In vivo 31P-NMR studies of myocardial high energy phosphate metabolism during anoxia and recovery.

31P NMR spectra of heart in-situ in live guinea pigs were obtained continuously in 20.5 s time blocks during 3 min of anoxia, during subsequent reoxygenation and, in separate animals, during terminal anoxia. Reversible anoxia resulted in rapid degradation of phosphocreatine (t 1/2 = 54.5 +/- 2.5 s) which recovered fully during reoxygenation. Heart Pi increased during anoxia and returned to basal levels after oxygen was restored. During 3 min of anoxia, no significant changes in ATP levels or pH were detected. The results demonstrate that it is feasible to measure rapid fluxes of high energy phosphates by 31P NMR in intact animals during and after anoxic stress to the myocardium.

Small bowel allograft rejection detected by serum intestinal fatty acid-binding protein is reversible.

We hypothesized that, following experimental small bowel transplantation, immunosuppressive therapy initiated on the day of the initial rise in serum intestinal fatty acid-binding protein (I-FABP) would result in graft salvage. In previously published work, we showed that I-FABP was not detectable in the serum of isografted Lewis rats, but could be measured in the peripheral circulation during small bowel allograft rejection. A clinically useful method to monitor trans- planted allografts for rejection should detect the problem early in its evolution so that treatment to reverse the process would salvage a functional organ. Lewis rats served as recipients of LBNF1 out-of-continuity small bowel allografts and were studied in two groups: group I (control) received no immunosuppression and group II received cyclosporine (CsA, 15 mg/kg/d, p.o.) when I-FABP rose to > or = 80 ng/ml. Serum I-FABP was measured daily until the time of sacrifice. Full-thickness graft biopsies were obtained on postoperative days 3 (baseline), 6 or 7 (elevated I-FABP), 10, and 14 (sacrifice). Following transplantation baseline serum I-FABP (day 2 or 3) averaged < or = 10.0 ng/ml. I-FABP remained at baseline through day 5 (range 0-50 ng/ml) in all animals and then rose abruptly on either day 6 or 7 (range 86-150 ng/ml; P < 0.001 vs. baseline). Histology on day 6 or 7 revealed a mild-to-moderate cellular rejection. Cyclosporine therapy reversed the rejection reaction and restored the bowel to normal histology. Serum I-FABP returned to baseline. In untreated animals, serum I-FABP remained elevated for several days and then returned to baseline levels coincident with fulminant rejection and mucosal sloughing. I-FABP was released into the peripheral circulation early in the evolution of acute rejection in this model of small bowel transplantation. Immunosuppressive therapy initiated when elevated levels of I-FABP were detected in the serum resulted in graft salvage. Cyclosporine immunotherapy consistently reversed rejection in this model. This article represents the first report of salvage of small bowel allografts when immunosuppressive therapy was instituted prospectively on the basis of a serum marker. Immunoreactive I-FABP appears to hold significant potential as a biochemical screening tool for acute rejection occurring In small bowell allografts.

Biochemical detection of small intestinal allograft rejection by elevated circulating levels of serum intestinal fatty acid binding protein.

BACKGROUND: Intestinal fatty acid binding protein (I-FABP) was investigated as a serum marker for acute intestinal allograft rejection. Its behavior was compared with that of another putative marker of intestinal damage, hexosaminidase. METHODS: Transplants were performed in three groups of rats: group 1, Lewis to Lewis; group 2, ACI to Lewis, no immunosuppression; and group 3, ACI to Lewis with cyclosporine given on posttransplant days 0 through 5. Daily serum I-FABP and hexosaminidase levels were quantitated and serial graft biopsy specimens were obtained. RESULTS: Serum I-FABP levels fell to 20 ng/ml or less in all animals between posttransplant days 3 and 4. In group 1, I-FABP levels remained at baseline throughout the experiment. In group 2, I-FABP levels rose dramatically on either day 6 or 7 and declined to baseline within 4 days of the peak. On the day that I-FABP levels increased, findings of biopsy specimens were consistent with early rejection. In group 3 the rise in serum I-FABP levels was delayed 2 to 10 days. Hexosaminidase did not correlate with rejection. CONCLUSIONS: Serum I-FABP content correlated with early histologic manifestations of rejection. Hexosaminidase was insensitive as a marker in this model. I-FABP, which has a human analog, has potential as a biochemical marker for early intestinal allograft rejection.

