Self-expanding intestinal expansion sleeves (IES) for short gut syndrome.

PURPOSE: Many disease processes (necrotizing enterocolitis, caustic esophageal injury, malrotation with volvulus), can result in short-gut syndrome (SGS), where remnant intestinal segments may dilate axially, but rarely elongate longitudinally. Here we mechanically characterize a novel model of a self-expanding mesh prototype intestinal expanding sleeve (IES) for use in SGS. METHODS: Gut lengthening was achieved using a proprietary cylindrical layered polyethylene terephthalate IES device with helicoid trusses with isometric ends. The IES is pre-contracted by diametric expansion, deployed into the gut and anchored with bioabsorbable sutures. IES expansion to its equilibrium dimension maintained longitudinal gut tension, which may permit remodeling, increased absorptive surface area while preserving vascular and nervous supplies. We performed mechanical testing to obtain the effective force-displacement characterization achieved on these prototypes and evaluated minimal numbers of sutures needed for its anchoring. Furthermore, we deployed these devices in small and large intestines of New Zealand White rabbits, measured IES length-tension relationships and measured post-implant gut expansion ex vivo. Histology of the gut before and after implantation was also evaluated. RESULTS: Longitudinal tension using IES did not result in suture failure. Maximum IES suture mechanical loading was tested using 4-6 sutures; we found similar failure loads of 2.95 ± 0.64, 4 ± 1.9 and 3.16 ± 0.24 Newtons for 4, 6 and 8 sutures, respectively (n = 3, n.s). Pre-contracted IES tubes were deployed at 67 ± 4% of initial length (i.l.); in the large bowel these expanded significantly to 81.5 ± 3.7% of i.l. (p = 0.014, n = 4). In the small bowel, pre-contracted IES were 61 ± 3.8% of i.l.; these expanded significantly to 82.7 ± 7.4% of i.l. (p = 0.0009, n = 6). This resulted in an immediate 24 ± 7.8% and 36.2 ± 11% increase in gut length when deployed in large and small bowels, respectively, with maintained longitudinal tension. Maintained IES induced tension produced gut wall thinning; gut histopathological evaluation is currently under evaluation. CONCLUSION: IES is a versatile platform for gaining length in SGS, which may be simply deployed via feeding tubes. Our results need further validation for biocompatibility and mechanical characterization to optimize use in gut expansion.

External carotid artery pseudoaneurysm following upper respiratory infection masquerading as a pharyngeal abscess in an 8-month-old.

Pseudoaneurysms are very rare with an incidence of less than 0.1% in the pediatric population. Approximately 30 cases of carotid artery aneurysms in children have been published in the literature, usually affecting children over one year of age. We present one of the youngest cases in the literature; the patient is an 8-month old female with a strep throat infection complicated by pseudoaneurysm development of the external carotid artery. Because of the rarity of these lesions, there is little known regarding the types of clinical presentation and management. They are commonly the result of direct arterial trauma; however, they can also occur secondary to infection, connective tissue disease or arteritis. We are presenting a case with a highly atypical presentation. When present, pseudoaneurysms harbor the potential risk of life-threatening hemorrhage and warrant immediate management. It is important to be aware of cases and the treatment modalities used to guide future diagnosis and planning.

The use of a hemoglobin-based oxygen-carrying solution (HBOC-201) for extracorporeal membrane oxygenation in a porcine model with acute respiratory distress syndrome.

OBJECTIVE: To evaluate whether hemoglobin-based oxygen-carrying solution (HBOC)-201 (Biopure) is an effective alternative to donor blood for extracorporeal membrane oxygenation support in a porcine model of acute respiratory distress syndrome (ARDS). DESIGN: Randomized animal clinical trial. SETTING: Animal surgical research laboratory. SUBJECTS: Immature Yorkshire swine were assigned to one of three groups: 1, noninjured animals, donor porcine blood primed circuit; 2, ARDS-injured, HBOC-201 primed circuit; or 3, ARDS-injured, donor blood primed. INTERVENTIONS: ARDS injury was induced in groups 2 and 3 with oleic acid infusion before bypass. All animals were placed on full venoarterial extracorporeal membrane oxygenation support for 8 hrs. MEASUREMENTS AND MAIN RESULTS: Physiologic variables and laboratory samples were measured at baseline and hourly for 8 hrs. Data analysis consisted of repeated-measures analysis of variance with post hoc analysis. We found that 100% of animals survived on extracorporeal membrane oxygenation for the duration of the study period. HBOC-supported animals had comparable oxygen delivery to both donor blood groups. Mean pulmonary artery pressure, heart rate, and lactate concentrations were higher in the injury groups. Blood pressure was mildly increased in HBOC animals (p <.05 vs. control animals). Methemoglobin concentrations in the HBOC group were elevated and increased over time on extracorporeal membrane oxygenation (p <.001). CONCLUSIONS: HBOC-201 appears to be an effective alternative circuit-priming agent for use during extracorporeal membrane oxygenation. HBOC offers the advantages of rapid availability and diminished donor blood cell exposure. The efficacy of HBOC in longer duration bypass, and its associated methemoglobinemia, need to be further investigated.

