Biomedical subjects

J Mandell

Publications and source records attributed to J Mandell.

At least 73 records · Page 4Linked to original sources

PubMed1991

The role of the kidney in lung growth and maturation in the setting of obstructive uropathy and oligohydramnios.

The contribution of the kidneys to lung development, which includes growth and maturation, is uncertain but it appears to be complex. Obstructive uropathy with oligohydramnios produces pulmonary hypoplasia characterized by small lungs (decreased lung volume/body weight) and retarded maturation (reduced total airspace). Lung growth and maturation were studied in a model of early gestation obstructive uropathy to understand better their relationship and their prenatal regulation. Of 26 fetal sheep studied at near term (135 days of gestation) 9 had bladder obstruction created at 60 days of gestation, 11 had bladder obstruction at 60 days with in utero decompression at 95 days, and 6 served as controls and shams. Amniotic fluid volume was measured, kidneys were prepared and evaluated histologically, lungs were inflation-fixed and volumes were measured, and airspace volume percentage was measured morphometrically. Experimental and serendipitous variations in the condition of the kidneys and amniotic fluid at delivery permitted an analysis of the contribution of the kidneys and the amniotic fluid to lung growth and maturation. Impairment of growth and maturation was dissociated in certain animals, and this dissociation was referable to the histological status of the kidneys and the presence or absence of amniotic fluid at delivery. Growth was normal when amniotic fluid was present or likely to have been present in late gestation, even with structurally damaged kidneys. With severe renal damage amniotic fluid was not restored even with in utero decompression and it resulted in severely impaired lung growth. Maturation was normal only in the presence of amniotic fluid and intact kidneys. The dissociation of lung growth and structural maturity suggests their independent regulation. The data suggest that the kidneys are important in early lung growth, while the presence of amniotic fluid contributes to growth later in gestation. Lung maturity requires both factors, suggesting a primary kidney contribution with the amniotic fluid acting in a permissive or supportive role.

Amniotic Fluid↗

PubMed1991

Urinary levels of renal tubular enzyme N-acetyl-beta-D-glucosaminidase in relation to grade of vesicoureteral reflux.

Elevated urinary levels of the renal tubular enzyme N-acetyl-beta-D-glucosaminidase (NAG) have been shown to be associated with tubular damage. To determine whether urinary levels of NAG would be abnormal and/or vary with the severity of vesicoureteral reflux, bladder urine was obtained from 31 children without reflux and 32 children with various grades of reflux. Nonrefluxing controls were obtained from children undergoing evaluation for a history of infection, hematuria or voiding abnormality. Patients with evidence of obstruction, neuropathic bladder dysfunction, urinary tract infection or renal failure were excluded. Bladder (32 cases) and ureteral (5 cases) urine from children with reflux was obtained at cystography or at antireflux surgery. Control and reflux patients were not significantly different with regard to sex or age. The mean urinary NAG level in nonrefluxing control patients was 10.63 IU/mg. (range 0.94 to 26.61, standard error of mean 0.43). Mean urinary NAG for all patients with reflux was 16.47 IU/mg. (range 2.85 to 52.02, standard error of mean 0.9). Two children with intrarenal reflux had urinary NAG levels of 52 and 48 IU/mg. Urinary NAG levels are elevated with higher grades of reflux and this relatively simple assay may have clinical usefulness in the assessment of tubular dysfunction associated with reflux.

Acetylglucosaminidase↗

PubMed1991

Effect of in utero vesicostomy on pulmonary hypoplasia in the fetal lamb with bladder outlet obstruction and oligohydramnios: a morphometric analysis.

