How do they get here: Does the method of transportation impact salvage for patients with testicular torsion?

INTRODUCTION: A growing number of patients are arriving at our tertiary care center for evaluation of possible testicular torsion using ambulance or helicopter transport. In many cases the parents arrive by car before the patient arrives. Are these advanced methods of medical transport worth the expense and risk in the case of suspected testicular torsion? OBJECTIVE: We evaluated the total number of patients presenting to our emergency room for suspected testicular torsion to see if the means of transport affected testicular survival. STUDY DESIGN: Retrospective. RESULTS: As shown below in the table, the means of transport did not impact on testicular salvage. DISCUSSION: It is understandable that many patients with scrotal pain seek treatment closer to home because of their pediatrician's recommendation and/or family preference. However once evaluated many patients are transferred because of a lack of urologists willing to evaluate and treat the pediatric patients in community settings or because of a lack of anesthesia support. These patients are often transported by ambulance or helicopter. Our data would suggest that there is no improvement in the testicular salvage rate seen with these more advanced means of medical transportation compared with transfer by private car even when we restrict the analysis to patients traveling from over 40 miles away. We suspect that important time is lost while waiting to make such transfer arrangements. Furthermore transfer by ambulance or helicopter is more expensive and these costs are often passed on to families. Transfer by helicopter is also riskier. While an argument can be made in favor of medical transport over long distances or long driving times, this data suggests that many of these transfers could be accomplished by car with no effect on testicular salvage rates. CONCLUSION: The rate of testicular salvage was not affected by the means of transport to our tertiary facility. Only 4 patients would have required advanced of medical transport if this were limited to those facilities over 100 miles or 1.5 hours driving time away. This would achieve a substantial cost savings with no measurable change in outcome.

Efficacy and tolerability of albiglutide versus placebo or pioglitazone over 1 year in people with type 2 diabetes currently taking metformin and glimepiride: HARMONY 5.

AIMS: To investigate the efficacy and tolerability of albiglutide, a weekly glucagon-like peptide-1 receptor agonist, when added to metformin and glimepiride in a triple therapy regimen in people with type 2 diabetes mellitus. METHODS: This was a 156-week, randomized, double-blind, parallel-group, multicentre study. In the present paper we describe the primary results, namely those at 52 weeks. Adult participants (n = 685) were randomly assigned to albiglutide (30 mg/week), pioglitazone (30 mg/day) or placebo. If needed, blinded uptitration of albiglutide (to 50 mg/week) and pioglitazone (to 45 mg/day) was allowed. The participant's current dose of metformin (>1500 mg/day) was maintained throughout. The glimepiride dose (4 mg/day), standardized before randomization, could be decreased if persistent hypoglycaemia occurred. RESULTS: The week 52 model-adjusted difference in change of glycated haemoglobin (primary endpoint) for albiglutide versus placebo was -0.87 [95% confidence interval (CI) -1.07, -0.68]%-units (p < 0.001), and for albiglutide versus pioglitazone it was 0.25 (95% CI 0.10, 0.40)%-units; therefore, not non-inferior. In the albiglutide group only, fasting plasma glucose reduced rapidly in the first 2 weeks. Confirmed hypoglycaemia occurred in 14% of participants on albiglutide, 25% on pioglitazone and 14% on placebo. The mean (± standard error) weight change was -0.42 (±0.2) kg with albiglutide, +4.4 (±0.2) kg (p < 0.001) with pioglitazone, and -0.40 (±0.4) kg with placebo and serious adverse events occurred in 6.3, 9.0 and 6.1% of participants in the respective groups. Injection site reactions occurred in 13% of participants on albiglutide and resulted in treatment discontinuation for four participants (1.4%). CONCLUSIONS: Albiglutide, as part of triple therapy, provided effective glucose-lowering and was generally well tolerated.

Albiglutide does not impair the counter-regulatory hormone response to hypoglycaemia: a randomized, double-blind, placebo-controlled, stepped glucose clamp study in subjects with type 2 diabetes mellitus.

