate increment proportionate to weight. Protein concentration was unchanged, suggesting that weight increase was not due to changes in renal water. Protein/DNA ratios were unchanged, indicating a predominantly hyperplastic process. Ribonucleic acid/DNA ratios decreased, possibly indicating a high rate of proliferation. Total glomerular number at term did not increase with in utero compensatory renal growth. Unilateral ureteral obstruction created early in gestation produced compensatory renal growth of the intact kidney in the fetal lamb. This process demonstrates an early but transient growth rate acceleration, hyperplasia and no increase in total glomerular or nephron number. The occurrence of compensatory renal growth in the fetal kidney with minimal functional renal demand would suggest that its mechanisms may be independent of functional demand. This model is unique and well suited to study compensatory renal growth.

Adaptation, Physiological↗
PubMed1993

Sonography with sonicated albumin in the detection of vesicoureteral reflux.

The primary radiological procedures for diagnosing vesicoureteral reflux are fluoroscopic and radionuclide cystography. Ultrasonography, with no ionizing radiation, would be useful as a screening tool for the diagnosis of reflux due to its absence of radiation exposure. We evaluated the usefulness of ultrasonography with sonicated albumin in the diagnosis of vesicoureteral reflux. Sonicated albumin contains approximately 3 to 5 x 10(8) microspheres per ml., which are echogenic. Sonicated albumin was tested in vitro, alone, and in human and porcine urine to assess microsphere stability. Urine dilutions, specific gravity, temperature and pH were used as variables. The mode of delivery was also tested in vitro and in vivo. These studies showed that sonicated albumin microspheres were stable over a wide range of chemical variables and urine composition. Sonicated albumin produced an image of uniform echogenicity when it was pre-loaded into a Foley catheter and followed by saline infusion in vitro. Fluoroscopic cystograms, using standard radiopaque contrast media, in 5 Hanford mini-swine in which unilateral reflux had been created previously confirmed the presence of reflux unilaterally. Sonographic cystograms with various dilutions of sonicated albumin in 0.9% sodium chloride (1:100, 1:250, 1:500, 1:750 and 1:1,000) were performed. At a dilution of 1:100 sonicated albumin produced dramatic echogenicity in the bladder and refluxing ureters during sonographic imaging. The microspheres appeared to be stable for prolonged periods (more than 40 minutes), thus allowing for a careful sonographic assessment of the entire genitourinary tract. Sonicated albumin may be valuable for the sonographic detection of vesicoureteral reflux.

Albumins↗
PubMed1993

Human fetal compensatory renal growth.

The occurrence of prenatal compensatory renal growth has remained in question, despite the general acceptance of this phenomenon postnatally. We measured by ultrasound imaging the renal length of 22 human fetuses with a solitary kidney or contralateral multicystic dysplastic kidney, and compared it to measurements in 40 normal control fetuses. Renal length was normalized to fetal biparietal diameter. Analysis of covariance showed that the solitary kidneys were significantly larger than normal controls (p < 0.0001), although the rate of growth was not significantly increased above normal. These data document the presence of compensatory renal growth in human fetuses with solitary or functionally solitary kidneys.

Adaptation, Physiological↗
PubMed1993

Juvenile cystic kidneys (jck): a new mouse mutation which causes polycystic kidneys.

We have characterized a new recessive mutation in the mouse which predisposes to the development of polycystic kidney disease. This mutation, called juvenile cystic kidneys (jck), arose in a transgenic line of mice, but appears unrelated to the transgene since it segregates freely from it. While focal cysts are evident in affected animals as early as three days of life and the disease is progressive, the mice are fertile and generally survive to four or more months of age. Complementation analysis indicates that the jck mutation is not allelic with three other known recessive polycystic kidney mutations (cpk and two as yet unnamed mutations), and linkage studies demonstrate it is unlikely to be allelic with a fourth (pcy). The study of these five mutations and their interactions should prove useful for understanding the mechanisms required to maintain the normal integrity of renal tubules.

Alleles↗
PubMed1992

The prophylactic value of clean intermittent catheterization and anticholinergic medication in newborns and infants with myelodysplasia at risk of developing urinary tract deterioration.

