Correlation between prenatal urinary matrix metalloproteinase activity and the degree of kidney damage in a large animal model of congenital obstructive uropathy

Background/Purpose

We aimed to determine whether the profile of matrix metalloproteinase (MMP) activity in fetal urine correlates with the degree of kidney damage in the setting of congenital obstructive uropathy.

Methods

Fetal lambs underwent either a sham operation or creation of a complete urinary tract obstruction. Necropsies were performed before term, when urinary MMP profiling was performed by zymography; and kidney damage was assessed histologically by multiple semiquantitative analyses and histomorphometric measurements.

Results

There was a significant correlation between inner medullary thickness and MMP-9 (P = .005) and 63-kd MMP-2 (P = .019) activities. In like manner, the only MMPs associated with kidney fibrosis were MMP-9 and 63-kd MMP-2. Matrix metalloproteinase-9 activity was a highly significant independent predictor of the total combined kidney fibrosis score (P < .001) as well as of higher fibrosis grades in each of 6 kidney areas analyzed (all with P < .01). The activity of 63-kd MMP-2 correlated significantly with higher fibrosis in select areas.

Conclusions

In a fetal ovine model, urinary MMP activity correlates with the degree of kidney damage. The presence of MMP-9 (in particular) and that of 63-kd MMP-2 are independent predictors of severity. Prenatal urinary MMP profiling may enhance patient stratification and counseling in the setting of congenital obstructive uropathy.     

Intravenous landiolol, a novel β(1)-adrenergic blocker, reduces the minimum alveolar concentration of sevoflurane in women

Study Objective

To investigate the effect of intravenous (IV) landiolol, a novel β₁-adrenergic blocker, on the minimum alveolar concentration (MAC) of sevoflurane in adult women.

Design

Prospective, randomized study.

Setting

University hospital.

Patients

42 ASA physical status 1 and 2 women, aged 24-57 years, who were scheduled to undergo elective abdominal surgery.

Interventions

Anesthesia was induced in all patients by vital capacity rapid inhalation induction of sevoflurane. In the landiolol group, administration of landiolol began when patients took a vital-capacity breath: 0.125 mg/kg/min for one minute and then 0.04 mg/kg/min. Normal saline was administered in the control group.

Measurements

MAC was determined by a technique adapted from the conventional up-down method.

Main Results

The MAC of sevoflurane was 2.2% ± 0.2% in the control group and 1.7% ± 0.2% in the landiolol group, a statistically significant difference (P = 0.0005).

Conclusions

IV landiolol reduces the MAC of sevoflurane in women by approximately 20%.     

Diaphragmatic repair through fetal tissue engineering: a comparison between mesenchymal amniocyte- and myoblast-based constructs

Purpose

We have previously shown that fetal tissue engineering is a preferred alternative to diaphragmatic repair in a large animal model. This study was aimed at comparing diaphragmatic constructs seeded with mesenchymal amniocytes and fetal myoblasts in this model.

Methods

Neonatal lambs (n = 14) underwent repair of an experimental diaphragmatic defect with identical scaffolds, either seeded with labeled autologous cells (mesenchymal amniocytes in group 1 and fetal myoblasts in group 2) or as an acellular graft (group 3). At 1 to 12 months postoperatively, implants were harvested for multiple analyses.

Results

Repair failure (reherniation or eventration) was significantly higher in group 3 than in groups 1 and 2, with no difference between groups 1 and 2. Seeded fetal myoblasts quickly lost their myogenic phenotype in vivo. All grafts contained cells with a fibroblastic-myofibroblastic profile. Elastin concentrations and both modular and ultimate tensile strengths were significantly higher in group 1 than in groups 2 and 3. There were no differences in glycosaminoglycans and type I collagen levels among the groups.

Conclusions

Diaphragmatic repair with a mesenchymal amniocyte-based engineered tendon leads to improved structural outcomes when compared with equivalent fetal myoblast-based and acellular grafts. The amniotic fluid is a preferred cell source for tissue-engineered diaphragmatic reconstruction.     

