Early urodynamic findings after complete primary repair of exstrophy.

INTRODUCTION: Detrusor contraction in bladder exstrophy (BE) patients following reconstruction is poorly understood as there are few published studies assessing urodynamic findings in this population. Understanding the ability of the detrusor to contract in BE patients early after closure may be able to inform the longer-term management and potential for the development of future continence in this population. OBJECTIVE: We sought to evaluate early detrusor contraction using urodynamic studies (UDS) in children who had previously undergone complete primary repair of bladder exstrophy (CPRE). We hypothesized that a majority of children with BE would display the presence of normal detrusor contractile function after CPRE. STUDY DESIGN: A retrospective review of our prospectively collected database was performed for all patients with a diagnosis of classic BE who underwent primary CPRE between 2013 and 2017. From this cohort we identified patients with at least one post-operative UDS at 3 years of age or older who had undergone an initial CPRE. Our primary outcome was the presence of a detrusor contraction demonstrated on UDS. RESULTS: There were 50 children (31 male, 19 female) with CBE who underwent CPRE between 2013 and 2017.There were 26 (13 male, 13 female) who met inclusion criteria. Median age was 3.5 (IQR: 3.2-4.7) years at the time of UDS Sixteen of the 26 (61.5%) generated a sustained detrusor contraction generating a void, with a median peak voiding pressure of 38 cm H20 (IQR: 28-51). The median bladder capacity reached was 48 ml, which represented a median of 30% of expected bladder capacity. The median post void residual (PVR) for the entire cohort was 26 ml (IQR: 9, 47) or 51% (IQR: 20%-98%) of their actual bladder capacity, while the median PVR for those children with a sustained detrusor contraction was 18 ml (IQR: 5, 46) or 33% (IQR: 27%, 98%) of their actual bladder capacity. Intraoperative bladder width and bladder dome to bladder neck length did not correlate with the presence of voiding via a detrusor contraction (p = 0.64). DISCUSSION: We present the first study assessing early UDS finding of detrusor contraction in BE patients after CPRE. In our cohort, 61.5% of patients were able to generate a sustained detrusor contraction on UDS which is a higher percentage than has been reported in previous series. A difference in initial surgical management may account for these findings. CONCLUSION: At short term follow up, the majority of children in our cohort were able to produce sustained detrusor contractions sufficient to generate a void per urethra with a modest post void residual volume. Long-term follow-up and repeated UDS will be needed to track detrusor contractility rates, bladder capacities, compliance, post void residuals and ultimately continence rates over time.

Investigation of somatic NKX2-5 mutations in congenital heart disease.

BACKGROUND: Reports of somatic mutations found in hearts with cardiac septal defects have suggested that these mutations are aetiologic in pathologic cardiac development. However, the hearts in these reports had been fixed in formalin for over 22 years. Because of the profound implication of this finding, we attempted to replicate it using fresh frozen tissue obtained in the current era from 28 patients with septal defects who underwent cardiac surgery and who were enrolled in our congenital heart disease tissue bank. METHODS: Our cohort included patients with atrial septal defects (ASD, n = 13), ventricular septal defects (VSD, n = 5), and atrioventricular canal defects (AVCD, n = 10). Cardiac tissue samples were collected both from diseased tissue located immediately adjacent to the defect and from anatomically normal tissue located at a site remote from the defect (right atrial appendage). Tissue samples were immediately frozen in liquid nitrogen and stored at -80 degrees C. Genomic DNA was isolated and amplified using the same methodology described in the previously published reports. 42 pathologic cardiac tissue samples were sequenced. RESULTS: One non-synonymous germline sequence variant was identified in one patient. Two synonymous germline sequence variants were identified in two separate patients. A common single nucleotide polymorphism (SNP) was identified in 16 patients. Based on the incidence of somatic mutations described in the previously published reports, our study was adequately powered to replicate the previous studies. No evidence of somatic mutations was found in this study. CONCLUSION: Somatic mutations in NKX2-5 do not represent an important aetiologic pathway in pathologic cardiac development in patients with cardiac septal defects.

