|
Young
JY, Kim DS, Muratore CS, Kurkchubasche AG, Tracy TF Jr, Luks
FI.
High incidence of postoperative bowel obstruction
in newborns and infants.
J Pediatr Surg. 2007 Jun;42(6):962-5
BACKGROUND: Postoperative
bowel obstruction (PBO) plagues patients of all ages after intraabdominal
surgery. We examined the incidence, risk factors, and the need
for operative intervention of PBO. METHODS: We reviewed all children
who underwent a laparotomy or laparoscopy. Parameters included
age, diagnosis, type and number of procedures, complications,
time interval to PBO, treatment of PBO, morbidity, and mortality.
RESULTS: From 2001 to 2005, 2187 abdominal operations were performed.
Overall, 61 patients (2.8%) developed a PBO; 43 (70.5%) required
reoperation. Postoperative bowel obstruction was more common
in patients younger than 1 year (28/601, 4.7%) compared with
older children (33/1586, 2.1%; P = .01, beta = .80). In infants,
PBO was not influenced by initial diagnosis (P = .26) or whether
the initial operation was clean/clean-contaminated or contaminated/dirty
(P = .12). In children older than 1 year, nonoperative treatment
was more likely to be successful if PBO occurred within 12 weeks
of initial operation (12/16 vs 3/14; P = .01). In contrast, all
but one infant (16/17) with early PBO required reoperation. CONCLUSION:
The incidence of PBO is significantly higher in newborns and
infants than in older children (who have rates comparable to
those reported in adults). Infants are significantly more likely
to require operative intervention, particularly if PBO occurs
early after the initial operation.
Chang J, Tracy TF Jr, Carr SR,
Sorrells DL Jr, Luks FI.
Port insertion and removal
techniques to minimize premature rupture of the membranes in
endoscopic fetal surgery.
J Pediatr Surg. 2006 May;41(5):905-9
BACKGROUND: Premature rupture
of membranes (PROM) remains a significant complication of fetal
surgery. Rates of 40% to 100% have been reported after both open
and endoscopic fetal surgery. We describe a technique of endoscopic
port insertion and removal that minimizes trauma to the membranes.
METHODS: Twenty-seven consecutive patients undergoing endoscopic
laser ablation for twin-to-twin transfusion syndrome were reviewed.
In each case, a minilaparotomy was performed, and the amniotic
cavity was entered under direct vision of the uterus using a
Seldinger technique. The entry site was carefully dilated to
accommodate a 4.0-mm-diameter cannula. A gelatin sponge plug
was placed at port removal. Postoperative management and outcome
were evaluated. RESULTS: Median gestational age at operation
was 21.3 weeks. Median operating time was 60 minutes. One patient
delivered intraoperatively because of fetal distress. Seventeen
(65.4%) patients required postoperative tocolysis (median duration,
12 hours). Median postoperative gestation was 6.5 weeks (range,
1-20 weeks). Only 1 (4.2%) of 24 patients with successful gelatin
sponge placement developed PROM. CONCLUSIONS: Meticulous technique
and atraumatic insertion and removal of ports help minimize the
risk of postoperative amniotic leak after endoscopic fetal surgery.
Our PROM rate of 4.2% contrasts sharply with previously reported
rates after similar operations.
Gehring S, Dickson EM, San Martin ME,
van Rooijen N, Papa EF, Harty MW, Tracy TF Jr, Gregory
SH.
Kupffer
cells abrogate cholestatic liver injury in mice.
Gastroenterology.
2006 Mar;130(3):810-22 Abstract
BACKGROUND & AIMS: Biliary
obstruction and cholestasis can cause hepatocellular apoptosis
and necrosis. Ligation of the common bile duct in mice provides
an excellent model in which to study the underlying mechanisms.
Kupffer cells play a key role in modulating the inflammatory
response observed in most animal models of liver injury. This
study was performed to determine the role of Kupffer cells in
the injury attending cholestasis. METHODS: Mice were not treated
or were rendered Kupffer cell-depleted by intravenous inoculation
of multilamellar liposome-encapsulated dichloromethylene diphosphonate,
the common bile duct was ligated and divided; sham-operated animals
served as controls. Similarly, interleukin-6 (IL-6)-deficient
and tumor necrosis factor-receptor-deficient mice underwent bile
duct ligation (BDL) or sham operations. RESULTS: Serum alanine
transaminase levels were increased in all BDL mice at 3 days
after surgery, but were significantly higher in IL-6-deficient
mice or mice rendered Kupffer cell-depleted before ligation.
Histologic examination of BDL livers showed portal inflammation,
neutrophil infiltration, bile duct proliferation, and hepatocellular
necrosis. Photoimage analyses confirmed more necrosis in the
livers of Kupffer cell-depleted and IL-6-deficient animals. Purified
Kupffer cells derived from BDL animals produced more IL-6 in
culture. Similarly, Kupffer cells obtained by laser capture microdissection
from the livers of BDL mice expressed increased levels of IL-6
messenger RNA. Recombinant mouse IL-6 administered 1 hour before
BDL completely reversed the increased liver damage assessed otherwise
in Kupffer cell-depleted mice. CONCLUSIONS: These findings indicate
that Kupffer cells abrogate cholestatic liver injury by cytokine-dependent
mechanisms that include the production of IL-6.
Harty MW, Huddleston HM, Papa EF, Puthawala
T, Tracy AP, Ramm GA, Gehring S, Gregory SH, Tracy TF Jr.
Repair
after cholestatic liver injury correlates with neutrophil infiltration
and matrix metalloproteinase 8 activity.
Surgery. 2005 Aug;138(2):313-20
Abstract
BACKGROUND: Although timely
surgical treatment of liver disease can interrupt inflammation
and reduce fibrosis, the mechanisms of repair are unknown. We
questioned whether these mechanisms of repair include changes
in the inflammatory infiltrate and associated biological activity
of matrix metalloproteinases (MMPs) 8 and 2. METHODS: Rats (n
>or= 3) underwent biliary ductal suspension for 7 days followed
by decompression. Livers were collected after 7 days of obstruction
(d0) and after 2, 5, and 7 days of repair (d2, d5, d7, respectively),
and assessed morphometrically for collagen, polymorphonuclear
cells (PMNs), Kupffer cells (KCs), and inflammatory mononuclear
phagocytes (MNPs). In situ zymography was performed by using
fluorogenic substrates for MMP-8 and MMP-2 to spatially localize
enzymatic activity. RESULTS: Cholestatic injury resulted in significantly
elevated (P <or= .001) collagen deposition (3-fold), and elevated
numbers of MNPs (10-fold), KCs (5-fold), and PMNs (4-fold), compared
with shams. PMNs remained elevated through d7, while collagen
deposition, KCs, and MNPs returned to sham levels by d2. In situ
zymography showed no significant changes in MMP-2 activity after
cholestatic injury and repair. MMP-8 activity was significantly
(P <or= .05) elevated only during repair. Activity was localized
to fibrotic portal triads containing PMNs. CONCLUSIONS: Cholestatic
injury results in increased fibrosis, MNPs, KCs, and PMNs but
no MMP-2 or MMP-8 activity. Biliary decompression results in
increased MMP-8 activity co-localized to areas of portal fibrosis
and PMN accumulation. We conclude that secretion of MMP-8 by
neutrophils may play a critical role in resolving the fibrotic
scar generated during cholestasis.
Lui F,
Gormley P, Sorrells DL Jr, Biffl WL, Kurkchubasche AG, Tracy
TF Jr, Luks FI.
Pediatric trauma patients with
isolated airway compromise or Glasgow Coma Scale less than 8:
does immediate attending surgeon's presence upon arrival make
a difference? J Pediatr Surg. 2005 Jan;40(1):103-6.
BACKGROUND/PURPOSE: Optimal trauma
care requires an attending pediatric surgeon to head a trauma
team for the most severely injured patients. Recently, the American
College of Surgeons-Committee on Trauma has added "Glasgow
Coma Scale (GCS) <8" and "airway compromise"
to the existing anatomical and physiological criteria for immediate
attending presence. This report analyzes the outcome of children
who met these isolated criteria and were treated before the change
in guidelines was made. METHODS: The trauma registry of this
level I trauma center was queried for all pediatric patients
with GCS <8 or airway compromise. Age, sex, initial GCS, Revised
Trauma Score, Injury Severity Score, outcome, and probability
of survival (TRISS methodology) were recorded. The subgroup of
patients for whom an attending surgeon was not immediately present
was further analyzed. RESULTS: Over a 5-year period, 2895 trauma
patients (aged 0-16 years) were admitted. One hundred fifteen
patients had a GCS <8 and/or airway compromise. In 61 cases,
an attending surgeon was not present upon patient arrival. Of
these patients, 24 died (group D), 15 were discharged to a rehabilitation
facility (group R), and 22 were discharged home (group H). Ten
patients with a probability of survival of lower than 0.5 survived.
Only 4 of the 24 patients who died had a probability of survival
of >0.5 (mean, 0.697). All 4 had an Injury Severity Score
>25 and a GCS < or =4. All deaths were reviewed through
a quality improvement program and were deemed nonpreventable
by objective reviewers. Patient outcome was not affected by the
presence or absence of an attending surgeon upon patient arrival.
CONCLUSIONS: Outcome of severely injured children with GCS <8
or airway compromise met and, in some cases, exceeded expectations
of survival according to the TRISS methodology. The lack of immediate
attending surgeon's presence does not appear to have negatively
influenced the outcome in these children. Based on this series,
there is no evidence to justify mandatory immediate presence
of an attending surgeon for these 2 criteria alone.
Vrochides
DV, Sorrells DL Jr, Kurkchubasche AG, Wesselhoeft CW Jr, Tracy
TF Jr, Luks FI.
Is there a role for routine preoperative
endoscopic retrograde cholangiopancreatography for suspected
choledocholithiasis in children? Arch Surg. 2005 Apr;140(4):359-61.
HYPOTHESIS: Endoscopic retrograde
cholangiopancreatography (ERCP) is frequently used preoperatively
in adult patients with suspected choledocholithiasis. Cholelithiasis
occurs much less often in children, and the indications for ERCP
are not established. We hypothesized that the natural history
of choledocholithiasis in children is spontaneous passage of
stones through the papilla and that these children can be managed
without routine preoperative ERCP. DESIGN: Retrospective analysis
of patients treated over a 10-year period. SETTING: Tertiary
care children's hospital. PATIENTS: All patients with cholecystectomy
for biliary disease. INTERVENTIONS: Cholecystectomy; intraoperative
cholangiography for suspected choledocholithiasis: hyperbilirubinemia,
gallstone pancreatitis, and ultrasonographic evidence of common
bile duct dilation or common bile duct stones; and postoperative
ERCP for symptomatic choledocholithiasis: pain and jaundice.