AIM: To determine if the glucagon-like peptide-1 (GLP-1) receptor agonist albiglutide, once weekly, impairs counter-regulatory responses during hypoglycaemia. METHODS: We conducted a randomized, double-blind, parallel, placebo-controlled study in subjects with type 2 diabetes mellitus. A single dose of albiglutide 50 mg (n = 22) or placebo (n = 22) was administered on day 1. Glucose was clamped on day 4 (to coincide with the approximate albiglutide maximum plasma concentration) at 9.0, 5.0, 4.0, 3.3 and 2.8 mmol/l (162, 90, 72, 59.4 and 50.4 mg/dl), with a post-clamp recovery period to 3.9 mmol/l (70 mg/dl). Hormone measurements were made at each plateau and adverse events (AEs) were recorded. RESULTS: The counter-regulatory hormones glucagon, epinephrine, norepinephrine, growth hormone and cortisol were appropriately suppressed when plasma glucose levels were >4.0 mmol/l (>72 mg/dl), but increased in the albiglutide and placebo groups with glucose levels <3.3 mmol/l (<59.4 mg/dl) in response to hypoglycaemia. The area under the curve geometric mean ratios (albiglutide : placebo), calculated from the clamped plateau of 4.0 mmol/l (72 mg/dl) to the glucose recovery point, were not significantly different for any of the counter-regulatory hormones. When plasma glucose levels were >5.0 mmol/l (>90 mg/dl), albiglutide increased pancreatic ß-cell secretion of C-peptide in a glucose-dependent manner to a greater extent than did placebo, and it was suppressed in each group when levels were <4.0 mmol/l (<72 mg/dl). No significant difference between groups was observed in the recovery time to glucose level ≥3.9 mmol/l (≥70 mg/dl). There were no clinically relevant differences in AEs or other safety variables. CONCLUSIONS: A single 50-mg dose of albiglutide was well tolerated and did not impair the counter-regulatory response to hypoglycaemia. These data provide mechanistic evidence supporting the low intrinsic hypoglycaemic potential of albiglutide.

[Urethral valves. Fate of the bladder and upper urinary tract]. / UrethralklappenSchicksal der Blase und des oberen Harntrakts.

Posterior urethral valve is a condition that leads to characteristic changes in the bladder and upper tracts. The bladder develops hypertrophic changes including muscular hypertrophy, dilatation of the prostatic urethra (keyhole appearance), and progressive hydroureteronephrosis. The voiding cystourethrogram confirms the diagnosis and documents vesicoureteral reflux and accompanying bladder changes. The follow-up of the serum creatinine level is a parameter for renal recovery. In our opinion, primary endoscopic ablation of the valves followed by a wait-and-see attitude is the most efficacious management of posterior urethral valves. The development of the bladder function is controlled by ultrasound and voiding cystourethrogram. Urodynamics provide a formal and objective means of assessing bladder function, but should be carefully applied in infants. Valve ablation in a neonate with significant reflux and a markedly trabeculated bladder can remodel itself remarkably within the 1st year of life. The persistence of hydronephrosis, bladder wall thickening and trabeculation, and persistent elevation of serum creatinine can all be harbingers that a degree of bladder outlet obstruction persists and one needs to rule out a persistent anatomic obstruction. At what point a functional obstruction occurs and which management is reasonable are still issues of debate and require the vigilance of a pediatric urologist to sort out. Dysfunctions of the bladder such as hyperreflexia, hypertonic, small capacity bladder, sphincter incompetence and/or myogenic failure should be adequately treated.

Contribution of hepatic lipase, lipoprotein lipase, and cholesteryl ester transfer protein to LDL and HDL heterogeneity in healthy women.