Endoscopic gastrostomy placement in the child with gastroesophageal reflux: is concomitant antireflux surgery indicated?

Background/Purpose

Previously, we performed concomitant antireflux surgery in patients with abnormal pH study undergoing gastrostomy. This increased complications without always alleviating the troublesome symptom of vomiting. In contrast, vomiting with normal preoperative pH study generally disappeared after gastrostomy placement. Therefore, we changed policy to perform only gastrostomy, regardless of pH study results. Subsequent antireflux surgery is performed only as necessary. We report here our results.

Methods

We retrospectively reviewed patients undergoing gastrostomy from April 1997 to January 2004. For patients with abnormal preoperative pH studies, detailed data were recorded including medical history, indication for gastrostomy, operative technique, symptoms of gastroesophageal reflux (GER), and use of antireflux medication. Symptomatic GER postgastrostomy was managed pharmacotherapeutically. If this proved inadequate, patients underwent antireflux surgery.

Results

Twenty-eight patients with abnormal pregastrostomy pH study entered the study. Median age was 3 years and 2 months. Seventy-five percent were neurologically impaired. Indication for gastrostomy was inadequate oral nutrition in 26 of 28 patients. Only 3 of 28 patients were asymptomatic for GER. Of the 25 symptomatic patients 19 improved postgastrostomy (6 did not). Antireflux surgery ultimately proved indicated in 2 patients (7% [2/28]). The asymptomatic patients remained asymptomatic.

Conclusions

For patients with abnormal pH study presenting primarily for gastrostomy placement, concomitant antireflux surgery is not indicated.     

Survival of severe congenital diaphragmatic hernia has morbid consequences

Background/Purpose

Fetal tracheal occlusion (TO) was developed in an attempt to enhance prenatal lung growth and improve survival in fetuses with severe congenital diaphragmatic hernia (CDH). We conducted a randomized, controlled clinical trial in 24 fetuses with severe left CDH (liver herniated into the thorax and low lung-to-head ratio) to compare survival after endoscopic fetal TO vs standard perinatal care (control) and prospectively followed up the 16 survivors (9 control, 7 TO) to compare neurodevelopmental, respiratory, surgical, growth, and nutritional outcomes.

Methods

At 1 and 2 years old, subjects underwent evaluation consisting of medical and neurological history and physical, developmental testing, nutritional assessment, oxygen saturation and pulmonary function testing, chest radiograph, and echocardiogram. Growth and developmental measures were corrected for prematurity. Data were analyzed by Mann-Whitney rank sum test, Fisher's Exact test, and logistic and linear regression.

Results

Infants with TO were significantly more premature at birth (control vs TO, 37.4 ± 1.0 vs 31.1 ± 1.7 weeks; P < .01). Growth failure (z score for weight <2 SDs below mean) was severe in both groups at 1 year of age (control vs TO, 56% vs 86%; P = .31). There was considerable catch-up growth by age 2 years (growth failure: control vs TO, 22% vs 33%; P = .19). There were no differences in other growth parameters. There were also no differences in neurodevelopmental outcome at 1 and 2 years. Supplemental oxygen at hospital discharge was a significant predictor of worse neurodevelopmental outcome at 1 and 2 years old (P = .05 and P = .02, respectively). Hearing loss requiring amplification has been diagnosed in 44% of the group (control vs TO, 44% vs 43%; P = 1.0).

Conclusions

In this group of infants with severe CDH, there were no differences in outcome at 2 years old despite significant prematurity in the TO group. Oxygen supplementation at hospital discharge identified the most vulnerable group with respect to neurodevelopmental outcome, but all infants had significant growth failure, and hearing impairment is a substantial problem in this population. Severe CDH carries significant risk of chronic morbidity.     

Lung Transplantation With Grafts From Elderly Donors: A Single-Center Experience

Introduction

Use of extended criteria donors is one of the strategies to face the scarcity of donors for lung transplantation.