MAIN OUTCOME MEASURES: Incidence and complications of choledocholithiasis
and frequency of ERCP. RESULTS: One hundred patients (63 females)
were studied. Indications included acute cholecystitis (10%),
chronic cholecystitis (59%), gallstone pancreatitis (26%), and
choledocholithiasis (5%). An intraoperative cholangiography was
performed in 45 patients, and common bile duct stones were identified
in 13. Expectant management of asymptomatic common bile duct
stones was associated with sonographic resolution within 1 week.
One patient with intraoperative cholangiography-proven choledocholithiasis
required ERCP for symptoms 24 hours after operation. One additional
patient, who did not undergo intraoperative cholangiography,
developed symptomatic choledocholithiasis and required ERCP.
There were no choledocholithiasis- or ERCP-related complications.
CONCLUSIONS: This study suggests that choledocholithiasis occurs
frequently in children and that spontaneous passage of common
bile duct stones is common. This could explain the relatively
high incidence of gallstone pancreatitis. Conservative management
of choledocholithiasis is successful in the majority of patients.
Routine preoperative or postoperative ERCP is usually not indicated.
De
Paepe ME, Mao Q, Luks FI.
Expression of apoptosis-related
genes after fetal tracheal occlusion in rabbits. J Pediatr
Surg. 2004 Nov;39(11):1616-25.
BACKGROUND/PURPOSE: Late-gestation
lung remodeling is associated with alveolar type II cell apoptosis
early in the saccular stage (day 28 in fetal rabbits). Intrauterine
tracheal occlusion (TO), a potent stimulus of fetal lung growth
and maturation, significantly increases type II cell apoptosis.
The aim of this study was to determine the effect of fetal TO
on the spatiotemporal expression of key apoptosis-related signaling
molecules. METHODS: Tracheal occlusion of fetal rabbits was performed
at gestational day 25 (term, 31 days), and apoptotic gene expression
was studied between days 26 and 28. RESULTS: At days 26 and 27,
the protein levels of Fas and Fas-ligand (FasL) in lung lysates
were similar in TO fetuses and sham-operated controls. At day
28, however, synchronous with the onset of TO-induced pulmonary
distension and type II cell apoptosis, the FasL protein content
was 8-fold higher in TO lungs compared with controls (P <
.01), whereas Fas levels were comparable. In contrast, Bax and
Bcl-2 protein levels were similar in TO and control fetuses at
all time-points. TO significantly increased the cellular concentration
of immunoreactive FasL in type II cells and bronchial epithelial
Clara cells. Furthermore, bronchoalveolar lavage fluid (BAL)
from TO fetuses at day 28 induced significantly more type II
cell apoptosis in vitro compared with control BAL, an effect
that was inhibited by neutralizing anti-FasL antibody. CONCLUSIONS:
Our findings show that TO results in time-specific increase of
both cellular and soluble FasL in fetal lungs and implicate the
Fas/FasL pathway as a pivotal autocrine and/or paracrine regulator
of TO- induced type II cell apoptosis.
Spencer
AU, Yu S, Tracy TF, Aouthmany MM, Llanos A, Brown MB, Brown M,
Shulman RJ, Hirschl RB, Derusso PA, Cox J, Dahlgren J, Strouse
PJ, Groner JI, Teitelbaum DH, Stechmiller JK.
Parenteral
nutrition-associated cholestasis in neonates: multivariate analysis
of the potential protective effect of taurine. J PEN J Parenter
Enteral Nutr. 2005 Sep-Oct;29(5):337-44.
BACKGROUND:
Neonates receiving parenteral nutrition (PN) are at risk for
PN-associated cholestasis (PNAC); however, no preventive factors
for PNAC have been clearly identified. Despite reports suggesting
that taurine may prevent PNAC in neonates, such an effect of
taurine has not yet been definitively demonstrated. We determined
whether taurine supplementation reduces the incidence of PNAC
in premature or critically ill neonates. METHODS: This study
was part of a prospective, randomized, multi-institutional trial
designed to assess cholecystokinin vs placebo as a potential
preventive therapy of PNAC. Taurine supplementation of PN varied
between institutions. The presence or absence of taurine in PN
was analyzed by multivariate analysis, with a primary outcome
measure of serum conjugated bilirubin (CB) as a measure of PNAC.
RESULTS: Taurine reduced PNAC in premature infants (estimated
maximum CB [95% confidence interval] 0.50 mg/dL [-0.17 to 1.18]
for those receiving taurine, vs 3.45 mg/dL [1.79-5.11] for neonates
not receiving taurine, approaching significance, p = .07). Taurine
significantly reduced PNAC in infants with necrotizing enterocolitis
(NEC; estimated maximum CB 4.04 mg/dL [2.85-5.23], NEC infants
receiving taurine, vs 8.29 mg/dL [5.61-10.96], NEC infants not
receiving taurine, p < .01). There were too few neonates with
surgical anomalies to evaluate the effect of taurine in this
group. CONCLUSIONS: Within specific subgroups of neonatal patients,
taurine supplementation does offer a very significant degree
of protection against PNAC. Patients with NEC or severe prematurity
are most likely to benefit substantially from taurine supplementation.
Cloutier
DR, Baird TB, Gormley P, McCarten KM, Bussey JG, Luks FI. Pediatric
splenic injuries with a contrast blush: successful nonoperative
management without angiography and embolization. J Pediatr
Surg. 2004 Jun;39(6):969-71.
BACKGROUND: The
presence of a contrast blush on computed tomography (CT) in adult
splenic trauma is a risk factor for failure of nonoperative management.
Arterial embolization is believed to reduce this failure rate.
The significance of a blush in pediatric trauma is unknown. The
authors evaluated the outcome of children with blunt splenic
trauma and contrast extravasation. METHODS: The trauma registry
was queried for all pediatric patients with blunt splenic injuries.
Admission CT was reviewed for injury grade and presence of an
arterial blush by a radiologist blinded to patient outcome. Hospital
and office charts were reviewed for success of nonoperative management,
late splenic rupture, and other complications. RESULTS: One hundred
seven children with blunt splenic trauma were identified over
a 6-year period. Mean injury grade was 2.9. Six patients required
emergency splenectomy. An additional 7 patients met hemodynamic
criteria for surgical intervention (3 splenectomies, 4 splenorrhaphies).
Admission CT was available in 63 patients. An arterial blush
was identified in 5 (9.7%). Four remained stable and were treated
conservatively. One underwent splenectomy for hemodynamic instability.
There were no cases of delayed splenic rupture, failed nonoperative
treatment, or long-term complications. CONCLUSIONS: Contrast
blush in children with blunt splenic trauma is rare, and its
presence alone does not appear to predict delayed rupture or
failure of nonoperative treatment. Based on this limited series,
splenic artery embolization does not have a place in the management
of splenic injuries in children.
Luks
FI, Carr SR, Plevyak M, Craigo SD, Athanassiou A, Ralston SJ,
Tracy TF Jr. Limited prognostic value of a staging system for
twin-to-twin transfusion syndrome. Fetal Diagn Ther. 2004
May-Jun;19(3):301-4.
OBJECTIVE: Severe twin-to-twin
transfusion syndrome (TTTS) is usually classified according to
a staging system (I-V) based on ultrasonographic findings of
polyhydramnios in the recipient, oligohydramnios in the donor,
the presence or absence of the donor's bladder, Doppler waveform
changes and (impending) hydrops. Stage correlates with the severity
of disease, and it is assumed that, without intervention, severe
TTTS will evolve in succession from stage I to stage V (fetal
demise). However, this progression has not been validated in
longitudinal studies. Herein, we report on the natural progression
of severe TTTS in a cohort of patients from a regional Fetal
Treatment Program. METHODS: Eighteen patients with severe TTTS,
diagnosed between 15 and 25 weeks of gestation, were managed
over a 28-month period. Data were collected until delivery, endoscopic
surgical intervention or dual fetal demise. Patients were evaluated
at least once a week. Stage, estimated fetal weight, percent
recipient/donor body weight discordance and survival were recorded.
RESULTS: The present study represents a total follow-up of 108
patient-weeks. Of 90 week-to-week evaluations, 65 showed no change
in stage; 11 showed downstaging (by more than 1 stage in 3, or
27%), and 13 showed upstaging (by more than 1 stage in 8, or
62%). Nine patients (all stage II or above) underwent endoscopic
laser ablation. Overall survival was 67%, and survival of at
least 1 twin occurred in 78% of pregnancies. Weight discordance
between the donor and recipient did not predict outcome. CONCLUSION:
The current staging system for severe TTTS may not be helpful
in predicting the direction, degree or speed of progression of
the condition. Indications for intervention should remain stage-related,
and not based on projected progression.
De
Paepe ME, Friedman RM, Poch M, Hansen K, Carr SR, Luks FI. Placental
findings after laser ablation of communicating vessels in twin-to-twin
transfusion syndrome. Pediatr Dev Pathol. 2004 Mar-Apr;7(2):159-65.
Epub 2004 Mar 17.
As laser ablation of placental
vascular communications gains acceptance as treatment option
for severe twin-to-twin transfusion syndrome (TTTS), pathologists
are increasingly confronted with the interpretation of laser-treated
placentas. We present our preliminary institutional experience
with the gross and microscopic analysis of these specimens. Patients
underwent selective ablation for severe TTTS (Quintero stages
II to V) between 16 and 25 wk gestation and the placentas were
examined between < 24 h and 19 wk postoperatively. The placental
vasculature was injected with gelatin-dye mixtures. The type
and number of vascular anastomoses were recorded, followed by
routine histopathological analysis of the placenta. Foci of laser
impact were identified in all placentas examined within 1 month
after laser coagulation. Located along the recipient side of
the dividing membrane, the laser-treated vessels appeared hemorrhagic
and showed a characteristic abrupt interruption of dye filling
after vascular injection. In placentas examined more than 1 month
after intervention, the most frequent gross finding was the absence
or relative paucity of intertwin anastomoses, associated with
subchorionic fibrin deposition. Microscopically, laser-treated
vessels showed varying degrees of necrosis, associated with focal
hemorrhage, avascular villi, and fibrin deposition in the underlying
parenchyma. In some cases of intrauterine fetal demise or placental
disruption, no definite laser scars were identified. As expected,
the number of residual anastomoses (all types) was significantly
smaller in laser-treated placentas than in control monochorionic
placentas (2.4 +/- 2.2 [ n = 10] vs. 6.2 +/- 3.2 [ n = 70], P
< 0.01). Velamentous cord insertion was noted in 50% of cases;
markedly uneven placental sharing in 60%. Detailed analysis of
laser-treated placentas and clinicopathological correlation may
lead to a better understanding of the pathophysiology of TTTS
and continued refinement of therapeutic approaches for this often
lethal condition.
Oka T,
Kurkchubasche AG, Bussey JG, Wesselhoeft CW Jr, Tracy TF Jr,
Luks FI. Open and laparoscopic appendectomy are equally safe
and acceptable in children. Surg Endosc. 2004 Feb;18(2):242-5.
Epub 2003 Dec 29.