Intestinal fatty acid binding protein in serum and urine reflects early ischemic injury to the small bowel.

BACKGROUND: Intestinal fatty acid binding protein (I-FABP) is a 15 kd protein that constitutes 2% to 3% of enterocyte protein. Normally I-FABP is undetectable in serum. The purpose of this study was to determine whether I-FABP could be detected in peripheral serum and/or urine early in the evolution of intestinal ischemic injury. METHODS: I-FABP and two putative biochemical markers of mesenteric ischemia, hexosaminidase and lactate dehydrogenase, were quantitated in the serum of rats subjected to mesenteric ischemia produced by: (1) 0.5 hours, 1 hour, or 3 hours of superior mesenteric artery (SMA) occlusion followed by reperfusion; (2) 1 hour of mesenteric occlusion to a 10 cm segment of jejunum followed by reperfusion; and (3) arterial ligation to a 10 cm segment of jejunum without reperfusion. I-FABP was also quantitated in the urine and intestinal mucosa of these animals. RESULTS: The baseline serum I-FABP level was < or = 4.0 ng/ml in all animals. In control animals, I-FABP remained unchanged throughout the experiment. In the ischemia/reperfusion groups, I-FABP immediately appeared in the serum on reperfusion. With segmental arterial ligation, I-FABP was detected in the serum within 15 minutes. Urinary content of I-FABP rose 60 minutes after its initial appearance in the serum, and its elimination paralleled serum I-FABP levels. Serum hexosaminidase and lactate dehydrogenase levels only rose after 3 hours of SMA occlusion with reperfusion. One hour of SMA occlusion and reperfusion resulted in only mild to moderate mucosal injury, whereas 3 hours of SMA ischemia with reperfusion produced areas of transmural necrosis. CONCLUSIONS: I-FABP is released into the peripheral circulation after reversible intestinal ischemic injury and has potential as a biochemical marker to facilitate the early detection of mesenteric ischemia.

Results of a pilot trial comparing prolonged intravenous antibiotics with sequential intravenous/oral antibiotics for children with perforated appendicitis.

HYPOTHESIS: For children with perforated appendicitis, the use of a prolonged course of intravenous (i.v.) antibiotics is equivalent to a short course of i.v. antibiotics followed by sequential conversion to oral (PO) antibiotics. DESIGN: Prospective, randomized, clinical trial. SETTING: Multicenter study in tertiary children's hospitals. PATIENTS: Children (aged 5-18 years) with perforated appendicitis found at laparotomy. INTERVENTION: Children were randomized after appendectomy either to a 10-day course of a combination of i.v. ampicillin, gentamicin sulfate, and clindamycin (n = 10); or to a short course of a combination of i.v. ampicillin, gentamicin, and clindamycin, followed by conversion to a combination of p.o. amoxicillin and clavulanate potassium plus metronidazole (n = 16). MAIN OUTCOME MEASURES: The primary outcome measure was clinical success, which was rated as complete, partial, or failure. Secondary outcome measures included return of oral intake, duration of fever, return of normal white blood cell count, and patient charges. Treatment equivalence was determined using confidence interval analysis. RESULTS: We found treatment equivalence between the i.v. and i.v./p.o. groups, with 6 (60%) complete and 4 (40%) partial successes for the 10 patients in the i.v. group and 15 (94%) complete and 1 (6%) partial successes for the 16 patients in the i.v./p.o. group (P< or =.05). There was no difference in return of oral intake, duration of fever, or return of normal white blood cell count between the groups. Conversion to oral therapy results in savings of approximately $1500 per case. CONCLUSION: There is treatment equivalence between prolonged i.v. therapy and i.v. therapy followed by conversion to oral antibiotic therapy in children with perforated appendicitis.

Does prostacyclin (PGI2) cardioplegic infusion improve myocardial protection after ischemic arrest?