OBJECTIVE: To determine if prophylactic use of clean intermittent catheterization and oxybutynin chloride is effective in preventing urinary tract deterioration in myelodysplastic children with high bladder pressure and detrusor-sphincter dyssynergia. DESIGN: Sequential, nonrandomized trial. SETTING: Referral-based urodynamics facility and myelodysplasia program at a major city pediatric hospital. PARTICIPANTS: Twenty-six of 71 consecutive newborns with myelodysplasia who exhibited these urodynamic findings were treated prophylactically over 5 years, whereas 56 of 105 consecutive newborns with the same findings treated during the previous 7 years were treated expectantly. INTERVENTION: Clean intermittent catheterization and oxybutynin therapy were begun when these specific urodynamic findings were detected. MEASUREMENTS AND RESULTS: Follow-up urodynamic studies and roentgenographic assessment of the urinary tract were performed periodically over 5 years. Oxybutynin eliminated uninhibited contractions in two of 14 newborns and lowered peak contractile pressure in the remaining 12. Oxybutynin also lowered bladder-filling pressure at capacity in all 12 additional neonates with only hypertonicity. Twenty-four (92%) of 26 children had normal kidney function and drainage during the observation period, two (8%) developed hydroureteronephrosis, and one of these two had vesicoureteral reflux. In a prior study of children similarly at risk who were treated expectantly, the roentgenographic appearance of the upper urinary tract had changed in 48%. Minimal side effects were noted with oxybutynin, and no adverse effects of clean intermittent catheterization were detected. CONCLUSIONS: Oxybutynin effectively reduces uninhibited contractions and lowers detrusor filling pressure, while clean intermittent catheterization allows bladder emptying at low pressures with no measurable side effects in these neonates. The overall effect maintains the integrity of the upper urinary tract in almost all myelodysplastic children at risk of urinary tract deterioration. Expectant therapy can no longer be advocated when these "at risk" children are identified because prophylactic treatment is so effective.

Boston↗
PubMed1992

Urinary tract infection in infants in spite of prenatal diagnosis of hydronephrosis.

The efficacy of preventing neonatal urinary infection in infants by diagnosing hydronephrosis in the fetus on obstetrical ultrasonography was studied. 426 infants had uroradiologic evaluation between 1984 and June 1991 because they had hydronephrosis detected in utero. Thirteen with posterior urethral valves were excluded. Of the remaining 413, 13 (3.1%) presented with urinary infection in the first 6 months of life. Ten of the 13 were boys and 7 were not circumcised. Eleven of the 13 infants less than 2 months old were formula-fed. The causes of hydronephrosis were reflux alone in 6, ureteropelvic junction obstruction in 6 (with coexisting ipsilateral reflux in 4), and primary megaureter in 1. Ultrasonography alone was insufficient to exclude reflux. Amoxicillin-resistant bacteria were the causative organisms in all 10 for whom bacteriology data was available. Four categories of management failure were identified: 1) failure of communication of the prenatal findings, 2) antibiotics not prescribed, 3) antibiotics prescribed but not administered, and 4) infection in spite of continuous antibiotic prophylaxis. Uncircumcised formula-fed male infants with reflux seemed to be at special risk for infection.

Anti-Bacterial Agents↗
PubMed1992

The prenatal diagnosis of imperforate anus with rectourinary fistula: dilated fetal colon with enterolithiasis.

The finding of extraluminal calcifications is commonly reported and usually indicates intrauterine intestinal perforation with intraperitoneal extravasation of meconium, most often associated with intestinal obstruction and/or atresias. Intraluminal calcification of meconium is more rare and appears to result from the mixing of stagnant urine and meconium in utero. The presence of the intraluminal calcifications in a dilated loop of intestine, particularly with an associated urinary tract abnormality, should suggest a rectourinary fistula. Two cases of prenatally diagnosed imperforate anus with rectourinary fistulae are reported.

Adult↗
PubMed1992

The effect of obstruction on the developing bladder.