BACKGROUND: The aim of this
study was to evaluate prospectively whether laparoscopic (LA)
and open appendectomy (OA) are equally safe and feasible in the
treatment of pediatric appendicitis. METHODS: A total of 517
children with acute appendicitis were randomly assigned to undergo
LA or OA appendectomy, based on the schedule of the attending
surgeon on call. Patient age, sex, postoperative diagnosis, operating
time, level of training of surgical resident, length of postoperative
hospitalization, and minor and major postoperative complications
were recorded. Chi-square analysis and the Student t-test were
used for statistical analysis. RESULTS: In all, 376 OA and 141
LA were performed. The two groups were comparable in terms of
patient demographics and the incidence of perforated appendicitis.
The operative time was also similar (47.3 +/- 19.7 vs 49.9 +/-
12.9 min). The overall incidence of minor or major complications
was 11.2% in the OA group and 9.9% in the LA group. CONCLUSION:
Pediatric patients with appendicitis can safely be offered laparoscopic
appendectomy without incurring a greater risk for complications.
Nevertheless, a higher (but not significantly higher) abscess
rate was found in patients with perforated appendicitis who underwent
laparoscopy.
Bussey
JG, Luks F, Carr SR, Plevyak M, Tracy TF Jr. Minimal-access fetal
surgery for twin-to-twin transfusion syndrome.Surg Endosc.
2004 Jan;18(1):83-86. Epub 2003 Nov 21.
Background:
Laser ablation of placental vessels effectively halts severe
twin-to-twin transfusion syndrome (TTTS), but fetal surgery remains
a dangerous approach. The authors present the technical aspects
of endoscopic fetal surgery in their initial clinical experience.
Methods: Altogether, 11 women underwent endoscopic fetal surgery
for severe TTTS. Access to the recipient's sac was obtained by
the Seldinger technique via minilaparotomy. A 12-Fr peel-away
introducer was used as a cannula to accommodate a custom-curved
9-Fr sheath containing a 1.9-mm semirigid fiber endoscope. Laser
ablation was performed on all unpaired vessels crossing the intertwin
membrane using a 400- micro m neodymium: yttrium-aluminum-garnet
(Nd: YAG) fiber. The cannula was removed over a gelatin sponge
plug. Results: The median operating time was 65 min (range, 45-105
min). No patient experienced amniotic leak postoperatively. The
length of hospital stay was 2.8 +/- 1.6 days. Immediate improvement
of the TTTS was noted in all but two patients. Pneumonia developed,
in one mother leading to premature labor. There were no other
major surgical complications. Fetal survival at 2 weeks was 73%.
Conclusions: The safety and efficacy of endoscopic fetal surgery
for severe TTTS can be optimized with the application of current
minimal-access techniques. The superiority of this approach over
less invasive means is still being evaluated through prospective
studies.
Biffl
WL, Schiffman JD, Harrington DT, Sullivan J, Tracy TF Jr, Cioffi
WG. Legal prosecution of alcohol-impaired drivers admitted to
a level I trauma center in Rhode Island. J Trauma. 2004 Jan;56(1):24-9.
BACKGROUND:
Despite harsh legislation, driving under the influence of alcohol
(DUI) is exceedingly common, and alcohol-related motor vehicle
crashes (MVCs) account for significant morbidity, mortality,
and economic loss. Legal sanctions can keep offenders off the
road (protecting other drivers and pedestrians) and ensure compliance
with treatment programs (reducing recidivism). However, even
with clear evidence of a transgression, the law seems to be inconsistently
enforced among trauma patients. The purpose of this study was
to measure the rate of legal prosecution among impaired drivers
admitted to a trauma center after MVCs, and to determine the
recidivism rate among these individuals. METHODS: Our trauma
registry was queried to identify intoxicated drivers admitted
during an 18-month period. Court records identified patients
who had been charged with traffic offenses, including prior (2
years) and subsequent (1 year) charges. RESULTS: Blood alcohol
concentration (BAC) was measured in 387 (74%) of 525 drivers,
of whom 137 (35%) had BAC > or =100 mg/dL. Of 113 state residents,
22 (19%) were charged with an offense related to the MVC. Of
12 charged with DUI, 10 were convicted, for an overall DUI conviction
rate of just 9%. Seven (32%) of those who were charged had prior
or subsequent charges. Of 91 patients not charged for the index
event, 31 (34%) had prior or subsequent charges. CONCLUSION:
Alcohol is involved in a large percentage of MVCs in our region.
The infrequency of prosecution for DUI despite property damage
and/or personal injury, and the high recidivism rate, are significant
social concerns. These data suggest the need for processes to
facilitate legal prosecution--possibly including revision of
legislation involving reporting of BACs.
Ambruso
DR. Knall C. Abell AN. Panepinto J. Kurkchubasche A. Thurman
G. Gonzalez-Aller C. Hiester A. deBoer M. Harbeck RJ. Oyer R.
Johnson GL. Roos D. Human neutrophil immunodeficiency syndrome
is associated with an inhibitory Rac2 mutation. Proceedings
of the National Academy of Sciences of the United States of America.
97(9):4654-9, 2000 Apr 25.
A 5-week-old
male infant presented with severe bacterial infections and poor
wound healing, suggesting a neutrophil defect. Neutrophils from
this patient exhibited decreased chemotaxis, polarization, azurophilic
granule secretion, and superoxide anion (O(2)(-)) production
but had normal expression and up-regulation of CD11b. Rac2, which
constitutes >96% of the Rac in neutrophils, is a member of
the Rho family of GTPases that regulates the actin cytoskeleton
and O(2)(-) production. Western blot analysis of lysates from
patient neutrophils demonstrated decreased levels of Rac2 protein.
Addition of recombinant Rac to extracts of the patient neutrophils
reconstituted O(2)(-) production in an in vitro assay system.
Molecular analysis identified a point mutation in one allele
of the Rac2 gene resulting in the substitution of Asp57 by an
Asn (Rac2(D57N)). Asp57 is invariant in all defined GTP-binding
proteins. Rac2(D57N) binds GDP but not GTP and inhibits oxidase
activation and O(2)(-) production in vitro. These data represent
the description of an inhibitory mutation in a member of the
Rho family of GTPases associated with a human immunodeficiency
syndrome.
Ramm
GA. Carr SC. Bridle KR. Li L. Britton RS. Crawford DH. Vogler
CA. Bacon BR. Tracy TF. Morphology of liver repair following
cholestatic liver injury: resolution of ductal hyperplasia, matrix
deposition and regression of myofibroblasts. Liver. 20(5):387-96,
2000 Oct.
BACKGROUND/AIMS:
Myofibroblasts are the primary cells responsible for increased
matrix deposition in hepatic fibrosis. Activation of hepatic
stellate cells and portal fibroblasts to myofibroblasts during
cholestatic liver injury is accompanied by increased expression
of the activation marker, alpha-smooth muscle actin (SMA), and
collagen genes. In contrast to our understanding of injury, the
cellular mechanisms of liver repair are not well defined. This
study was designed to examine the morphological relationship
between bile duct hyperplasia, matrix deposition and myofibroblast
phenotype in a model of chronic cholestatic liver injury and
repair. METHODS: Reversible extrahepatic obstruction was accomplished
in rats using a soft vessel loop suspended from the anterior
abdominal wall: duct manipulation alone was performed in sham-operated
controls. After 7 days, rats were either sacrificed or decompressed
by release of the loop and subsequently sacrificed 2-10 days
after reversal. Liver sections were obtained for in situ hybridization
for procollagen alpha1(I) mRNA, immunohistochemical staining
for SMA and cytokeratin 19, and histochemical staining for reticulin.
RESULTS: Cholestatic livers demonstrated bile duct hyperplasia,
which reversed to normal within 10 days after decompression.
Fibrosis was also substantially reduced during this period. SMA-positive
myofibroblasts were abundant and localized to regions adjacent
to proliferating ducts and excess matrix in the obstructed animals.
Decompressed livers showed a dramatic time-dependent reduction
in the number of SMA-positive cells and in the expression of
procollagen I mRNA. CONCLUSIONS: Our results show that the disappearance
of bile duct hyperplasia after biliary decompression is accompanied
by a similarly rapid loss of SMA-positive myofibroblasts. Both
cellular events may abrogate enhanced matrix synthesis and allow
repair to occur.
Phornphutkul
C. Okubo T. Wu K. Harel Z. Tracy TF Jr. Pinar H. Chen S. Gruppuso
PA. Goodwin G. Aromatase p450 expression in a feminizing adrenal
adenoma presenting as isosexual precocious puberty. Journal
of Clinical Endocrinology & Metabolism. 86(2):649-52, 2001
Feb.
A 7-yr-old girl presented
with isosexual precocious puberty secondary to a feminizing adrenal
adenoma. The adrenal tumor was found to express aromatase messenger
ribonucleic acid. Enzyme kinetic studies revealed a high level
of aromatase activity in the adrenal tumor, with a K(m) of 45
nmol/L and a maximum velocity of 25.6 pmol/mg.h. Aromatase activity
was approximately 500-fold higher in the tumor than in adjacent
normal adrenal tissue. Although histopathological examination
of the tumor was most consistent with a benign adenoma, the aromatase
transcripts present in the tumor corresponded to those previously
associated with malignant as well as benign tumors. We consider
the pattern of aromatase expression sufficient to warrant continued
follow-up for tumor recurrence. Our case demonstrates that isosexual
precocious puberty secondary to a feminizing adrenal tumor can
be due to estrogen synthesis from the tumor itself rather than
peripheral aromatization as had been previously theorized.
Luks
FI. Roggin KK. Wild YK. Piasecki GJ. Rubin LP. Lesieur-Brooks
AM. De Paepe ME. Effect of lung fluid composition on type II
cellular activity after tracheal occlusion in the fetal lamb.
Journal of Pediatric Surgery. 36(1):196-201, 2001 Jan.
BACKGROUND/PURPOSE: Fetal tracheal
occlusion (TO) causes accelerated lung growth. However, prolonged
TO is associated with a decline in the type II cell number. Type
II cell function after TO is unclear. Herein, the authors examine
type II cell function after TO and the role of tracheal fluid.
METHODS: Fetal lambs (term, 145 days) underwent TO at 122 days.
Tracheal pressure was recorded daily. In one group of animals
(TF; n = 6), lung fluid was aspirated, measured, and reinfused
daily. In their respective twins, NS group, lung fluid was replaced
milliliter per milliliter with normal saline (NS; n = 6). At
death near term, lung weight was obtained, and tissues were processed
for stereologic volumetry. Type II cells were quantitated using
antisurfactant protein B immunohistochemistry. Surfactant protein
B-mRNA expression was studied by Northern analysis. Wilcoxon
signed rank test and single factor analysis of variance (ANOVA)
were used for statistical analysis (P<.05 was significant).
