Heterogenous Renal Injury Biomarker Production Reveals Human Sepsis-Associated Acute Kidney Injury Subtypes.

To identify mechanisms associated with sepsis-acute kidney injury based on the expression levels of renal injury biomarkers, neutrophil gelatinase-associated lipocalin, and kidney injury molecule-1 in renal biopsies which may allow the identification of sepsis-acute kidney injury patient subtypes. DESIGN: Prospective, clinical laboratory study using "warm" human postmortem sepsis-acute kidney injury kidney biopsies. SETTING: Research laboratory at university teaching hospital. SUBJECTS: Adult patients who died of sepsis in the ICU and control patients undergoing tumor nephrectomy. MEASUREMENTS AND MAIN RESULTS: Reverse transcription quantitative polymerase chain reaction and immunohistochemical staining were used to quantify messenger RNA and protein expression levels of neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 in the kidney of sepsis-acute kidney injury patients and control subjects. Morphometric analysis was used to quantify renal and glomerular neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 protein levels. Neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 messenger RNA and protein levels were increased in kidneys of sepsis-acute kidney injury patients compared with control kidney tissue. Neutrophil gelatinase-associated lipocalin was localized in the distal tubules, collecting ducts, the adventitia of the renal arterioles, and in the glomerular tufts of renal biopsies from sepsis-acute kidney injury patients. In contrast, kidney injury molecule-1 was localized at the brush border of the proximal tubules. There was no correlation between neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 levels. Furthermore, renal neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 levels were not associated with the extent of renal injury, the severity of critical illness, or serum creatinine levels at either ICU admission or day of expiration. By laser microdissecting glomeruli, followed by reverse transcription quantitative polymerase chain reaction, we identified heterogenous glomerular neutrophil gelatinase-associated lipocalin production in the kidney of sepsis-acute kidney injury patients. CONCLUSION: We found differences in the expression of neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 in patients with the same syndrome "sepsis-acute kidney injury" meaning there is no single pathway leading to sepsis-acute kidney injury. This underscores the beliefs that there are many/different pathophysiological pathways that can cause sepsis-acute kidney injury. Hence, patients with criteria that meet the definitions of both acute kidney injury and sepsis can be divided into subtypes based on pathophysiological features.

Kidney histopathology in lethal human sepsis.

PURPOSE: The histopathology of sepsis-associated acute kidney injury (AKI) in critically ill patients remains an understudied area. Previous studies have identified that acute tubular necrosis (ATN) is not the only driver of sepsis-AKI. The focus of this study was to identify additional candidate processes that may drive sepsis-AKI. To do this we immunohistochemically characterized the histopathological and cellular features in various compartments of human septic kidneys. METHODS: We studied the following histopathological features: leukocyte subsets, fibroblast activation, cellular proliferation, apoptosis, and fibrin deposition in the glomerulus and the tubulointerstitium in human post-mortem kidney biopsy tissue. Biopsy tissue samples from 27 patients with sepsis-AKI were collected 33 min (range 24-150) after death in the ICU. The unaffected part of the kidneys from 12 patients undergoing total nephrectomy as a result of renal carcinoma served as controls. RESULTS: Immunohistochemical analysis revealed the presence of more neutrophils and macrophages in the glomeruli and more neutrophils in the tubulointerstitium of renal tissue from patients with sepsis compared to control renal tissue. Type II macrophages were predominant, with some macrophages expressing both type I and type II markers. In contrast, there were almost no macrophages found in control kidneys. The number of activated (myo)fibroblasts was low in the glomeruli of sepsis-AKI kidneys, yet this was not observed in the tubulointerstitium. Cell proliferation and fibrin deposition were more pronounced in the glomeruli and tubulointerstitium of sepsis-AKI than in control kidneys. CONCLUSIONS: The extensive heterogeneity of observations among and within patients emphasizes the need to thoroughly characterize patients with sepsis-AKI in a large sample of renal biopsy tissue from patients with sepsis.

Renal Klotho is Reduced in Septic Patients and Pretreatment With Recombinant Klotho Attenuates Organ Injury in Lipopolysaccharide-Challenged Mice.

