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Biomedical subjects

J W Duckett

Publications and source records attributed to J W Duckett.

At least 19 recordsLinked to original sources

Evolution in the management of infant pyeloplasty.

Improving diagnostic modalities, evolving concepts regarding perinatal renal physiology, and advances in surgical technique have contributed to an evolution in the management of infant pyeloplasties. Currently, the majority of patients present with a prenatal diagnosis of ureteropelvic junction obstruction and do not require surgical intervention prior to 4 weeks of age. Postnatal ultrasound, voiding cystourethrography, and nuclear renography complete the diagnostic evaluation, with intravenous urography and retrograde pyelography being unnecessary in the majority of infants. A decreasing incidence of complications and a shortening of hospital stay has been documented. We presently prefer a dismembered, nonintubated technique performed through a dorsal lumbotomy approach.

Clinical Protocols

The predictive value of ultrasonography in evaluation of infants with posterior urethral valves.

Between 1981 and 1989, 28 infants less than 6 months old with posterior urethral valves underwent ultrasound evaluation as part of the initial evaluation at our hospital. The single ultrasound feature that correlated with subsequent renal function was the status of corticomedullary differentiation. The presence of corticomedullary junctions in at least 1 kidney in 17 infants was always associated with a serum creatinine level of 0.8 mg./dl. or less in long-term followup. Of 11 patients with absent corticomedullary differentiation 7 had eventual creatinine levels of greater than 0.8 mg./dl. with 5 of them suffering clinically significant renal insufficiency. An association between vesicoureteral reflux and absent corticomedullary junctions was also found.

Follow-Up Studies

Is lamina propria matrix responsible for normal bladder compliance?

Immunohistochemistry using monoclonal and polyclonal antibodies to extracellular matrix proteins is a highly sensitive tool for the characterization of matrix components. For the first time in the normal and noncompliant human bladder we have used antibodies to collagen types I, III and IV, and elastin to provide morphological correlation with mechanical properties noted clinically. In the normal bladder elastin and collagen types I and III showed intense localization in the lamina propria with modest localization in the detrusor layer. In contrast, lamina propria staining in the noncompliant bladder was essentially unchanged, while there was intense localization within the detrusor layer. Significantly, this intense localization consisted of collagen type III and elastin with little increase in type I. Type IV collagen is associated with basement membranes and individual smooth muscle cells, and shows commensurate increase in specimens with muscle hypertrophy and/or hyperplasia. These observations suggest that in the normal bladder the lamina propria may be a major structural capacitance layer with the smooth muscle covering it. The collagen fibers of the lamina propria may gradually unfold during filling, thus, accounting for normal compliance while in the noncompliant bladder the capacitance layer shifts outward to the infiltrated smooth muscle, thus, preventing the normal expansion of the lamina propria. The smooth muscle infiltration consists of a deposition of collagen type III and elastin with little increase of collagen type I, and it results in a loss of compliance. The pattern of localization would suggest that the smooth muscle is responsible for this accumulation.

Adolescent

Lithogenic properties of enterocystoplasty.

Calculi formed in 26 of 87 patients (30%) following augmentation enterocystoplasty, of which 23 formed within the reservoir, at a mean interval of 25 months postoperatively. The calculi were composed principally of triple phosphates suggesting an important etiological role of bacteriuria and the urease reaction. Open cystolithotomy was the most successful means of removing the calculi.

Humans

An absent testis is associated with contralateral testicular hypertrophy.

Surgical exploration was done in 109 boys ages birth through 9 years with unilateral impalpable testes by physical examination under anesthesia. Of the patients 51 (47%) had an absent testis and 58 had intra-abdominal testes. At open biopsy of the contralateral descended testis the 3 dimensions of the exposed testis were recorded and testicular volume was calculated. The mean volume of the contralateral descended testes of boys with an absent testis was greater than that of boys with intra-abdominal testes at all ages. The differences were significant (p = 0.0019 to 0.0117) from birth through year 4 but not from years 5 through 9. However, the standard deviations ranged from 27 to 74% of the means, and there was broad overlap of the volumes of the 2 groups. These findings indicate that, although the volume of the contralateral descended testis of boys with an absent testis is significantly greater than that of boys with intra-abdominal testes, the volume of the contralateral descended testis is not a reliable criterion for differentiating an absent testis from an intra-abdominal testis in a boy with a unilateral impalpable testis. Surgical exploration continues to be the method of choice for making the diagnosis of an absent testis.

Adaptation, Physiological

Managing apparent ureteropelvic junction obstruction in the newborn.

