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Biomedical subjects

Hiep T Nguyen

Publications and source records attributed to Hiep T Nguyen.

11 recordsLinked to original sources

Increased echogenicity as a predictor of poor renal function in children with grade 3 to 4 hydronephrosis.

PURPOSE: Prenatally diagnosed hydronephrosis is a common finding that often requires further radiological evaluation to determine whether it is associated with compromised renal function. We hypothesize that findings on postnatal renal sonography may help determine which patients require more extensive evaluation of renal function in the assessment for prenatal hydronephrosis. We show that increased renal parenchymal echogenicity on postnatal US is a strong predictor of compromised renal function. MATERIALS AND METHODS: A total of 97 patients diagnosed with prenatal hydronephrosis presented to our institution for furosemide (99m)technetium MAG3 renogram evaluation of renal function between January 2000 and December 2001. All patients had SFU grade 3 to 4 hydronephrosis noted on postnatal US before age 6 months. For these 97 patients (178 renal units) we correlated the degree of renal parenchymal echogenicity and parenchymal thinning on the first postnatal sonogram with the differential renal function as determined by furosemide MAG3 renography. RESULTS: Among 97 patients diagnosed with prenatal hydronephrosis 10 of 20 renal units (50%) with markedly increased echogenicity had severely decreased relative renal function of less than 10%, while 136 of 151 (90%) with normal echogenicity exhibited normal relative renal function of 40% or greater. Increased echogenicity on US yielded a sensitivity of 100% and specificity of 99% for predicting relative renal function of 20% or greater. In predicting relative renal function of 40% or less sensitivity and specificity were 48% and 100%, respectively. CONCLUSIONS: Increased renal parenchymal echogenicity found on the first postnatal ultrasound can be used as a predictor of impaired relative renal function as measured on furosemide MAG3 renogram.

Female↗

Fetal sheep development on ultrasound and magnetic resonance imaging: a standard for the in utero assessment of models of congenital abnormalities.

OBJECTIVE: To establish normative data for the size, conspicuity, and imaging characteristics of normal developing fetal sheep organs on ultrasound (US) and magnetic resonance (MR) imaging. METHODS: US and MR images of ten normal pregnant sheep, at 40, 65, 90, 115, and 140 gestational days (term = 145 days), were scored for organ conspicuity and imaging characteristics. Imaging biometry was correlated with specimens. Gestational age-based growth parameters were modeled using regression. RESULTS: Imaging biometry showed excellent correlation with specimens. Kidney, bladder, stomach, lung, liver, and spine were seen well from 65 days to term by US. More organs were consistently visible from 90 days to term by MR than by US. Most organ imaging characteristics tended not to change throughout gestation. CONCLUSION: Normal fetal sheep biometry, organ conspicuity, and imaging characteristics are established for US and MR and have potential use for the in utero assessment of sheep models of congenital abnormalities.

Animals↗

Antenatal hydronephrosis as a predictor of postnatal outcome: a meta-analysis.

OBJECTIVE: Antenatal hydronephrosis is diagnosed in 1% to 5% of all pregnancies; however, the antenatal and postnatal management of hydronephrosis varies widely. No previous studies define the risk of postnatal pathology in infants with antenatal hydronephrosis. Our objective was to review the current literature to determine whether the degree of antenatal hydronephrosis and related antenatal ultrasound findings are associated with postnatal outcome. METHODS: We searched Medline (1966-2005), Embase (1991-2004), and the Cochrane Library databases for articles on antenatal hydronephrosis. We required studies to have subjects selected on the basis of documented measurements of antenatal hydronephrosis and followed to a postnatal diagnosis. We excluded case reports, review articles, and editorials. Two independent investigators extracted data. RESULTS: We screened 1645 citations, of which 17 studies met inclusion criteria. We created a data set of 1308 subjects. The risk of any postnatal pathology per degree of antenatal hydronephrosis was 11.9% for mild, 45.1% for moderate, and 88.3% for severe. There was a significant increase in risk per increasing degree of hydronephrosis. The risk of vesicoureteral reflux was similar for all degrees of antenatal hydronephrosis. CONCLUSIONS: The findings of this meta-analysis can potentially be used for prenatal counseling and may alter current postnatal management of children with antenatal hydronephrosis. Overall, children with any degree of antenatal hydronephrosis are at greater risk of postnatal pathology as compared with the normal population. Moderate and severe antenatal hydronephrosis have a significant risk of postnatal pathology, indicating that comprehensive postnatal diagnostic management should be performed. Mild antenatal hydronephrosis may carry a risk for postnatal pathology, but additional prospective studies are needed to determine the optimal management of these children. A well-defined prospective analysis is needed to further define the risk of pathology and the appropriate management protocols.

