Prenatal urinary matrix metalloproteinase profiling as a potential diagnostic tool in fetal obstructive uropathy

Background/Purpose

The diagnostic evaluation, patient stratification, and prenatal counseling for congenital obstructive uropathy remain sub-optimal. Matrix metalloproteinase (MMP) expression profiles are emerging as a valuable diagnostic tool in assorted disease processes. We sought to determine whether congenital obstructive uropathy impacts MMP expression in fetal urine.

Methods

Fetal lambs (n = 25) were divided in two groups: group I (n = 12) underwent a sham operation and group II (n = 13) underwent creation of a complete urinary tract obstruction. Gelatin zymography panels for 4 MMP species were performed on fetal urine in both groups at comparable times post-operatively. Statistical analysis was by the Fisher's exact test (P < .05).

Results

Overall fetal survival was 80% (20/25). A variety of significant differences in MMP expression between the two groups were identified. The following profiles were present only in obstructed animals: any MMP other than MMP-2 (P = .029), including any MMP other than 63 kDa and 65 kDa (P = .009); 2 or more MMPs excluding MMP-2s (0.029); and 3 or more MMPs (P = .029).

Conclusions

Limited matrix metalloproteinase expression is present in the urine of normal ovine fetuses. Fetal obstructive uropathy impacts urinary MMP expression in various distinguishable patterns. Prenatal urinary MMP profiling may become a practical and valuable diagnostic tool in the evaluation of congenital obstructive uropathy.     

Imbalance of metallaproteinase/tissue inhibitors of metalloproteinase system in renal transplant recipients with chronic allograft injury

Introduction

Nowadays, renal allografts continue to be lost at the rate of 2% to 4% per year beyond the first year after transplantation due to chronic allograft injury. Excessive accumulation of extracellular matrix results from overproduction and/or defective degradation by proteolytic enzymes, among which metalloproteinases (MMPs) play a major role. The aim of this study was to assess the role of MMPs in renal transplant recipients (RTR) in the context of allograft injury or proteinuria.

Materials and methods

Plasma and urine MMP-2 and MMP-9 and tissue inhibitors of metalloproteinases (TIMPs) were assessed by enzyme-linked immunoassay in 150 RTR including 66% males with an overall mean age of 49.2 ± 11.5 years. The subjects were examined at a mean of 73.4 ± 41.2 months (range = 12-240) after kidney transplantation. Thirty-seven healthy volunteers including 54% male with an overall mean age of 48.4 ± 14.1 years served as a control group.

Results

Renal transplant recipients displayed significantly decreased plasma MMP-2 activity compared with healthy controls (P < .000) probably due to increased inhibitory plasma (p) TIMP-2 activity (P = .0029), and lower plasma MMP-2:TIMP-2 index (P < .0001). Plasma MMP-9 and pTIMP-1 activities were twofold increased in RTR compared with controls (P = .0015 and P < .000) but with a nearly stable plasma MMP-9:TIMP-1 index (P = NS). There was no difference between RTR and controls according to urine (u) MMP-2 activity, but uMMP-9 was increased in RTR compared with healthy controls (P = .0032). Urine MMP-9 potential was probably diminished by increased uTIMPs (uTIMP-2, P = .017; uTIMP-1, P = .000), which contributed to graft impairment or proteinuria.

Conclusion

Our study revealed profibrotic MMP/TIMP constellations in RTR that show an imbalance in plasma MMP-2 and MMP-9 with increased plasma and urinary TIMPs. The net proteolytic potential of increased plasma and urinary MMP-9 may be diminished significantly by enhanced plasma and urine TIMP activities.     

Extracellular matrix dynamics associated with tissue-engineered intravascular sclerotherapy

Background

The extracellular dynamics after intravascular sclerotherapy with an injectable, fibroblast-based engineered construct is unknown.

Methods

Rabbits underwent ethanol sclerotherapy of a jugular vein segment. Control animals (n = 40) underwent no further treatment or an acellular collagen hydrogel was injected. Experimental animals (n = 20) received a tissue-engineered construct. After 1, 2, 4, and 20 to 24 weeks, segments were evaluated for collagen, glycosaminoglycan (GAG), matrix metalloproteinase (MMP) 2 and 9, and tissue inhibitors of MMP (TIMPs) 1 and 2 and scored on a scale of 0 to 3. Groups and time points were compared using nonparametric statistical analysis.