Methods

Between November 2002 and May 2009, we performed 52 LTs in 50 recipients, 10 of whom (group A) received lungs from donors aged 55 years or older (median, 58.5; range, 56-66 years) for comparison with 28 patients (group B) transplanted with lungs from donors younger than 55 years (median, 25.5; range, 15-54 years). We excluded 9 children and 3 recipients of combined liver plus lung transplantations from the study.

Results

Recipient age, gender, and indications for transplantation did not differ significantly between the 2 groups. Neither were there significant differences in PaO2/FiO2 ratios before lung retrieval, or length of the ischemic time The first PaO2/FiO2 on arrival to the intensive care unit (ICU) and the median length of ICU stay were similar. All patients, except 2 who died in the operating theatre, were extubated between 3 and 216 hours after the transplantation. Hospital mortality was similar in both groups: 3 patients in group A and 2 in group B (P = .1). The median portions of the predicted 1-second forced expiratory volume (FEV1) at 6 months after transplantation did not differ in the 2 groups: 62.4% in group A versus 70% in group B (P = .85).

Conclusion

Lung grafts from donors older than 55 years can be effectively used for transplantation, thus increasing the total organ pool.     

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.     

New clinical and therapeutic perspectives in Currarino syndrome (study of 29 cases)

Purpose

The aim of the study was to clearly define the anomalies that compose the Currarino syndrome (CS). We highlight the frequency of associated malformations of the spinal cord and the possibility of a communication between the presacral tumor and the spinal canal, leading to neurological complications.

Methods

We studied 29 patients with CS, including 12 familial cases; histological examination of the presacral tumor was performed, and cytogenetic and molecular biology studies of the HLXB9 locus were carried out.

Results

All except 2 patients had a sacral malformation; 23 had an anorectal anomaly and 8 had isolated chronic intestinal pseudo-obstruction. There were 20 presacral tumors, one of which was malignant. There was a communication between the presacral tumor and the spinal canal in 12 cases, and tethering of the spinal cord in 17 cases.Twenty-five patients underwent surgery with a single-stage operation for 7, on both the intestinal and the presacral malformations, and, when required, the spinal cord anomalies.Twelve patients harbored a heterozygous point mutation of the coding sequence of HLXB9 gene.

Conclusion

By accurate evaluation of the 4 main features in the CS, the correct surgical management, including neurosurgery, can be performed in a 1-stage approach.     

The spleen--a potential source of new islets for transplantation?

Background/Purpose

Islet transplantation offers the potential to reverse diabetes soon after diagnosis and has achieved considerable success in adults. Its use in children has been limited by long-term immunosuppression requirements and donor pancreas shortages. An ideal alternative source of islets would be from autologous precursor cells. The aim of this study was to determine whether the spleen can produce insulin-producing cells (IPCs) in our established model of pancreatic development.

Methods

Embryonic quail spleens (day 4.5) and chick pancreatic epithelium (day 4) were microdissected and recombined in a ratio of 1:1 (n = 12), 2:1 (n = 9) and 2:2 (n = 5). They were cultured for 7 days, sectioned, and analysed by fluorescent immunochemistry. Controls were performed to ensure clean separation.

Results

Overall, 12 (46%) of 26 recombinants contained IPCs of splenic origin, occurring in 5 (42%) of 12 of the of 1 spleen-1 epithelium recombinants, 3 (33%) of 9 of the 2 spleen-1 epithelium recombinants, and 4 (80%) of 5 of the 2 spleen-2 epithelia recombinants. Controls were negative.

Conclusions

Preliminary results suggest developing avian spleens can differentiate into IPCs. Increased tissue mass enhanced the likelihood of this occurring. Mesenchyme-to-epithelia ratio did not influence this. The spleen could be an ideal autologous islet source for transplantation in children.     

Ethnic disparities are reduced in VA colon cancer patients

Background

Inequalities in access to care have been hypothesized to be the cause of ethnic disparities in colon cancer. The aim of this study was to determine if ethnic disparities in the outcomes of colon cancer patients exist in a system with equal access.