OBJECTIVES: To determine the applicability of recombinant Klotho to prevent inflammation and organ injury in sepsis in man and mice. DESIGN: Prospective, clinical laboratory study using "warm" human postmortem sepsis-acute kidney injury biopsies. Laboratory study using a mouse model of endotoxemia. SETTING: Research laboratory at a university teaching hospital. SUBJECTS: Adult patients who died of sepsis in the ICU and control patients undergoing total nephrectomy secondary to renal cancer; male C57BL/6 and Klotho haploinsufficient mice. INTERVENTIONS: Lipopolysaccharide (0.05 mg/kg) injection and kill after 4, 8, and 24 hours. Mice received recombinant Klotho (0.05 mg/kg) 30 minutes prior to lipopolysaccharide (1 mg/kg) injection. Mice treated with saline were included as controls. MEASUREMENTS AND MAIN RESULTS: Quantitative reverse transcription polymerase chain reaction and immunohistochemical staining were used to quantify Klotho messenger RNA and protein expression in the kidney of sepsis-acute kidney injury patients and the kidney and brain of mice. The messenger RNA and protein expression of damage markers, inflammatory cytokine, chemokines, and endothelial adhesion molecules were also determined in mice. Renal neutrophil influx was quantified. We found significantly lower renal Klotho messenger RNA and protein levels in sepsis-acute kidney injury biopsies than in control subjects. These findings were recapitulated in the kidney and brain of lipopolysaccharide-challenged mice. Decreased Klotho expression paralleled an increase in kidney damage markers neutrophil gelatinase-associated lipocalin and kidney injury molecule-1. Administration of recombinant Klotho prior to lipopolysaccharide injection attenuated organ damage, inflammation and endothelial activation in the kidney and brain of mice. Furthermore, less neutrophils infiltrated into the kidneys of recombinant Klotho mice compared with lipopolysaccharide only treated mice. CONCLUSIONS: Renal Klotho expression in human sepsis-acute kidney injury and in mouse models of sepsis was significantly decreased and correlated with renal damage. Recombinant Klotho intervention diminished organ damage, inflammation, and endothelial activation in the kidney and brain of lipopolysaccharide-challenged mice. Systemic Klotho replacement may potentially be an organ-protective therapy for septic patients to halt acute, inflammatory organ injury.

Endothelium-targeted delivery of dexamethasone by anti-VCAM-1 SAINT-O-Somes in mouse endotoxemia.

Microvascular endothelial cells play a pivotal role in the pathogenesis of sepsis-induced inflammatory responses and multiple organ failure. Therefore, they represent an important target for pharmacological intervention in the treatment of sepsis. Glucocorticosteroids were widely used in the treatment of sepsis but vast evidence to support their systemic use is lacking. The limited effects of glucocorticoids in the treatment of sepsis may be explained by differential effects of drug initiated NF-κB inhibition in different cell types and insufficient drug delivery in target cells. The current study aimed therefore to investigate the effects of an endothelial targeted delivery of dexamethasone in a mouse model of endotoxemia induced by two consecutive i.p. injections of lipopolysaccharide (LPS). To achieve endothelial cell specific delivery of dexamethasone, we modified SAINT-O-Somes, a new generation of liposomes that contain the cationic amphiphile SAINT-C18 (1-methyl-4-(cis-9-dioleyl) methyl-pyridinium chloride, with antibodies against vascular cell adhesion molecule-1 (VCAM-1). In LPS challenged mice, the systemic administration of free dexamethasone had negligible effects on the microvascular inflammatory endothelial responses. Dexamethasone-loaded anti-VCAM-1 SAINT-O-Somes specifically localized at VCAM-1 expressing endothelial cells in the microvasculature of inflamed organs. This was associated with a marginal attenuation of the expression of a few pro-inflammatory genes in kidney and liver, while no effects in the lung were observed. This study reveals that, although local accumulation of the targeted drug was achieved, endothelial targeted dexamethasone containing anti-VCAM-1 SAINT-O-Somes exhibited marginal effects on inflammatory endothelial cell activation in a model of endotoxemia. Studies with more potent drugs encapsulated into anti-VCAM-1 SAINT-O-Somes will in the future reveal whether this delivery system can be further developed for efficacious endothelial directed delivery of drugs in the treatment of sepsis.

Organ-Specific Differences in Endothelial Permeability-Regulating Molecular Responses in Mouse and Human Sepsis.