Results

Collagen content was higher in animals that received fibroblasts (P < .05). Glycosaminoglycan analysis showed a higher grade only at 1 week (P < .05). Collagen and GAG deposition were prominent at weeks 1 through 4, and decreased over time. Both MMP-2 and MMP-9 and TIMP-1 and TIMP-2 grade decreased with time (P < .01) in all groups, with no differences between groups.

Conclusion

Enhancement of intravascular sclerotherapy by tissue engineering stems, at least in part, from increased local deposition of collagen and GAG. MMP and TIMPs may play a role in recanalization after experimental sclerotherapy. Tissue engineering may be a valuable adjunct for the treatment of vascular malformations.     

Pretreatment with small-dose ketamine reduces predicted effect-site concentration of propofol required for loss of consciousness and Laryngeal Mask Airway insertion in women

Study Objective

To investigate the effect of small-dose ketamine on the predicted effect-site concentration of propofol required for loss of consciousness (LOC) and Laryngeal Mask Airway (LMA) insertion.

Design

Randomized, double-blinded study.

Settings

Operating room.

Patients

50 ASA physical status 1 and 2 women scheduled for elective breast or gynecological surgery.

Interventions

Patients were randomly allocated to a ketamine group or a control group. Thirty seconds before propofol injection, ketamine group patients received ketamine 0.2 mg/kg, while control group patients received saline. Propofol was given in a target-controlled infusion and target blood concentration was gradually increased until LOC. The effect-site concentrations for attempting LMA insertion was predetermined by modifying Dixon's up and down method. LMA insertion was attempted without muscular blocking agents.

Measurements

Pain scores on propofol injection, effect-site concentrations at LOC, hemodynamic variables, and patient movement or side effects on LMA insertion were recorded.

Main Results

The effect-site concentration of propofol required for LOC was 2.14 μg/mL for the control group and 1.66 for the ketamine group (P = 0.0082). The predicted effect-site concentration of propofol alone at which 50% of patients did not move with LMA insertion (EC₅₀LMI) was 3.59 μg/mL (95% CI: 3.18∼4.19 μg/mL). Pretreatment with ketamine 0.2 mg/kg decreased EC₅₀LMI from 3.59 (3.18∼4.19) to 2.39 (1.22∼2.99).

Conclusions

Pretreatment with ketamine 0.2 mg/kg reduced the propofol concentration required for both LOC (22%) and LMA insertion (33%) in women.     

Different pattern of matrix metalloproteinases expression in alveolar versus embryonal rhabdomyosarcoma

Background/purpose

The matrix metalloproteinases (MMPs), a family of enzymes that degrade the extracellular matrix (ECM), are important in neoplastic cell invasion and metastasis. Data for rhabdomyosarcoma (RMS), the most frequent soft tissue sarcoma of childhood, are lacking. The aim of this study was to assess their expression in this tumor and to evaluate the correlation with clinicopathologic parameters.

Methods

Immunohistochemical expression of MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, TIMP-1, and TIMP-2 was investigated in 33 human RMSs, 12 alveolar, and 21 embryonal histologic subtypes (12 high risk and 9 low/standard risk). Evaluation of the results was based on the percent of positive neoplastic cells and on staining intensity (negative, moderate, and strong). In situ zymography was carried out on 4 frozen RMS samples (2 alveolar and 2 high-risk embryonal).

Results

Alveolar type showed a stronger MMP-1, -2 and -9 expression in comparison with embryonal (P = .006, P <.001, and P <.001, respectively). Intratumoral vessels and perivascular ECM were positive for MMP-9 in the majority of RMSs. Both TIMPs had negative results.

Conclusions

Gelatinases MMP-2 and MMP-9 and collagenase MMP-1 overexpression seem to contribute to the more aggressive phenotype of alveolar rhabdomyoblastic cells. Further characterization of the expression of MMPs and consequent utilization of their inhibitors in aggressive alveolar RMSs might lead to the development of novel anticancer therapies.     