Case Management↗

JNK/SAPK and p38 SAPK-2 mediate mechanical stretch-induced apoptosis via caspase-3 and -9 in NRK-52E renal epithelial cells.

BACKGROUND/AIMS: In renal epithelial cells, mechanical forces produced from urinary obstruction serve as potential mediators of apoptosis by activating specific intracellular signaling pathways. In this study, we sought to further define the role of JNK and p38 SAPK-2 pathway and caspase activation in stretch-induced apoptosis. METHODS: Immortalized cell lines derived from the various components of the nephron were subjected to cyclical stretch and their differential apoptotic response was assessed. Pharmacologic inhibitors and Western blot analysis were used to assess the involvement of the MAPK pathways. Caspases' activity was assessed with ELISA and by Western blot analysis. RESULTS: Stretch-induced apoptosis was dependent upon the cell phenotype and the degree of stretch. In NRK-52E cells, it was mediated through both JNK and p38 SAPK-2 pathways, and inhibition of either pathway reduced the degree of stretch-induced apoptosis. Stretched cells showed increased activity of caspase-3 and -9 but not -2 or -8. Stretch-induced apoptosis was modulated by inhibition of caspase-3 and to a lesser extent by caspase-9. CONCLUSION: These findings suggest that stretch induces apoptosis in renal epithelial cells through the specific activation of JNK/SAPK and p38 SAPK-2 pathways and is dependent on the activation of caspase-3 and -9.

Animals↗

Molecular mechanism of apoptosis induced by mechanical forces.

In all biological systems, a balance between cell proliferation/growth and death is required for normal development as well as for adaptation to a changing environment. To affect their fate, it is essential for cells to integrate signals from the environment. Recently, it has been recognized that physical forces such as stretch, strain, and tension play a critical role in regulating this process. Despite intensive investigation, the pathways by which mechanical signals are converted to biochemical responses is yet to be completely understood. In this review, we will examine our current understanding of how mechanical forces induce apoptosis in a variety of biological systems. Rather than being a degenerative event, physical forces act through specific receptor-like molecules such as integrins, focal adhesion proteins, and the cytoskeleton. These molecules in turn activate a limited number of protein kinase pathways (p38 MAPK and JNK/SAPK), which amplify the signal and activate enzymes (caspases) that promote apoptosis. Physical forces concurrently activate other signaling pathways such as PIK-3 and Erk 1/2 MAPK, which modulate the apoptotic response. The cell phenotype and the character of the physical stimuli determine which pathways are activated and, consequently, allow for variability in response to a specific stimulus in different cell types.

Animals↗

Growth and stretch response of human exstrophy bladder smooth muscle cells: molecular evidence of normal intrinsic function.

OBJECTIVE: To establish primary cultures of smooth muscle cells (SMC) from human exstrophic bladders (E-SMC), and determine their in vitro growth dynamics and responses to mechanical stretch. MATERIALS AND METHODS: Primary cultures of E-SMC from three patients were established from exstrophic bladder tissue using an explant method. Growth dynamics were assessed using tetrazolium-dye uptake. The DNA synthesis rate in response to cyclic stretch-relaxation was determined with thymidine-incorporation assays. Expression of the SMC mitogen heparin-binding epidermal growth factor-like growth factor (HB-EGF) mRNA in response to mechanical stretch was determined using semiquantitative reverse transcription-polymerase chain reaction. RESULTS: The approximate doubling time of the E-SMC grown in the presence of serum was 4 days, consistent with growth rates of SMC reported previously. E-SMC exposed to stretch had greater DNA synthesis, albeit to a lesser extent than previously seen with non-exstrophic SMC. The expression of HB-EGF was also increased in cells exposed to mechanical stimuli, consistent with our previous finding of stretch-regulated HB-EGF gene expression in bladder SMC. CONCLUSIONS: E-SMC had growth characteristics similar to those previously reported in non-exstrophic cells. E-SMC also had stretch-induced expression of HB-EGF mRNA. These observations provide evidence that despite development in an abnormal defunctionalized state, E-SMC retain the potential for normal growth, and may modulate this response through mechanisms similar to those operating in normal bladder SMC.