In patients with sepsis-induced multi-organ dysfunction syndrome, diverging patterns of oedema formation and loss of function in organs such as lung and kidney suggest that endothelial permeability-regulating molecular responses are differentially regulated. This potential differential regulation has been insufficiently studied at the level of components of adherens and tight junctions. We hypothesized that such a regulation by endothelial cells in sepsis takes place in an organ-specific manner. We addressed our hypothesis by studying by quantitative real time polymerase chain reaction the expression of a predefined subset of EC permeability-related molecules (occludin, claudin-5, PV-1, CD-31, endomucin, Angiopoietin-1, Angiopoietin-2, Tie2, VEGFA, VEGFR1, VEGFR2, and VE-cadherin) in kidney and lung after systemic lipopolysacharide injection in mice, and in kidneys of patients who died of sepsis. We showed that baseline endothelial expression of permeability-related molecules differs in mouse kidney and lung. Moreover, we showed differential regulation of these molecules after lipopolysacharide injection in the two mouse organs. In lung we found a decrease in expression levels of molecules of the adherence and tight junctions complex and related signaling systems, compatible with increased permeability. In contrast, in kidney we found expression patterns of these molecules compatible with decreased permeability. Finally, we partially corroborated our findings in mouse kidney in human kidneys from septic patients. These findings may help to understand the clinical difference in the extent of oedema formation in kidney and lung in sepsis-associated organ failure.

Histone Deacetylase Inhibition and IκB Kinase/Nuclear Factor-κB Blockade Ameliorate Microvascular Proinflammatory Responses Associated With Hemorrhagic Shock/Resuscitation in Mice.

OBJECTIVE: To investigate the consequences of histone deacetylase inhibition by histone deacetylase inhibitor valproic acid and IκB kinase/nuclear factor-κB signaling blockade by IκB kinase inhibitor BAY11-7082 on (microvascular) endothelial cell behavior in vitro as well as in mice subjected to hemorrhagic shock/resuscitation in vivo. DESIGN: Prospective, randomized laboratory investigation using an established mouse model of hemorrhagic shock. SETTING: Research laboratory at university teaching hospital. SUBJECTS: Endothelial cells and C57BL/6 male mice. INTERVENTIONS: Endothelial cells were incubated with tumor necrosis factor-α in the absence or presence of valproic acid or BAY11-7082 in vitro. Mice were subjected to hemorrhagic shock by blood withdrawn until the mean arterial pressure of 30 mm Hg and maintained at this pressure for 90 minutes. At 90 minutes, subgroups of mice were resuscitated with 4% human albumin in the absence or presence of vehicle, valproic acid (300 µg/g body weight) or BAY11-7082 (400 µg per mouse). Mice were killed 1 hour and 4 hours after resuscitation. MEASUREMENTS AND MAIN RESULTS: Valproic acid and BAY11-7082 selectively diminished tumor necrosis factor-α-induced endothelial proinflammatory activation in vitro. In vivo, both systemic and local inflammatory responses were significantly induced by hemorrhagic shock/resuscitation. The decreased histone acetylation in kidneys after hemorrhagic shock/resuscitation was restored by valproic acid treatment. In glomerular endothelial cells, the nuclear translocation of nuclear factor-κB, which was induced by hemorrhagic shock/resuscitation, was eliminated by BAY11-7082 treatment while enhanced in the presence of valproic acid. Both valproic acid and BAY11-7082 significantly attenuated the hemorrhagic shock/resuscitation-induced protein expression of endothelial cell adhesion molecules E-selectin and vascular cell adhesion molecule-1 in the microvasculature of kidneys and liver, although messenger RNA expression levels of these molecules analyzed in whole-organ lysates of kidneys, lungs, and liver were not extensively affected. The reduced protein expression of adhesion molecules was paralleled by diminishing the adhesion/transmigration of neutrophils in kidneys and liver after hemorrhagic shock/resuscitation. CONCLUSION: Suppression of histone deacetylase activity and blockade of IκB kinase/nuclear factor-κB signaling during resuscitation ameliorate microvascular endothelial proinflammatory responses in organs in mice after hemorrhagic shock.

Propofol infusion syndrome heralded by ECG changes.