Hepatic lipase (HL) and cholesteryl ester transfer protein (CETP) have been independently associated with low density lipoprotein (LDL) and high density lipoprotein (HDL) size in different cohorts. These studies have been conducted mainly in men and in subjects with dyslipidemia. Ours is a comprehensive study of the proposed biochemical determinants (lipoprotein lipase, HL, CETP, and triglycerides) and genetic determinants (HL gene [LIPC] and Taq1B) of small dense LDL (sdLDL) and HDL subspecies in a large cohort of 120 normolipidemic, nondiabetic, premenopausal women. HL (P<0.001) and lipoprotein lipase activities (P=0.006) were independently associated with LDL buoyancy, whereas CETP (P=0.76) and triglycerides (P=0.06) were not. The women with more sdLDL had higher HL activity (P=0.007), lower HDL2 cholesterol (P<0.001), and lower frequency of the HL (LIPC) T allele (P=0.034) than did the women with buoyant LDL. The LIPC variant was associated with HL activity (P<0.001), HDL2 cholesterol (P=0.034), and LDL buoyancy (P=0.03), whereas the Taq1B polymorphism in the CETP gene was associated with CETP mass (P=0.002) and HDL3 cholesterol (P=0.039). These results suggest that HL activity and HL gene promoter polymorphism play a significant role in determining LDL and HDL heterogeneity in healthy women without hypertriglyceridemia. Thus, HL is an important determinant of sdLDL and HDL2 cholesterol in normal physiological states as well as in the pathogenesis of various disease processes.

The decompensated detrusor V: molecular correlates of bladder function after reversal of experimental outlet obstruction.

PURPOSE: Calcium ion homeostasis has a significant role in smooth muscle function. Its regulation requires complex storage and release mechanisms via ion pumps and channels located within intracellular storage sites (sarcoplasmic reticulum) and at the plasma membrane. We have previously reported a dramatic loss of the 2 major sarcoplasmic reticulum proteins sarcoplasmic endoplasmic reticulum calcium magnesium adenosine triphosphatase (SERCA2) and the ryanodine sensitive ion channel, also called the ryanodine receptor, after outlet obstruction. In our current study we investigated the correlation of the expression of these 2 major sarcoplasmic reticulum components with bladder function recovery after the reversal of outlet obstruction. METHODS AND METHODS: Standard partial bladder outlet obstruction was created in adult New Zealand White rabbits. Voiding patterns were monitored 2 and 4 weeks postoperatively, and rabbits were selected for outlet obstruction reversal based on a voiding pattern consistent with a decompensated state, as indicated by a frequency of greater than 30 voids daily and an average voided volume of less than 4 cc. Bladder biopsy was done when outlet obstruction was reversed. Voiding performance was monitored postoperatively and the animals were sacrificed 2 weeks later. Voiding patterns and muscle strip studies enabled us to define 2 functional outcome categories after reversal, namely normal versus minimally improved. Microsomal membrane protein fractions were prepared from the same bladder tissues before and after reversal, and probed by Western blot analysis for SERCA2 and ryanodine receptor expression. RESULTS: Western blot analysis revealed a major loss of SERCA2 and ryanodine receptor expression at the time of reversal and biopsy. In 65% of bladders obstruction reversal resulted in a normalized voiding pattern with a recovery of ryanodine receptor expression that was 15% to 65% of control values. In contrast, in the 35% of bladders with persistent voiding symptoms there was minimal recovery of ryanodine receptor expression. SERCA2 expression increased slightly in each group after reversal but did not differ in bladders with normalized versus improved function. CONCLUSIONS: Bladder decompensation is highly associated with a loss of sarcoplasmic reticulum function. Furthermore, the decompensated detrusor recovers function after obstruction reversal, which is associated with the recovery of these sarcoplasmic reticulum components.

The contribution of intraabdominal fat to gender differences in hepatic lipase activity and low/high density lipoprotein heterogeneity.

