Platelet-activating factor in infants at risk for necrotizing enterocolitis.

BACKGROUND: Platelet-activating factor (PAF) is a heterogeneous phospholipid that has been implicated as participating in a number of perinatal disease processes including necrotizing enterocolitis (NEC). METHODS: Baseline blood levels of PAF and related lipids (PAF-LL) were measured for 164 infants at risk for NEC from 3 neonatal intensive care units. Serial levels were obtained from the 11 infants in whom NEC developed. RESULTS: The mean peak PAF-LL in the infants without NEC was 2.03 +/- 1.96 ng/mL. Infants with stage II (n = 6) and III (n = 5) NEC had elevated peak PAF-LL values (mean peak value 13.6 +/- 6.9 ng/mL). No PAF-LL measurements obtained from infants during stage II or III NEC were <2.03 ng/mL. Three infants had PAF-LL elevations before the development of any clinical or radiographic evidence of NEC. PAF-LL level increased as the severity of NEC increased and decreased with its resolution. Setting a PAF-LL level of 10.2 ng/mL as a cutoff for NEC had a positive predictive value of 100%. CONCLUSIONS: PAF-LL determinations can complement clinical and radiographic studies to diagnose and follow the progression of NEC. PAF-LL may have a role in the evolution of NEC.

Endoscopic features of smooth muscle tumors in children with AIDS.

BACKGROUND: Smooth muscle tumors are the second most common malignancy encountered in children with acquired immunodeficiency syndrome (AIDS). This study reviewed the incidence and endoscopic appearance of smooth muscle tumors in the gastrointestinal tract of children with AIDS undergoing endoscopy. METHODS: Retrospective review of all endoscopic records (n = 70) of children with AIDS from August 1988 to December 1997 at a tertiary care inner city hospital. RESULTS: Three children with advanced AIDS (4%) were found to have smooth muscle tumors, all of which had the typical appearance of submucosal nodules with central ulceration. Some were hemorrhagic. They measured less than 1 to 4 cm in diameter. Two children had multiple tumors. All lesions except for one were located in the colon. Colonic biopsies revealed a leiomyoma in one patient and a smooth muscle tumor of uncertain malignant potential in another. The forceps biopsy of the single gastric mass was not deep enough to make the diagnosis of a smooth muscle tumor. A nonmalignant smooth muscle tumor grew from less than 5 mm to more than 4 cm in 1 year and was removed surgically. All three children are alive without any evidence of local spread or distant metastases despite no specific therapy for the smooth muscle tumor. CONCLUSIONS: Smooth muscle tumors in the GI tract of children with AIDS are relatively common. Further study of the long-term outcome for children infected with the human immunodeficiency virus who have these lesions are needed to establish prognosis and management guidelines.

Endoscopic features of intestinal smooth muscle tumor in a child with AIDS.

Intestinal leiomyosarcomas are exceedingly rare in immunologically intact children, except during infancy. While leiomyosarcomas account for less than 2% of all soft tissue tumors in childhood, they are the second most frequent malignancy in children with the acquired immunodeficiency syndrome (AIDS). In this cohort they are often located in unusual sites for primary soft tissue tumors. This report describes a young girl with advanced AIDS, referred for evaluation of abdominal pain, hematochezia, and wasting syndrome. Colonoscopy revealed two 1- to 2-cm submucosal nodules with central umbilication. Repeat colonoscopy 18 months later revealed no changes in these lesions. Biopsy revealed a submucosal spindle-cell lesion, with necrosis and cellular atypia. Initially it was characterized as a partially excised low-grade leiomyosarcoma. However, the final consensus diagnosis was smooth muscle tumor of uncertain malignant potential. Because of her advanced AIDS, there was no attempt at surgical resection or chemotherapy. Thirty-six months after initial referral, she remains alive without radiographic or clinical evidence of local extension or metastases. Additional data are required to determine the long-term outcome of these indolent submucosal tumors in the digestive tracts of children with AIDS.

Neonatal hypoperistalsis associated with perinatal zidovudine administration.