To determine whether prostacyclin (PGI2) plays a beneficial role in the blood-perfused heart undergoing global ischemia, 20 isolated canine hearts were studied after sustaining one hour of cardioplegic arrest under moderate hypothermia (27 degrees to 28 degrees C). Left ventricular function (peak systolic pressure, rate of rise of left ventricular pressure [dP/dt], and compliance change in left ventricular volume), myocardial edema, coronary blood flow, and oxygen content were measured during the preischemic period and at 15 and 30 minutes during reperfusion. Results showed an improved hemodynamic recovery (peak systolic pressure, p = 0.018 at 30 minutes; dP/dt, p = 0.020 at 15 minutes) in the group of hearts treated with PGI2 infusion compared with controls. There was no difference in ventricular compliance or myocardial edema between the two groups. This benefit was attributed to a significant increase in myocardial blood flow (p = 0.028 at 15 minutes) and oxygen delivery (p = 0.021 at 15 minutes) during the reperfusion period with PGI2. These data suggest a potential clinical role for PGI2 when applied to the globally ischemic heart in the improvement of myocardial resuscitation during the early reperfusion period.

Effect of maternal diabetes on the fetal exocrine pancreas.

To test the hypothesis that fetal pancreatic exocrine and endocrine function are stimulated in parallel in the diabetic pregnancy, 68 mothers with gestational and pregestational diabetes who underwent amniocenteses after 34 weeks' for the evaluation of fetal lung maturity were enrolled. Amniotic fluid specimens were analyzed for C-peptide and trypsin content. Amniotic fluid specimens were obtained from 92 non-diabetic women undergoing amniocenteses for lung maturity, preterm labor, or premature rupture of membranes. Groups were compared using the Wilcoxon rank-sum test, Kruskal Wallis rank sum test, and Spearman's rank correlation test. C-peptide amniotic fluid concentrations were significantly greater in diabetics (median 0.6 ng/ml) than non-diabetics (median 0.4 ng/ml, P= 0.0001), in pregestational (median 0.6 ng/ml) vs. gestational diabetics (median 0.4 ng/ml, P = 0.006), and greater in proportion to severity of disease according to diabetic class (A1 = 0.4 ng/ml, A2 = 0.55 ng/ml, B = 0.6 ng/ml, C = 0.7 ng/ml, D = 0.85 ng/ml, P = 0.04). No significant differences were detected in amniotic fluid trypsin between the diabetic and non-diabetic or the gestational and non-gestational diabetic groups. There was no correlation between C-peptide and trypsin within the diabetic groups. Stimulation of the exocrine and endocrine pancreas does not occur in parallel in the fetus of the diabetic mother. Although originating as a single organ, pancreatic exocrine and endocrine functions are distinct in both physiologic and pathologic conditions.

Intestinal mucosal injury in critically ill surgical patients: preliminary observations.

This was a prospective study designed to evaluate the extent to which intestinal mucosal compromise occurs in adult critical care patients with and without systemic inflammatory response syndrome (SIRS) and to correlate the degree of intestinal injury with outcome. Ten patients from a university hospital surgical intensive care unit were identified who manifested SIRS at the time of admission to the intensive care unit. Five other critical care patients without SIRS were also evaluated. The Acute Physiology and Chronic Health Evaluation II score was determined. Intestinal mucosal viability was assessed by serial measurement of serum and urine iFABP intestinal fatty acid binding protein (iFABP), a sensitive and specific marker for mucosal injury. Outcome in terms of the development of multiorgan dysfunction syndrome, adult respiratory distress syndrome, and survival was determined. iFABP was detectable in the serum or urine in 8 out of 10 patients with SIRS. Among the 4 patients with detectable serum iFABP, 2 died and 1 developed severe adult respiratory distress syndrome. Nine of 11 patients without detectable serum iFABP recovered without major morbidity. iFABP was detectable in most patients with SIRS, suggesting that subclinical intestinal mucosal compromise is a frequent component of this syndrome. When iFABP was detectable, particularly in the serum, the prognosis was poor, even in the absence of SIRS, indicating that iFABP may be a relevant and independent predictor of outcome in critical care patients.

Elevation of circulating intestinal fatty acid binding protein in a luminal contents-initiated model of NEC.