Methods

A review of 214 consecutive patients who underwent elective colon resection for adenocarcinoma at 1 institution was conducted. Statistical analysis was performed using independent t tests and χ² tests. The Kaplan-Meier method was used for survival estimates.

Results

Of the 214 patients who underwent colon cancer resection, 38% (n = 82) were African American, while 62% (n = 132) were Caucasian. There was no significant difference in the stage of disease at presentation and between the mean times from diagnosis to surgical resection for African American and Caucasian patients. Also, there were no differences in survival.

Conclusion

There does not appear to be a disparity in outcomes for colon cancer patients where equal access to medical care exists. This is based on findings of equal stages at presentation, time to referral, and survival among groups.     

A decade of using intraluminal tracheal/bronchial stents in the management of tracheomalacia and/or bronchomalacia: is it better than aortopexy?

Background

We compared the efficacy and clinical outcomes of aortopexy versus tracheal stents in the management of tracheomalacia.

Methods

A retrospective analysis of 25 consecutive patients undergoing aortopexy (n = 11; 8 boys, 3 girls) or tracheal stents (n = 14; 9 boys, 5 girls) between 1993 and 2003 was performed.

Results

Both treatment groups, aortopexy versus stents, were comparable in their mean age of diagnosis, timing of intervention, surgical indications (“dying spell” or failed extubation), and previous underlying conditions. The operative time (190 vs 72 minutes) and blood loss (26 vs 0 mL) were significantly greater in aortopexy group (P < .01). There were no perioperative deaths in either group. Interestingly, 4 of 11 patients in the aortopexy group developed pericardial effusion (P < .01). With stents in place for a mean of 15 (range 2-41) months, 3 of 8 patients with stent removal had significant granulation tissue requiring further dilatation. No death was observed in aortopexy group, whereas 1 stent-related death and 1 cardiac arrest requiring median sternotomy occurred during stent removal in 44 and 32 months' follow-up, respectively.

Conclusion

Both aortopexy and tracheal stents are effective treatment modalities in the management of tracheomalacia. However, although aortopexy is associated with early perioperative complications, tracheal stents are associated with higher failure rate and more severe stent-related morbidity and mortality.     

The hidden mortality of congenital diaphragmatic hernia: a 20-year review

Aims

The true mortality associated with congenital diaphragmatic hernia (CDH) is hidden because survival analyses do not include fetuses with CDH. A retrospective review of all postmortems (PMs) with a diagnosis of CDH over a 20-year period was carried out to highlight this hidden mortality and also measure the nature and number of associated anomalies.

Methods

Postmortem case record details were reviewed for the period January 1986 to December 2005. Data were collected on live birth, stillbirth, therapeutic abortion, and spontaneous abortion.

Results

There was a decline in the annual number of PMs during the period of the study. The median for the four 5-year intervals being 609 (570-657), 528 (488-565), 515 (413-537), and 373 (357-388). A total of 130 PMs were identified, which included a diagnosis of CDH; 97 (75%) were left sided, 22 (17%) were right sided, and 11 (8%) were bilateral. There were 69 live births, 46 therapeutic abortions, 10 stillbirths, and 5 intrauterine deaths; 22% were right sided/bilateral in the live and therapeutic abortion groups, whereas 53% were right sided/bilateral in the latter 2 groups. Of 130, 82 (63%) had major associated anomalies, and 50% of these had at least 1 further major anomaly. The commonest categories of anomalies were cardiac (30), gastrointestinal/abdominal wall defect (28), and neural tube defects (25).

Conclusions

The true incidence of CDH is considerably higher than that seen in neonatal surgical practice. The decline in number of PMs in our region will exacerbate the underestimation of the true incidence. There is a higher incidence of right-sided/bilateral hernias and more than one major anomaly in those who die in utero.     

Choosing the right physical laparoscopic simulator? Comparison of LTS2000-ISM60 with MISTELS: validation, correlation, and user satisfaction

Background

The LTS 2000-ISM60 (LTS; Realsim Systems, Alburquerque, NM, USA) is a computer enhanced video-laparoscopic training system. Our purpose was to validate the LTS and to correlate its scoring performance with that of the McGill Inanimate System for Training and Evaluation of Laparoscopic Skills (MISTELS), a widely used and well-validated physical simulator.