Hepatic lipase (HL) hydrolyzes triglyceride and phospholipid in low and high density lipoprotein cholesterol (LDL-C and HDL-C, respectively), and elevated HL activity is associated with small, dense atherogenic LDL particles and reduced HDL2-C. Elevated HL activity is associated with increasing age, male gender, high amounts of intraabdominal fat (IAF), and the HL gene (LIPC) promoter polymorphism (C nucleotide at -514). We investigated the mechanisms underlying the difference in HL activity between men (n = 44) and premenopausal women (n = 63). Men had significantly more IAF (144.5 +/- 80.9 vs. 66.5 +/- 43.2 cm(2), respectively; P < 0.001), higher HL activity (220.9 +/- 94.7 vs.129.9 +/- 53.5 nmol/mL.min; P < 0.001), more dense LDL (Rf, 0.277 +/- 0.032 vs. 0.300 +/- 0.024; P = 0.01), and less HDL2-C (0.19 +/- 0.10 vs. 0.32 +/- 0.16 mmol/L; P < 0.001) than women. After adjusting for IAF and the LIPC polymorphism, men continued to have higher (but attenuated) HL activity (194.5 +/- 80.4 vs.151.0 +/- 45.2, respectively; P = 0.007) and lower HDL2-C (0.23 +/- 0.11 vs. 0.29 +/- 0.14 mmol/L; P = 0.02) than women. Using multiple regression, HL activity remained independently related to IAF (P < 0.001), gender (P < 0.001), and the LIPC genotype (P < 0.001), with these factors accounting for 50% of the variance in HL activity. These data suggest that IAF is a major component of the gender difference in HL activity, but other gender-related differences, perhaps sex steroid hormones, also contribute to the higher HL activity seen in men compared with premenopausal women. The higher HL activity in men affects both LDL and HDL heterogeneity and may contribute to the gender difference in cardiovascular risk.

Hormonal therapy for the subfertility of cryptorchidism.

BACKGROUND: The subfertility of cryptorchidism correlates with severely reduced total germ cell counts in prepubertal testicular biopsies of undescended testes. Reduced total germ cell counts are associated with defects in the two prepubertal steps in maturation and proliferation in germ cells: first, the transformation of the fetal stem cell pool (gonocytes) into the adult stem cell pool (adult dark spermatogonia) at two to three months of age and, second, the transformation of adult dark spermatogonia into primary spermatocytes (meiosis) at 4-5 years. The defects in maturation are associated with blunting of the normal surges in gonadotropins and testosterone. Prepubertal treatment with gonadotropin-releasing hormones would theoretically trigger normal germ cell maturation and proliferation and thereby improve total germ cell counts and improve fertility. Prepubertal treatment of cryptorchidism with the GnRH analogue Buserelin has resulted in improved total germ cell counts and improved spermiograms. The purpose of this report is to describe the results of treatment of cryptorchidism with the GnRH analogue Naferelin. PATIENTS: Twelve boys with cryptorchidism, 6 unilateral and 6 bilateral, and severely reduced germ cell counts in testicular biopsies were treated with Naferelin following successful orchidopexy and bilateral testicular biopsies. Response of the total germ cell counts was assessed in follow-up bilateral biopsies within 5 months of completing the hormonal therapy. RESULTS: Eight of the 12 boys (5 of the 6 with unilateral and 3 of the 6 with bilateral cryptorchidism) showed improvement in the total germ cell counts in one or both testes. All 8 had a poor prognosis for fertility pretreatment and a good prognosis for fertility posttreatment. Of the 5 with unilateral cryptorchidism who improved, 2 showed improvement in both testes; and 3, only in the contralateral descended testes. All 3 of the boys with bilateral cryptorchidism who improved showed improvement in both testes. Testes with absence of germ cells and older patients tended to show no improvement. Of the 6 contralateral descended, 5 (83%) improved, and of the 18 undescended testes, 8 (44%) improved. CONCLUSIONS: In this preliminary study, Naferelin therapy appears to induce improvement in the total germ cell counts and the prognosis for future fertility in 75% of patients.

The decompensated detrusor IV: experimental bladder outlet obstruction and its functional correlation to the expression of the ryanodine and voltage operated calcium channels.