Progression of eIF4e gene amplification and overexpression in benign and malignant tumors of the head and neck.

BACKGROUND: The overexpression of eukaryotic initiation factor 4E (eIF4E) results in the up-regulation of gene products of mRNAs with long 5' untranslated regions (5' UTRs). The degree of gene amplification increases from the tumor free zone to the tumor core. This led the authors to hypothesize that the degree of eIF4E gene amplification and oncoprotein overexpression is progressive in the cells from normal head and neck tissue, to benign tumors, and eventually to invasive carcinomas (HNCA). METHODS: Using competitive polymerase chain reaction (PCR) and Western blot analysis, benign specimens from similar sites of 10 noncancer patients, 8 pleomorphic adenoma specimens, and 18 HNCA specimens were studied. DNA and protein extracts from each specimen were quantified for eIF4E gene copy number and level of eIF4E protein expression. RESULTS: There was no detectable eIF4E gene amplification and oncoprotein overexpression in benign tissue from noncancer patients (1.1 +/- 0.5 gene copy number [mean +/- standard deviation] and 0.9 +/- 0.5-fold protein elevation, respectively). Four of the eight pleomorphic adenomas analyzed showed eIF4E gene amplification of at least twofold, but none demonstrated protein elevation of any significance. In contrast, all HNCA specimens had detectable eIF4E gene amplification and protein overexpression. Furthermore, the mean degree of eIF4E gene amplification and overexpression was found to increase as cells from benign head and neck tissues (1.1 +/- 0.5 and 0.9 +/- 0.5), benign tumors (2.2 +/- 1.3 and 1.02 +/- 0.19), and HNCA (4.3 +/- 1.2 and 15.5 +/- 9.3) were compared. CONCLUSIONS: Progressive eIF4E gene amplification and overexpression were detected when normal tissues, benign tumors, and HNCA were compared. The degree of gene amplification and overexpression is variable within each tissue category. However, progression to malignant phenotype appears to be associated with an increasing degree of eIF4E gene amplification and overexpression.

Anal duct carcinoma: case report and review of the literature.

This report details the clinical course of two patients with true anal duct carcinoma. The incidence of this malignancy is low. The tissues of origination are the glands of the anal duct. The features that differentiate this tumor from the usual rectal carcinoma are prominent ductal structures, abundant mucin production with organized mucinous pools, and infiltration into the perirectal soft tissue. The clinical management of anal duct carcinoma remains a surgical challenge. The extent of surgical resection must be radical because of the infiltrative nature of the tumor. This report describes treatment of two patients with anal duct carcinoma. The first patient was a black woman with no previous history of rectal disease. Her operative procedure was an abdominoperineal resection with posterior vaginectomy. Nine months after initial surgery a local recurrence was resected. The second patient was a white man with a previous history of hemorrhoidectomy and anal fissure. He underwent an abdominoperineal resection but had positive dermal skin margins on permanent sections despite wide perirectal soft tissue resection. A secondary resection with confirmed clear margins of the skin was performed 2 weeks postoperatively. One management aspect of anal duct carcinoma that needs emphasis is the need for wide local excision of the perirectal soft tissues.

Pattern of amplification and overexpression of the eukaryotic initiation factor 4E gene in solid tumor.