OBJECTIVE: This paper presents the cases of two infants exposed to perinatal zidovudine in whom hypoperistalsis and intestinal pseudoobstruction developed. STUDY DESIGN: Clinical case reports were prepared of two infants born to women infected with human immunodeficiency virus who were treated with perinatal zidovudine at a single inner-city medical school. RESULTS: None of the previously described causes for this rare condition contributed to the symptoms in these two infants. In addition, the symptoms resolved shortly after discontinuation of zidovudine administration. CONCLUSIONS: Although a strict cause-and-effect relationship between the medication and the impairment in intestinal peristalsis was not proved, awareness of this association should be helpful for physicians caring for infants exposed to perinatal zidovudine.

Hypergastrinemia, dysuria-hematuria and metabolic alkalosis: complications associated with gastrocystoplasty.

PURPOSE: To help determine the etiology and most appropriate treatment regimen for hypergastrinemia, dysuria-hematuria and metabolic alkalosis following augmentation gastrocystoplasty. MATERIALS AND METHODS: Two patients who presented with refractory metabolic alkalosis (1 with dysuria-hematuria) underwent extensive laboratory evaluation, complete upper gastrointestinal evaluation and intravesical pH probe placement. RESULTS: Both patients eventually required high dose oral potassium chloride supplementation. Bladder mucosal pH was not reflected by buffered urinary pH. Both patients demonstrated significant gastroesophageal reflux and diminished overall gastric acid output. CONCLUSIONS: Outpatient maintenance on potassium chloride supplementation may be warranted in select patients and appears to be preferable to histamine blockade or omeprazole. Postoperative screening esophagogastroscopy and an additional surgical maneuver might be indicated to prevent possible adverse sequelae of reflux esophagitis. Gastrocystoplasty may be an inappropriate operation in children with renal insufficiency who have not had metabolic acidosis.

NADPH-diaphorase activity in piglet intestinal mucosa.

The distribution of the enzyme synthesizing nitric oxide (NO) has been characterized in several mammalian enteric nervous systems. Two methods, immunohistochemical staining, employing anti-nitric oxide synthase antibodies, and histochemical localization of NADPH-diaphorase (NADPH-D), have given the same results. On the other hand, few studies have investigated nitric oxide synthase (NOS) in the gastrointestinal mucosa. Our study demonstrated the presence and distribution of the enzyme, NADPH-D, throughout all layers of the neonatal piglet intestinal tract. In the neonatal piglet, NADPH-D activity was found in nerve fibers parallel to the circular and to the longitudinal muscles and in the ganglion cells of Auerbach's plexus. However, the majority of NADPH-D activity was localized to the mucosa. Furthermore, the most intense activity in the mucosa was observed in villous epithelial cells. Other mucosal cells which were NADPH-D positive included the glandular epithelium and crypt cells. In addition, glandular epithelium in the deeper submucosa had very strong NADPH-D activity. Our results support the hypothesis that locally produced NO mediates physiological functions in the intestinal mucosa and submucosa.

Macrosialin, a macrophage-restricted membrane sialoprotein differentially glycosylated in response to inflammatory stimuli.

Rat monoclonal antibody FA/11 has been used to identify macrosialin, a sialoglycoprotein confined to murine mononuclear phagocytes and related cells. Originally identified as a macrophage-associated glycoprotein predominantly localized in intracellular membranes (Smith, M.J., and G.L.E. Koch. 1987. J. Cell Sci. 87:113), the antigen is widely expressed on tissue macrophages, including those in lymphoid areas, and is expressed at low levels on isolated dendritic cells. Immuno-adsorption experiments reported here show that macrosialin is identical to the major 87-115-kD sialoglycoprotein previously identified by lectin blotting in exudate but not resident peritoneal macrophages (Rabinowitz, S., and S. Gordon. 1989. J. Cell Sci. 93:623). Resident peritoneal macrophages express low levels of macrosialin antigen in a glycoform that does not bind 125I wheat germ agglutinin or 125I peanut agglutinin; inflammatory stimuli upregulate expression of this antigen (up to 17-fold), in an alternative glycoform that is detected by these lectins. Pulse-chase experiments reveal a 44-kD core peptide that initially bears high-mannose chains (giving Mr 66 kD) and is subsequently processed to a mature protein of Mr 87-104 kD. Each glycoform contains N-linked glycan, as well as O-linked sugar structures that show alternative processing. Poly-N-acetyllactosamine structures are detected in the exudate cell glycoform only. This new marker for mononuclear phagocytes illustrates two strategies by which macrophages remodel their membranes in response to inflammatory stimuli. Its predominantly intracellular location and restricted cell distribution suggest a possible role in membrane fusion or antigen processing.