BACKGROUND: Propofol infusion syndrome (PRIS) is well known, often associated with, lethal complication of sedation with propofol. PRIS seems to be associated with young age, traumatic brain injury (TBI), higher cumulative doses of propofol, and the concomitant use of catecholamines. Known manifestations of PRIS are metabolic acidosis, rhabdomyolysis, and cardiac failure. While fatal PRIS can occur suddenly and rapidly, there is no sensitive test or early warning sign, and the only preventive measure is to limit propofol dosage and its duration. METHODS: DESCRIPTION OF A SINGLE CASE: A case report was used for investigation purposes of this study. RESULTS: We report the case study of a young patient with severe TBI, receiving propofol sedation because of high intracranial pressure. Seven days after the trauma, the patient developed metabolic acidosis and refractory circulatory shock, probably caused by PRIS. Reversal of T-waves was seen on the electrocardiogram (ECG) 29 h before circulation failure occurred. In the absence of other signs of cardiac dysfunction or ischemia, these reversed T-waves probably represent an early warning sign of developing PRIS. CONCLUSION: From the findings of this study, we conclude that meticulous observation and analysis of the ECG during propofol sedation might result in earlier recognition of developing PRIS.

Intra-arterial blood pressure reading in intensive care unit patients in the lateral position.

BACKGROUND: Routine lateral turning of patients has become an accepted standard of care to prevent complications of immobility. The haemodynamic and oxygenation effects for patients in both lateral positions (45°) are still a matter of debate. We aimed to study the effect of these positions on blood pressure, heart rate and oxygenation in a general intensive care population. DESIGN: Observational study. METHOD: Twenty stable intensive care unit patients had intra-arterial blood pressure recordings in the supine and lateral positions with the correction of hydrostatic height compared with a fixed reference point (phlebostatic level). A multilevel model was used to analyse the data. RESULTS: Mean arterial pressure readings in the lateral positions were, on average, 5 mmHg higher than in the supine position (p < 0.001). There were no significant differences between mean arterial pressure recordings in the left and right lateral position (p = 1.0). No important differences in oxygenation and heart rate were observed. After correction for covariates, the effects persisted. CONCLUSION: Our study demonstrated an increase, albeit small, in blood pressure in the lateral positions. No major differences between the left and right lateral position were found. No important differences in oxygenation and heart rate were observed. RELEVANCE TO CLINICAL PRACTICE: Turning haemodynamically stable patients in the intensive care unit has no important effects on blood pressure measurements when continuous hydrostatic height correction is applied.

The repair of a large duodenal defect by a pedicled gastric seromuscular flap.

PURPOSE: The aim was to evaluate the efficacy of a pedicled gastric seromuscular flap for the closure of a large duodenal defect. METHODS: A large defect of the second duodenal part was repaired by a gastric seromuscular flap. Of 35 rats, 9 rats were euthanized at 2 weeks, 12 rats at 2 months, and 14 rats at 4 months for the histopathological evaluation of the patch and normal duodenum (control) adjacent to the patch. RESULTS: All rats survived. The patch was completely covered by neomucosa in all of the 4-month rats, and in 8 of the 12 2-month rats. The villous height of the neomucosa was significantly higher in the 4-month rats in comparison to the other rats (P < 0.001). However, a normal duodenum had higher villi than in that of the patches (P < 0.001). The crypt density of the neomucosa was significantly increased in the 4-month rats in comparison to the 2-week and the 2-month rats (P < 0.001 and P < 0.05 group, respectively). The crypt density was higher in the controls than in the neomucosa covered patch of the 2-week and the 2-month rats (P < 0.001 and P < 0.05, respectively). The crypt depth of the neomucosa increased significantly in the 4-month rats and in the controls versus the 2-week rats (P < 0.05). CONCLUSION: The new mucosal barrier overlaying the patch appeared to be satisfactory. This technique, which has not been described previously, is likely to be useful for the repair of the large duodenal defect.

Laparoscopic appendectomy without clip or ligature. An experimental study.

BACKGROUND: We aimed to test the efficacy and safety of closure of the appendeceal stump with only laparoscopic bipolar electrocautery in rats. METHODS: In this study, 40 female Wistar-Albino rats were used. In group I (n = 10), appendix vermiformis, approximately 1 cm in width, was completely ligated with 3/0 silk suture close to cecum, and removed. In group II (n = 20) and group III (n = 10), the appendeceal stump was coagulated by bipolar cautery. The coagulation of 70 mA took 10 s, and was repeated one more time. The stump was divided, and checked to ensure complete occlusion. Groups I and II underwent relaparotomy at 15 days, cecum was taken out, and the burst pressure of the stump was measured. Group III did not undergo relaparotomy; the burst pressure was measured during the first laparotomy. RESULTS: All rats survived. At relaparotomy, no intra-abdominal complications were detected, including intestinal obstruction, abscess, and leakage. Omentum and fatty tissue of uterus was adhered to the appendix stump in group I, but only fatty tissue of uterus was adhered on the stump in group II. Although the intracecal pressure reached 30 cmH(2)O, at which pressure the cecum was highly stretched, ligated (group I) or coagulated (group II) stumps did not burst or opened. In group III, the burst or opening pressure of the stump (11.2 +/- 2.7 cmH(2)O) was significantly lower than in groups I and II (p < 0.001). Of group II rats, 80% had complete epithelial regeneration at the coagulated stump sites in contrast to ligated rats (p < 0.001) with severe inflammatory changes, abscess, and necrosis. CONCLUSIONS: At late course, coagulated stumps did not allow the leakage or burst, unlike ligated stumps. However, coagulation of the stump seemed to contribute more to epithelial healing. This experimental model suggests that the closure of the stump with only bipolar coagulation was a safe and feasible method.