BACKGROUND: An abundance of eukaryotic initiation factor 4E (eIF4E), a rate-limiting initiation component in protein synthesis of mRNAs with long 5'-UTRs, has been shown to upregulate a number of oncogene products. Elevation of eIF4E protein has been detected both in infiltrating ductal carcinoma of the breast (IDCA) and in head and neck squamous cell carcinoma (HNSCC) specimens. We hypothesized that malignant progression in solid tumor is associated with progressive eIF4E gene amplification and protein overexpression in cells sampled from the tumor-free resection margin, transition zone (area adjacent to cancer), and tumor core (center of tumor). MATERIALS AND METHODS: Thirty-eight resected specimens were evaluated: 10 IDCA, 13 HNSCC, and 15 benign specimens from similar sites of noncancer patients. IDCA and HNSCC specimens were divided into three different zones: (1) tumor core, (2) transition zone, and (3) tumor-free zone. Quantitative PCR for the eIF4E gene and Western blots for the eIF4E protein were performed on each of these zones and on the normal controls of benign tissue. Immunohistochemical staining was performed to localize the eIF4E protein overexpression in situ. RESULTS: The eIF4E gene was amplified in the tumor core of both IDCA (3.8 +/- 1.4, P < 0.05, Student's t test) and HNSCC (4.3 +/- 1.4, P < 0.05) specimens. Similarly, the eIF4E protein was overexpressed in the cells from these same sites (17.4 +/- 7.3- and 14.0 +/- 9.7-fold elevation, respectively, P < 0.0001). In the transition zone of IDCA and HNSCC, the degrees of eIF4E gene amplification (4.2 +/- 1.0 and 3.7 +/- 1.2, respectively) and overexpression (4.0 +/- 1.0 and 4.4 +/- 4.6, respectively) were intermediate. In contrast, the eIF4E gene copy number and protein level were near baseline in the tumor-free zone. CONCLUSIONS: Progressive eIF4E gene amplification and protein overexpression were present in cells sampled from the microscopically tumor-free margin to tumor core in surgical specimens of both HNSCC and IDCA. In this study, eIF4E gene amplification and protein overexpression appear to be associated with malignant progression in these two solid tumors.

Progressive amplification and overexpression of the eukaryotic initiation factor 4E gene in different zones of head and neck cancers.

PURPOSE: Eukaryotic initiation factor 4E (eIF4E) binds to mRNA as the initial rate-limiting step in protein synthesis. Amplification and overexpression of the eIF4E gene has been associated with malignant transformation. The objectives of this study were to 1) quantify the eIF4E gene in head and neck squamous cell carcinoma (HNSCC) specimens, 2) quantify eIF4E protein elevation and examine its association with eIF4E gene amplification, and 3) determine whether there is progression in eIF4E gene amplification and protein overexpression in the tumor-free resection margin, the transition zone, and the tumor core of HNSCC specimens. MATERIALS AND METHODS: Eighteen HNSCC specimens were divided into three zones: 1) tumor core; 2) transition zone; and 3) "tumor-free" margin. Competitive polymerase chain reaction was performed to determine eIF4E gene copy number. eIF4E protein expression was quantified using Western blot analysis. RESULTS: All 18 HNSCC specimens tested had significant eIF4E gene amplification (4.3+/-1.2; P < .05). In contrast, none of the 10 benign specimens from noncancer patients had any eIF4E gene amplification (1.1+/-0.5). In the 12 HNSCC specimens examined for the three zones, the tumor core and transition zone showed eIF4E gene amplification (5.2+/-1.1 and 3.5+/-0.9, respectively) compared with the "tumor-free" margin (2.1+/-1.1; P < .05). The tumor core and transition zone showed significant efF4E protein elevation (15.5+/-9.3, 4.4+/-4.6, respectively) compared with the "tumor-free" margin (0.9+/-0.5, P < .05). CONCLUSIONS: The eIF4E gene is amplified and overexpressed in HNSCC. Amplification and elevation of eIF4E were highest in the tumor core, intermediate in the transition zone, and lowest in the tumor-free margin. There appears to be progression of eIF4E gene amplification and overexpression from the "tumor-free" margin to the tumor core.

Competitive PCR to detect eIF4E gene amplification in head and neck cancer.

BACKGROUND: The protein eukaryotic initiation factor 4E (elF4E) binds to messenger ribonucleic acid (mRNA) as the initial step in protein synthesis. Overexpression of elF4E results in upregulation of specific proteins essential to cell growth and division. Overexpression of elF4E has been found in head and neck squamous cell carcinoma (HNSCC) and breast carcinoma. This study's purpose is to determine whether elF4E overexpression is present and associated with elF4E gene amplification in HNSCC. METHODS: Competitive polymerase chain reaction (PCR) was performed on eight HNSCC and seven intraoral benign lesions to determine the copy number of elF4E relative to a reference gene, gastrin. Western blots were performed to quantify elF4E protein expression. RESULTS: All eight HNSCC specimens demonstrated significant (p < .005) overexpression of elF4E protein (14.1+/-10.4) and elF4E gene amplification (4.5+/-1.2). Benign tissue did not exhibit elF4E protein overexpression or gene amplification. CONCLUSIONS: Overexpression and associated gene amplification of elF4E were present in HNSCC but not in benign tissue. Gene amplification of elF4E may be an important mechanism for elF4E overexpression.