PURPOSE: Calcium ion homeostasis has a significant role in smooth muscle function. Its regulation requires complex storage and release mechanisms via ion pumps and channels located within intracellular storage sites (sarcoplasmic reticulum) and at the plasma membrane. A prominent component of the sarcoplasmic reticulum is the ryanodine sensitive ion channel which releases calcium from the sarcoplasmic reticulum into the cytosol. At the level of the plasma membrane the voltage operated calcium channel (dihydropyridine sensitive) serves to allow an influx of extracellular calcium. Our prior studies have shown a loss of sarcoplasmic endoplasmic reticulum Ca++Mg++ATPase expression following outlet obstruction. In this study we correlate ryanodine and voltage operated calcium channel protein expression with bladder function following partial outlet obstruction. MATERIALS AND METHODS: Standardized partial bladder outlet obstructions were created in adult New Zealand white rabbits, which were divided into control, sham operated and obstructed groups. Muscle strip studies further subcategorized the obstructed group into compensated (force greater than 50% of control) and decompensated (force less than 50% of control) and were correlated with in vivo determinations of voiding frequency and voided volumes. Microsomal membrane protein fractions were prepared from the same bladder tissue and were used for Western blot analysis using specific monoclonal antibodies. RESULTS: Increased voiding frequency and decreased voided volumes correlated with the definitions of compensated and decompensated. The Western blots revealed a near disappearance of ryanodine expression in the decompensated group with minimal changes in the expression of the voltage operated calcium channel. CONCLUSIONS: Bladder performance as measured in vivo and in vitro after outlet obstruction is influenced in part by smooth muscle cell ability to maintain calcium homeostasis via the sarcoplasmic reticulum. Bladder decompensation is highly associated with a loss of sarcoplasmic reticulum function with lesser changes taking place in those calcium regulatory proteins at the plasma membrane.

Changes in LDL density across the menopausal transition.

BACKGROUND: The risk of coronary artery disease increases in women after menopause. This increased risk may be associated with alterations in the lipid profile characterized by changes in LDL particle size and buoyancy. Characterization of lipoprotein levels and LDL buoyancy across the stages of the menopausal transition has yet to be reported. METHODS: Plasma lipoprotein concentrations, LDL buoyancy, and body mass index (BMI) were studied cross-sectionally in five groups of women: premenopausal women (n = 42), women in early menopausal transition (n = 35), middle menopausal transition (n = 19), late menopausal transition (n = 20), and postmenopausal women (n = 14). No women were taking estrogen. RESULTS: The postmenopausal women had significantly higher low-density lipoprotein cholesterol (LDL-C) and total cholesterol than premenopausal women (P < 0.05). LDL-C and Apo B was significantly higher in women in the late menopausal transition compared to premenopausal women (P < 0.05). All women in the menopausal transition and postmenopause had significantly more dense LDL than premenopausal women (P < 0.05). Multiple regression analysis revealed that the change in LDL buoyancy associated with the menopausal transition period could be explained by changes in triglyceride and HDL-C, related to changes in body mass index. CONCLUSIONS: These data suggest that the menopausal transition is associated with more dense LDL and higher LDL-C levels in comparison to premenopausal women. It appears that whereas LDL-C may change late in the menopausal transition, the production of denser LDL particles appears early in the menopausal transition, both acting to worsen the lipoprotein profile. Increased triglyceride and decreased HDL appeared to account for the shift toward small, dense LDL, presumably related to increased BMI. The change in LDL density may contribute to the higher incidence of atherosclerosis in postmenopausal women.

PLTP activity in premenopausal women. Relationship with lipoprotein lipase, HDL, LDL, body fat, and insulin resistance.