Does noncomplicated acute appendicitis cause bacterial translocation?

It is unknown whether noncomplicated acute appendicitis cause bacterial translocation. In this study, we aimed to test development of the bacterial translocation in the patients who were operated for acute appendicitis. In this prospective study, 10 control patients who underwent elective operations because of other reasons, and 18 patients with noncomplicated acute appendicitis were evaluated. No patients took prophylactic antibiotic. After laparotomy, samples were obtained from peritoneal leaf just close to wound edge, and peritoneal swab culture from right paracolic region. Before appendectomy, a mesenteric lymph node (MLN) adjacent to the terminal ileum was taken out. Tissue samples were placed in a sterile container for microbiological analysis, and 10% formalin for histopathological analysis. Control samples had no bacterial translocation. Only 3 of 18 (16.6%) patients with appendicitis included bacterial translocation to MLN. There was no significant difference between both groups. No bacterial colonization was detected in the peritoneal tissue and peritoneal swab culture. Peritoneal tissue injury score was 2 +/- 1.4 in controls and 2.8 +/- 1.7 in the patients with appendicitis (P>0.05). MLN injury score was 2.5 +/- 1.3 in controls and 3.2 +/- 1.5 in the patients with appendicitis (P>0.05). No patient developed wound and systemic infection. No significant bacterial translocation frequency and tissue injury score was identified in the children with noncomplicated acute appendicitis. This result suggests that antibiotic prophylaxis may be unnecessary in such patients.

Effect of antiepileptic drugs on plasma lipids, lipoprotein (a), and liver enzymes.

We conducted a study to assess the effect of phenobarbital, carbamazepine, and valproate on serum lipid profiles and lipoprotein (a) in 64 children with epilepsy (aged between 1 and 15 years) admitted to the child neurology outpatient clinic between July 2000 and July 2002. The children were separated as group 1 (18 children), treated with phenobarbital, 5 mg/kg/day; group 2 (22 children), treated with carbamazepine, 10 to 15 mg/kg/day; and group 3 (24 children), treated with sodium valproate, 20 mg/kg/day. Plasma lipoprotein (a), total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, apolipoprotein A and apolipoprotein B levels, and liver enzymes alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and gamma-glutamyltransferase were determined before the initiation of the treatment and at 3, 6, and 12 months of the treatment period. The mean age of children in group 1 was significantly low compared with those in groups 2 and 3 (P <.05). The mean pretreatment lipid levels among the groups were not significantly increased. The mean lipoprotein (a) levels were significantly increased in all groups at 3, 6, and 12 months of the treatment period (P <.05). The increase in alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol at 3, 6, and 12 months was statistically significant in group 1 (P <.05). The higher levels in lipoprotein (a) (mean > 30 mg/dL) were observed only in carbamazepine-treated patients at 6 and 12 months. The percentage of children with lipoprotein (a) levels over 30 mg/dL was 44%, 63%, and 33% in the phenobarbital-, carbamazepine-, and valproate-treated children, respectively. Antiepileptic drugs significantly increase the level of lipoprotein (a), which is a major risk factor for atherosclerosis, and also have variable effects on other lipid parameters. Lipoprotein (a) levels should be closely followed in patients receiving antiepileptic drugs. (J Child Neurol 2006;21:70-74).

Severe ischemia of the glans penis following circumcision: a successful treatment via pentoxifylline.