Peritoneoscopic versus surgical placement of peritoneal dialysis catheters: a prospective randomized study on outcome.

The most commonly used technique for insertion of peritoneal dialysis (PD) catheters is open surgical approach by minilaparotomy. Percutaneous implantation via the peritoneoscopic technique is expanding. Studies have suggested that PD catheters placed peritoneoscopically have longer survival rate than surgically placed ones. However, these studies were not randomized, where the surgical group had more patients who were obese or had prior abdominal surgery, and therefore, the selection of patients may have biased the results. We conducted a prospective randomized study in which patients underwent PD catheter placement by either the surgical or the peritoneoscopic technique. In the period from October 1992 through October 1995, 148 double-cuff, curled-end, swan-neck PD catheters were placed in 148 patients. The outcome of the 76 patients in whom the PD catheters were placed peritoneoscopically was compared with that of the 72 patients in whom the catheters were placed surgically. Early peritonitis episodes (within 2 weeks of catheter placement) occurred in 9 of 72 patients (12.5%) in the surgical group, versus 2 of 76 patients (2.6%) in the peritoneoscopy group (P = 0.02). This higher rate of infection was most likely related to a higher exit site leak in the surgical group (11.1%) as compared with the peritoneoscopy group (1.3%). Moreover, peritoneoscopically placed catheters were found to have better survival (77.5% at 12 months, 63% at 24 months, and 51.3% at 36 months) than those placed surgically (62.5% at 12 months, 41.5% at 24 months, and 36% at 36 months) with P = 0.02, 0.01, and 0.04, respectively. We conclude that peritoneoscopically placed PD catheters have a longer survival rate than surgically placed ones. Furthermore, the rate of exit site leak and early infection is lower in the peritoneoscopic method.

Detection of eIF4E gene amplification in breast cancer by competitive PCR.

BACKGROUND: Initiation factor eIF4E binds to mRNA as the initial step for protein translation. Overexpression of the eIF4E oncoprotein has been found in breast cancer but not in benign breast tissue. The objective of this study is to determine if eIF4E oncoprotein overexpression is associated with eIF4E gene amplification in breast cancer using Western blots and competitive polymerase chain reaction (PCR). METHODS: Unknown concentrations of DNA extracted from breast specimens were amplified by PCR using a set of primers spanning intron 2/exon 3 of the eIF4E gene. In the same PCR tube, an internal control consisting of a known concentration of an eIF4E DNA template with 20-base pair (bp) deletion was used as the competitive reference standard (CRS) for competitive PCR. Gel electrophoresis of the PCR products was performed and the bands quantified by densitometry. eIF4E gene amplification was then determined relative to a nonamplified gene (gastrin). Using an anti-eIF4E rabbit antibody, Western blots were performed on benign and malignant breast specimens. Quantification was accomplished by developing blots with a color assay using nitro blue tetrazolium (NBT) and 5-bromo-4-chloro-3-indolyl phosphate (BCIP), scanned and analyzed by densitometry. RESULTS: Twenty-two breast specimens (14 cancer, 8 control) from patients were examined for eIF4E gene amplification and oncoprotein expression. In all fourteen specimens from stage I-III breast cancer patients, eIF4E overexpression was detected at 3- to 30-fold ( 16.71 +/- 7.83) elevations. Similarly, all 14 specimens demonstrated eIF4E gene amplification by competitive PCR (3.69 +/- 1.27). In the eight benign breast specimens examined, all were negative for eIF4E overexpression and gene amplification. CONCLUSIONS: Overexpression of eIF4E was associated with eIF4E gene amplification in breast cancer specimens. No overexpression or gene amplification was detected in benign breast tissues. eIF4E gene amplification may be one mechanism for eIF4E oncoprotein overexpression.

Septic complications after splenectomy for sickle cell sequestration crisis.