Plasma phospholipid transfer protein (PLTP) is thought to play a major role in the facilitated transfer of phospholipids between lipoproteins and in the modulation of high density lipoprotein (HDL) particle size and composition. However, little has been reported concerning the relationships of PLTP with plasma lipoprotein parameters, lipolytic enzymes, body fat distribution, insulin, and glucose in normolipidemic individuals, particularly females. In the present study, 50 normolipidemic healthy premenopausal females were investigated. The relationships between the plasma PLTP activity and selected variables were assessed. PLTP activity was significantly and positively correlated with low density lipoprotein (LDL) cholesterol (r(s) = 0.53), apoB (r(s) = 0.44), glucose (r(s) = 0.40), HDL cholesterol (r(s) = 0.38), HDL(3) cholesterol (r(s) = 0.37), lipoprotein lipase activity (r(s) = 0.36), insulin (r(s) = 0.33), subcutaneous abdominal fat (r(s) = 0.36), intra-abdominal fat (r(s) = 0.29), and body mass index (r(s) = 0.29). HDL(2) cholesterol, triglyceride, and hepatic lipase were not significantly related to PLTP activity. As HDL(2) can be decreased by hepatic lipase and hepatic lipase is increased in obesity with increasing intra-abdominal fat, the participants were divided into sub-groups of non-obese (n = 35) and obese (n = 15) individuals and the correlation of PLTP with HDL(2) cholesterol was re-examined. In the non-obese subjects, HDL(2) cholesterol was found to be significantly and positively related to PLTP activity (r(s) = 0.44). Adjustment of the HDL(2) values for the effect of hepatic lipase activity resulted in a significant positive correlation between PLTP and HDL(2) (r(s) = 0.41), indicating that the strength of the relationship between PLTP activity and HDL(2) can be reduced by the opposing effect of hepatic lipase on HDL(2) concentrations. We conclude that PLTP-facilitated lipid transfer activity is related to HDL and LDL metabolism, as well as lipoprotein lipase activity, adiposity, and insulin resistance.

A hepatic lipase gene promoter polymorphism attenuates the increase in hepatic lipase activity with increasing intra-abdominal fat in women.

High hepatic lipase (HL) activity is associated with an atherogenic lipoprotein profile of small, dense LDL particles and lower HDL(2)-C. Intra-abdominal fat (IAF) is positively associated with HL activity. A hepatic lipase gene (LIPC) promoter variant (G-->A(-250)) is associated with lower HL activity, higher HDL(2)-C, and less dense LDL particles. To determine whether the LIPC promoter polymorphism acts independently of IAF to regulate HL, 57 healthy, premenopausal women were studied. The LIPC promoter A allele was associated with significantly lower HL activity (GA/AA=104+/-34 versus GG=145+/-57 nmoles x mL(-1) x min(-1), P=0.009). IAF was positively correlated with HL activity (r=0.431, P<0.001). Multivariate analysis revealed a strong relationship between both the LIPC promoter genotype (P=0. 001) and IAF (P<0.001) with HL activity. The relationship between IAF and HL activity for carriers and noncarriers of the A allele was curvilinear with the carriers having a lower apparent maximum level of plasma HL activity compared with noncarriers (138 versus 218 nmoles x mL(-1) x min(-1), P<0.001). In addition, the LIPC A allele was associated with a significantly higher HDL(2)-C (GA/AA=16+/-7 versus GG=11+/-5 mg/dL, P=0.003). We conclude that the LIPC promoter A allele attenuates the increase in HL activity due to IAF in premenopausal women.

Bladder augmentation with urothelial preservation.