Does caval reconstruction technique affect early graft function after liver transplantation? A preliminary analysis

Background

In the past decades, the inferior vena cava (IVC) reconstruction technique has undergone several evolutions, such as biopump, piggyback technique (PB), and laterolateral approach (LLPB). Several advantages are reported comparing the PB technique to biopump use. However, comparison between PB and LLPB has not been as well investigated. The aim of this study was to compare the results in terms of immediate graft function and intermediate graft survival among 3 subgroups characterized by distinct caval reconstruction techniques.

Methods

We retrospectively analyzed a cohort of 200 consecutive adult patients who underwent liver transplantation from January 2001 to December 2009. The patients were stratified according to 3 caval reconstructive techniques: biopump (n = 135), PB (n = 32) and LLPB (n = 33).

Results

The LLPB group showed the shortest cold and warm ischemia times and the best immediate postoperative graft function. Survival analysis revealed LLPB patients to present the best 1-year graft survival rates: namely, 90.9% versus 75.0% and 74.1% among the PB and biopump groups, respectively (log-rank tests: LLPB vs biopump: P = .03; LLPB vs PB: P = .05). In our experience, LLPB showed the best graft survivals with an evident reduction in both cold and warm ischemia times. However, it is hard to obtain an irrefutable conclusion owing to the retrospective nature of this study, the small sample, and the different periods in which the groups were transplanted.

Conclusions

LLPB technique was a safe procedure that minimized the sequelal of ischemia-reperfusion damage. This technique yielded results superior to venovenous bypass. No definitive conclusions can to be obtained in this study comparing classic PB or LLPB.     

Can levels of interleukins and matrix metalloproteinases in the amniotic fluid predict postnatal bowel function in fetuses with gastroschisis?

Purpose

The aim of this study was to determine whether interleukin or matrix metalloproteinase (MMP) levels in the amniotic fluid can predict the postnatal condition of the bowel in fetuses with gastroschisis (GS).

Methods

Eleven pregnant women with a fetus with GS underwent amniocentesis. Levels of IL-1α, IL-1β, and IL-6 were measured in 10 of 11 specimens, and MMP-1, MMP-3, and MMP-8 levels were measured in 7 of 11 specimens. Neonates who tolerated complete oral feeding within 21 days were considered to have good bowel status (GS/good: n = 4, 4 in interleukin study or 3 in MMP study); those who did not were considered to have poor bowel status (GS/poor: n =7, 6 in interleukin study or 4 in MMP study). Seventy-eight women undergoing amniocentesis for other reasons served as controls.

Results

Interleukin-1 levels were considerably lower in the pregnancies complicated by GS than in controls. Matrix metalloproteinases 3 and 8 levels were significantly higher in the GS pregnancies than in controls. Neonates with poor bowel status had higher MMP-3 and MMP-8 levels than those with good bowel status.

Conclusion

Amniotic fluid MMP-3 and MMP-8 levels may prove useful to assess the condition of the bowel in fetuses with GS.     

Vesicoamniotic shunt for complete urinary tract obstruction is partially effective

Purpose

The long-term outcome for children after antenatal intervention for obstructive uropathies is disappointing. We reported that renal dysplastic changes are well established 3 weeks after obstruction in a fetal lamb model. We used this model to explore renal development and bladder function after fetal intervention.

Methods

We created an obstructive uropathy in fetal lambs at 60 days gestation by ligating the urethra and urachus. A vesicostomy (female) or urethrostomy (male) were performed 21 days later. The fetuses were killed at term (145 days) and bladder volume and compliance were measured. The urinary tract was processed for histologic examination.

Results

Twenty two fetuses were shunted. Nine were miscarried or were still-born. Thirteen survived, and 11 had a successful shunt with a small bladder (8 ± 5 mL) compared with controls (71 ± 19 mL) (P < .05). Shunted bladders had poor compliance. Histologically, they had thickened submucosal connective tissue with hypertrophied muscle. Histology of the renal tissue demonstrated relatively well-preserved renal architecture with reduced nephron mass (oligonephronia) in 2 lambs and multicystic dysplastic change in 3. Six (55%) had normal nephrogenesis.

Conclusions

In our model, shunt operations after obstructive uropathy fail to preserve bladder function. Shunting ameliorated the development of cystic dysplasia, but half of the lambs had oligonephronia or multicystic dysplastic kidney. These might develop renal failure later in life.     