Short-term outcomes of the multi-institutional bladder exstrophy consortium: Successes and complications in the first two years of collaboration.

INTRODUCTION/BACKGROUND: Bladder exstrophy is a rare diagnosis that presents major reconstructive challenges. To increase experience and proficiency in the care of bladder exstrophy (BE), the Multi-Institutional BE Consortium (MIBEC) was formed, with a focus on refining technical aspects of complete primary repair of bladder exstrophy (CPRE) and subsequent care. OBJECTIVE: Outcome measures included successful CPRE (absence of dehiscence), complications, and integrated points of technique and care over the short-term. STUDY DESIGN: Boston Children's Hospital, Children's Hospital of Philadelphia and Children's Hospital of Wisconsin alternately served as the host, with observation, commentary and critique by visiting collaborating surgeons. CPRE with bilateral iliac osteotomy was performed at 1-3 months of age. High-definition video capture of the surgery allowed local and distant broadcast to facilitate real-time observation and teaching, and recording of all procedures. RESULTS: From February 2013 to February 2015, MIBEC participating surgeons performed CPRE on 27 consecutive patients (22 classic BE, five epispadias). There were no dehiscences in 27 patients (0%, 95% CI 0-12.5%). Thirteen girls and 14 boys underwent CPRE at a median age of 2.3 months (range 0.1-51.6). One boy had a hypospadiac urethral meatus at CPRE completion. Hydronephrosis of mild or moderate grade was present postoperatively in eight girls and two boys. Additional results, per gender, are presented in the Summary table below. DISCUSSION: Absence of dehiscence in this cohort was comparable or compared favorably with the literature. However, several girls had significant obstructive complications following CPRE. The rate of bladder outlet obstruction (BOO) in girls was increased compared with published reports. A low complication rate was noted in the boys following CPRE, which was comparable to reports in the literature, and early signs of continence and spontaneous voiding were noted in some boys and girls. Limitations included variation in patient age at presentation, thereby introducing a wide age range at CPRE. Outcome data were limited by short follow-up regarding voiding with continence. CONCLUSION: This collaborative effort proved beneficial regarding significantly increased surgeon exposure to CPRE, refinement of CPRE technique, surgeon learning and expertise. Technical refinement of CPRE is ongoing.

Carnitine metabolism in human subjects. II. Values of carnitine in biological fluids and tissues of "normal" subjects.

Carnitine values in "normal" or "control" human subjects are assembled in the second part of this review. Data were found on blood, skeletal muscle, urine, heart muscle, and semen. Factors that affect these measures are related to the data.

Carnitine metabolism in human subjects. I. Normal metabolism.

Carnitine (vitamin BT) is a compound which is involved with lipid metabolism. This article deals with the carnitine content of foods and diet, the absorption, transport, storage, and excretion of carnitine in humans. The metabolic functions and biosynthesis of carnitine are also reviewed.

Carnitine metabolism in human subjects. III. Metabolism in disease.

Carnitine metabolism is reviewed in lipid storage myopathies, diabetes, vomiting sickness of Jamaica, malnutrition, hyperthyrodism, Duchenne dystrophy, and a few other disease states.

Dietary carnitine effects on carnitine concentrations in urine and milk in lactating women.

The effect of dietary carnitine on urinary excretion of free and total carnitine and on breast-milk secretion of the carnitine fractions in 15 control and 16 lactating women aged 21-40 y was measured. Free and total carnitine excretions, obtained from 24-h urine collections, correlated with carnitine consumed on the collection day (P less than 0.03, P less than 0.01, respectively) but not with the mean intake calculated from 3-d diet records. The immediate responses of the control and lactating groups were not significantly different. Urinary excretion of carnitine (n = 31) was 82 +/- 13 mumol/d for free excretion and 226 +/- 22 mumol/d for total excretion. Milk free, acid-soluble acyl-, acid-insoluble acyl-, or total carnitine did not correlate with dietary carnitine or with the duration of lactation (1-10 mo). Milk total carnitine was 45 +/- 3 mumol/L. With the carnitine content of breast milk remaining stable for greater than or equal to 10 mo, the importance of exogenous carnitine throughout infancy is suggested.