A model of early gestation bladder outlet obstruction and oligohydramnios in the fetal lamb is characterized by small, immature lungs (pulmonary hypoplasia). The current study examines how in utero relief of urinary tract obstruction produced early in gestation modifies pulmonary hypoplasia. Bladder obstruction was created at 60 days gestation in fetal sheep (term = 140 days); 11 fetuses then underwent in utero decompression at 95 to 100 days; six were left obstructed. Five normal fetuses served as controls and two underwent sham obstruction and vesicostomy. All were delivered and sacrificed near term (135 days), the right lung was inflation-fixed and its volume determined. Relative volumes of alveoli, alveolar ducts, and tissue, alveolar surface area, and alveolar numerical density were estimated morphometrically. Kidneys were examined histologically. In all animals persistent bladder obstruction produced oligohydramnios. Bladder obstruction to term produced pulmonary hypoplasia with a mean right lung volume-to-body weight ratio (LV:BW) of 14.3 cc./kg. (normal = 36.4, p less than 0.001). Structural immaturity was evidenced by an airspace fraction of only 57% (normal = 68%, p less than 0.05). Kidneys in these animals were not dysplastic; there was hydronephrosis or evidence of spontaneous urinary decompression. In eight of the 11 animals, decompression improved the LV:BW ratio to 28.4 cc./kg. (vs. obstructed, p less than 0.001; vs normal, p less than 0.05) and normalized maturity. All had increased amniotic fluid at delivery; kidneys in 7/8 animals were normal, and the other had moderate hydronephrosis. One of the 11 animals had normal kidneys, oligohydramnios, immature lungs, but with normal volume. Oligohydramnios was present in the other two of 11 fetuses despite successful decompression and they had markedly dysmorphic kidneys and profoundly hypoplastic and immature lungs (LV:BW 5.1 cc./kg.). Even after 35 days (25% gestation) of obstruction, in utero urinary tract decompression permits better lung growth and maturation than in persistently obstructed animals. The degree of renal damage from obstruction appears to be a critical determinant in the correction of pulmonary hypoplasia.

Animals↗

PubMed1991

Structural genitourinary defects detected in utero.

Fetal genitourinary anomalies are detected with increasing frequency due to the large numbers of fetuses that undergo screening ultrasonography (US) for nonspecific indications. One hundred seventy-seven patients were evaluated for fetal urinary abnormalities over a 2-year period. Fetal hydronephrosis accounted for 154 (87%) of the cases, with the remaining diagnoses including multicystic dysplastic kidney, autosomal recessive polycystic kidney disease, and renal agenesis or hypodysplasia. Ureteropelvic junction obstruction was the most common postnatal anatomic abnormality (29%), with a large number of cases of prenatally diagnosed hydronephrosis resolving either prenatally (33%) or postnatally (24%). Prenatal US findings were retrospectively analyzed with regard to the degree of hydronephrosis at different stages of gestation. Data showed that there is a gradual rise in anteroposterior renal pelvic diameter during gestation and that there is a correlation between this diameter and the ultimate renal outcome in regard to surgical repair. This information can provide guidance in making recommendations to parents and physicians.

Congenital Abnormalities↗

PubMed1991

Increased renal parenchymal echogenicity in the fetus: importance and clinical outcome.

Pre- and postnatal ultrasound (US) findings and clinical course in 19 fetuses (16-40 menstrual weeks) with hyperechoic kidneys (renal echogenicity greater than that of liver) and no other abnormalities detected with US were evaluated to determine whether increased renal parenchymal echogenicity in the fetus indicates renal disease. Four infants (21%) were healthy at birth and had normal postnatal sonograms. Another 10 infants (53%) survived, but abnormalities were found at neonatal US. Postnatal diagnoses in these 10 neonates included unilateral renal dysplasia (n = 3), unilateral multicystic dysplastic kidney and a contralateral hyperechoic kidney (n = 2), hydronephrosis (n = 2), and renal abnormalities of unknown type (n = 3). Five fetuses with either infantile polycystic kidney disease (n = 4) or bilateral multicystic dysplasia (n = 1) did not survive. Oligohydramnios was predictive of a poor prognosis. Hyperechoic renal parenchyma in the fetus was associated with sonographic or functional abnormalities in 15 of 19 cases (79%) and a 74% survival rate.

Female↗

PubMed1991

Fetal abdominal wall defect: a new complication of vesicoamniotic shunting.

Vesicoamniotic shunting for fetal obstructive uropathy is beneficial in selected cases. We report a new complication, fetal abdominal wall defect secondary to vesicoamniotic shunting. Placement of the shunt should be as low and as close to the fetal midline as possible in order to reduce the risk of this complication.

Abdominal Muscles↗

PubMed1990

The urodynamic consequences of posterior urethral valves.