Necrotizing enterocolitis (NEC) continues to produce significant morbidity and mortality, due in part to the difficulty in detecting its initial manifestations at a stage when compromised intestine may potentially be salvaged. We have previously reported our findings that intestinal fatty acid binding protein (I-FABP) is a sensitive biochemical marker for early intestinal mucosal injury due to mesenteric ischemia. In this study we evaluated the potential of serum I-FABP as a marker for incipient NEC in a nonischemic model of NEC in the rat. Intraluminal instillation of a solution of casein (10 mg/mL) and calcium gluconate (50 mg/mL) in saline acidified to pH 4.0 with propionic acid resulted in a rapid and prolonged increase in serum I-FABP from a baseline of < or = 4.0 ng/mL to 171 +/- 40 ng/mL. Instillation of the same electrolyte solution with either casein or propionic acid alone resulted in a less dramatic elevation of serum I-FABP to 19 +/- 4 ng/mL and 76 +/- 30 ng/mL, respectively. In both cases baseline values of < or = 4.0 ng/mL were reached within 60 minutes. In control animals, which received saline alone, serum I-FABP was undetectable throughout the experiment. Simultaneously, we found that serum hexosaminidase, a putative biochemical marker for intestinal ischemia and NEC, was unchanged in all groups. Light microscopy of the intestinal specimens obtained three hours after instillation of casein and organic acid demonstrated superficial villus necrosis and villus blunting, but no areas of transmural necrosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Cholecystectomy for suspected biliary dyskinesia in children with chronic abdominal pain.

BACKGROUND/PURPOSE: The authors reviewed their experience with a group of children with chronic abdominal pain, delayed gallbladder emptying, and no cholelithiasis. Clinical presentation, diagnostic evaluation, and effect of cholecystectomy on symptoms were investigated. METHODS: Twenty-nine children were suspected of having biliary dyskinesia. Diagnosis was based on symptoms of upper abdominal pain in conjunction with a lack of sonographically apparent gallstones, a cholecystikinin (CCK)-stimulated gallbladder ejection fraction of less that 40% at 30 minutes, and a lack of any other clear cause for symptoms. All patients underwent cholecystectomy. RESULTS: The duration of symptoms before operation was between 3 weeks and 4 years. All patients were evaluated by abdominal ultrasonography and CCK cholescintigraphy. Symptoms were relieved completely in 23 (79%) of the patients who underwent cholecystectomy. Five children had persistent pain after cholecystectomy and one had nausea. CONCLUSIONS: Symptoms suggestive of biliary colic in children without evidence for cholelithiasis frequently may represent biliary dyskinesia. CCK cholescintigraphy should be pursued in these patients. Relief of symptoms after cholecystectomy should be expected in a majority of those with an ejection fraction of less that 40%.

Does early ultrasonography affect management of pediatric appendicitis? A prospective analysis.

BACKGROUND: Appendicitis remains a difficult diagnosis in children. Ultrasonography is increasingly used for the diagnosis of appendicitis, although the proper clinical role for this test remains unclear. METHODS: To evaluate the clinical utility of ultrasonography in appendicitis, the authors analyzed prospectively all children evaluated for possible appendicitis from January 1 through December 31, 1997. Children with a high clinical suspicion of appendicitis were referred for surgery (n = 122). Children with equivocal findings of appendicitis were referred for early ultrasonography (EUS) and formed the study cohort (n = 103). An initial management plan was made to operate or observe each patient, and a risk of appendicitis (doubtful, possible, probable) was assigned by a pediatric surgery fellow. EUS was then performed, and its effect on management was assessed. RESULTS: Using clinical judgment to operate at initial presentation, the sensitivity was 38% and specificity was 95%. Using EUS alone, the sensitivity was 87% and specificity was 88%. The management of 30 of 103 patients (30%) was changed after EUS, including a decision to operate in 28 patients and a decision not to operate in two patients. CONCLUSIONS: EUS appears to have substantial clinical utility in children with equivocal findings of appendicitis, and its use complements the clinical management. The use of EUS can improve patient care and reduce hospital resource utilization.

Predictors of postoperative respiratory complications in premature infants after inguinal herniorrhaphy.