Congenital bladder obstruction causes significant immediate and long-term consequences yet its pathophysiology remains poorly understood. A model of early fetal bladder obstruction in sheep has been developed to study the response of the developing bladder to high grade obstruction, with particular emphasis on the regulation of growth and development. Congenital bladder obstruction was produced in fetal sheep at 60 days of gestation and studied at 95 days of gestation (14 sheep) or term (12 sheep). A total of 24 age-matched normal sheep served as controls. Bladders were analyzed by total weight, stereological estimation of smooth muscle cell size, number and total mass, deoxyribonucleic acid concentration, muscarinic cholinergic receptor density, myosin isoform analysis and/or passive cystometrics. Congenital bladder obstruction caused a 4.6 times increase in bladder weight at term reflecting a 5.8 times increase in smooth muscle mass. This increase was predominantly that of cellular hypertrophy and less so of hyperplasia, based upon increased cell volume, increased protein-to-deoxyribonucleic acid ratio, and no significant increase in total cell number. Muscarinic cholinergic receptor number per smooth muscle cell increased 3.2 times but it did not change relative to myosin content. The ratio of myosin heavy chain isoforms SM1:SM2 is developmentally regulated and was seen to change from 1.6 at 100 days of gestation to 1.13 at term in normals. After 5 weeks of obstruction SM1:SM2 was 1.27 and it was 1.25 at term, indicating an effect on the developmental regulation of smooth muscle. Rapid fill cystometry in vivo measured the rate of stress relaxation to assess accommodative properties. The half-decay time was increased in all 3 obstructed bladders tested to greater than 15 seconds at 50% capacity (normal less than 5 seconds), suggesting reduced compliance. This study shows that an in utero model of bladder obstruction is feasible. Congenital bladder obstruction produces a variety of structural, biochemical and functional changes in the developing bladder indicative of alterations in the regulation of growth and differentiation.

Actins↗
PubMed1992

The response of the fetal kidney to obstruction.

In a fetal ovine model the renal effects of different anatomic levels of fetal urinary obstruction were studied. Parameters of prenatal renal growth and differentiation were characterized and correlated with the patterns of renal response to in utero obstruction. Complete ureteral or urethral obstruction was produced in the sheep fetus at 55 to 60 days of gestation. Animals were delivered and sacrificed at near term (140 days), and the kidneys were removed and prepared for analysis. Parameters examined included weight, histology, glomerular number and total surface area, as well as urinary sodium, creatinine, osmolarity and N-acetyl glucosaminidase. Three patterns of response were identified, producing hydronephrotic, cystic or dysgenetic kidneys. Hydronephrotic kidneys were usually the result of bladder outlet obstruction or ureteral obstruction with spontaneous urinary decompression. These kidneys were large (20.7 gm. versus normal 10.8 gm., p less than 0.0001), with thinning of cortical parenchyma that was structurally intact. Glomerular number and surface area were normal. Cystic kidneys were large (14.2 gm., p less than 0.05) with grossly visible cysts and an effaced medulla. Cortical structure was distorted by cysts but basic elements were intact. Glomerular number and surface area were not reduced. Dysgenetic kidneys were small (3.9 gm., p less than 0.0001) with markedly abnormal cortical structure and little recognizable medulla. Histological elements similar to fetal structures were present, including cuboidal/columnar tubular epithelium and peritubular mesenchymal collars. Glomerular number and surface area were significantly less than normal (p less than 0.001). The kidneys contralateral to unilaterally obstructed kidneys were significantly larger than normal (16.2 gm., p less than 0.0001), with normal histology, glomerular number and surface area, indicating in utero contralateral renal hypertrophy. Urinary sodium was variably affected in the hydronephrotic kidneys and was identical to plasma in the dysgenetic kidneys. These results indicate the technical feasibility of in utero models of urinary obstruction. Renal growth and patterns of differentiation were markedly affected by in utero obstruction. They should be a major focus in the investigation of congenital obstructive uropathy, since normal processes of renal growth and differentiation form the basis for postnatal function.

Animals↗
PubMed1992

Late onset severe oligohydramnios associated with genitourinary abnormalities.

We evaluated the diagnosis, gestational age at presentation, timing and mode of delivery, and ultimate outcome in those fetuses with third trimester onset of severe oligohydramnios who also had urinary tract abnormalities. A total of 8 fetuses with obstructive uropathy or cystic renal disease was seen during a 2-year period with the onset of severe oligohydramnios noted between 27 and 33 weeks. Immediate and late postnatal pulmonary function was excellent in 5 of the 8 subjects. Three neonates had respiratory distress but only 1 died at birth. Ultimate renal function varied in the 7 survivors. Those with supravesical obstructive uropathy achieved a normal serum creatinine, while the neonates with renal cystic disease and infravesical obstruction did not.