We evaluated urodynamically 41 patients with posterior urethral valves because of signs or symptoms of incontinence (35), frequency (3), hydronephrosis (2) and infection (1). Findings included normal urodynamic evaluations in 3 patients, 2 had high voiding pressures secondary to outlet resistance and 1 had incontinence on the basis of external urethral sphincter damage. In the remainder 3 patterns of bladder dysfunction were identified. Myogenic failure with overflow incontinence occurred in 14 patients. In this group clean intermittent catheterization or Valsalva's voiding was used for emptying. Hyperreflexic bladders were seen in 10 patients. Pharmacological suppression of instability was effective in 5 of 7 patients treated; 1 required bladder augmentation. Eleven children had a small capacity bladder and poor compliance. Post-void residuals were low and these bladders were generally but not always stable. Pharmacological bladder relaxation was successful in 3 patients, 3 underwent augmentation, 1 did well with alpha-agonists and followup is unavailable on the other 4. These 3 patterns of bladder dysfunction represent an overlapping constellation of residual urodynamic abnormalities due to previous bladder outlet obstruction. Individual patients may show facets of several types of dysfunction associated with 1 predominant pattern.

Child↗

PubMed1990

Flow cytometric evaluation of multicystic dysplastic kidneys.

The most appropriate management of the multicystic dysplastic kidney remains controversial. At issue is the long-term risk of the development of malignancy in the multicystic dysplastic kidney. The association between renal dysplasia and neoplasia has not been confirmed, with only 6 cases of malignancy reported. Nephroblastomatosis, a probable precursor of Wilms tumor, has been found in 5 to 7% of the cases of multicystic dysplastic kidney when specifically sought. In an attempt to determine whether a relationship exists between renal dysplasia and neoplasia in terms of abnormalities of cellular deoxyribonucleic acid content we performed flow cytometric evaluation on 30 formalin fixed, paraffin embedded archival specimens of multicystic dysplastic kidneys. None of the kidneys had evidence of malignancy. Nuclear deoxyribonucleic acid ploidy studies were performed on single dissociated nuclei prepared by the technique of McLemore and associates and stained with propidium iodide. All specimens demonstrated a diploid pattern of deoxyribonucleic acid, including 3 specimens with nephroblastomatosis or extensive papillary growth, and no specimen demonstrated a tetraploid or aneuploid pattern. The mean G0/G1 fraction was 85.94% (standard deviation 4.59) and the mean S/G2/M fraction was 12.54% (standard deviation 4.72). These findings do not support or negate the potential for neoplasm associated with multicystic dysplastic kidney, since a diploid deoxyribonucleic acid pattern does not eliminate the possibility of the future development of malignancy.

DNA↗

PubMed1990

Paratesticular rhabdomyosarcoma: results of therapy in 18 cases.

The management of paratesticular rhabdomyosarcoma has evolved more slowly than that for testicular germ cell tumors, mainly due to its lower incidence and the lack of standardized treatment protocols. With gradual refinements in staging and therapy the prognosis has improved. Between 1960 and 1988, 18 patients 2 to 18 years old were treated at the Children's Hospital. Management consisted of inguinal orchiectomy, staging evaluation and retroperitoneal lymph node dissection, followed by chemotherapy and radiotherapy according to the stage of the disease. In 11 patients (61%) the disease was confined to the scrotum, while 7 presented with spread to the retroperitoneal lymph nodes, including 3 children with more distant metastases. Histological study revealed predominantly embryonal characteristics except for 1 alveolar cell type. Chemotherapy consisted of actinomycin D in 2 patients, vincristine, actinomycin D and cyclophosphamide in 2, pulse vincristine, actinomycin D and cyclophosphamide in 10, and doxorubicin plus vincristine, actinomycin D and cyclophosphamide in 4. A total of 17 patients remain free of disease (median followup 4 years) with 1 death. The actuarial survival without relapse and over-all survival rate are 89 and 94%, respectively. We conclude that paratesticular rhabdomyosarcoma represents a favorable subgroup of rhabdomyosarcoma.

Actuarial Analysis↗

PubMed1990

Fetal pyelectasis: a possible association with Down syndrome.

Two hundred ten consecutive fetuses were identified as having renal pyelectasis among 7400 patients scanned during 1 year. Seven of these 210 fetuses had Down syndrome. We reviewed images of the kidneys of 44 fetuses with Down syndrome collected over 5 years and found that 25% of these affected fetuses had pyelectasis. The incidence of Down syndrome was 3.3% when fetal pyelectasis was present.