RESULTS: In both experimental groups, intratracheal pressure
rose from 1.9+/-1.0 torr to 3.7 to 4.8 torr by day 1, and remained
constant thereafter. Lung fluid volume increased from 11.9+/-4.2
on day 0 to 36.8+/-8.0 mL/kg in TF, and to 28.4+/-9.3 mL/kg in
NS by day 1 (P<.05). At death, lung weight/body weight ratio
was higher in TF (5.45% +/- 0.91%) than in NS (4.40% +/- 0. 67%)
or control (3.83%+/-0.58%; P<.05). Type II numerical density
was substantially reduced after TO: 57.7+/-12.8 x 10(6)/mL (TF)
and 45.0 +/-25.9 x 10(6)/mL (NS), versus 82.3+/-13.6 x 10(6)/mL
in controls. Ultrastructurally, remaining type II cells in TF
were enlarged and engorged with lamellar bodies; in NS, they
were smaller and contained fewer lamellar bodies. Surfactant
protein B mRNA expression was significantly decreased in NS,
but not in TF, compared with controls. CONCLUSIONS: Type II cell
function as well as overall lung growth are stimulated by TO.
Lung growth after TO is therefore not unavoidably detrimental
to type II cells. After isobaric saline exchange of lung fluid,
type II cell function is severely inhibited, confirming the role
of tracheal fluid composition in type II stimulating type II
cell function.
Roggin
KK. Chwals WJ. Tracy TF. Institutional Review Board approval
for prospective experimental studies on infants and children.
Journal of Pediatric Surgery. 36(1):205-8, 2001 Jan.
BACKGROUND/PURPOSE: The Declaration
of Helsinki requires Institutional Review Board (IRB) approval
for experimental studies on human subjects. The authors questioned
whether published prospective surgical experimental studies document
IRB approval for infants and children. METHODS: Prospective studies
were identified in 5 surgical and 2 major pediatric journals
from 1997 through 1999. Documentation of IRB approval was recorded.
Results were analyzed using Pearson chi(2) tests and a multivariate
regression model. Statistical significance was defined as P less
than .05. RESULTS: A total of 149 prospective experimental studies
on pediatric subjects were evaluated; the majority being interventional
or therapeutic studies (105 of 149). More than 75% were from
academic medical centers (125 of 149), grant-supported (110 of
149), and appeared in surgical journals (110 of 149). Slightly
less than 25% of studies (40 of 149) documented IRB approval.
Observational studies, grant support, and publication in nonsurgical
journals all correlated positively with IRB approval and were
statistically significant variables (P<.001, P<.001, P<.001,
respectively). Interventional or therapeutic, institutionally
or privately-funded studies found in surgical journals were most
likely to avoid IRB documentation (P<.001). CONCLUSIONS: The
majority of prospective pediatric studies in the surgical journals
omit IRB documentation. Strict requirements for specific IRB
approval and documentation in compliance with the Declaration
of Helsinki would allow higher ethical standards for the clinical
investigation of infants and children.
Roggin
KK. Kim JC. Kurkchubasche AG. Papa EF. Vezeridis AM. Tracy TF.
Macrophage phenotype during cholestatic injury and repair: the
persistent inflammatory response. Journal of Pediatric Surgery.
36(1):220-8, 2001 Jan.
BACKGROUND/PURPOSE:
Biliary decompression for congenital or acquired obstruction
(eg, biliary atresia) does not uniformly lead to liver repair,
restore function, or prevent cholangitis. The authors hypothesize
that failed repair is caused by altered macrophage (Mo) phenotypes
central to an ongoing inflammatory and fibrogenic response. METHODS:
In adult rats, biliary obstruction was performed by suspension
of the common bile duct for 5 or 7 days. Decompression followed
release of the loop until death during the course of liver repair.
To determine Mo phenotype in the presence or absence of resident
macrophages, animals were either administered gadolinium chloride
or saline before injury and repair. At death, hepatic Mo were
isolated, stained with MAC-1 (CD11b/CD 18) and OX-3 (MHC class
II), and quantified with flow cytometry. Liver sections were
immunostained for ED-1 and ED2; positive Mo were counted per
square millimeter of tissue. RESULTS: Obstruction led to bile
duct proliferation, fibrosis, and inflammation. Decompression
relieved jaundice and ductal hyperplasia. After injury, hepatic
Mo showed an 80% phenotypic conversion to MAC-1 and OX-3-positive
cells. Cells isolated from livers at 9 days of repair persisted
with 60% MAC-1 and 77% OX-3 expression. Gadolinium reduced Kupffer
cells at all stages of repair. Recruited Mo in treated animals
increased 4-fold greater than controls. CONCLUSIONS: Kupffer
cells appear to limit the recruitment and persistence of a systemic
macrophage phenotype in liver injury and repair. Cell surface
markers for systemic macrophages appear after injury and persist
during repair, despite adequate biliary decompression. After
biliary decompression, this macrophage phenotype accounts for
inflammatory complications such as cholangitis and ongoing fibrosis.
Liao,
S. L.; Luks, F. I.; Piasecki, G. J.; Wild, Y. K.; Papadakis,
K., and De Paepe, M. E. Late-gestation tracheal occlusion in
the fetal lamb causes rapid lung growth with type II cell preservation.
J Surg Res. 2000 Jul; 92(1):64-70.
BACKGROUND: Fetal tracheal occlusion
(TO) results in varying degrees of lung growth. This study examines
whether gestational age influences lung growth response following
TO. MATERIALS AND METHODS: Fetal lambs (term = 145 days) underwent
TO early (108 days, n = 6) or late (122 days, n = 6) in gestation.
Aspirated lung fluid volume (LFV) and intratracheal pressure
(ITP) were recorded daily. Two weeks after TO, the fetuses were
sacrificed. Lung growth was assessed by lung weight and stereologic
volumetry. Type II cellular density was assessed by computer-assisted
morphometry using antisurfactant protein B antibody. RESUTLS:
After early TO, ITP remained below 2 mm Hg for all but one of
the first 5 days. In late TO, ITP rose to 4.8 +/- 1.7 mm Hg by
Day 1 and remained elevated. LFV remained lower after early than
after late TO (P < 0.05) for 8 days. Thereafter, pressure
and volume reached similar levels in both TO groups; both were
significantly higher than their respective controls (P < 0.05).
Parenchymal fraction (1 - air- space fraction) was significantly
smaller after late TO (22.8 +/- 1.2%) than after early TO (31.3
+/- 0.5%). Type II density was 38.0 +/- 12.4 x 10(6)/mL after
early TO and 84.0 +/- 24.3 x 10(6)/mL in control (P < 0.05);
the difference between late TO and control was not significant.
CONCLUSIONS: Late tracheal occlusion in fetal lambs caused more
rapid lung growth than earlier TO, although ultimate lung size
was similar in both groups. Late TO also resulted in greater
air-space fraction and better preservation of the type II cell
population than early TO. Late- gestation tracheal occlusion
may therefore be preferable to prolonged occlusion initiated
earlier. Copyright 2000 Academic Press.
Luks,
F. I.; Wild, Y. K.; Piasecki, G. J., and De Paepe, M. E. Short-term
tracheal occlusion corrects pulmonary vascular anomalies in the
fetal lamb with diaphragmatic hernia. Surgery. 2000 Aug; 128(2):266-72.
BACKGROUND: Sustained fetal tracheal
occlusion (TO) results in accelerated lung growth but causes
severe type II cell depletion. Temporary TO fails to cause lung
growth in a congenital diaphragmatic hernia (CDH) model but preserves
type II cells and corrects pulmonary hypertension. Herein, we
study the pulmonary vascular changes caused by temporary TO.
METHODS: CDH was created in 12 fetal lambs (65-70 d; term, 145
days). In 6 lambs, the trachea was occluded for 2 weeks (CDH
+ TO; 108-122 d). Animals were killed at 136 days. The lungs
were processed with elastin stains and anti-alpha-smooth muscle
actin antibody. Partial or circumferential presence of inner
and outer elastic lamina was used to determine muscularization
of pulmonary arterioles. The percent of medial wall thickness
was plotted against vessel diameter for each group. RESULTS:
Lung weight/body weight was smaller in lambs with CDH (1. 35%
+/- 0.56%) and CDH + TO (1.70% +/- 0.34%) than in control lambs
(3.55% +/- 0.56%; P <.05, single-factor analysis of variance).
The smallest muscularized vessel was 113 +/- 50 &mgr;m, and
the largest nonmuscularized vessel was 138 +/- 49 &mgr;m
in lambs with CDH, significantly different from control lambs
(185 +/- 69 &mgr;m and 350 +/- 116 &mgr;m, respectively)
and lambs with CDH + TO (185 +/- 97 &mgr;m and 245 +/- 100
&mgr;m, respectively; P <.05). In lambs with CDH, only
25% of vessels of less than 60 &mgr;m were nonmuscularized,
compared with 81% in control lambs (P <.05) and 74% in lambs
with CDH + TO.Conclusions. Temporary tracheal occlusion, from
108 to 122 days, corrects the abnormal muscularization of pulmonary
arterioles seen in CDH. These morphometric findings parallel
physiologic results at birth and further suggest that short-term
occlusion, which preserves surfactant-producing type II pneumocytes
without lung growth, may be sufficient to improve neonatal outcome
of diaphragmatic hernia.
Kurkchubasche,
A. G.; Halvorson, E. G.; Forman, E. N.; Terek, R. M., and Ferguson,
W. S. The role of preoperative chemotherapy in the treatment
of infantile fibrosarcoma. J Pediatr Surg. 2000 Jun; 35(6):880-3.
Infantile fibrosarcoma (IFS)
is a rare tumor most often affecting the extremities of infants
and young children. Unlike its adult counterpart, IFS has a low
potential for metastatic spread, and surgical extirpation alone
has therefore resulted in an excellent prognosis. The amputation
rate, however, exceeds 50%. The dramatic response in 2 recent
cases to preoperative chemotherapy, given in an attempt to avoid
amputation, prompted this report and a review of the literature.
Wild
YK, Piasecki GJ, De Paepe ME, Luks FI. Short-term tracheal occlusion
in fetal lambs with diaphragmatic hernia improves lung function,
even in the absence of lung growth. Journal of Pediatric Surgery.
35(5):775-779, 2000 May.
Background: Prolonged tracheal
occlusion (TO) accelerates lung growth, but impairs surfactant
production. Short-term TO results in less lung growth, but preserves
type II cell function. We studied the effects of short-term TO
on lung physiology in diaphragmatic hernia.Methods: Diaphragmatic
hernia was created in nine fetal lambs at 90-95 d. Five were
left uncorrected (CDH), four underwent 2-week TO (108-122 d;
CDH+TO). Five unoperated lambs served as controls. Near term
(136 d), fetuses were ventilated for 90-150 min. Pulmonary arterial
pressure, postductal blood gases, quasi-static compliance, total
lung capacity (TLC) and lung weight/body weight (LW/BW) were
measured. Results: There was an overall survival rate of 89%
at term. Short-term occlusion did not induce lung growth (TLC
and LW/BW 6.07 ± 2.92 mL/kg and 0.022 ± 0.008 in
CDH, 4.86 mL/kg and 0.019 ± 0.005 in CDH+TO, 10.81 ±
3.55 mL/kg and 0.036 ± 0.006 in controls, respectively).