Bladder Exstrophy↗

Children with a febrile urinary tract infection and a negative radiologic workup: factors predictive of recurrence.

OBJECTIVES: To determine the recurrence rate and risk factors for urinary tract infection (UTI) in children who present with a febrile UTI and have a negative radiologic evaluation. Febrile UTIs with no urinary tract abnormalities are a common cause of morbidity in children. METHODS: We performed a retrospective review of all children referred to our medical center after a febrile UTI. RESULTS: We reviewed 850 charts. Of 850 children, 78 had had a febrile UTI and normal ultrasound and voiding cystourography findings. Of the 78 children, 25 had had a recurrent UTI (3 boys and 22 girls). Forty-five percent of the girls with a febrile UTI developed a recurrent UTI and 14% of the boys had a recurrent UTI (P = 0.02). Three boys (two younger than 1 year of age) were uncircumcised and had one recurrent febrile UTI. Eleven (39%) of 28 girls who first presented at younger than 1 year of age and 7 (58%) of 12 girls who presented at 5 years of age or older had recurrent UTIs. The recurrence rate in the 2 to 5-year-old age group was 24% (4 of 17). Seven of the older girls exhibited symptoms of dysfunctional elimination syndrome. CONCLUSIONS: In children with a febrile UTI and a negative radiologic evaluation, recurrence was more common in girls. Boys who were uncircumcised may be at an increased risk of infection during the first year of life. In girls, the age at the time of the first infection was not predictive of recurrence. Although dysfunctional voiding and elimination may contribute to recurrent febrile UTIs in young children, an association seems to be present in children 5 years old and older.

Child↗

Abnormal dimercapto-succinic acid scans predict an increased risk of breakthrough infection in children with vesicoureteral reflux.

PURPOSE: The management of high grade vesicoureteral reflux remains controversial, with breakthrough infections being an indication for surgical repair. We sought to determine if technetium dimercapto-succinic acid (DMSA) scan could help predict which children are at risk for breakthrough urinary tract infection. MATERIALS AND METHODS: A retrospective review was performed on children presenting with a febrile urinary tract infection and prenatal hydronephrosis who were found to have vesicoureteral reflux and underwent a DMSA scan. Reflux was tabulated according to the highest grade. DMSA results were graded as 0-normal, no parenchymal or size defects, grade 1-focal parenchymal defects or less than a quarter of a renal unit involved, or grade 2-severe defects to include at least half of a renal unit, bilateral defects or unilateral atrophy. RESULTS: A total of 120 consecutive patients were evaluated. An abnormal DMSA scan was documented in 57 (33 females and 24 males), and 35 with grade 1 and 22 with grade 2 defects. Of the patients 53 females and 10 males had a normal scan. Of the 57 children with an abnormal DMSA scan 6% presented with grades 1 and 2 vesicoureteral reflux, 24% with grade 3, 38% with grade 4 and 26% with grade 5. Of the children with grades 3 to 5 reflux 60% had a subsequent breakthrough infection. Of the 63 children with a normal DMSA scan 11% presented with grade 1 reflux, 28% with grade 2, 48% with grade 3, 11% with grade 4 and 2% with grade 5. Of these children 5 had a subsequent breakthrough infection. CONCLUSIONS: An abnormality on DMSA scan in the presence of grade 3 to 5 reflux correlates with a greater chance of having a breakthrough infection (60%). We conclude that children with grade 3 to 5 vesicoureteral reflux and an abnormal DMSA scan are at increased risk for breakthrough urinary tract infection.

Child↗

The outcome of bladder neck closure in children with severe urinary incontinence.