A total of 97 newborns with apparent ureteropelvic junction obstruction was evaluated from mid 1984 to 1989. Evaluation and management are described. Of these patients 39 with an affected kidney showing good initial differential function (greater than 35%) by diethylenetriaminepentaacetic acid scan and 2 showing diminished function (less than 35%) were followed nonoperatively. Six patients (15%) eventually required pyeloplasty for diminishing function (4), urinary tract infections (1) or symptoms of colic (1). The 4 patients with diminishing function improved after pyeloplasty to at least the initial level. A total of 12 patients with good initial function (greater than 35%) of the affected kidney underwent early pyeloplasty (within 6 weeks of diagnosis). They were compared to the similar group of patients managed nonoperatively and followed by sequential renal scans. Eventual changes in percentage differential function in the nonoperative and early surgery groups were +2.8% and +4.1%, respectively. Changes in extraction factor were +0.8% (nonoperative group) and +0.9% (surgery group). No statistically significant difference was found. In the kidney with apparent ureteropelvic junction obstruction and good function, an initial nonoperative approach with sequential renal scan followup and pyeloplasty as needed appears to be reasonable and has resulted in no permanent loss of function.

Follow-Up Studies

Surgical results: International Reflux Study in Children--United States branch.

A total of 87 patients in the United States underwent surgical correction of vesicoureteral reflux as part of the International Reflux Study in Children. Of the 66 patients randomized to surgical treatment 2 were transferred to the medical group before surgery was performed, while 23 patients originally assigned to receive medical management ultimately underwent surgery. Of the patients 17 (20%) were less than 1 year old, while the remaining children were evenly distributed by age in 2-year intervals up to age 9 years. Reimplantation was performed by the Cohen technique in 52% and by the Politano-Leadbetter technique in 28% of the patients. Bilateral reimplantation was done in 70 patients (80%). The results were satisfactory, with no obstructions. In 81% of the patients average followup was 3.9 years, although followup of less than 1 year in 19% was satisfactory to determine obstruction. Only 3% of the children were lost to followup. Postoperative reflux, which was noted in 5 patients, resolved in all but 1 ureter. These results reflect the experience of senior surgeons in pediatric urology.

Child

Meatal advancement and glanuloplasty hypospadias repair after 1,000 cases: avoidance of meatal stenosis and regression.

We first described the meatal advancement and glanuloplasty (MAGPI) procedure in 1981 as a technique to repair distal hypospadias. During the last 10 years our experience has increased to more than 1,000 cases. Case selection is critical to surgical outcome. Excessively thin or rigid ventral parameatal skin, or a meatus that is too proximal or too wide must be avoided. To prevent the ventral meatal wall from falling back and leaving a retrusive meatus, the glans wrap to support the advanced ventral urethral wall requires a solid approximation of glans tissue in 2 layers. Meatal stenosis may be avoided by an adequately deep dorsal Heineke-Mikulicz tissue rearrangement, making the incision from within the urethral meatus distally into the glanular urethral groove. The MAGPI procedure is routinely performed on an outpatient basis without urinary diversion. A review of our experience with 1,111 cases during a 12-year period reveals that a secondary procedure was required in only 1.2%. The overall success rate with the MAGPI procedure suggests that it should continue to be an important operation in the reconstruction of distal hypospadias.

Follow-Up Studies

Early postnatal testicular maldevelopment in cryptorchidism.

It has been previously postulated that many cases of cryptorchidism are manifestations of a forme fruste of hypogonadotropic hypogonadism. In support of this theory the earliest postnatal histological abnormality in cryptorchid testes demonstrated by this morphometric study of semithin microscopic sections of testicular biopsies was hypoplasia of the Leydig cells, which was obvious from the first month of life. The second abnormality, defective transformation of gonocytes into adult dark spermatogonia, was significant from early in life. No reduction in the mean number of germ cells was detected in the first 7 months of life. The abnormal persistence of the untransformed gonocytes resulted in a total germ cell count that was similar to normal controls until the seventh month, when secondary degeneration of untransformed gonocytes led to a decrease in the total germ cell count. These findings are compatible with the hypothesis that the blunted neonatal surge of gonadotropins previously demonstrated in cryptorchid boys triggers a cascade of hormonal and secondary histological abnormalities that may culminate in a reduced fertility potential in adults. Early replacement hormonal therapy deserves further investigation as a rational approach to the treatment of germ cell maldevelopment and reduced fertility potential associated with cryptorchidism.

Biopsy

Evidence in favor of the mechanical (intrauterine torsion) theory over the endocrinopathy (cryptorchidism) theory in the pathogenesis of testicular agenesis.