Amniocentesis↗

PubMed1990

Current concepts in the perinatal diagnosis and management of hydronephrosis.

Perinatal urology has become a significant facet of pediatric urologic practice. This article reviews the approaches to the diagnosis of prenatal hydronephrosis and its typical sonographic appearances in relation to the underlying pathology. A review of the outcomes of prenatal uropathology serves as a basis on which to interpret reports of prenatal intervention for hydronephrosis. A critical review of the experience of prenatal intervention is conditionally supportive of its benefits, but this view must be tempered by a recognition of the inherent risk to the mother and fetus. Included within this view is a recognition that not all hydronephrosis is caused by obstruction. More specific prognostic indicators of renal and pulmonary functional reserve are critically needed to permit appropriate patient selection. This must be coupled with more rigorous assessment of outcomes and complete reporting of the results. Continued basic and clinical research is important in developing these data. A management strategy for hydronephrosis in the prenatal and postnatal periods is presented, based on the goal of permitting maximal renal as well as pulmonary development in utero and in the newborn period.

Ethics, Medical↗

PubMed1990

Experimental congenital obstructive uropathy.

Continued experimental work in congenital obstructive uropathy is essential to support the rapidly advancing field of fetal medicine. It is possible to reproduce the clinically relevant obstructive lesions in an experimental model. On the basis of data from these models, the tentative conclusion is that in utero intervention is beneficial in severe congenital obstructive uropathy associated with oligohydramnios. The limited human experience provides insufficient data to confirm this hypothesis but has demonstrated the technical feasibility of prenatal interventions. There is a critical need for further refinement in understanding the complex pathophysiology of congenital obstructive uropathy, not only the renal consequences, but also the pulmonary and systemic effects. There remains the particular need to resolve the determinants and indicators of functional salvageability of the kidneys and lungs in congenital obstructive uropathy.

Animals↗

PubMed1989

Congenital midureteral obstruction.

Congenital midureteral obstruction, caused either by a ureteral valve or stricture, is an exceedingly rare entity. When encountered, it is generally misdiagnosed as either primary megaureter or ureteropelvic junction obstruction, leading to a less than optimal surgical approach. Seven children with midureteral obstruction were seen over the past 17 years. Two of the patients presented with hydronephrosis on prenatal ultrasonography, and five with urinary tract infection. In only three was the diagnosis suspected on intravenous urography and voiding cystourethrography alone. Five of the seven cases had either antegrade or retrograde pyelography, prior to or at the time of their operative procedure, and in four of these a correct diagnosis was made. Notably, in five of the seven cases, recognition of the midureteral lesion prior to the surgical incision allowed the approach to be modified and a more appropriate technique (ureteroureterostomy) to be performed. The etiology of midureteral valve and stricture has been attributed to improper recanalization, insufficient vascular supply, or persistence of ureteral folds. Three of our patients had contralateral renal dysgenesis, suggesting an underlying ureteral bud abnormality.

Child↗

PubMed1989

The use of rectus fascia to manage urinary incontinence.

The surgical management of urinary incontinence in children is one of the most difficult challenges facing pediatric urologists today. We have critically looked at our experience using a rectus fascial sling to prevent incontinence. Eleven girls (6 to 22 years old) with urinary incontinence from neurogenic bladder dysfunction (9), surgical injury to the bladder (1) or urogenital sinus abnormality (1) comprise this study. All had failed regimens of pharmacological therapy and intermittent catheterization. Three patients had undergone prior bladder neck reconstruction and 2 an augmentation cystoplasty in an attempt to control the incontinence. Urodynamic studies revealed several reasons for the continued wetting in these individuals: a changing neurological lesion leading to a loss of innervation and concomitantly lowered urethral resistance in 2 patients, adequate urethral resistance at rest but decreasing resistance with bladder filling in 4, no increase in urethral resistance with increases in abdominal pressure in 4 and urethral instability (a decrease in resistance following a cough or Valsalva's maneuver) in 1 apparently neurologically normal girl. Eight patients are dry 3 to 24 months postoperatively on intermittent catheterization. All have demonstrated either an increase in urethral resistance at rest or an adequate level of resistance during filling of the bladder or a sudden increase in abdominal pressure. Of the remaining 3 patients 1 is dry for 2 to 3 hours but then leakage occurs, 1 is improved but damp and 1 patient is wet 3 months postoperatively. The use of rectus fascia to improve outlet resistance seems to be a viable alternative in the management of incontinence in selected female subjects.