PURPOSE: We evaluated the outcome of children who underwent bladder neck closure for the management of severe urinary incontinence. MATERIALS AND METHODS: Bladder neck closure was performed in 12 patients with bladder exstrophy, 4 with myelomeningocele and 4 with urogenital sinus anomalies for severe urinary incontinence that persisted after multiple failed bladder outlet procedures. The effectiveness of bladder neck closure and the need for subsequent surgeries were ascertained. RESULTS: Mean followup was 5.4 years (range 1 to 12). At 3 months after surgery 40% of the patients were completely dry, 20% had leakage via the stoma and 40% had a urethral fistula. After additional surgeries 85% of the patients were completely continent 2 years following bladder neck closure (15% declined further surgeries or had an ileal conduit). Of the 15 patients with followup longer than 3 years only 40% remained completely dry, and leakage via the stoma developed in 47% after being dry for 1 year. Repeat urodynamic studies did not show any adverse changes in bladder dynamics in the incontinent patients. Stomal stenosis occurred in 30% of the patients and bladder stones developed in 40%. None of the patients had hydronephrosis or bladder perforation. The early complication of fistula formation and the late development of leakage via the stoma appear to be related in part to compliance with intermittent catheterization. CONCLUSIONS: Bladder neck closure is an effective method of achieving urinary continence in children in whom other bladder outlet surgery has failed. However, its success is dependent in part upon compliance with intermittent catheterization. Finally children who have undergone bladder neck closure are at an increased risk for stomal stenosis and bladder stones.

Adolescent↗

Laparoscopic linear cutting stapler failure.

OBJECTIVES: To characterize the frequency and nature of problems with linear cutting staplers to help prevent complications in the future. These devices are often used during laparoscopic urologic procedures. METHODS: We retrospectively reviewed the experience with laparoscopic linear cutting staplers at two institutions routinely performing urologic laparoscopy and analyzed the difficulties with any staplers. Data from the Food and Drug Administration Center for Devices and Radiological Health were also examined to determine the prevalence and types of reported problems. RESULTS: In performing approximately 460 laparoscopic cases, we encountered 5 problems (1%) with endovascular gastrointestinal anastomosis staplers. Fifty-five additional cases in 50 patients were documented in the Food and Drug Administration database. Of the 55 patients, 15 (27%) required open conversion to manage the problem, 8 (15%) received blood transfusions, and 2 (4%) died postoperatively. Twenty-two events occurred during 19 laparoscopic donor nephrectomies (35%) without associated graft dysfunction, damage, or loss. All phases of instrument use were subject to problems; however, abnormal firing of the stapler and improper staple formation were the most common and morbid aspects of device malfunction. CONCLUSIONS: Despite the general reliability of linear cutting staplers, difficulties were encountered in every step of use. Most situations were successfully managed by prompt identification and appropriate intracorporeal maneuvers. Nevertheless, significant morbidity may occur, and conversion to an open operation should be considered. Many potential problems can be avoided by surgeon and staff education, and one should be aware of the alternative methods of tissue ligation currently available.

Equipment Failure↗

Growth and metabolic consequences of bladder augmentation in children with myelomeningocele and bladder exstrophy.

OBJECTIVE: Bladder augmentation using intestinal segments is reported to cause decreased linear growth in bladder exstrophy and myelomeningocele patients. We studied changes in calcium metabolism, height, bone chemistry, and bone density in exstrophy and myelomeningocele patients after bladder augmentation. METHODS: Thirty-three patients were prospectively admitted to the Pediatric Clinical Research Center at the University of California San Francisco for 24 hours. Blood and urine were analyzed for electrolytes, and serum was obtained for markers of calcium metabolism. Dual radiograph bone densitometry of the forearm was performed. Myelomeningocele patients were compared with nonaugmented myelomeningocele patients matched by age, gender, level of defect, and ambulatory status. Exstrophy augmented patients were compared with nonaugmented exstrophy patients. The bone densities in both groups were compared with normal children. Laboratory values and percentile heights were statistically analyzed using the Student t test; bone densitometry was analyzed using the Tukey test. RESULTS: Twenty-two patients with myelomeningocele and 11 with bladder exstrophy were studied. Mean follow-up was 3.7 years postaugmentation (range: 1-13 years). The results indicate a significant difference in serum bicarbonate and chloride levels between myelomeningocele patients who underwent ileal augmentation and those who did not. Although this may be indicative of chronic metabolic acidosis, there was no affect on growth or bone density when compared with controls. There were no other significant differences in laboratory values, or percentile heights, nor were any differences noted in patients who underwent gastrocystoplasty. In the exstrophy group, there were no observable differences in percentile height or laboratory values between the augmented and nonaugmented group. There were no significant differences in bone density between these 2 groups when matched for age and gender. No significant difference was seen in bone density when these groups were compared with normal children. CONCLUSION: Bladder augmentation is safe and does not impact negatively on the linear growth or bone densities of patients with myelomeningocele or bladder exstrophy.

Adolescent↗