Methods

Participants (n = 124) included medical students, residents, fellows, and attending surgeons from general surgery, gynecology, and urology in 3 Canadian universities. They were classified in groups based on laparoscopic experience: novice, intermediate, competent, and expert. Participants (n = 124) were tested on the LTS, and 74 were tested on both the LTS and the MISTELS. A user satisfaction questionnaire was completed after each performance.

Results

LTS metrics showed a progressive improvement in total scores according to academic level as well as level of laparoscopic experience (P < .001). Good correlation was found between the LTS and the MISTELS (r = .79). Level of user satisfaction was highest with LTS.

Conclusions

Based on laparoscopic experience and academic level, the LTS has a comparable discriminating capability for level of performance with that of the MISTELS. The higher degree of user satisfaction attributed to the LTS could justify its use as a training and assessment tool for surgical specialties.     

Staircase falls: High-risk groups and injury characteristics in 464 patients

Introduction

Few data are available about the epidemiology and injury characteristics in staircase falls. The available literature mainly concerns children and autopsy studies.

Objective

To describe the epidemiology and injury characteristics of staircase falls, and to identify high-risk groups for these falls.

Methods

All patients who reported to an academic Accident & Emergency (A&E) department in 2005 after a staircase fall were selected in the Dutch Injury Surveillance System These data were linked to the hospital Trauma Registry database.

Results

Four hundred and sixty-four patients (42% male, p = 0.001), with a median age of 35 years were included. Children under five suffered significantly more head injuries. Male patients showed significantly more thoracic injuries than female patients. Spinal column fractures were only seen in patients over 25 years of age. Older patients tended to accumulate more rib fractures and lower extremity fractures and were admitted more frequently than the younger patients. Sixty-one patients (13%) required admission. Two patients, both with severe traumatic brain injury (TBI), died. National data on staircase falls were comparable with our hospital data. However, in comparison to the national population data, senior citizens in this study had an incidence that was markedly higher than in the younger patients.

Conclusion

Injuries due to staircase falls occur in all age groups, however, children under five years are relatively over-represented with higher rates of head injury. Senior citizens showed a markedly higher incidence than younger patients. Most injuries occur to the distal extremities and are relatively mild.     

Expression of Pancreatic Endocrine Markers by Prolactin-Treated Rat Bone Marrow Mesenchymal Stem Cells

Background

Mesenchymal stem cells (MSCs) are an attractive source for generation of cells with β-cell properties. Previous studies have demonstrated the ability of prolactin to induce an increase in β-cell mass and maturation, which suggests beneficial effects of its use in MSC differentiation protocols.

Objective

To evaluate the expression of endocrine differentiation markers in rat MSCs treated in vitro with prolactin.

Methods

Mesenchymal stem cells from bone marrow of Wistar rats were isolated, expanded, and characterized. Differentiation of MSCs was induced in medium containing 23 mmol/L of glucose, and nicotinamide, 2-mercaptoethanol, and exendin-4, in the presence or absence of 500 ng/mL of rat recombinant prolactin. Expression of endocrine markers and prolactin receptor genes was evaluated using real-time polymerase chain reaction, and compared between culture stages and presence vs absence of prolactin in the culture medium. Expression of insulin, somatostatin, glucagon, and pancreatic and duodenal homeobox 1 was also evaluated at immunofluorescence microscopy.

Results

Isolated cells were mostly MSCs, as confirmed at fluorescent-activated cell sorting and cytochemistry. Pax6, Ngn-3, Isl1, NeuroD1, Nkx2.2, and Nkx6.1 exhibited varied expression during culture stages. The long form of the prolactin receptor messenger RNA was induced in prolactin-treated cultures (P < .05). The somatostatin gene was induced in early stages of differentiation (P < .05), and its expression was induced by prolactin, as confirmed using immunofluorescence.