However, pulmonary hypertension in CDH (47.4 ± 12.32/35.8
± 12.19 torr) was corrected by short-term occlusion (20.2
± 4.0/16.0 ± 4.8 torr in CDH+TO, P<0.05, single-factor
ANOVA; similar to control). Best pO2 and pCO2 improved after
occlusion (CDH: 48.6 ± 6.7 torr and 107.1 ± 34.3
torr, respectively; CDH+TO: 101.5 ± 16.3 torr and 81.9
± 2.4 torr; control: 291.4 ± 4.7 torr and 37.7
± 17.3), as did oxygenation index (P<0.05, CDH vs.
CDH+TO) (CDH: 97.2 ± 23.0, CDH+TO: 28.7 ± 3.1,
control: 5.6 ± 0.6). Conclusions: Short-term TO corrects
pulmonary hypertension and improves gas exchange in fetal lambs
with diaphragmatic hernia, despite failure to produce accelerated
lung growth. Inducing lung maturation and correcting the physiologic
derangement in diaphragmatic hernia may be more important than
achieving lung growth alone.
Roggin
K K, Breuer CK, Carr SR, Hansen K, Kurkchubasche AG, Wesselhoeft
CW, Jr., Tracy TF, Jr., Luks FI. The unpredictable character
of congenital cystic lung lesions. Journal of Pediatric Surgery.
35(5):801-805, 2000 May.
Background: The spectrum of congenital
cystic disease of the lung ranges from hydrops and neonatal respiratory
distress to asymptomatic lesions. Operative management is dictated
by the presence of symptoms, recurrent infection, and the risk
of malignant transformation.
Methods: Since 1995, all consecutive congenital cystic lung lesions
were followed for symptoms, operative treatment, and correlation
of presumptive with pathologic diagnosis. Results: Twelve cystic
lung lesions were identified. Six were diagnosed with mediastinal
shift before 25 weeks of gestation; in four of six, the shift
subsequently resolved. Overall, six of seven lesions that were
followed serially decreased in size. Two patients were symptomatic
in utero; one underwent thoracoamniotic shunting, one pleurocentesis
for impending hydrops. Postnatally, these two, and two others
required urgent surgery. Four of eight asymptomatic patients
had elective resection by 16 months and four await operation.
In five of the eight operative cases (63%), there was a discrepancy
between preoperative and pathologic diagnosis. There were four
hybrid CAM/sequestrations. Conclusions: At least 80% of congenital
cystic lung lesions decreased in size regardless of gestational
age or presence of mediastinal shift. Antenatal intervention
is therefore rarely indicated. Because of uncertain pathologic
diagnosis, even stable asymptomatic lesions should be resected.
Roggin K K, Papa EF, Kurkchubasche A G, Tracy TF,Jr.
Kupffer cell inactivation delays repair in a rat model of reversible
biliary obstruction. Journal of Surgical Research. 90(2):166-73,
2000 May
Background. During cholestatic
liver injury, Kupffer cells (KC) and activated macrophages modulate
cell proliferation and subsequent matrix deposition. The role
of KC in the restoration of cell architecture and matrix metabolism
during repair following chronic cholestatic liver injury is unknown.
Materials and methods. To determine the effect of KC inactivation,
adult male Sprague-Dawley rats underwent bile duct suspension
(BDS) for 5 days followed by reversal of the obstruction. Saline
(control) and gadolinium chloride (10 mg/kg) were administered
1 day prior to BDS and 1 day prior to reversal, to inactivate
KC during both injury and repair. Serum bilirubin and quantitative
cell morphometry were compared to verify the reversibility of
the model. Collagen content of the liver was measured in trichrome-stained
paraffin sections using NIH imaging software. Results. Reversibility
of the obstruction was verified by normalization of direct serum
bilirubin, which peaked at 8.42 +/- 0.76 mg/dL following 5 days
of BDS and returned to sham-operated levels 2 days after reversal,
0.36 +/- 0.15 mg/dL. Hematoxylin and eosin (H&E)-stained
paraffin-embedded liver sections from gadolinium-treated animals
at 4 and 7 days after reversal exhibited persistent bile duct
proliferation, matrix deposition, and inflammation. Gadolinium-treated
animals had altered collagen metabolism compared to saline controls.
Whereas the collagen content in the saline group slowly returned
to sham-operated levels over time, the treatment group demonstrated
progressive accumulation of collagen during repair which was
statistically significant at 7 days following reversal (8.79%/mm(2)
+/- 2.17 in gadolinium group vs 2.33%/mm(2) +/- 0.34 in saline
group, P = 0.0003). Conclusions. These results demonstrate that
inactivation of resident hepatic macrophages during liver repair
impairs collagen metabolism, inhibits the resolution of fibrosis,
and allows the persistence of inflammatory cell infiltrates in
the portal areas. This is the first evidence of profibrogenic
responses in the absence of an intact KC compartment during repair
after cholestatic injury.
Lessin MS. Wesselhoeft CW. Luks FI. DeLuca FG.
Primary repair of long-gap esophageal atresia by mobilization
of the distal esophagus. European Journal of Pediatric Surgery.
9(6):369-72, 1999 Dec.
Long-gap esophageal atresia remains a difficult problem for the
pediatric surgeon. Several strategies for lengthening of the
proximal esophageal segment have been used with relative success.
Autogenous tissue conduits have resulted in less than optimal
long-term results. Five patients since 1991 with long gap esophageal
atresia (2 with distal tracheo-esophageal fistula [Type C], and
3 with isolated esophageal atresia [Type A]) underwent mobilization
of the distal esophagus to the level of the diaphragm in order
to perform a primary anastomosis. A retrospective analysis evaluated
the timing of repair, when oral feeds were successfully begun,
with particular attention to any ischemic sequelae related to
the distal esophageal dissection. Two patients underwent immediate
repair, three had delayed repair. There were no anastomotic leaks.
Three patients healed without stricture. Of four patients who
survived long-term, three patients are eating well and only one
still requires jejunoenteric supplementation. Classic teaching
dictates that dissection of the distal esophagus should not be
done because of disruption of its segmental blood supply. In
this series, distal esophageal mobilization was successful in
facilitating a primary anastomosis. These results are encouraging
as an alternative to the high morbidity and marginal long-term
results of interposition grafting or gastric transposition.
Luks FI. Logan J. Breuer CK. Kurkchubasche AG.
Wesselhoeft CW Jr. Tracy TF Jr. Cost-effectiveness of laparoscopy
in children. Archives of Pediatrics & Adolescent Medicine.
153(9):965-8, 1999 Sep.
BACKGROUND: Laparoscopy may offer
fast recovery and improved cosmesis, but its cost has been perceived
as excessive. OBJECTIVE: To analyze the total hospital costs
of laparoscopy vs open surgery. DESIGN: Retrospective cost-effectiveness
analysis evaluating all cases performed in a 36-month period
(September 1995 to August 1998). Cases were evaluated for operative
time, itemized cost of supplies, and length of hospitalization.
SETTING: Operations performed by pediatric surgeons in a tertiary
care children's hospital. PATIENTS: Consecutive children undergoing
laparoscopic or open appendectomies, cholecystectomies, fundoplications,
and splenectomies. Patients were not randomized to laparoscopy,
or open surgery. INTERVENTIONS: Laparoscopic procedures performed
with a core set of reusable equipment and a limited number of
disposable instruments. MAIN OUTCOME MEASURES: Cost surplus of
laparoscopy was evaluated, and compared with savings associated
with decreased hospital stay, to obtain cost-effectiveness of
laparoscopy per procedure. RESULTS: There were 26 laparoscopic
and 359 open appendectomies; 33 laparoscopic and 3 open cholecystectomies;
16 laparoscopic and 18 open fundoplications; and 16 laparoscopic
and 7 open splenectomies. Excess operating costs per procedure
were $442.00 for appendectomy, $634.60 for fundoplication, $847.50
for cholecystectomy, and $1551.30 for splenectomy. Hospital stay
was decreased for all laparoscopies, resulting in an overall
savings per laparoscopic procedure of $2369.90 for appendectomy,
$5390.90 for fundoplication, $1161.00 for cholecystectomy, and
$858.90 for splenectomy. CONCLUSIONS: Laparoscopy is cost-effective,
particularly for fundoplication, appendectomy, and cholecystectomy.
Detailing the costs of supplies, operating time, and length of
stay allows interinstitutional comparison and critical cost-analysis
of laparoscopy. With a more selective use of reusable instruments
and further shortening of operative time, the global savings
of laparoscopy may increase.
Lessin MS. Luks FI. Brem AS. Wesselhoeft CW Jr.
Primary laparoscopic placement of peritoneal dialysis catheters
in children and young adults. Surgical Endoscopy. 13(11):1165-7,
1999 Nov.
BACKGROUND: Primary placement
of peritoneal dialysis catheters in children often requires suturing
of the catheter into the pelvis. We describe our experience with
a gasless laparoscopy technique in children and young adults.
METHODS: During an 18-month period, 12 patients (mean age, 14
years) underwent primary laparoscopic placement of peritoneal
dialysis catheters. A single umbilical port was used for abdominal
wall elevation, telescope, and catheter. A needleholder was introduced
via an accessory port at the future catheter exit site or through
the umbilical port. Omentectomy was performed through the umbilical
incision. The catheter was tunneled to the lateral abdominal
wall. Follow-up data (>/= 15 months) included time to initiation
of dialysis, hospitalization, and outcome. End points were cure,
transplantation, or death. RESULTS: Diet was started on the day
of surgery and dialysis on the following day. Four patients had
seven complications, including leakage and entanglement of the
catheter in tubal fimbriae. Long-term revision-free catheter
survival was 67% at 24 months. CONCLUSIONS: This minimal access
technique for primary placement of peritoneal dialysis catheters
includes securing of the catheter tip in a dependent location
and omentectomy. It allows nearly immediate use of the catheter,
leads to a minimal hospital stay, and has acceptable long-term
patency.
De
Paepe ME. Sardesai MP. Johnson BD. Lesieur-Brooks AM. Papadakis
K. Luks FI. The role of apoptosis in normal and accelerated
lung development in fetal rabbits. Journal
of Pediatric Surgery. 34(5):863-70; discussion 870-1, 1999 May.