There are 2 competing theories regarding the pathogenesis of testicular agenesis--the endocrinopathy/cryptorchidism and the mechanical/intrauterine torsion theories. We compare the number of Leydig cells, total number of germ cells and the transformation of adult dark spermatogonia into primary spermatocytes in semithin sections of testicular biopsies from 59 contralateral descended testes of patients with testicular agenesis with those in the contralateral descended testes from 250 patients with unilateral cryptorchidism. The contralateral descended testes from boys with testicular agenesis demonstrated higher numbers of Leydig cells, higher numbers of total germ cells and a higher rate of transformation of adult dark spermatogonia into primary spermatocytes than did the contralateral descended testes from the patients with unilateral cryptorchidism. These findings favor the mechanical/intrauterine torsion theory over the endocrinopathy/cryptorchidism theory in the pathogenesis of testicular agenesis.

Biopsy

Gonadal differentiation: a review of the physiological process and influencing factors based on recent experimental evidence.

The sexual differentiation of a gonad is determined in normal embryology by the presence or absence of the TDF gene, a short segment of DNA localized near the tip of the short arm of the Y chromosome. Under the stimulus of this gene, the somatic cells of the genital ridge differentiate into Sertoli cells and secrete anti-müllerian hormone. This hormone inhibits the germ cells from entering meiosis and may well also trigger the formation of the primary sex cords. Once the Sertoli cells are formed, further differentiation of the gonad is independent of the TDF presence, although this gene may further contribute to the normal functioning of the male gonad. In true hermaphroditism the normal regulation of the gonadal differentiation is missing. Gonadal differentiation may revert to a more primitive evolutionary level at which the rate of growth of the gonad determines its sexual direction. When this exceeds a certain threshold a testis may develop despite the absence of the TDF gene.

Animals

The MAGPI hypospadias repair in 1111 patients.

The meatal advancement and glanduloplasty (MAGPI) procedure was first described in 1981 for the repair of distal hypospadias. In the past decade, our experience has grown to more than 1000 procedures. An excellent surgical result requires careful case selection, avoiding cases with thin or rigid ventral parameatal skin or a meatus too proximal or too wide. The glans wrap to support the advanced ventral urethral wall requires a solid tissue approximation in two layers to prevent a retrusive meatus. Meatal stenosis can be avoided by assuring an adequate dorsal Heineke-Mikulicz tissue rearrangement and making an incision from within the urethral meatus well distally into the urethral groove. The MAGPI procedure routinely is performed on an outpatient basis without any urinary diversion. Our experience in 1111 cases during 12 years has required a second procedure in 1.2% of cases. The overall success rate with the MAGPI procedure suggests that it should continue to be used in the repair of distal hypospadias.

Follow-Up Studies

Developmental aspects of bladder contractile function: sensitivity to extracellular calcium.

The urinary bladders of 1-day and 1-week-old rabbits generate higher intravesical pressures in response to bethanechol and field stimulation than bladders isolated from mature 8-week-old rabbits. Yet the density of cholinergic receptors in the rabbit bladder does not change with maturation (1 day to 8 weeks). In an effort to better understand the molecular mechanisms by which newborn rabbit bladders generate greater pressures than the bladders of adult rabbits, we studied the effect of maturation on the relationship between extracellular calcium and contraction. Our results showed quite clearly that (1) at physiologic concentrations of calcium (2.5 mumol/l), isolated bladder strips of 1-day- and 1-week-old rabbits contracted in response to bethanechol to 98% of their maximal tension as opposed to 68% for their 8-week-old counterparts, (2) the ED50 (for calcium) for the 1-day and 1-week bladders was 0.4 mmol/l whereas the ED50 for the adult bladder strips was 2.2 mmol/l, and (3) the neonatal bladders demonstrated a much greater sensitivity to diltiazem than the adult bladders. The contractile response to calcium of the neonatal bladders was significantly inhibited by 1 mumol/l diltiazem whereas the 8-week-old bladders showed no inhibition at this concentration. In a second series of experiments, the effect of extracellular calcium on concentration was correlated with the intracellular concentration of free calcium using the calcium fluoride FURA-2 and surface spectrofluorometry. These studies confirmed that the increased contractile response of the neonatal bladder strips to calcium or cholinergic agonists was associated with an increase in the maximal intracellular free calcium concentration.

Animals

Effects of pregnancy on muscarinic receptor density and function in the rabbit urinary bladder.