PURPOSE: Bladder reconstruction is performed because the characteristic properties of a healthy bladder are no longer present. The bladder manifests poor capacity, poor compliance and potential or actual changes in the upper tracts that may lead to damage. Augmentation procedures provide a means to improve capacity and compliance, and they may be performed with catheterizable channels to facilitate bladder emptying. Natural tissues or synthetic materials may be used but urothelial preservation is desirable. Demucosalized augmentation with a gastric flap and auto-augmentation with peritoneum are techniques that have been used in the last 5 years. MATERIALS AND METHODS: We retrospectively evaluated the records of 13 patients who underwent demucosalized augmentation with a gastric flap and 8 who underwent augmentation with peritoneum from 1992 to 1995. Average age of the 11 girls and 10 boys was 8 years (range 6 to 12). The diagnosis was myelomeningocele in 15 patients, exstrophy in 2, and the VATER association, posterior urethral valves, spinal cord injury and nonneurogenic neurogenic bladder in 1 each. Concurrent procedures included appendicovesicostomy creation, a fascial sling or wrap and ureteroneocystostomy. RESULTS: Mean followup is 50 months for patients who underwent demucosalized augmentation with a gastric flap and 47 for those who underwent augmentation with peritoneum. Outcome was defined as good-dry for 4 hours, catheterization without difficulty and a stable upper tract; poor-a secondary procedure (augmentation) required because the initial procedure did not improve bladder capacity, compliance, continence or the degree ofhydronephrosis, and fair-dry for less than 4 hours, some problems with incontinence, or compliance 10 ml/cm water or less. Of the patients who underwent demucosalized augmentation with a gastric flap the outcome was good in 5, fair in 4 and poor in 4 who required repeat augmentation. Of the 8 patients who underwent auto-augmentation with peritoneum the outcome was good in 5 and poor in 2, and 1 was lost to followup. CONCLUSIONS: Augmentation with urothelial preservation may result in a good capacity, compliant bladder in certain patients but a poorly compliant, small capacity bladder in others. Our overall results underscore the lack of understanding of the properties and characteristics of these bladders and of stromal-epithelial interaction that occurs after augmentation. Such an understanding is critical before this procedure can be recommended routinely.

Complete primary closure of bladder exstrophy. Epispadias and bladder exstrophy repair.

Bladder exstrophy remains one of the most challenging problems in pediatric urology. Recent efforts have focused on primary reconstruction rather than urinary diversion to treat exstrophy. Complete primary closure appears to offer improved continence and decreases the number of surgical procedures required to treat exstrophy.

Laparoscopic and histologic evaluation of the inguinal vanishing testis.

OBJECTIVES: Visual inspection of the spermatic cord vessels and vas deferens during laparoscopy now frequently determines further treatment. We set out to explore the implications of atretic spermatic cord vessels and vas deferens entering the inguinal ring, a finding noted on laparoscopic examination in some patients with a nonpalpable testis, and that we refer to as the inguinal vanishing testis. METHODS: We reviewed our series of 35 patients with nonpalpable testes with regard to the laparoscopic, surgical, and histopathologic findings of the involved gonadal structures. RESULTS: We noted atretic vessels and vas deferens entering the inguinal ring in 14 patients in this series. All 14 patients underwent open inguinal exploration. Histopathologic findings revealed fibrosis and hemosiderin deposits alone in 13 patients. One specimen had a microscopic focus of residual seminiferous tubules. No specimen contained dysgenetic gonadal tissue. CONCLUSIONS: We submit that patients with inguinal vanishing testes do not need to undergo inguinal exploration to remove residual testicular tissue. Only rarely will viable seminiferous tubules be found, so the risk of malignant degeneration is remote. The histopathologic findings suggest that the inguinal vanishing testis occurs secondary to a vascular accident in utero or in the neonatal period.

A unique new model to study the effects of urinary diversion in the developing rabbit bladder.