BACKGROUND/PURPOSE: During
fetal development, the mammalian lung undergoes progressive
parenchymal involution. Intrauterine tracheal occlusion induces
accelerated architectural maturation of the fetal lungs
associated with depletion of the surfactant-producing
type II cells. This study investigates the spatiotemporal
pattern of apoptosis during normal fetal lung development
and its modulation in tracheal occlusion-induced accelerated
fetal lung growth. METHODS: Fetal rabbit lungs were studied
at 25 to 31 days' gestational age (DGA; term, 31 DGA),
corresponding to late pseudoglandular through terminal
air sac stages of fetal lung development. Intrauterine
tracheal ligation (TL) was performed at 24 DGA. TL fetuses were
monitored until 29 DGA, a time-point previously shown
to coincide with significant type II cell depletion. Apoptotic
cells were identified by light and electron microscopy,
as well as terminal deoxynucleotidyl transferase-mediated
dUTP-FITC nick-end labeling (TUNEL). Epithelial (type I and II)
cell apoptosis was studied by TUNEL labeling in conjunction
with antisurfactant protein and anticytokeratin immunohistochemistry.
DNA fragmentation was analyzed by gel electrophoresis.
Sham-operated littermates served as controls. RESULTS:
The number of apoptotic cells progressively increased with
advancing lung growth and architectural maturation (apoptotic
index [Al] 1.2 +/- 0.7 x 10(-3) at 25 DGA v 4.2 +/- 1.4
x 10(-3) at 31 DGA; P< .05, analysis of variance).
In TL fetuses, the apoptotic rate was significantly higher than
in non-TL fetuses from the third postligation day on,
coinciding with the onset of significantly increased airspace
distension (Al 4.9 +/- 1.3 x 10(-3) in TL v2.6 +/- 0.4
x 10(-3) in controls at 29 DGA; P< .05, Student's ttest).
Apoptosis occurred in parenchymal cells and in isolated
cells within the airspaces. The apoptotic activity of
type II cells was significantly higher in TL fetuses than
C fetuses at 29 DGA (type II Al 25.5 +/- 6.3 x 10(-3) in
TL v2.3 +/- 0.8 x 10(-3) in C; P< .001). Electron microscopic
studies confirmed the presence of apoptotic nuclei in
interstitial macrophages and in degenerating intraluminal
type II cells. DNA analysis showed nucleosomal bands.
CONCLUSIONS: Normal fetal lung development is associated with
a progressive increase of epithelial and interstitial
apoptotic activity, a process enhanced by TL. Tracheal
occlusion induces a significant increase of type II cell
apoptosis, which likely contributes to the observed type II cell
depletion after TL. We speculate that fetal type II cell
apoptosis after TL may be induced by mechanical distension
(stretch) of the airspaces.
Kokoska
ER. Silen ML. Tracy TF Jr. Dillon PA. Kennedy DJ. Cradock
TV. Weber TR. The impact of intraoperative culture
on treatment and outcome in children with perforated appendicitis.
Journal of Pediatric Surgery. 34(5):749-53, 1999 May.
BACKGROUND: Most protocols
for the operative treatment of perforated appendicitis
use a routine culture. Although isolated studies suggest that
routine culture may not be necessary, these recommendations
generally are not based on objective outcome data. METHODS:
The authors reviewed the records of 308 children who underwent
operative treatment for perforated appendicitis between
1988 and 1998 to determine if information gained from routine
culture changes the management or improves outcome. Inclusion
criteria included either gross or microscopic evidence
of appendiceal perforation. RESULTS: Mean patient age
was 7.5 years, 51% were boys, and there was no mortality.
The majority of children (96%) underwent culture that was positive
for either aerobes (21%), anaerobes (19%), or both (57%).
Antibiotics were changed in only 16% of the patients in
response to culture results. The use of empiric antibiotics,
as compared with modified antibiotics, was associated with a
lower incidence of infectious complication, shorter fever
duration, and decreased length of hospitalization. We
also investigated the relationship between culture isolates
and antibiotic regimens with regard to outcome. The utilization
of antibiotics suitable for the respective culture isolate or
organism sensitivity was associated with an increased
incidence of infectious complication and longer duration
of both fever and length of hospitalization. Finally,
the initial culture correlated poorly with subsequent intraabdominal
culture (positive predictive value, 11%). CONCLUSION:
These outcome data strongly suggest that the practice
of obtaining routine cultures can be abandoned, and empiric
broad spectrum antibiotic coverage directed at likely
organisms is completely adequate for treatment of perforated
appendicitis in children.
Tackett
LD. Breuer CK. Luks FI. Caldamone AA. Breuer JG. DeLuca
FG. Caesar RE. Efthemiou E. Wesselhoeft CW Jr. Incidence
of contralateral inguinal hernia: a prospective analysis.
Journal of Pediatric Surgery. 34(5):684-7; discussion 687-8,
1999 May.
BACKGROUND/PURPOSE: Contralateral
groin exploration in children with unilateral inguinal
hernia is still controversial, particularly in infants.
The authors have attempted to determine the age- and gender-stratified
incidence of contralateral hernia and the necessity of
routine bilateral procedures. METHODS: This is a prospective
study of 656 patients during a 34-month period at a single
institution. Patients with unilateral hernia underwent
an ipsilateral procedure only, regardless of age, gestational
age, or gender. Follow-up was 6 to 40 months (mean, 25.5
months). Chi-square analysis was used for intergroup comparison
(P < .05 significant). RESULTS: Of 656 children, 108
(16.5%) presented with synchronous bilateral hernias.
Bilateral inguinal hernia was significantly more common in premature
infants (28.0%) and young children (33.8% if <6 months,
27.4% if <2 years). Of the remaining 548, a metachronous
contralateral hernia developed in 48 (8.8%) at a median
interval of 6 months (range, 4 days to 7 years). This incidence
was 13 of 105 (12.4%) in infants less than 6 months of
age, 20 of 189 (10.6%) in children less than 2 years of
age, 8 of 54 (14.8%) in premature infants, 6 of 81 (7.4%)
in girls, and 8 of 29 (27.6%) in children with an incarcerated
hernia. In the latter group, P < .05, chi2 analysis.
CONCLUSION: Routine contralateral inguinal exploration,
without clinical evidence of a hernia, may be advisable
in children with incarceration and possibly in premature
infants. The low incidence of contralateral hernias in all other
patients, regardless of gender or age, does not justify
routine contralateral exploration.
Silen
ML. Kokoska ER. Fendya DG. Kurkchubasche AG. Weber TR.
Tracy TF. Rollover injuries in residential driveways:
age-related patterns of injury. Pediatrics. 104(1):e7,
1999 Jul.
BACKGROUND: The major
objective of the present study was to determine the severity
of nonfatal injuries sustained by children (<16 years old)
when a motor vehicle rolls over them. We also sought to
determine whether younger children (<24 months old)
demonstrated different patterns of injury and/or a worse
outcome, compared with older children (>24 months old). METHODS:
We reviewed the medical records of 3971 consecutive admissions
to a single trauma service at an urban children's hospital
between March 1990 and October 1994. During this time
period, 26 (0.7%) children presented with rollover injuries
incurred by motor vehicles in residential driveways. Outcome
was measured by length of both intensive care unit admission
and hospitalization. RESULTS: Two children died shortly
after admission and were excluded from the remainder of
the study. Younger children (<24 months old) had significantly
higher injury severity scores and lower pediatric trauma
scale scores. Both the duration in the intensive care
unit and the length of hospitalization were significantly
longer in younger children, compared with children >24
months old. One explanation for these observations was that younger
children had a significantly higher incidence of both
head and neck and extremity injury but a similar incidence
and severity of chest and abdominal trauma, compared with
older children. Injuries requiring operative intervention were
rare. CONCLUSION: Younger patients sustaining rollover
injuries in the residential driveway have a worse outcome,
in part, because of the head and neck or extremity injures
that they incur. The majority of rollover injuries can
be managed conservatively. pediatric trauma, driveway, pedestrian
events, rollover injuries, injury severity score, pediatric
trauma scale.
Lessin
MS. Chan M. Catallozzi M. Gilchrist MF. Richards C. Manera L.
Wallach MT. Luks FI. Selective
use of ultrasonography for acute appendicitis in children.
American Journal of Surgery. 177(3):193-6, 1999 Mar.
BACKGROUND: To evaluate
the role of ultrasonography in children with equivocal
signs of acute appendicitis, and correlate with initial clinical
impression and pathological findings. METHODS: This is
a prospective evaluation of all children presenting with
a possible diagnosis of appendicitis during a 14-month
study period. Patients with unequivocal clinical signs
of appendicitis underwent appendectomy without ultrasonography.
Patients with equivocal signs had documentation of the
clinical impression and subsequent abdominal ultrasound. Statistical
analysis of results was performed using the chi-square
test (P <0.05 significant). RESULTS: Two hundred fifteen
consecutive children were enrolled. Signs were unequivocal
in 116 and equivocal in 99. Seven patients in the first group
had a normal appendix at operation. Of the 99 patients
with equivocal signs, there were 28 true positives, 3
false positives, 64 true negatives, and 4 false negatives.
In equivocal cases, sensitivity of the initial clinical
impression versus ultrasound was 50% and 88%, respectively (P
<0.05). Specificity was 85% and 96%, respectively.
The positive and negative predictive values improved from
63% to 90% and 78% to 94%, respectively, with the use
of ultrasonography. CONCLUSIONS: The low false positive rate
(6%) in clinically obvious cases of appendicitis does
not, in our opinion, warrant ultrasonography. In clinically
equivocal cases, ultrasonography is a fast, sensitive,
and specific diagnostic modality to diagnose or rule out
appendicitis, avoiding the need for prolonged observation and/or
hospitalization.
Sadiq
HF. Das UG. Tracy TF. Devaskar SU. Intra-uterine
growth restriction differentially regulates perinatal brain and
skeletal muscle glucose transporters. Brain Research.
823(1-2):96-103, 1999 Mar 27.
Employing Western blot
analysis, we investigated the effect of maternal uterine
artery ligation causing uteroplacental insufficiency with
asymmetrical intrauterine growth restriction (IUGR) upon fetal
(22d) and postnatal (1d, 7d, 14d and 21d) brain (Glut
1 and Glut 3) and skeletal muscle (Glut 1 and Glut 4)
glucose transporter protein concentrations. IUGR was associated
with a approximately 42% decline in fetal plasma glucose (p<0.05)
and a approximately 25% decrease in fetal body weights
(p<0.05) with no change in brain weights when compared
to the sham operated controls (SHAM). In addition, IUGR
caused a approximately 45% increase in fetal brain Glut 1
(55 kDa) with no change in Glut 3 (50 kDa) protein concentrations.
This fetal brain Glut 1 change persisted, though marginal,
through postnatal suckling stages of development (1d-21d),
with no concomitant change in brain Glut 3 levels at day
1. In contrast, in the absence of a change in fetal skeletal
muscle Glut 1 levels (48 kDa), a 70% increase was observed
in the 1d IUGR with no concomitant change in either fetal
or postnatal Glut 4 levels (45 kDa). The change in skeletal
muscle Glut 1 levels normalized by d7 of age. We conclude
that IUGR with hypoglycemia led to a compensatory increase in
brain and skeletal muscle Glut 1 concentrations with a
change in the brain preceding that of the skeletal muscle.