Female↗
PubMed1992

Formation of urothelial structures in vivo from dissociated cells attached to biodegradable polymer scaffolds in vitro.

The use of autologous urothelium would be advantageous for urothelial replacement in many genitourinary reconstructive procedures. Urothelial tissue grafts might be created using isolated populations of transitional epithelium or tissue in concert with an appropriate synthetic substrate. We describe the results of experiments designed to determine the feasibility of using biodegradable polymers as delivery vehicles for the creation of new urothelial structures in vivo from dissociated cells. Primary cultures enriched in uroepithelial cells were obtained from New Zealand white rabbits using a new technique of cell harvest. Cells were seeded onto nonwoven meshes of polyglycolic acid polymers in culture and, after 1 to 4 days in vitro, the cell-polymer scaffolds were implanted into the mesentery, omentum or retroperitoneum of athymic mice. Polymers implanted without cells served as controls. Animals were sacrificed at 5, 10, 20 and 30 days after implantation and 75 implants were examined histologically. Ten days after implantation isolated single cell layers were seen lining the polymer fibers. At 20 and 30 days polymer degradation was evident and urothelial cells lined the polymer in continuous layers of 1 to 3-cell thickness. Anticytokeratin western blots demonstrated the presence of a urothelium-associated cytokeratin in cell-polymer implants recovered after 30 days. These results demonstrate that urothelial cells can be successfully harvested, survive in culture and attach to artificial biodegradable polymers. The urothelial-polymer scaffolds can be implanted into host animals and the implanted cells can achieve spatial orientation as the polymer undergoes biodegradation. These findings suggest that it may be possible to use autologous urothelium, reconfigured on a synthetic substrate, in reconstructive procedures involving the ureter, bladder and urethra.

Animals↗
PubMed1992

Perforation of the augmented bladder.

In 12 of 264 children treated with enterocystoplasty 15 spontaneous perforations occurred. Of the 12 children 9 had myelodysplasia. All segments of the gastrointestinal tract were used for the augmentation and most were detubularized. Surgery to increase bladder outlet resistance was done in 8 cases. At the time of each perforation 9 children had sterile cultures, however, 3 died of overwhelming sepsis. Presenting signs included abdominal pain in 8 cases, septic shock in 4 cases and shoulder pain in 4 older myelodysplastic children with diaphragmatic irritation from escaping urine. Cystography demonstrated a leak in 10 of 11 cases. Urodynamic studies revealed good compliance with low maximum filling pressure in 8 of 10 children. Hyperreflexia was noted in only 5 cases and outlet resistance greater than 85 cm. water was demonstrated in 5. Histological analysis showed changes in the bowel wall consistent with ischemia but suture granulomas were present in areas adjacent to the perforation site or thinned areas in biopsy or autopsy specimens. In addition to the theory that overdistention may cause enterocystoplasty perforation, current detubularization techniques may produce areas of relative ischemia, which become accentuated when the augmented bladder is distended beyond a reasonable volume.

Adolescent↗
PubMed1992

Endoscopic treatment of vesicoureteral reflux with a self-detachable balloon system.

There is controversy about the use of polytetrafluoroethylene (Teflon) paste in children for the endoscopic treatment of vesicoureteral reflux due to evidence of particle migration. However, there are definite advantages in treating patients endoscopically. It is evident that the ideal substance should be able to be delivered endoscopically, conserve its volume, and be nonmigratory and nonantigenic. Towards this goal we developed a catheter with an inflatable, detachable and self-sealing silicone balloon that would fit through a 19 gauge cystoscopic needle. Hydroxy-ethyl-methyl acrylate, a hydrophilic polymer that solidifies within 60 minutes after the addition of ferrous sulfate, was chosen as the filling material for the balloon. Conceptually, the sealed balloon would prevent the migration of hydroxy-ethyl-methyl acrylate and the solidified polymer would prevent volume loss. To test this system reflux was created in 6 Hanford mini-pigs by unroofing the ureters bilaterally. In 2 pigs a previously described method of open surgery was used and in the other 4 reflux was created endoscopically using the resectoscope and laparoscopic scissors. The presence of bilateral reflux was confirmed 4 weeks later with a cystogram and the balloon was implanted unilaterally through a cystoscope. The opposite ureter served as an internal control in all animals. A repeat cystogram was performed 2 to 4 weeks after implantation, demonstrating resolution of reflux in the treated side and persistence of reflux in the opposite untreated ureter. Serial cystograms, ultrasound and excretory urography showed no reflux on the implanted side nor any evidence of obstruction. Tissue sections from various organs showed no evidence of particle migration, granuloma formation or inflammatory reaction. Short-term results show that the balloon implants are able to correct reflux without evidence of obstruction.