Urinary, plasma, and erythrocyte carnitine concentrations during transition to a lactoovovegetarian diet with vitamin B-6 depletion and repletion in young adult women.

The purpose of the present study was to determine whether vitamin B-6 depletion and repletion influence carnitine concentrations in the plasma, erythrocytes, and urine of young adult women consuming a low-carnitine (30 micromol/d), lactoovovegetarian diet. Doses of vitamin B-6 were administered sequentially as follows: 1.60 mg/d during adjustment for 9 d, 0.46 mg/d during depletion for 27 d, 1.26 mg/d during the first repletion for 21 d, 1.66 mg/d during the second repletion for 21 d, and 2.06 mg/d during the third repletion for 14 d. Urinary carnitine tended to decline but was not significantly different throughout the 92-d study period. Plasma short-chain acylcarnitine and total carnitine decreased during vitamin B-6 depletion; however, the ratio of plasma acylcarnitine to total carnitine was not significantly different during changes in vitamin B-6 intake. Erythrocyte long-chain acylcarnitine increased during vitamin B-6 depletion, but the ratio of erythrocyte acylcarnitine to total carnitine did not respond to changes in vitamin B-6 intake. Plasma free and total carnitine concentrations were only weakly correlated with plasma pyridoxal-P concentration (r = 0.28 and r = 0.29, respectively; P < 0.01). No significant correlations were observed between urinary carnitine excretion or erythrocyte carnitine concentrations and plasma or erythrocyte pyridoxal-P concentrations. Thus, a vitamin B-6 intake of 0.5 mg/d does not affect carnitine concentrations in biological fluids and therefore is unlikely to affect endogenous carnitine synthesis over 27 d. The changes in carnitine indexes that we observed were probably due to adaptation to a vegetarian pattern of exogenous carnitine consumption.

Vitamin B-6 requirement and status assessment of young women fed a high-protein diet with various levels of vitamin B-6.

The vitamin B-6 requirement of young women consuming a constant high-protein diet (1.55 g/kg body wt) and the effect of various ratios of vitamin B-6 to protein on this requirement were studied. Eight women were fed a lactoovovegetarian basal diet containing 0.45 mg vitamin B-6 (2.66 micromol as pyridoxine) and 30 micromol carnitine for 92 d. The protocol consisted of successive baseline adjustment (9 d), depletion (27 d), and repletion (two 21-d and then one 14-d) periods. Vitamin B-6 intakes were 1.60, 0.45, 1.26, 1.66, and 2.06 mg, resulting in ratios of vitamin B-6 (in mg) to protein (in g) for the five periods of 0.016, 0.005, 0.013, 0.017, and 0.021, respectively. Direct and indirect as well as short- and long-term vitamin B-6 status measures were assessed weekly. Regression analysis revealed that the amount of dietary vitamin B-6 required to normalize urinary 4-pyridoxic acid, plasma pyridoxal-P, erythrocyte pyridoxal-P and pyridoxal, and erythrocyte alanine and aspartate aminotransferase activity coefficients to predepletion baseline values was 1.94 mg vitamin B-6/d (0.019 mg vitamin B-6/g protein). This study suggests that the current vitamin B-6 recommended dietary allowance of 1.6 mg/d based on 0.016 mg/g protein is not an adequate intake and may require reevaluation.

Minimally invasive direct access for repair of atrial septal defect in adults.