Adolescent↗

PubMed1989

The unrecognized neuropathic bladder of infancy.

Four infants presented with hydroureteronephrosis and incomplete emptying of the bladder secondary to detrusor-sphincter dyssynergia. None of the patients had other signs suggestive of neurological dysfunction. It is presumed but not proved that these infants manifested a urodynamic reaction in response to a perinatal insult involving the brainstem area. Long-term followup has demonstrated a persistent but nonprogressive neurourological disturbance.

Electromyography↗

PubMed1989

Congenital obstructed megaureters in early infancy: diagnosis and treatment.

Fetal screening during maternal ultrasonography has changed the mode and age of presentation of congenital uropathies, particularly congenital obstructed megaureter. We studied 47 infants less than 8 months old with primary obstructed megaureter. Surgical correction in 42 patients with moderate to severe obstruction was performed at a mean age of 1.8 months in those detected prenatally and 3.8 months in those presenting after birth. All infants showed functional and structural urographic improvement with a mean followup of 2.3 years. Reflux was seen postoperatively in 8 patients, which subsided spontaneously in 3, continues to be followed in 2 and resulted in repeat reimplantation in 3. Five infants had mild obstruction, which was managed nonoperatively and 2 showed progressive obstruction, which required repair at ages 20 and 28 months. Repair of obstructed megaureters in early infancy improves renal drainage and offers the potential for preventing renal damage before the development of symptoms or infection. With proper attention to detail, excellent results may be achieved.

Dilatation, Pathologic↗

PubMed1989

Pulmonary development in the fetal lamb with severe bladder outlet obstruction and oligohydramnios: a morphometric study.

The lethal feature of male newborns with severe bladder outlet obstruction and oligohydramnios is pulmonary hypoplasia. We report a fetal lamb model of bladder outlet obstruction created in the early second trimester, and morphometric analysis of the profound pulmonary hypoplasia that resulted. At 55 to 65 days of gestation 8 consecutive male fetuses underwent surgical clipping of the urethra and urachus near the abdominal wall. A sham operation was performed in 1 female fetus. The lambs were delivered by cesarean section 10 weeks later. The right lungs were immediately fixed at a distending pressure of 25 cm. water. The results of the morphometric studies were compared to control animals from our earlier study of normal fetal lamb lung development; slides for both studies were scored in a blind, randomized fashion by 1 of us (S. G. D.). Although mean body weights for the groups were similar, mean right lung volume in the operated lambs was 63.8 cM.3 compared to 158 cM.3 in the control animals and 137 cM.3 in the sham operated fetus (p less than 0.0005). Relative volume of respiratory tissue was 87 per cent in the operated animals, and 92 per cent in the controls and the sham operated fetus (p less than 0.0005). Microscopic morphometry revealed an increased relative volume of inter-alveolar tissue in the experimental animals (35 compared to 23 per cent in the normal lambs, p less than 0.05), with a corresponding decrease in relative airspace volume. Alveolar numerical density and alveolar surface density were not statistically different between the groups, although total alveolar number and surface area were substantially decreased in the operated lambs due to the reduced mean lung volume. Mean alveolar wall thickness was increased at 3.6 microM. in the operated group versus 2.1 microM. in the normal group (p less than 0.0005) and 2.8 microM. in the sham operated fetus. Thus, the lung in the lamb with severe bladder outlet obstruction is hypoplastic and immature.

Amniotic Fluid↗

PubMed1989

Strictures in the ileal portion of ileocecal conduits in children and young adults.

Patients with ileocecal conduits are at risk for development of late complications. We present 3 patients who had strictures in the ileal portion of the ileocecal conduit, leading to deterioration of the upper urinary tract. The pathogenesis of these strictures appears to result from chronic inflammation. Long-term periodic upper urinary tract screening with ultrasonography is important for early detection of this complication. When new or increasing hydronephrosis is found a loopogram or antegrade pyelogram (if the ileocecal valve is competent) should be performed to evaluate the ileal portion of the ileocecal conduit.

Adolescent↗