Animals↗
PubMed1992

Prenatal diagnosis of the megacystis-megaureter association.

A total of 11 male neonates with hydronephrosis and a large bladder in utero had the megacystis-megaureter association. Prenatal ultrasound findings included bilateral hydroureteronephrosis; a large, smooth, thin-walled bladder, and normal volume of amniotic fluid. Postnatal studies demonstrated grades 4 to 5 bilateral reflux, a large bladder without obstruction and in 2 infants nonfunction of a kidney or renal moiety. Of 7 infants initially managed nonoperatively 5 have undergone surgery due to persistent reflux or breakthrough urinary infections. The prenatal diagnosis of the megacystis-megaureter association can be suspected with reasonable accuracy. Prompt postnatal continuous antibiotic prophylaxis and uroradiological confirmation allow for nonemergency management of this condition with excellent results.

Female↗
PubMed1991

Pulmonary development in the fetal lamb: morphometric study of the alveolar phase.

The alveolar stage of intra-uterine lung development was analyzed morphometrically in 18 fetal lambs at 112, 124, 142, or 148 (term) days of gestation. The right lungs were fixed at uniform distending pressure and the tissue embedded in Epon for light microscopy. Over the whole period, right lung volume (VL) increased more rapidly than body weight to reach a mean value of 185 cm3 at term. The increase in VL was greatest between 112 and 124 days gestation. Throughout the period of study the distal lung consisted of alveolar-like air-spaces lined by walls with a single capillary system. Despite this mature morphology, further differentiation took place as established by two independent measurements. First, interalveolar wall thickness decreased from 4.12 +/- .03 microns at 112 days to 2.55 +/- .02 microns at term. Secondly, alveolar surface area increased at a greater rate than lung volume (as VL 1.06), suggesting a moderate increase in surface complexity, but not a subdivision of existing air-spaces. This latter finding was supported by numerical density values which remained fairly constant. We conclude that throughout this period active growth involves the addition of alveolar units of basically similar size. This is a similar process to the one noted previously in postpneumonectomy compensatory growth.

Animals↗
PubMed1991

The long-term results of artificial sphincters in children.

To determine the long-term efficacy of the artificial urinary sphincter, 36 consecutive children in whom a prosthesis was implanted between August 1978 and July 1985 were followed for a minimum of 5 years and re-evaluated within the last 3 months. Of the 36 sphincters 27 (75%) are currently in place; 2 of these 27 sphincters are dysfunctional due to fluid leakage. Of the 25 functioning sphincters 14 have required no further prosthetic operation, 10 needed 1 revision and 1 patient had 5 revisions. Fluid leakage, occurring in 12 patients, was the most common complication requiring reoperation. Twenty patients are completely continent (11 of whom without any medication) and 5 are occasionally damp. The over-all success rate at 2 and 5 years was 84 and 62%, respectively. The mean survival time of the prosthesis was 7.2 years and the mean standard interval was greater than 10.5 years. Patients with higher balloon pressures (81 to 100 cm. water) had more complications, and a decreased rate of success than those with lower pressure balloons (51 to 80 cm. water, p = 0.02). There was no difference in success rates between boys and girls (p = 0.98), although girls who had a prior bladder neck operation tended to have a higher rate of cuff erosion. Sphincters placed after 1980 (model AS800) had a lower reoperation rate than those placed earlier. In selected instances, the artificial urinary sphincter appears to be a viable long-term alternative for management of children with intractable incontinence who have either failed or are unsuitable for other methods of treatment.

Child↗