Patients with sickle cell disease (SCD) are predisposed to infections. There is a paucity of recent information on the incidence of post-splenectomy infectious complications in these patients. The purpose of this study was to determine whether splenectomy increases infectious complications in SCD. Twenty-nine patients with SCD had splenectomy for sequestration crises at our hospital between 1988 and 1992; 16 of them received all of their follow-up care at our institution. These 16 charts were reviewed for infectious-related admissions, hospital days, days of i.v. antibiotics, positive cultures, and episodes of sepsis. For each patient, these parameters in the pre- and postoperative period were compared and expressed as number per year. The mean age at time of splenectomy was 2.5 +/- 0.4 years and the mean follow-up was 4.5 +/- 0.4 years. There was no significant difference in the pre- and postoperative periods for admissions, hospital days, days of i.v. antibiotics, positive cultures, or episodes of sepsis per year. There were also no operative deaths. The incidence of pre-splenectomy sepsis was 0.04 +/- 0.03 episodes per year compared to 0.09 +/- 0.04 (P = ns) episodes/year after splenectomy. Sepsis occurred at an average of 20.8 (range 2-30) months postoperatively; Streptococcus pneumoniae was the most common causative organism. The total mortality after splenectomy in SCD patients was 3.4% (1/29) over a nearly 5-year period. Although infections are common in children with SCD, there was no increase in infections or episodes of sepsis in SCD patients who underwent splenectomy.

Inhibition of nitric oxide with aminoguanidine reduces bacterial translocation after endotoxin challenge in vivo.

BACKGROUND: Administration of lipopolysaccharide (LPS) has been shown to increase bacterial translocation (BT) in vivo and in vitro. In addition, LPS upregulates inducible nitric oxide synthase expression in the intestinal epithelium-a phenomenon that can either enhance microbial killing, or alternatively, promote BT by impairing the gut barrier. OBJECTIVE: To determine the effect, if any, of an inhibitor of nitric oxide synthase, namely, aminoguanidine (AG), on BT after LPS challenge. DESIGN: Sprague-Dawley rats were randomized to receive either AG or normal saline solution via subcutaneously placed osmotic pumps (Alzet), followed 18 hours later by LPS injection (5 mg/kg or 20 mg/kg intraperitoneally). Quantitative cultures of the cecum, mesenteric lymph nodes, liver, and spleen were obtained, and plasma nitrite and nitrate levels were measured at 24 hours. Transmembrane potential difference and mucosal permeability to fluorescein isothiocyanate-labeled dextran and fluorescein isothiocyanate-labeled Escherichia coli C25 were measured in the Using chamber. The intestinal membrane was examined by light, transmission electron, and confocal laser microscopy. RESULTS: Rats that were given high-dose LPS had elevated levels of nitrite and nitrate and a 100% incidence of BT. In contrast, AG infusion significantly reduced both BT (22%) and nitrite and nitrate levels. Animals that received LPS and normal saline solution had a significantly lower transmembrane potential difference than those that received LPS and AG. High-dose LPS resulted in sloughing of the apical enterocytes at the villus tips where bacterial entry seemed to occur, as seen with confocal laser microscopy. CONCLUSIONS: Inhibition of nitric oxide production with AG decreases BT after high-dose LPS challenge. The mechanism may involve increased cellular viability and decreased damage to the gut mucosal barrier in rats that receive AG.

Inflammatory cytokines, nitric oxide, and necrotizing enterocolitis.

Numerous theories have been proposed to explain the pathogenesis of necrotizing enterocolitis (NEC). Current evidence suggests that injury to the intestinal barrier as a result of various perinatal insults may facilitate invasion of the intestinal wall by bacteria. An inflammatory cascade ensues, characterized by local release of various cytokines that may contribute to further tissue destruction and hemodynamic instability in NEC. Molecular biological probes show increased expression of inducible nitric oxide synthase and interferon-gamma in the intestine of infants with NEC. Studies are planned to define the role of these inflammatory mediators in a rat model of NEC.

HLA in human serum--quantitation of class I by enzyme immunoassay.

A solid-phase, enzyme-linked immunoassay was used to quantitate the soluble fraction of HLA-class I. The sera of 318 individuals were studied, as well as the urine of six individuals with normal renal function. The stability of blood concentrations of the soluble HLA was also evaluated. The data justify the following six conclusions. (1) All normal people have circulating HLA (mean = 357 ng/ml). (2) The population can be divided into one group of low secretors (mean = 162.4 +/- 65.2 ng/ml) and another group of high secretors (mean = 540.7 +/- 185.9 ng/ml) (P less than 0.01). (3) Blood levels in each individual are reasonably consistent over short (days) and long (years) periods of time. (4) The mean concentration of soluble HLA-class I in all renal failure patients was 590 ng/ml, significantly higher than normal (P = less than 0.05); it was highest in patients on peritoneal dialysis (mean = 683 ng/ml) in spite of substantial chronic loss in peritoneal dialysate. (5) Renal allograft recipients with stable allograft function also had mean values greater than normal at 554 ng/ml (P less than 0.05). (6) Soluble HLA-class I was not detected in the urine of individuals with normal renal function.