Sonographic evaluation of portal hypertension in children.

Portal hypertension, an expected consequence of cirrhosis, often has an insidious course in children. A noninvasive technique using abdominal sonography has been previously employed by several investigators as a means of diagnosing this condition. Their technique involves sonographically measuring the diameter of the lesser omentum, which increases as a result of engorged collaterals. In this communication, the method is successfully employed in two children, an infant in whom cirrhosis developed who eventually died from acquired immunodeficiency syndrome, and one whose portal hypertension was relieved after orthotopic liver transplantation. Although successful in these two instances, the theoretical basis on which this technique is based is critically evaluated. Anatomical relationships are reviewed that would caution sonographers who attempt to duplicate these studies. Modifications of the technique that will minimize potential false positive results are also discussed.

Degradation of pigeon liver fatty acid synthetase in the absence of exogenous proteinases.

The homogeneity of pigeon liver fatty acid synthetase has been rigorously tested by physicochemical techniques and crossed-rocket immunoelectrophoresis. The enzyme has also been incubated for 1 h at 100 degrees C in 2% sodium dodecyl sulfate and 0.1 M dithiothreitol. The number of protein components on gel electrophoresis and of dansylated amino acids increased as a function of incubation time. Furthermore, the minor proteins observed after gel electrophoresis cross-reacted with antibody raised to the synthetase. Proteolysis was not chemically mediated by the detergent, the reducing agent or the buffer conditions chosen. Several commercially prepared proteins were not degraded by this procedure, and two proteins were recalcitrant to hydrolysis when included in the same incubation mixture as the synthetase. The inclusion of certain microbial proteinase inhibitors decreased the amount of degradation. This demonstrated that hydrolysis of the synthetase is mediated by a specific vertebrate enzyme which retains activity under denaturing conditions at 100 degrees C. Further degradation is also observed after individual treatment of four limited digestion products from the pigeon liver fatty acid synthetase, suggesting the possibility of an inherent proteolytic activity within the complex.

Limited elastase digestion of pigeon liver fatty acid synthetase with retention of all partial enzyme activities.

Pigeon liver fatty acid synthetase which contains two subunits of 240,000 daltons each has been treated with elastase. This treatment yields four protein fragments which can be separated on sodium dodecyl sulfate (SDS)-gel electrophoresis. After the subunit protein has been treated with elastase, all of the partial enzyme activities catalyzed by the complex are present, but enzyme activity for fatty acid synthesis is lost. The formation of protein fragments during proteolysis has been followed by densitometric scanning of the SDS gels. The results of these scans have suggested that (a) there are two peptide components present in the highest molecular weight band, (b) both are rapidly digested to yield the second and third largest peptides, and (c) a further cleavage of the third largest peptide gives rise to the smallest of the four major peptides. Crossed-rocket immunoelectrophoretic analysis of the four protein fragments has confirmed these conclusions and established also that the three smallest peptides are homogeneous. Each of the four peptides has been isolated by preparative SDS-gel electrophoresis, and antibody to one has been prepared. This antibody fraction immunotitrates overall fatty acid synthetase activity and immunoprecipitates the native enzyme. Immunoelectrophoresis of the four elastase-digested synthetase products against this antibody showed some cross-reactivity with a peptide that was neither the precursor nor the product of the immunogen. This cross-reacting antibody was removed by reaction with the nonrelated protein to yield antibody specific for one region of the fatty acid synthetase complex.