Conclusion

Culture of rat bone marrow MSCs in differentiation medium induces expression of pancreatic endocrine-specific genes, and somatostatin and prolactin receptor expression was also induced by prolactin.     

The respiratory advantage of laparoscopic Nissen fundoplication

Background/purpose

Laparoscopic Nissen fundoplication is replacing the open approach in the treatment of children with gastroesophageal reflux. The postoperative respiratory advantages seem obvious but remain unproven. The authors hypothesized that laparoscopic Nissen fundoplication provides postoperative respiratory advantages in neurologically normal children as well as those with mental retardation or profound neurologic impairment.

Methods

The charts of all laparoscopic Nissen fundoplications over a 4-year period were reviewed. Sixty-one laparoscopic procedures were compared with the most recent 61 consecutive open Nissen fundoplications. The following variables were reviewed: age, weight, gender, preexisting comorbidities, operating time, postoperative pulmonary complications, and length of stay. Categorical data were compared for significance utilizing χ² cross tabulation. Variables representing numerical data were compared by t test.

Results

Although there appeared to be a trend toward sicker patients in the open group, the laparoscopic group showed significantly improved rates of extubation, shorter recovery room stays, shorter durations of chest physiotherapy, fewer intensive care unit admissions, more rapid resumption of baseline feedings, and overall decreased length of stay (P < 0.05). Pulmonary benefits also were noted in the neurologically impaired population when analyzed separately.

Conclusions

Laparoscopic Nissen fundoplication confers a definable benefit with a significant pulmonary advantage in both neurologically normal children and those with neurologic impairment.     

Structural changes of smooth muscle in congenital ureteropelvic junction obstruction

Background/Purpose

Ureteropelvic junction (UPJ) obstruction is the most common cause of congenital hydronephrosis. Previous studies have reported that the excess amount of collagen restricting mobility and resiliency of the UPJ is the result of an impaired collagen production by anomalous smooth muscle cells (SMCs). Our purpose was to evaluate the role of SMC differentiation in the pathogenesis of UPJ obstruction.

Methods

Surgical specimens of UPJ from 21 patients (8 girls/13 boys) who were subjected to dismembered pyeloplasty were examined immunohistochemically using monoclonal antibodies against smooth muscle (SM) myosin heavy chain isoforms including SM1, SM2, and SMemb. The age ranged from 1 month to 13 years. Ureteropelvic walls taken from 14 forensic autopsy cases, with no urological abnormalities, served as age-matched control group.

Results

The immunohistochemical expression of SM1 and SM2 in UPJ obstruction was significantly increased when compared with controls (P < .05). In contrast, there was no statistical difference of expression of SMemb.

Conclusion

Our findings supported the hypothesis that the primary anomaly in UPJ obstruction may be attributed to a malfunction of SMCs in the ureter.     

Congenital spigelian hernias and cryptorchidism

Purpose

Spigelian hernias in childhood are rare. Only 24 infants in the English literature have been identified to have spigelian hernias, and 12 of these have been associated with cryptorchidism. Spigelian hernias are more commonly seen in the adult population and are considered to be acquired because they are typically associated with trauma or other etiologies of increased intraabdominal pressure. In the infant however, the etiology remains unclear, but a congenital defect in abdominal wall development is suspected.

Methods

We discuss the presentation and treatment of 4 additional patients with spigelian hernias (2 siblings included) associated with cryptorchidism.

Results

The hernias occurred within the well-described spigelian hernia belt in the semilunar line at the level of the semicircular fold of Douglas. Of the 6 repaired spigelian hernias, 5 were closed primarily with absorbable suture similar to previously reported cases; the sixth hernia required a patch closure because of its large size. All cryptorchid testes (7) were repaired in single-stage orchiopexies.

Conclusions

Spigelian hernias are rare entities in infants. We present 4 new cases of spigelian hernias associated with cryptorchidism and, with previously reported cases, discuss the probability of a congenital origin of these hernias in infants.