Pressure-limited vesico-amniotic shunt tube for fetal obstructive uropathy

Introduction

In utero shunting (vesico-amniotic shunt) of obstructive uropathy in fetal lambs produces a shrunken, noncompliant bladder. We hypothesized that using a ventriculo-peritoneal shunt for the vesico-amniotic shunt may preserve the filling/emptying cycle and thus normal bladder development.

Materials and Methods

We created obstructive uropathy in 60-day gestation fetal lambs, ligating the urethra and urachus. Vesico-amniotic shunting was performed 21 days later using the valve end of a ventriculo-peritoneal shunt (valve shunt) or silastic tubing (nonvalve shunt). They were delivered at term (145 days), and the bladder volume was measured and compared to normal term fetuses. The lambs were sacrificed, and the kidneys and bladder removed for histology.

Results

Twenty-seven lambs were shunted. Of 14 valve shunts, 8 were effective. Of 13 nonvalve shunts, 11 were effective. The mean bladder volume was 57 ± 41 mL with a valve shunt and 8.8 ± 4.7 mL with a nonvalve shunt (P < .05) (normal term lambs, 65 ± 18 mL, n = 5). Histology of the shunted bladders showed increased fibrosis in the submucosal and muscle layers. This was less obvious in lambs with a valve shunt.

Conclusion

A pressure controlled shunt for fetal obstructive uropathy improves bladder volume but does not prevent bladder wall fibrosis.     

The early effects of urinary tract obstruction on glomerulogenesis

Purpose

Our obstructive uropathy model in fetal lambs showed that renal cystic changes appeared 3 weeks after obstruction. In this study, the authors investigated the changes resulting from complete urinary tract obstruction in the first 7 days after obstruction.

Methods

An obstructive uropathy was created in fetal lambs at 60 days’ gestation by ligating the urethra and urachus. They were delivered 48 hours, 3 days, 5 days, and 7 days later by cesarian section. The kidneys were removed and processed for histologic examination.

Results

Eighteen fetuses were operated on and 15 (4 at 48 hours, 4 at 3 days, 2 at 5 days, and 5 at 7 days; 83%) survived. Macroscopically, bladder dilatation and slightly dilated ureters were identified from 48 hours. Microscopically, dilatation of proximal tubules started from 48 hours after obstruction and increased by 7 days. Glomerular cysts in the nephrogenic zone also were identified from 48 hours. Dysplastic changes were not found.

Conclusions

The first areas in the developing kidney that suffer damage after obstructive uropathy are the proximal tubule and the nephrogenic zone. This change started 48 hours after obstruction. Shunting procedures need to be performed considerably earlier than previously thought.     

Importance of Renal Mass on Graft Function Outcome After 12 Months of Cadaveric Donor Kidney Transplantation

Background

Few studies have measured cadaveric kidney weight to investigate its relation to recipient kidney function related to it. The aim of this study was to evaluate kidney weight (cadaveric donor) and its relationship to creatinine clearance (CrCl) after 12 months posttransplantation.

Methods

We evaluated 81 renal transplantation recipients from cadaveric donors. We collected donor and recipient demographic, clinical and anthropometric data. Data about kidney weight were obtained through kidney measurement using an electronic machine at the moment of transplantation.

Results

The mean kidney weight was 201.4 ± 10.2 g (200.5 ± 11.6 g in women and 210.3 ± 14.1 g in men). Kidney weight correlated with CrCl at 12 months (0.001). The CrCl at 12 months showed a significant correlation of graft weight/recipient weight ratio (P < .01).

Conclusion

The cadaveric donor kidney weight significantly influenced the CrCl at 12 months after transplantation.     

Effects of early vesicostomy in obstructive uropathy on bladder development

Purpose

Creation of a vesico-amniotic shunt for obstructive uropathy removes the normal fetal urination cycle. It is unclear how this affects bladder function at term. The authors measured the bladder volume and reviewed the bladder histology after fetal vesicostomy.

Methods

The authors created an obstructive uropathy in fetal lambs at 60 days’ gestation by ligating the urethra and urachus. Vesicostomy (female) or urethrostomy (male) were performed 21 days after obstruction to release the obstruction. The fetuses were killed at term (145 days).