Since Glut 1 is the isoform of proliferating cells, fetal
brain weight changes were not as pronounced as the decline
in somatic weight. The increase in Glut 1 may be protective against
glucose deprivation in proliferating fetal brain cells
and postnatal skeletal myocytes which exhibit 'catch-up
growth', thereby preserving the specialized function mediated
by Glut 3 and Glut 4 towards maintaining the intracellular
glucose milieu.
Papadakis
K. Chen EA. Luks FI. Lessin MS. Wesselhoeft CW Jr.
DeLuca FG. The changing presentation of pyloric stenosis.
American Journal of Emergency Medicine. 17(1):67-9, 1999 Jan.
Metabolic abnormalities
described in pyloric stenosis are now rare, probably because
of prompter recognition of the disease. This report reviews the
trend in presentation over three decades. All infants
treated for pyloric stenosis during three mid-decade target
periods were reviewed. Comparison between the 1975 group
and the 1985 group and between the 1995 group and previous decades
were designed to identify the impact of ultrasonography,
since this modality has only been available in the last
decade. Parameters included age at diagnosis and incidence
of water and electrolyte imbalance as measures of delay
in presentation. Two hundred eighty-three patients were reviewed.
Mean age (weeks) at presentation was 5.4+/-3.0 in 1975,
4.6+/-2.0 in 1985, and 3.4+/-1.3 in 1995 (P < .05,
ANOVA). Overall, 88% had no electrolyte anomalies on admission.
There was no statistical difference in frequency of abnormal
results between the three decades. Total and postoperative
hospitalization was significantly shorter in the recent
period: in 1985, 5.34 and 4.36 days; in 1985, 4.48 and
3.4 days; and in 1995, 3.8 and 2.8 days. These data show
that pyloric stenosis is now recognized earlier than in previous
decades. The availability of ultrasonography cannot solely
be credited for earlier diagnosis, since this trend was
already apparent before its introduction. The "classic"
metabolic derangements associated with pyloric stenosis have
been highly uncommon for the past three decades.
Kokoska
ER. Silen ML. Tracy TF Jr. Dillon PA. Cradock TV. Weber
TR. Perforated appendicitis in children: risk
factors for the development of complications.
Surgery. 124(4):619-25; discussion 625-6, 1998 Oct.
BACKGROUND: Many aspects
of the management of perforated appendicitis in children
remain controversial. The objective of this study was to define
risk factors associated with the development of postoperative
complications in children undergoing treatment for perforated
appendicitis. METHODS: We reviewed all children (age <
16 years) who were treated for perforated appendicitis
at Cardinal Glennon Children's Hospital between 1988 and 1997.
Inclusion criteria included either gross or microscopic
evidence of appendiceal perforation. RESULTS: Of 285 children
with perforated appendicitis, 279 underwent immediate
operative treatment. Mean patient age was 7.7 years and
there were no deaths. Major postoperative complications
included intra-abdominal abscess (n = 17), ileus (n = 7), mechanical
intestinal obstruction (n = 6), and wound infection (n
= 4). All children who had a postoperative abscess had
more than 5 days of symptoms before operation. Within
this subgroup, drain placement was associated with not only
decreased postoperative abscess formation and but also shorter
duration of fever and length of hospitalization. The incidence
of mechanical obstruction or ileus was not increased and
the rate of wound infection was actually lower after drainage.
CONCLUSIONS: Drain placement appears to be helpful in
children with late diagnosis but is of little benefit when the
duration of symptoms is less than 5 days. Thus it is likely
that drains are most useful in patients with well-established
and localized abscess cavities
Papadakis K. De Paepe ME. Tackett LD. Piasecki
GJ. Luks FI. Temporary tracheal occlusion
causes catch-up lung maturation in a fetal model of diaphragmatic
hernia. Journal of Pediatric Surgery. 33(7):1030-7,
1998 Jul.
BACKGROUND: The lungs
of infants born with diaphragmatic hernia are hypoplastic,
immature, and surfactant-deficient. Tracheal occlusion in utero,
which is being proposed as antenatal treatment of diaphragmatic
hernia by promoting compensatory lung growth, decreases
surfactant production as well, through loss of type II
pneumocytes. The authors studied whether temporary tracheal
occlusion might cause 'catch-up' lung growth and maturation,
without negative effects of prolonged tracheal occlusion
on the surfactant system. METHODS: Diaphragmatic hernia
was created in time-dated fetal lambs (65 to 75 days).
At 108 days, the trachea was occluded with an embolectomy catheter
(DH + TO, n = 6). After day 14, the balloon was deflated.
Six congenital diaphragmatic hernia (CDH) fetuses were
left unobstructed (DH). For comparison, a group of fetuses
without diaphragmatic hernia were subjected to prolonged
tracheal ligation (TL; 4-week tracheal ligation, n = 3). Unoperated
littermates (n = 8) were used as controls (CTR). All were
killed near term. Lung tissue was processed for light
and electron microscopy (computerized stereologic morphometry).
Type II pneumocytes were identified with antisurfactant
protein B antibody. RESULTS: Four animals in DH + TO and four
in DH survived to term. Lung fluid volume (LFV) at 108
days was 5.2 +/- 4.4 mL in DH and 24.6 +/- 6.8 mL in controls
(P < .05, Student t test). In DH + TO, LFV increased
ninefold (to 48.3 +/- 13.3 mL) by 1 week postocclusion,
suggesting accelerated lung growth. At term, lung weight to body
weight ratio (LW/BW) was higher in TL (9.85% +/- 1.81%)
than in CTR (3.55% +/- 0.56%; P < .05, analysis of
variance); LW/BW and parenchymal volume tended to be greater
in DH + TO than in DH, and air-exchanging parenchymal
volume in DH + TO was similar to CTR (v a 50% reduction
in DH), indicating some degree of hyperplasia after temporary
occlusion. Pneumocyte II numerical density was decreased
more than 10-fold in TL (60 +/- 22 v 826 +/- 324 in CTR, P <
.001; it was slightly lower in DH + TO than in CTR, but
individual type II pneumocyte cell volume was greater
in the latter, and they appeared more mature than in DH
(increased granulation by light microscopy, fewer glycogen
granules, and abundant lamellar bodies by electron microscopy).
Surfactant was also seen in the air spaces in DH + TO
and CTR; it was absent in unobstructed CDH and in TL.
CONCLUSIONS: Temporary tracheal occlusion in utero does
not cause the dramatic decrease in type II pneumocytes seen after
prolonged occlusion. Although only minimal increase in
lung volume is seen in CDH, catch-up parenchymal growth
and maturation occur, most notably in the surfactant-producing
system.
Papadakis K. Luks FI. Deprest JA. Evrard VE. Flageole
H. Miserez M. Lerut TE. Single-port tracheoscopic
surgery in the fetal lamb. Journal of Pediatric Surgery.
33(6):918-20, 1998 Jun.
BACKGROUND/PURPOSE: Endoscopic
fetal surgery could help avoid many of the problems associated
with open fetal surgery, but the use of multiple ports
may be too traumatic to the membranes. The authors describe a
single-port technique of tracheoscopic surgery in the
fetus. METHODS: Time-dated pregnant ewes (95 to 105 days;
term, 145 days) underwent midline laparotomy under general
halothane anesthesia. A 5-mm-diameter balloon-tipped cannula
was introduced in the uterus by Seldinger technique. A
1.2-mm semirigid mini-endoscope, fitted inside a 9F, 20
degrees curved sheath, was introduced under continuous,
low-pressure irrigation, inside the fetus' mouth, and
advanced into the trachea. RESULTS: Endotracheal procedures,
including temporary (n = 11) and permanent balloon tracheal
occlusion (n = 30) and placement of a barbed guide wire
for endotracheal occlusion device insertion (n = 12),
were performed by introducing a 1-mm diameter instrument alongside
the telescope. These were successfully performed in 52
of the 53 fetuses. The rigidity of the telescope allowed
controlled access to the pharynx; its curve allowed full
tracheobronchial endoscopy with the fetus in utero. CONCLUSIONS:
The present technique marries the control and optical
quality of a rigid endoscope with the physiological curve
only a flexible instrument could offer until now. The
types of procedures performed with this technique illustrate
its potential as a research tool; the size (1.2-mm diameter),
shape, and optical qualities of the telescope should make
clinical applications possible.
Lessin
MS. Luks FI. Laparoscopic appendectomy and duodenocolonic
dissociation (LADD) procedure for malrotation. Sorce
Pediatric Surgery International. 13(2-3):184-5, 1998 Mar.
The treatment of "asymptomatic"
intestinal malrotation remains controversial, particularly
beyond the neonatal period. Two cases illustrate the application
of laparoscopy for correction of malrotation: one in an older
child and another in an asymptomatic infant. Both patients
recovered well and were discharged 2 days after surgery.
Laparoscopic appendectomy and duodenocolonic dissociation
allows excellent visualization of the duodenocolic and Ladd's
bands and easily accommodates appendectomy. The availability
of this minimal-access technique should encourage correction
of malrotation in the asymptomatic patient.
Lechner AJ. Velasquez A. Knudsen KR. Johanns CA.
Tracy TF Jr. Matuschak GM. Cholestatic liver injury
increases circulating TNF-alpha and IL-6 and mortality
after Escherichia coli endotoxemia. American Journal
of Respiratory & Critical Care Medicine. 157(5 Pt 1):1550-8,
1998 May.
We employed a bile duct
ligation (BDL) model of cholestatic liver injury to test
the hypothesis that this form of preexisting hepatic dysfunction
alters the kinetics of circulating TNF-alpha and IL-6
after Escherichia coli endotoxemia, thereby augmenting
mortality and lung injury by a TNF-alpha:leukotriene (LT)
axis of inflammation. Male rats were catheterized 13 d
after BDL or sham surgery and studied while awake 18 to 24 h
later. Cholestasis after BDL was confirmed by baseline
serum bilirubin (BDL = 7.34 +/- 0.72 mg/dl, mean +/- SEM,
n = 17 versus Sham = 0.25 +/- 0.07, n = 20; p < 0.005)
and histopathology. Sham and BDL animals received E. coli
lipopolysaccharide serotype O55:B5 (LPS, 5 mg/kg i.v.) or 0.9%
NaCl (NS) ending at t = 0 and were monitored over 24 h
for vital signs and hemodynamics. In parallel studies,
lipoxygenase inhibition was performed using diethylcarbamazine
or the 5-lipoxygenase activating-protein inhibitor MK-886.