Severe ischemia or necrosis of glans penis is rare. We report the case of an 11-year-old boy with severe glanular ischemia occurring 24 h after circumcision. This was successfully treated with pentoxifylline injection for 5 days, and while the black color of the glans penis changed to brownish at 48 h, appearances were close to normal at 5 days. The patient did not require any surgical intervention, and was discharged without sequelae. We suggest that pentoxifylline might be considered as a treatment of choice for severe ischemia of glans penis.

Currarino syndrome associated with penoscrotal inversion and perineal fissure.

We present an unusual case of Currarino syndrome with a mucosa-lined deep perineal fissure extending to the sacrum, penoscrotal transposition, perineal hypospadias, and a penile ventral skin defect. The child had a sigmoid diverting colostomy because of high anal atresia. Magnetic resonance imaging illustrated absence of the levator ani and muscle complex in the pelvis. At 15 months, perianal examination pointed out a fistula orifice and a sac related to the fistula at the left side of the perineal fissure. The fistula, a fluid-filled sac extending to the sacrum, and mucosa overlying the perineal fissure were removed en bloc. The neck of the sac was ligated and divided at the level of the distal sacrum. In the same session, a Glenn-Anderson procedure was performed for penoscrotal transposition, and the penile chordee was released. X-ray showed a bony deformity of the sacrococcygeal region in the shape of a scimitar. Histopathological examination demonstrated that the sac contained glial neuronal islands and nerve fibers. The boy has no neurologic deficits and seems to be well. To our knowledge, these associated malformations are extremely rare.

Two rare cases of the Pentalogy of Cantrell or its variants.

The Pentalogy of Cantrell (PC) is a rare association of defects involving the lower sternum, abdominal wall, diaphragm, pericardium and heart. We report two rare cases of the PC (variant form), showing fatal progression. Case 1 only survived two hours because of severe cardio-respiratory failure. Physical examination showed midline abdominal and thoracic defects, ectopic heart, pericardial defect, diaphragmatic defect, bilateral undescended testis, scoliosis, and adherence between left upper limb and trunk. In addition, the autopsy revealed diaphragmatic agenesia, intraabdominal testis, bilateral lung hypoplasia and lymphocytic meningitis. Case 2 only survived 15 minutes. In addition to the physical findings, including lower sternal defect, ectopic heart, epigastric omphalocele and scoliosis, the autopsy showed left diaphragmatic agenesia, pericardial agenesia, bilateral lung hypoplasia, deformed rib cage, anterior thoracic myeloschisis, adreno-hepatic fusion, left renal agenesia, meckel diverticulum and multiple accessory spleens. When comparing with other cases of PC, the concurrence of bilateral intraabdominal testis and lymphocytic meningitis in case 1, and adreno-hepatic fusion, anterior myeloschisis, meckel diverticulum, multiple accessory spleens, and renal agenesia in case 2 have not been described previously.

Does massive proximal small bowel resection influence prostaglandin E2 synthesis in the stomach and ileum during adaptive process in rats?

It is unclear whether massive small bowel resection (SBR) affects prostaglandin E2 synthesis in the gastrointestinal tracts. Thus the aim of this study was to investigate possible changes over tissue levels of prostaglandin E2 in the stomach and ileum after massive proximal SBR. Female Swiss-Albino rats underwent control operation (groups 1, 3, 5) or an 80% SBR (groups 2, 4, 6). The specimens were obtained during relaparotomy at 3 days in groups 1 and 2, at 9 days in groups 3 and 4, at 15 days in groups 5 and 6. Group 2 vs. groups 1 and 6, group 4 vs. groups 3 and 6 had significant increase in the levels of gastric acid (P < 0.01, P < 0.05, respectively). Gastric prostaglandin E2 levels markedly increased in group 2 compared to group 1 (P < 0.01). Ileal prostaglandin E2 levels showed to be significantly higher in group 6 when compared with groups 2, 4, and 5 (P < 0.05). Gastric acidity increased at 3 and 9 days, decreased thereafter at 15 days following massive proximal SBR. While resected rats had increased levels of gastric prostaglandin E2 at 3 days, ileal prostaglandin E2 was markedly elevated at 15 days. Therefore, we conclude that prostaglandin E2 may have a possible role in regulating intestinal adaptation at the end of the adaptive process, and contribute to cytoprotective barrier function in the ileum and stomach at early and late periods of the intestinal adaptation, respectively.

Bladder augmentation with an omental pedicled gastric seromuscular flap without the necessity of gastric resection.