Results

Thirteen fetuses were shunted. Seven fetuses miscarried after shunting. Six survived, and 3 had a successful shunt with a very small bladder (5 to 7 mL). Two had incomplete shunts that failed some time after shunting. These both had huge bladders (399 mL). In one, the obstruction was unsuccessful. Histologic examination showed that the obstruction caused bladder muscle hypertrophy. Shunted lambs had severe fibrosis of the bladder wall and very poor bladder compliance.

Conclusions

Shunt operations after obstructive uropathy may salvage the kidney but fail to preserve bladder function. The fetus needs a normal urination cycle for normal bladder development. This requirement exists even when the obstruction is successfully bypassed.     

The role of estrogen in the formation of experimental abdominal aortic aneurysm

Objective

The current study sought to investigate the role of estrogen in the formation of experimental abdominal aortic aneurysm (AAA).

Methods

Elastase perfusion of infrarenal AAA animal model was performed in 20 female and 20 male Wistar rats that were randomly divided into an ovariectomized/sham-operated group and an estradiol (E2) experimental/saline control group, respectively. At day 14, E2 was detected, while the mRNA and protein expressions of matrix metalloproteinases 2 and 9 (MMP-2 and -9) in AAA tissue were detected by immunohistochemistry and polymerase chain reaction (PCR).

Results

The ovariectomized group showed lower estrogen levels and a higher aneurysm dilatation rate and significantly higher MMP-2 and -9 expression compared with the sham-operated group (P < .01), which was in accordance with MMP-2 and -9 mRNA expression. The E2 group showed higher estrogen levels and a lower aneurysm dilatation rate and significantly lower MMP-2 and -9 expression than did the saline control group (P < .01), which was in accordance with MMP-2 and -9 mRNA expression.

Conclusions

In the pathogenesis of AAA, estrogen may play an inhibitory role by decreasing expression of MMP-2 and MMP-9 synthesis.     

Increased expression of serum matrix metalloproteinase-9 in patients with moyamoya disease

Background

Moyamoya disease is a chronic occlusive cerebrovascular disease with unknown etiology characterized by an abnormal vascular network at the base of the brain, which can manifest both as ischemic stroke and as cerebral hemorrhage. It was also reported that the patients with moyamoya disease are more vulnerable to cerebral hyperperfusion such as postoperative hemorrhagic complication after extracranial-intracranial bypass surgery despite its low flow revascularization. However, the underlying mechanisms of its pathologic angiogenesis and the occurrence of hemorrhage are undetermined. Excessive degradation of the vascular matrix by MMPs, proteolytic enzymes that degrade all the components of extracellular matrix, can lead to instability of the vascular structure and can thereby cause bleeding. The MMPs also play an important role in tissue remodeling including angiogenesis in both physiologic and pathologic condition.

Methods

We examined the serum levels of MMP-2 and MMP-9 in 16 cases with definitive moyamoya disease by enzyme-linked immunosorbent assay and compared them with those from healthy controls.

Results

The serum MMP-9 level was significantly higher in moyamoya disease (40.18 ng/mL) than in healthy controls (13.75 ng/mL, P = .0372). There was no difference in serum MMP-2 level between moyamoya disease (646.65 ng/mL) and healthy control (677.60 ng/mL). Immunohistochemistry on the surgical specimens showed significant increase in MMP-9 expression within the arachnoid membrane of moyamoya disease.

Conclusion

The increased expression of MMP-9 may contribute to pathologic angiogenesis and/or to the instability of the vascular structure and could thereby cause hemorrhage in moyamoya disease.     

Effects of cyclosporine on metalloproteinase in endothelial cells

Objectives

Cyclosporine (CsA) is a potent agent widely used after organ transplantations and in treatment of various autoimmune disorders. Some patients suffer severe complications including renal and vascular toxicity that are influenced by the degree of endothelial damage. Dysregulation of metalloproteinase (MMP) activity is known to contribute to renal and vascular diseases. To investigate the possible mechanisms of posttransplantation complications in the kidney and vessels by CsA, we examined its effects on metalloproteinases in endothelial cells using human umbilical vein endothelial cells (HUVECs).