PURPOSE: Little is known about the developmental effects of high urinary diversion and bladder defunctionalization in infancy. Although clinical experience shows that a poorly functional bladder may result from urinary diversion in infancy, the mechanisms of change and specific bladder wall alterations have not been well characterized. We hypothesized that cyclic filling and emptying are necessary for normal bladder development. To investigate this important question we created a new animal model. MATERIALS AND METHODS: We designed a new method of hemibladder urinary diversion in 3-week-old New Zealand white rabbits. After vertical midline bladder division half of the bladder was formed into a functional reservoir, which remained in continuity with the ipsilateral ureter and urethra. The other bladder half was defunctionalized and isolated from the urine flow by ureteral ligation. Diversion was created for 3, 7, 14 and 28 days. Urodynamic evaluation was done in the functionalized hemibladders and age matched normal rabbit bladders to test the validity of the functionalized hemibladder as an internal control. Functional and defunctionalized hemibladders as well as age matched, nonoperated normal rabbit bladders were weighed, sectioned and stained to demonstrate muscle and connective tissue components. RESULTS: In 22 of the 27 healthy rabbits (81%) good quality diverted and functional bladder specimens were obtained after diversion. Defunctionalized hemibladders grew more slowly than functionalized bladders and normal age matched control bladders. Histological staining of the bladder wall demonstrated increased connective tissue between the muscle bundles within the diverted specimens than in functional bladders. CONCLUSIONS: Our successful model of urinary diversion may be used to study the developmental and histological effects of urinary diversion in the young bladder. Bladder growth and histological appearance are altered when the stimulus of cyclic filling and emptying is removed. Further studies using this model are warranted to define fully bladder changes that result from diversion and investigate the mechanism of the observed changes.

Lower urinary tract changes after early valve ablation in neonates and infants: is early diversion warranted?

PURPOSE: Severe hydronephrosis, high grade reflux and/or renal insufficiency often leads to proximal urinary tract diversion in male infants with posterior urethral valves. Even with this treatment progressive loss of renal function often occurs. Unfortunately with early diversion the bladder, already damaged by in utero obstruction, is also defunctionalized. Alternative treatment with valve ablation in the newborn period and without diversion may facilitate recovery of normal bladder function. MATERIALS AND METHODS: We retrospectively reviewed the records of infants treated for posterior urethral valves before age 1 year at our institution in the last 8 years. Treatment comprised primary valve ablation in 23 patients and urinary diversion in 8. Preoperative and serial postoperative voiding cystourethrograms were scored for degree of trabeculation, bladder neck hypertrophy and prostatic urethral dilatation in all patients undergoing primary valve ablation. Recovery of bladder and renal function after primary valve ablation was compared to that of patients treated with urinary diversion. RESULTS: All patients treated with primary valve ablation demonstrated marked improvement or resolution of bladder abnormalities on voiding cystourethrography by 1 year postoperatively. Bladder compliance and volume were statistically better than in patients treated with primary diversion. Upper tract diversion failed to halt progressive renal failure in 5 of the 6 patients who underwent diversion. Similarly primary valve ablation did not stop progressive renal failure in a matched group of patients. CONCLUSIONS: Early ablation of posterior urethral valves results in the recovery of normal bladder appearance and function when performed in the first months of life. Severe renal insufficiency tends to progress even with upper tract diversion. Furthermore, this treatment prevents normal bladder cycling, which may inhibit bladder recovery in the patient with posterior urethral valves.

Developmental regulation of collagen differential expression in the rabbit bladder.

PURPOSE: It has been suggested that the amount and relative ratios of different types of collagen influence bladder compliance. To understand the mechanisms regulating collagen synthesis and degradation in the bladder we investigated the gene expression of collagen types I and III in the rabbit bladder during normal development. MATERIALS AND METHODS: New Zealand white rabbits ages fetus to adult were used for this study. The mid portion of the bladder wall was harvested. Northern blot hybridization was performed to analyze quantitatively collagen types I and III messenger (m) ribonucleic acid (RNA), and in situ hybridization was done to localize the messages. Corresponding protein distributions were obtained by immunohistochemical staining. RESULTS: Types I and III collagen are developmentally regulated at the level of gene expression. The temporal and spatial distribution of the mRNA transcripts of alpha 1(I) and alpha 1(III) correlates with extracellular protein deposition. Differential distribution of the mRNA transcripts is also developmentally regulated. CONCLUSIONS: This study characterizes the relationship between collagen gene expression and normal rabbit bladder development. The expression of alpha 1(I) and alpha 1(III) alters as the bladder grows. High levels and nonconcordant up and down regulation of different types of collagen mRNA during early development demonstrate the complexity of the extracellular matrix in a young bladder. This observation may be important in our understanding of the injury response in a developing versus mature bladder.