There is a significant incidence of inguinal hernia in premature infants and the optimal timing of repair is controversial. A high rate of postoperative respiratory complications has been reported in this group. In this study, the records of 47 premature infants (mean gestational age, 30.3 weeks) who underwent herniorrhaphy while still in the neonatal intensive care unit were reviewed in an effort to define those conditions that are independent risk factors for complications. Forty-three percent of infants had complications, including postoperative assisted ventilation (34%), episodes of apnea and/or bradycardia (23%), emesis and cyanosis with first feeding (6%), and requirement for postoperative reintubation (4%). Although low gestational age and postconceptual age at operation, low birth weight for gestational age, and preoperative ventilatory assistance were significantly associated with postoperative complications, only a history of respiratory distress syndrome/bronchopulmonary dysplasia (odds ratio 2.3), a history of patent ductus arteriosus (odds ratio 2.5), and low absolute weight at operation (odds ratio 3.5 for 1,000-g decrease) were independent risk factors for postoperative complication. Despite previous reports citing postconceptual age as the factor having the greatest impact on postoperative complications, these results indicate that a history of respiratory dysfunction and size at operation may be more important predictors of postoperative respiratory dysfunction in preterm infants.

Diagnosis of acute and chronic cardiac rejection by magnetic resonance imaging: a non-invasive in-vivo study.

To evaluate the potential usefulness for characterization of tissue and anatomical changes associated with cardiac transplantation rejection by nuclear magnetic resonance imaging (MRI), sixteen dogs underwent heterotropic cardiac transplantation with six not immunosuppressed serving as controls. Myocardial biopsy and MRI were obtained and compared on a weekly basis. Untreated allografts showed a significant increase in T2 and intensity values by MRI compared to the native heart as early as one week after transplantation. The MRI findings corresponded to the histological progression of acute rejection process in both treated and untreated groups. The linear relationship between histology and MRI was 0.72 while the correlation between T2 and the water content was 0.92. Serial gated MRI correlated with chronic anatomical changes of transplant rejection with evidence of progressive or increasing myocardial wall thickness and decrease in ventricular chamber size.

Late-presenting congenital diaphragmatic hernia: diagnostic pitfalls and outcome.

PURPOSE: We sought to review the presentation, diagnosis, and outcome of a series of children with late-presenting, congenital diaphragmatic hernias (CDH). METHODS: Bochdalek and Morgagni hernias that were diagnosed after 30 days of age, between January 1989 and December 2009, were reviewed retrospectively. A medical record review and telephone survey were conducted in 2010. RESULTS: Thirty-one subjects, diagnosed with CDH between 45 days and 13 years of age (mean, 16 months), were reviewed. Bochdalek hernias were present in 18 (58%) and Morgagni hernias in 13 (42%). There were twenty (64%) left-sided, eight (26%) right-sided, and three (10%) bilateral CDH. Five (16%) had other congenital anomalies. Eight (25.8%), including a subject with strangulated intestine that required resection, were initially misdiagnosed, due mostly to failure to obtain or correctly interpret a chest radiograph. Thirty (97%) were repaired by an abdominal approach, including seven laparoscopic closures. Follow-up ranged from 1 to 20 years (median, 7 years). All subjects survived without recurrence. Unlike neonatally diagnosed CDH, neither right-sided hernia, patch repair, nor associated esophageal atresia predicted morbidity. CONCLUSION: Although diagnostic delays may lead to morbidity, if late-presenting CDH are expeditiously identified and repaired, their outcome is very good, in contrast to those that present in neonates.

Observation of 1(-)0(-) final states from psi(2S) decays and e(+)e(-) annihilation.

Using CLEO data collected from CESR e(+)e(-) collisions at the psi(2S) resonance and nearby continuum at sqrt[s]=3.67 GeV, we report the first significantly nonzero measurements of light vector-pseudoscalar hadron pair production (including rhopi, omegapi, rhoeta, and K(*0)K0 ) and the pi(+)pi(-)pi(0) final state, both from psi(2S) decays and direct e(+)e(-) annihilation.

Branching fractions for psi(2S)-to-J/psi transitions.

We describe new measurements of the inclusive and exclusive branching fractions for psi(2S) transitions to J/psi using e(+)e(-) collision data collected with the CLEO detector operating at CESR. All branching fractions and ratios of branching fractions reported here represent either the most precise measurements to date or the first direct measurements. Indirectly and in combination with other CLEO measurements, we determine B(chi(cJ) --> gamma(J/psi)) and B[psi(2S) --> light hadrons].