This report documents our early experience with minimally invasive direct-access surgical repair of atrial septal defect (ASD) in adults. We have developed minimally invasive techniques for direct-access ASD repair in adults while maintaining the efficacy of the open operative procedure. Between June 1996 and September 1998, 59 consecutive patients underwent repair of ASD, 34 (58%) of whom underwent minimally invasive direct-access surgical closure of ASD through a right parasternal, submammary, or upper hemisternotomy incision. Twenty-three (68%) were secundum type ASD, 5 (15%) were sinus venosus types, 2 (6%) were primum types, and 4 (122%) were patent foramen ovales. Twenty-six (77%) were women (mean age 39 +/- 15 years, range 18 to 79). The mean pulmonary-to-systemic shunt ratio (Qp/Qs) was 2.3 +/- 0.6 (n = 15). There were no operative or late deaths. Follow-up was 100% complete. Four patients (12%) developed major complications. All were alive and well at the time of follow-up and there was 1 late arrhythmia (atrial fibrillation). In all but 1 patient, New York Heart Association functional class was improved or unchanged (1.47 +/- 0.51 vs 1.06 +/- 0.25, p = 0.0001). These results indicate that minimally invasive direct-access repair of ASD in adults is safe and effective, and is broadly applicable to the entire spectrum of defects.

Human plasma causes rapid dysfunction in ex vivo pig hearts.

The use of hearts from large domestic animals represents a potential solution to the current human donor shortage. However, xenogeneic hyperacute graft rejection remains a major barrier to xenotransplantation. The purpose of this study was to use an ex vivo preparation to study variables that may correlate with hyperacute rejection in cardiac xenografts. Freshly excised hearts from 37 anesthetized pigs (10 to 37 kg) were perfused at 37 degrees C through the aorta with retrograde flow. The hearts functioned in a nonworking mode for 4 hours or until irreversible cardiac dysfunction occurred. Various perfusates were used: fresh whole autologous pig blood (n = 4), dog blood (n = 3), baboon blood (n = 5), human packed red blood cells (n = 2), human whole blood (n = 10), human whole blood and plasma (n = 3), and human plasma (n = 9), to which a modified Krebs-Henseleit bicarbonate buffer solution was added. Rapid loss of function was uniform and occurred most quickly (13 to 18 minutes) for hearts perfused with dog blood and human plasma. Isolated cardiac perfusion provided a means for the analysis of the cellular and plasma components of human blood to define which were required for rapid loss of function. The results indicated that the reaction was mediated by components present only in plasma.

Tension pneumopericardium as a complication of single-lung transplantation.

Tension pneumopericardium is distinctly uncommon in the adult population. We present a case of tension pneumopericardium as a complication of lung transplantation in a 54-year-old woman with thromboembolic pulmonary hypertension who underwent single-lung transplantation.

Nicardipine: myocardial protection in isolated working hearts.

The effectiveness of the calcium antagonist nicardipine in protecting the ischemic myocardium was evaluated using the hemodynamic recovery of isolated working rat hearts subjected to hyperkalemic cardiac arrest followed by ischemia at 37.5 degrees C and 10 degrees C. Rat hearts (n = 51) received 20 mL of cardioplegia and were subjected to 27 minutes of ischemia at 37.5 degrees C. Group A (control) did not receive nicardipine. Groups B through F received nicardipine in the cardioplegia with total doses ranging from 2 micrograms to 6 micrograms. Group A had 46% survival of ischemia, whereas groups C (3 micrograms) and D (4 micrograms) had survival rates of 88% and 100%, respectively (p less than 0.05). The recovery of aortic flow after ischemia was 35% in group A, compared with 76% in group B (2 micrograms) and 81% in group D (p less than 0.05). Group A had 49% postischemic recovery of cardiac output, whereas groups B and D had 82% and 85% recovery (p less than 0.05). The postischemic recovery of stroke volume was 48% in group A compared with 84% in group B, 87% in group D, and 73% in group E (5 micrograms) (p less than 0.05). Additional rats were exposed to 210 minutes of ischemia (n = 41) or 240 minutes of ischemia (n = 56) at 10 degrees C. Control groups did not receive nicardipine, whereas treatment groups received nicardipine in the cardioplegia with total doses ranging from 1.4 micrograms to 6.4 micrograms. There were no significant differences in the survival of ischemia or the recovery of function after ischemia at 10 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

Aggressive surgical and medical management of autosomal recessive polycystic kidney disease.