Methods

HUVECs isolated from umbilical cords by collagenase digestion were seeded in 6-well plates at a density of 1 × 10⁵ cells/well before treatment with 2-250 μmol/L CsA and a 24-hour incubation. Thereafter we performed gelatin zymography of MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, and MMp-13 to evaluate band density using a luminescent image analyzer system with controls calculated as 100%.

Results

MMP-1, MMP-3, MMP-8, MMP-9, and MMP-13 activities were increased after CsA treatment; MMP-1 = 121; MMP-3 = 164; MMP-8 = 133; MMP-9 = 124; and MMP-13 = 121. In contrast, MMP-2 activity was decreased after CsA treatment; MMP-2 = 79.

Conclusions

This study showed CsA to activate most MMPs (except MMP-2) in endothelial cells. This result suggests that CsA may dysregulate MMPs in endothelial cells.     

Renal transplantation in old recipients from expanded criteria donors selected by kidney biopsy

Background

In Spain, the number of ideal kidney transplant donors has fallen, with at the same time an increase in the number of older recipients on the waiting list.

Aim

To analyze the results of expanded criteria cadaveric donor kidney transplants into older recipients using grafts selected by kidney biopsy.

Patients and methods

We studied 360 kidney transplant recipients who had been followed to December 2009: 180 in the study group and 180 in a control group composed of younger patients who received grafts from non-expanded criteria donors between 1999 and 2006. A paraffin-embedded kidney biopsy was evaluated by the percentages of sclerosed glomeruli, arteriolar hyalinosis, intimal wall thickening, interstitial fibrosis, and tubular atrophy.

Results

Significant differences were observed in donor age (63.50 ± 5.46 vs 31.90 ± 13.29 years; P < .001) and recipient age (58.40 ± 8.80 vs 40.71 ± 13.23 years; P < .001). Donor renal function was significantly worse among the expanded criteria group (90.80 vs 108.11 mL/min/1.73 m²; P = .006), remaining so over time in the recipient (at 1 year: 42.08 vs 63.71 [P < .001]; at 3 years: 41.25 vs 62.31 [P < .001], and at 7 years: 38.17 vs 64.18 [P < .001]). Censored 7-year graft survivals were 73% versus 87% (P < .001) with similar patient survivals (90.5% vs 95%; P = .39).

Conclusions

Selection of expanded criteria donors by kidney biopsy resulted in good renal function as well as graft and patient survivals at 7 years in older recipients.     

Impact of early ureteric stent removal and cost-benefit analysis in kidney transplant recipients: results of a randomized controlled study

Introduction

Duration of retaining ureteric stent in kidney transplantation is still controversial. Our study aimed to compare healthcare expenditures in kidney transplant recipients with early or routine ureteric stent removal.

Methods

This study was a post hoc analysis of data from a single-center parallel randomized controlled open-label study. Ninety patients who underwent kidney transplantation at a university-based hospital in Thailand from April 2010 to January 2011 were enrolled. Patients were randomized to early ureteric stent removal (8 days) or routine ureteric stent removal (15 days) after kidney transplantation. The costs of direct health care associated with kidney transplantation, urologic complication, and urinary tract infection (UTI) within the postoperative period among the 2 groups were compared.

Results

Seventy-four patients (58% living donor) fulfilled the randomized criteria (early removal, n = 37; routine removal, n = 37). By intention-to-treat analysis, incidence of UTI in early stent removal was less than the routine stent removal group (15/37, 40.5% vs 27/37, 72.9%; P = .004). Urologic complication showed no significant difference between the early and routine groups (4/37 vs 2/37; P = .39). The cost-benefit analysis of early over routine stent removal was 2390 United States dollars (USD) per patient (11,182 vs 8792 USD). Presence of UTI significantly increase the hospitalization cost of 5131 USD per patient (mean cost = 12,209 vs 7078 USD; P < .001).

Conclusion

UTI in the early post-kidney transplantation period increases healthcare cost. Early ureteric stent removal can reduce UTI and reduce hospitalization cost. This approach shows cost-benefit in the early management of kidney transplant recipients.     

Matrix Metalloprotease Expressions in Both Reperfusion Lung Injury and Oleic Acid Lung Injury Models and the Protective Effects of Ilomastat

Objective

Our aim was to study the expressions of matrix metalloprotease 9 (MMP9) and the effects of the MMP inhibitor Ilomastat in both ischemia/reperfusion (I/R)- and oleic acid (OA)-induced lung injury models.