Bladder augmentation using gastrointestinal segments requires gastric or intestinal resection. This has several risks. In a rat model, we aimed to test the efficacy of a new procedure in which a gastric seromuscular (GSM) flap is separated from the gastric mucosa without the necessity of gastric resection, and this GSM flap, based on an omentum pedicle, is transferred to the bladder. A GSM flap based on an omental leaf was dissected from the gastric mucosa and rotated 180 degrees counter-clockwise, after ligation of the vessels relating to the omentum, until the mid-duodenum. After urodynamic analysis for control levels of bladder capacity and pressure, the GSM flap was anastomosed to the bladder with a continuous suture. Because four rats died due to bladder calculi, only 21 of 25 rats were killed at 1 month (n = 10) and 4 months (n = 11) for histopathological and urodynamic evaluations of the augmented bladder. Bladder capacity increased significantly in the augmented bladders compared to preaugmentation (P < 0.001). There was no significant difference between end-filling pressures of the augmented bladders and preaugmentation. Histopathological findings demonstrated that the muscular surface of the flap was completely re-epithelialized in all rats. Squamous metaplasia was detected in 30% (3/10) of the 1 month group rats, and in 55% (6/11) of 4 month rats (P > 0.05). Gross calculi formation appeared in 20% (2/10) of the 1 month group rats, and in 34% (4/11) of 4 month rats (P > 0.05). Our data show that the use of the GSM flap in the bladder of a rat resulted in the complete re-epithelialization of the flap and sufficient bladder capacity. Despite significant complications such as death, metaplasia and calculi, this technique may be considered as an alternative experimental model to traditional full-thickness patching, which needs gastric or intestinal resection.

A rare case of esophageal atresia with gastric outlet obstruction.

Although the combination of gastric outlet obstruction and esophageal atresia is rarely seen in neonates, it has been well described. We report the case of a 5-day-old newborn with esophageal atresia and tracheoesophageal fistula associated with complete gastric outlet obstruction due to a mucous plug. As the patient had intense gastric distention, severe respiratory distress requiring ventilatory therapy and complete pyloric obstruction in radiograms, emergency gastrostomy was performed before definitive operation. Definitive treatment consisted of tracheoesophageal fistula ligation and primary esophageal anastomosis. Exploratory laparotomy during the same session revealed a normal pyloric canal, completely obstructed by a firm mucous plug. The plug was removed by pylorotomy, and a pyloroplasty was performed to ease gastric evacuation. Postoperative feeding problems suggested gastric dysmotility as the possible cause for the mucous plug obstruction.

The effects of pentoxifylline on renal function and free radical production in unilateral ureteral obstruction.

There is an ongoing discussion about ureteral obstruction-related renal dysfunction. In this study, we aimed to test the effect of pentoxifylline (PTX) on both kidneys in unilateral ureteral obstruction (UUO), and to determine its interaction of with prostaglandin E2 (PGE2), and diclofenac sodium (DIS). A sham operation was performed in group 1. Placebo, PTX, DIS, and PTX+DIS were administrated to groups 2, 3, 4 and 5, respectively. The left ureter was ligated in all groups except group 1. At 24 h, technetium 99m diethylenetriamine penta-acetic acid scintigraphy was performed to determine renal function. Additionally, the tissue levels of thiobarbituric acid reactive substances (TBARS) and PGE2 in both kidneys were measured to determine cytotoxic and cytoprotective mechanisms. When the ipsilateral kidneys were evaluated: (1) UUO significantly reduced DTPA uptake and none of the medications used prevented the reduction, (2) UUO significantly increased TBARS production, and only PTX prevented the increase, (3) UUO caused a significant increase in PGE2 production, and only DIS significantly decreased this. When the contralateral kidneys were evaluated: (1) UUO significantly increased DTPA uptake but DIS and PTX+DIS prevented this, (2) UUO significantly elevated TBARS levels and DIS and PTX+DIS caused an additional elevation, (3) UUO significantly increased PGE2 production, and only DIS prevented this. In conclusion, UUO caused ipsilateral renal hypofunction and contralateral hyperfunction, which are related to increased TBARS and PGE2 levels. PTX markedly decreased free radical activity in the ipsilateral kidney. While PTX showed a placebo effect, DIS prevented the compensatory contralateral renal response through increased TBARS and decreased PGE2 levels. The beneficial effect of PTX on the ipsilateral kidney, and the hazardous effect of DIS on the contralateral kidney may be explained by more complex interactions among TBARS, PGE2, PTX, DIS and UUO-related renal dysfunction.