Blood was collected at baseline and at t = 1.5, 3.5, and 24 h
for formed elements and for serum endotoxin, TNF-alpha,
IL-6, bilirubin, and alanine aminotransferase (ALT). Organs
were evaluated at 24 h for histopathology, including neutrophil
(PMN) densities and wet/dry weight (W/D) ratios. Cholestasis
reduced survival after otherwise nonlethal endotoxemia,
with seven of 11 BDL + LPS rats dying within 24 h versus no deaths
in BDL + NS (n = 6), Sham + LPS (n = 14), or Sham + NS
(n = 6) animals (p < 0.01). Despite equivalent serum
endotoxin between groups, circulating TNF-alpha was 8-fold
higher in BDL + LPS than in Sham + LPS rats at 1.5 and 3.5 h
(p < 0.001), whereas serum TNF-alpha did not differ
between BDL + NS and Sham + NS rats. IL-6 likewise was
increased differentially by 1.5 h in BDL + LPS animals
(11.98 +/- 2.42 ng/ml) versus Sham + LPS rats (3.05 +/- 0.58
ng/ml, p < 0.05). Hypothermia, bradycardic hypotension,
and leukopenia were most severe and prolonged in BDL +
LPS rats, which also had significantly higher ALT values,
W/D ratios, and organ PMN counts. LT inhibition failed to reduce
BDL-related differences in serum cytokines or survival
after endotoxemia. Thus, cholestasis augments inflammatory
responses to gram-negative endotoxemia, sensitizing the
host to enhanced fluid flux in multiple organs and to
mortality by a LT-independent mechanism.
Kurkchubasche
AG. Cardona M. Watkins SC. Smith SD. Albanese CT.
Simmons RL. Rowe MI. Ford HR. Transmucosal
passage of bacteria across rat intestinal epithelium in the
Ussing chamber: effect of nutritional factors and bacterial virulence.
Shock. 9(2):121-7, 1998 Feb.
Transmucosal passage of
bacteria across the intestine, the essential and prerequisite
step for bacterial translocation, cannot be effectively studied
using in vivo models of translocation. We have adapted
the Ussing chamber into a fresh, sterile organ culture
system that can facilitate the study of bacterial-epithelial
interactions. Intestinal membranes were mounted in the
Ussing chamber and perfused with a solution rich in putative
mucosal micronutrients. The transmembrane potential difference
was constantly monitored as a marker of intestinal integrity.
Transmucosal passage of various bacteria across the normal
intestinal epithelium was quantitated, and the mucosal
membrane was examined by light and transmission electron
microscopy. The addition of potassium cyanide to the mucosal
perfusate resulted in an irreversible loss of potential
difference. Oxygen deprivation also led to a precipitous
drop in potential difference, but it was reversible with
prompt reoxygenation. In contrast, intestinal membranes perfused
with a solution consisting of Dulbecco's modified Eagle's
medium + 20 mM glutamine maintained their potential difference
for a sustained period (>180 min). Both the viability
and structural integrity of the ileal intestinal membrane were
maintained in culture ex vivo using this perfusate. Qualitative
differences were observed in the mechanism of transmucosal
passage of mild to moderately virulent bacteria such as
Escherichia coli C-25 and Proteus mirabilis M-13, which
pass through the intestinal epithelium without causing overt
damage to the mucosa, and more virulent organisms such
as Salmonella typhimurium, which cause extensive mucosal
damage by light and transmission electron microscopy.
The Ussing system should provide a useful model of intact organ
culture for the study of the mechanisms of bacterial translocation
and the pathogenesis of enteric infections
Lessin
MS. Luks FI. Wesselhoeft CW Jr. Gilchrist BF. Iannitti
D. DeLuca FG. Peritoneal drainage as definitive treatment
for intestinal perforation in infants with extremely low
birth weight (<750 g). Journal of Pediatric Surgery.
33(2):370-2, 1998 Feb.
BACKGROUND: Advances in
neonatal intensive care have improved the survival of
the extremely premature infant. However, survival at less than
25 weeks' gestational age remains tenuous, with intestinal
perforation presenting a significant mortality. METHODS:
During an 18-month period from 1995 to 1996, nine patients
weighing less than 750 g (range, 485 to 740 g; mean, 615 g)
presented with intestinal perforation. All patients were treated
with peritoneal drainage. Drains were removed after clinical
improvement and the cessation of peritoneal drainage.
RESULTS: Seven patients survived the initial drainage
procedure (78%). At a mean follow-up of 12 months, the six
long-term survivors are all tolerating full enteral feeds, and
none developed intestinal strictures or intraabdominal
abscess. No patient required subsequent celiotomy. Peritoneal
drainage has previously been considered in some centers
as temporary therapy in extremely ill neonates deemed unlikely
to survive operation. The authors have adopted drainage
as the sole treatment in selected patients. CONCLUSION:
Peritoneal drainage alone may be considered definitive
therapy for intestinal perforation in the majority of
micropremature infants.
Weber
TR. Kurkchubasche AG. Operative management
of asphyxiating thoracic dystrophy after pectus repair.
Journal of Pediatric Surgery. 33(2):262-5, 1998 Feb.
Pectus excavatum repair
usually results in unchanged or improved pulmonary function.
However, a small subset of patients will experience severely
impaired pulmonary function after pectus repair caused
by restrictive lung disease, and no adequate surgical
approach has been described for this condition. A procedure
is described that is a variation of an operation for Jeune's
thoracic dystrophy, that resulted in marked respiratory improvement
in this setting. A 14-year-old boy had undergone standard
pectus excavatum repair at age 4, from which he recovered
uneventfully. Beginning at age 10 to 12 years progressive
restrictive pulmonary disease, recurrent pneumonia, and
cor pulmonale developed, which resulted in almost constant shortness
of breath and the need for continuous nasal positive pressure
support. Pulmonary function test results were markedly
abnormal and worsening. He underwent an operative procedure
consisting of sternal split that was wedged open permanently
with rib struts, opening of pleura bilaterally, and six rib
resections bilaterally. His postoperative recovery was satisfactory,
and his pulmonary functions have shown steady improvement.
He is now completely off oxygen and pressure support,
has improved exercise tolerance, and has returned to school.
Severe restrictive lung disease after pectus repair can
be successfully managed with aggressive operative procedures.
Patients should have close follow-up after pectus repair
for the development of this potentially debilitating disorder
to allow earlier repair.
Olynyk JK. Yeoh GC. Ramm GA. Clarke SL. Hall PM.
Britton RS. Bacon BR. Tracy TF. Gadolinium chloride
suppresses hepatic oval cell proliferation in rats with
biliary obstruction. American Journal of Pathology.
152(2):347-52, 1998 Feb.
Liver injury due to bile
duct ligation (BDL) is histologically characterized by
cholestasis, bile ductular proliferation, hepatocellular damage,
portal fibrosis, and ultimately biliary cirrhosis. Stem
cells within the liver may act as progenitor cells for
small epithelial cells termed oval cells that can differentiate
into bile duct cells or hepatocytes, whereas myofibroblasts are
the principal source of collagen production in fibrosis.
The aims of this study were to determine 1) whether BDL
induces oval cell proliferation and 2) whether blockade
of Kupffer cells affects oval cell proliferation, bile duct
proliferation, and myofibroblast transformation in experimental
biliary obstruction. Male Sprague-Dawley rats were divided
into two groups to receive either a single dose of gadolinium
chloride (a selective Kupffer cell blocking agent) or
vehicle. One day later, the gadolinium- and vehicle-treated
groups were further subdivided to receive either BDL or sham
operation. The rats were sacrificed on day 7 postoperatively.
Serum was collected for measurement of aspartate aminotransferase,
gamma-glutamyl transpeptidase, and bilirubin levels. Liver
tissue was taken for evaluation of fibrosis, bile ductular
cells, oval cells, and myofibroblasts. BDL resulted in
elevated aspartate aminotransferase, gamma-glutamyl transpeptidase,
and bilirubin in serum, and gadolinium pretreatment did not
modify these effects. BDL induced marked oval cell proliferation,
which was completely prevented by gadolinium pretreatment.
Gadolinium did not affect the induction of bile duct expansion
or myofibroblasts after BDL. We conclude that experimental
biliary obstruction induces oval cell proliferation, which
can be prevented by gadolinium pretreatment. This suggests that
bile ductular proliferation and myofibroblast transformation
are not mediated by Kupffer cells and that ductular proliferation
can proceed in the absence of oval cells. Alternatively,
gadolinium may directly affect oval cell proliferation
after BDL.
De
Paepe ME. Johnson BD. Papadakis K. Sueishi K. Luks FI.
Temporal pattern of accelerated lung growth after tracheal occlusion
in the fetal rabbit. American Journal of Pathology.
152(1):179-90, 1998 Jan.
Tracheal occlusion in
utero is a potent stimulus of fetal lung growth. We describe
the early growth mechanics of fetal lungs and type II pneumocytes
after tracheal ligation (TL). Fetal rabbits underwent
TL at 24 days gestational age (DGA; late pseudoglandular
stage; term = 31 to 33 days) and were sacrificed at time
intervals ranging from 1 to 5 days after TL. Lung growth
was measured by stereological volumetry and bromodeoxyuridine
(BrdU) pulse labeling. Pneumocyte II population kinetics
were analyzed using a combination of anti-surfactant protein
A and BrdU immunohistochemistry and computer-assisted
morphometry. Nonoperated littermates served as controls. TL
resulted in dramatically enhanced lung growth (lung weight/body
weight was 5.00 +/- 0.81% in TL versus 2.52 +/- 0.13%
in controls at 29 DGA; P < 0.001, unpaired Student's
t-test). Post-TL lung growth was characterized by a 3-day
lag-phase typified by relative stagnation of growth, followed
by distension of airspaces, increased cell proliferation,
and accelerated architectural and cellular maturation
by postligation days 4 and 5. During the proliferation
phase, the replicative activity of type II cells was markedly
increased (type II cell BrdU labeling index was 10.0 +/-
4.1% in TL versus 1.1 +/- 0.3% for controls at 29 DGA;
P < 0.02), but their numerical density decreased (3.0 +/-
0.5 x 10(-3)/microm2 in TL versus 4.5 +/- 0.3 x 10(-3)/microm2
in controls at 29 DGA; P < 0.02), suggesting accelerated
terminal differentiation to type I cells. In conclusion,
post-TL lung development is characterized by a well defined
temporal pattern of lung growth and maturation. The rabbit model
lends itself well to study the regulatory mechanisms underlying
accelerated fetal lung growth after TL.
Fox
ES. Kim JC. Tracy TF. NF-kappaB activation and modulation
in hepatic macrophages during cholestatic injury.
Journal of Surgical Research. 72(2):129-34, 1997 Oct.
Cholestatic liver injury
induces an inflammatory response that follows the activation
of hepatic macrophages. Constitutive activation of the
transcription factor, NF-kappaB, was found in these macrophages
over the course of hepatic injury. Since NF-kappaB activation
has been shown to have a key role in the inflammatory
process, the modulatory effects of the antioxidant, alpha-tocopherol
succinate, and the glucocorticoid, dexamethasone, on NF-kappaB
activation were examined in this study. Male Sprague Dawley
rats underwent 2-7 days of common bile duct division and
ligation (CBDL) or sham laparotomy. Hepatic macrophages were
isolated by collagenase Pronase perfusion and purified
by centrifugal elutriation. Activation was determined
by electrophoretic mobility shift assay and ELISA. We
determined that NF-kappaB activation in injured hepatic macrophages
could only be inhibited by dexameth |