The treatment of autosomal recessive polycystic kidney disease (ARPKD) is evolving. Overall prognosis is difficult to determine, but most neonates without severe pulmonary hypoplasia will survive. It is difficult to predict which neonates with ARPKD requiring immediate ventilatory support have pulmonary hypoplasia incompatible with survival. Massively enlarged kidneys restricting diaphragmatic excursion can cause respiratory distress in addition to pulmonary hypoplasia. Three infants with ARPKD underwent bilateral nephrectomies and institution of peritoneal dialysis in an attempt to improve ventilatory status and assess long-term pulmonary function. Two children are alive at twelve and thirty months postoperatively and awaiting renal transplantation. One infant died of acute cardiorespiratory complications.

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.

Urologic manifestations of Wegener granulomatosis.

Wegener granulomatosis is a disease characterized by necrotizing granulomatous angiitis involving the upper and lower respiratory tracts and the kidneys. The introduction of cyclophosphamide in the treatment of Wegener granulomatosis has dramatically altered the rapidly fatal course of the disease and has altered our thinking regarding its management. Recently we have cared for 3 patients who demonstrated a dramatic spectrum of urinary tract pathology related to Wegener granulomatosis. The cases presented offer three points for consideration by the urologist: (1) the manifestations of the disease in the genitourinary tract can be varied and can present in a dramatic fashion; (2) the rapid progression of renal failure and the nearly uniform mortality associated with the disease have changed largely because of the use of cyclophosphamide; and (3) our approach toward patients with renal failure on the basis of Wegener granulomatosis can be altered, and renal transplantation is certainly feasible with the increased longevity afforded these patients by cyclophosphamide.

Posterior urethral valves in siblings.

The etiology and incidence of posterior urethral valves is unknown. We report on a pair of non-twin siblings with identical pathology stemming from type I posterior urethral valves as well as discordance in a pair of monozygotic twins. Familial posterior urethral valves have been reported before in both twin and non-twin siblings. The occurrence of identical pathology in non-twin siblings suggests the possibility of an inherited trait as does its occurrence in identical twins. However, non-identical clinical manifestation is as common as is identical presentation in both groups. There are also instances of discordance in monozygotic twins suggesting the possibility of a random mutation. As such, we recommend urologic evaluation of the male siblings of affected patients with posterior urethral valves. Further prospective and retrospective analyses are needed to define the genetic etiology of valves.

Urethral polyp presenting as interlabial mass in young girls.

We describe two young girls who presented with an interlabial mass. Histologic examination of each excised mass revealed a benign urethral polyp covered with transitional and squamous epithelium. Urethral polyps should be included in the differential diagnosis of an interlabial mass in young female patients.

How can obese weight controllers minimize weight gain during the high risk holiday season? By self-monitoring very consistently.

This study examined the efficacy of augmenting standard weekly cognitive-behavioral treatment for obesity with a self-monitoring intervention during the high risk holiday season. Fifty-seven participants in a long-term cognitive-behavioral treatment program were randomly assigned to self-monitoring intervention or comparison groups. During 2 holiday weeks (Christmas-New Years), the intervention group's treatment was supplemented with additional phone calls and daily mailings, all focused on self-monitoring. As hypothesized, the intervention group self-monitored more consistently and managed their weight better than the comparison group during the holidays. However, both groups struggled with weight management throughout the holidays. These findings support the critical role of self-monitoring in weight control and demonstrate the benefits of a low-cost intervention for assisting weight controllers during the holidays.

Use of bowel in undiversion.

Urinary undiversion is becoming an uncommon procedure because fewer patients are being diverted. The lessons learned from undiversion, however, have made possible early primary reconstructions in patients who would previously have been candidates for diversion. Intermittent clean catheterization and the use of bowel to augment or form a compliant storage vessel for urine have permitted reconstruction in patients with abnormal bladder and urethral function. Thus patients with neurogenic bladder or with severe lower urinary tract abnormalities can look forward to healthy kidneys and urinary continence without the use of appliances. Certainly there are yet many lessons to be learned, but the potential is just starting to be appreciated.