Materials and Methods

Real-time polymerase chain reactions and Western blots were used to assess mRNA and protein expressions of MMP9 in lung tissues after I/R or OA lung injury. Ischemia was induced by clamping one branch of the pulmonary artery for 60 minutes and then reperfusing for 120 minutes. In the OA model, lung injury was induced by intravenous infusion of OA (0.1 mL/kg) for 20 minutes and then observation for 6 hours. Lavage leukocyte concentration and wet/dry lung weight ratio were used to assess lung inflammation and injury. Blood samples were collected for assays of hydroxyl radicals and nitric oxide. The MMP inhibitor Ilomastat (100 μg/kg) was administered before I/R and OA infusion.

Results

mRNA and protein expressions of MMP9 were significantly increased in both lung injury models. Ilomastat decreased MMP9 mRNA and protein expressions but did not reach statistical significance. Blood concentrations of hydroxyl radicals and nitric oxide, wet/dry lung weight ratios, and lavage leukocyte concentrations were significantly higher in both experimental groups compared with the sham group (P < .001). Ilomastat significantly attenuated the extent of lung inflammation and injury induced by both I/R and OA.

Conclusion

MMP may play a critical role in the lung injury induced by I/R and OA infusion.     

Therapeutic Option for Infected Urinary Tract Fistulas in Renal Transplantation

Background

Approximately 20% of urinary tract fistulas after renal allografting are complicated by urinary tract infection, which presents a therapeutic challenge.

Objective

To evaluate an option for treatment of urinary tract fistulas associated with urinary tract infection and unsuitable for minimally invasive or primary surgical urinary tract repair.

Patients and Methods

The study included 650 recipients who underwent transplantation over 17 years. Urinary leakage was initially treated with indwelling bladder catheterization. Patients with fistulas refractory to treatment underwent surgical intervention to repair the urinary tract. In patients who were not candidates for primary repair of the urinary tract, temporary urinary diversion was performed, rather than classic percutaneous or open nephrostomy, using a ureteral stent (ie, a 6F or 8F Foley catheter with the balloon placed inside the renal pelvis).

Results

Overall, urinary leakage occurred in 36 patients (5.5%). Conservative management was successful in 14 vesical fistulas (42.4%) and no ureteral fistulas (0%). Three patients died of sepsis during conservative treatment, before the new surgical approach. Five of 36 urinary leaks (13.9%) were managed using ureteral intubation with an 8F Foley catheter, with a success rate of 80%.

Conclusion

Ureteral catheterization with an 8F Foley catheter is a feasible therapeutic option to treat complicated urinary tract fistulas unsuitable for primary surgical repair of the urinary tract.     

Serial amnioinfusions prevent fetal pulmonary hypoplasia in a large animal model of oligohydramnios

Background/Purpose

Severe neonatal pulmonary hypoplasia incurs mortality rates approaching 71% to 95%. We sought to determine the utility of serial amnioinfusions through a subcutaneously implanted intraamniotic catheter to prevent pulmonary hypoplasia in fetal obstructive uropathy.

Methods

Fetal lambs (n = 32) were divided into 3 groups. Group I (n = 12) underwent a sham operation, group II (n = 15) underwent a complete urinary tract obstruction via ligation of the urachus and urethra with a subcutaneous tunneled intraamniotic port-a-cath without amnioinfusions, and group III (n = 5) underwent a creation of a complete urinary tract obstruction with a port-a-cath as described in group II with serial amnioinfusions. Lung tissue was analyzed by lung volume to body weight ratios and stereology. Statistical analysis was performed by analysis of variance and Bonferroni comparisons (P < .05).

Results

Obstructed fetuses grossly had smaller lungs than treated and control animals. Lung volume to body weight ratios were statistically significant between groups. Airspace fractions were comparable between groups I and III (average = 0.53 and 0.55, respectively), although both were significantly greater than group II (average = 0.48) (P = .049).

Conclusions

Serial amnioinfusions through an intraamniotic port-a-cath prevented pulmonary hypoplasia in an ovine model of complete obstructive uropathy. The use of an easily accessible device for amnioinfusions may be a viable option to treat oligohydramnios.