The contractile response of the rabbit urinary bladder to field stimulation consists of both cholinergic and purinergic components. In general, approximately 60% of the contractile response to field stimulation is cholinergic and 40% is purinergic. Although the purinergic response represents a significant proportion of the initial (phasic) pressure response to field stimulation of the isolated whole bladder, it contributes only 10-15% of the ability of field stimulation to empty the bladder. The current study investigates the effects of pregnancy on the contractile responses of the isolated urinary bladder to cholinergic and purinergic stimulation. The results of these studies indicate that pregnancy induces substantial changes in the physiology and pharmacology of the urinary bladder. The following data are consistent with the theory that pregnancy substantially increases the relative purinergic component of the response to field stimulation (and presumably neuronal stimulation): (1) there was a significantly greater response of the bladders isolated from pregnant rabbits to low-frequency field stimulation; (2) atropine was more effective at inhibiting the pressure generation of bladders isolated from virgin female rabbits; (3) field stimulation was more effective at emptying bladders isolated from virgin female rabbits; (4) the response of the bladders from pregnant rabbits to bethanechol was significantly reduced, whereas the response to ATP was significantly increased. In addition to these effects of pregnancy on bladder physiology, pregnancy induced a 50% decrease in the muscarinic receptor density of the urinary bladder body, which correlated very well with the 50% decrease in the contractile response to bethanechol.

Animals

Low transurethral incision of single system intravesical ureteroceles in children.

Single system intravesical ureteroceles in children usually result in various degrees of hydroureteronephrosis requiring surgical intervention to provide drainage, decompression and preservation of renal function. Our experience with 7 symptomatic single system ureteroceles in 5 children managed by low transverse endoscopic ureterocele incision is reviewed. After endoscopic incision, hydroureteronephrosis decreased in all patients. Vesicoureteral reflux after incision was noted in only 1 kidney. The technique of short (2 to 3 mm.) low transverse ureterocele incision is recommended for the initial management of single system ureteroceles to relieve obstruction. Preservation of the flap valve ureteral antireflux mechanism is possible in most children. The technique is simply performed, can be safely done in the youngest child and, in many, obviates the need for a further operation.

Adolescent

Evaluation of fetal renal function: unreliability of fetal urinary electrolytes.

In the fetus with bilateral hydronephrosis it has been reported that a normal volume of amniotic fluid, absence of renal cortical cysts, urinary sodium less than 100 mEq./l., chloride less than 90 mEq./l. and osmolarity less than 210 mOsm. are prognostic factors indicative of good renal function, whereas oligohydramnios, cortical cysts and higher urinary levels of sodium, chloride or osmolarity suggest irreversible renal dysplasia. We report 5 cases in which the fetal urinary electrolytes were not predictive of ultimate renal function. In 3 instances fetal urinary electrolytes and osmolarity were abnormally elevated but the infants survived without ventilatory support. In 2 of these 3 patients the volume of amniotic fluid was normal. Diagnoses included posterior urethral valves, prune belly variant and bilateral ureteropelvic junction obstruction. In 2 cases with oligohydramnios fetal urinary electrolytes were suggestive of satisfactory renal function but the infants died of pulmonary hypoplasia and had bilateral renal dysplasia, prune belly syndrome and urethral atresia. Presently, the volume of amniotic fluid remains the most important prognostic sign in the fetus with bilateral hydronephrosis. Further work is necessary to identify other factors that may be more reliable as prognostic indexes of fetal renal function.

Electrolytes

Ontogeny of bladder function in the rabbit.

Although numerous experimental studies have addressed urinary bladder innervation, physiology and pharmacology, little information is available concerning the ontogeny of bladder function. The present study describes the developmental aspects of bladder mass, bladder capacity, pressure development and emptying in white New Zealand rabbits one day of age through maturity (11 to 15 weeks of age). The following studies were performed: Cystometry, pressure generation, rate of pressure generation, and emptying responses to field stimulation, cholinergic and purinergic stimulation using the in vitro whole bladder model. The results of these studies can be summarized as follows: 1) body weight and bladder weight increased in proportion to each other, bladder capacity increase proportionally with development until eight weeks of age, then increased substantially greater than body and bladder weight between eight and 11 to 15 weeks of age; 2) the ability to empty is similar for all ages; 3) pressure responsiveness to field stimulation, bethanechol, and ATP is greater at one day? of age, intermediate at one week of age, and similar for the other age groups; 4) The response to ATP (purinergic transmitter) is of an equal magnitude to the cholinergic response at one day, and reduces rapidly to approximately 45% of the cholinergic response by four weeks. Desensitization of the bladders to ATP reduced the response to field stimulation in the one day bladders to a significantly greater degree than the other age groups. These functional results indicate a marked alteration in cholinergic and purinergic response between the one day and the four week old rabbit bladders, with the response of the one week old bladders in between. The responses of the four, eight, and 11 to 15 week bladders was similar for equal volumes even though the bladder mass increased over threefold. This indicates that the ability of the bladder to generate pressure (during development) is not directly related to bladder mass.

Adenosine Triphosphate