Giulio J. Barbero

Outcome of reflux therapy on pediatric chronic sinusitis.

OBJECTIVE The cause of pediatric chronic sinusitis is multifactorial, but nasal edema appears to be the initial pathologic step. The objective of this study is to evaluate gastronasal reflux as a possible cause of pediatric sinusitis. METHODS Thirty children with chronic sinusitis were believed to be appropriate candidates for functional endoscopic sinus surgery. Children were evaluated retrospectively for their response to reflux therapy with regard to their sinus symptoms and avoidance of sinus surgery. RESULTS Two of the 30 children were eventually excluded because they were taken to surgery for the specific purpose of contact point release. Chart review at 24-month follow-up indicated that 25 of the 28 children (89%) avoided sinus surgery. CONCLUSION After reflux treatment, the number of children requiring sinus surgery was dramatically reduced. The results of this preliminary pediatric study indicate that gastronasal reflux should be evaluated and treated before sinus surgical intervention.

The rapid, quantitative determination of neutral sugars (as aldononitrile acetates) and amino sugars (as O-methyloxime acetates) in glycoproteins by gas--liquid chromatography.

Abstract O -Methyloximes have been prepared from 2-amino-2-deoxy- d -glucose, - d -mannose, and - d -galactose. The acetates of these derivatives yield stable compounds which are readily separated quantitatively by gas-liquid chromatography on a number of polar phases. The above compounds along with the aldononitrile acetates of neutral sugars can be easily separated from one another on a single column in one chromatographic run. The procedures developed were tested on a number of glycoproteins of known composition as reported by other workers utilizing more classical methodologies, resulting in excellent agreement in terms of sugar composition. An improved method is also described for converting neutral sugars to oximes which can be either converted to the trimethylsilyl derivatives or, upon acetylation, derivatized to aldononitrile acetates.

Anxiety in children with recurrent abdominal pain and their parents

Abstract Multiple assessments of anxiety were completed for children with recurrent abdominal pain (RAP), behaviorally disordered (BD) children, and healthy children, as well as for their parents. Children and mothers in both the RAP and BD groups had higher levels of anxiety than existed in healthy families. Fathers of RAP children reported significantly more anxiety than fathers in the two comparison groups. These data support the clinical observation that families of children with RAP have high levels of anxiety.

The Chronically Reserpinized Rat as a Possible Model for Cystic Fibrosis. II. Composition and Cilioinhibitory Effects of Submaxillary Saliva

Extract: Submaxillary saliva was obtained from rats treated for 7 days with a daily dose of 0.5 mg/kg reserpine and from untreated controls. Secretory (volume) response, total protein, total carbohydrate, and Na+ and Ca++ concentrations were compared. After pilocarpine stimulation, saliva from treated animals showed significantly elevated concentrations of Na+, Ca++, total protein, and total carbohydrate. Total volume output was only 20% and maximum flow rate was 50% of those in control animals. A single injection of guanethidine (2 mg/kg) 30 min before stimulation increased the volume output and resulted in normal protein concentrations in saliva from reserpinized animals. Treatment of the animals with isoproterenol (5 mg/kg daily) for 7 days after three doses of reserpine also partially restored the volume response to pilocarpine, but resulted in higher protein outputs. The reverse treatment (isoproterenol followed by reserpine) did not change the volume output but resulted in even higher ratios of secreted protein per unit of gland weight. Stimulation of salivary secretion with isoproterenol resulted in very high protein concentrations and in a markedly increased total protein output in reserpinized animals. Both pilocarpine and isoprote-renol-stimulated saliva from reserpinized rats showed ciliostatic effects when added to gills of fresh water mussels. Such effects were similar to those produced by serum from patients with cystic fibrosis.Since a decreased secretory response and elevated concentrations of Na+, Ca++, protein, and carbohydrate have been found in submaxillary saliva of cystic fibrosis (CF) patients, the results obtained in these experiments suggest that the reserpinized rat may provide a potential animal model for studying the pathogenesis of the disease. This view is further supported by the demonstration of cilioinhibitory properties in the saliva of treated animals, which are similar to those of CF serum.Speculation: Treatment of rats with reserpine for 7 days results in elevations of Na+, Ca++, protein, and carbohydrate concentrations in submaxillary saliva secreted after a pilocarpine stimulus. These findings are similar to those reported in submaxillary saliva from CF patients after parasympathomimetic stimulation and suggest a possible model for the study of the secretory abnormality in the disease. The demonstration of ciliotoxic properties in saliva from the treated animals, which closely resemble those of CF serum, lends support to the concept of an animal model.

Sulfated sialyl-oligosaccharides derived from tracheobronchial mucous glycoproteins of a patient suffering from cystic fibrosis.

Thirteen novel oligosaccharides, each possessing both a sulfate ester and a sialic acid residue, were isolated from tracheobronchial mucous glycoproteins from a patient with cystic fibrosis via cleavage by alkaline borohydride treatment, and by employing immobilized Limulus polyphemus lectin affinity chromatography, SynChroprep AX300 anion-exchange chromatography, Bio-Gel P-2 size-exclusion chromatography, and Hypersil 120A APS-2 high-performance liquid chromatography (HPLC). Proposed structures for the resulting purified sulfated sialyl-oligosaccharides were based on carbohydrate/permethylation analyses, periodate oxidation, complete sequential exoglycosidase digestion, analysis of desulfated products and, analysis by positive-ion fast-atom-bombardment mass spectrometry (FABMS). Sulfate esters on these sialyl-oligosaccharides resided on C-6 of a terminal or an internal D-galactose or 2-acetamido-2-deoxy-D-glucose residue or C-4 of a terminal D-galactose residue. The sialic acid residues were found to be either bound (2-->6)-alpha to 2-acetamido-2-deoxy-D-galactitol or (2-->3)-alpha or (2-->6)-alpha to a D-galactose residue occupying a nonreducing terminus. For this group of oligosaccharides, ranging in size from tri- to hepta-saccharides, it was also observed that a sialic acid residue and a sulfate ester did not residue on the same oligosaccharide branch when more than one branch existed. On linear unbranched sulfated sialyl-oligosaccharides, the sialic acid residue was bound to a D-galactose residue occupying a nonreducing terminus with the sulfate ester residing on an internal D-galactose or a 2-acetamido-2-deoxy-D-glucose residue. These results demonstrate that it is possible for sialic acid and a sulfate ester to exist on the same oligosaccharide and that this oligosaccharide can be as small as a trisaccharide.

The chronically reserpinized rat as a possible model for cystic fibrosis. I. Submaxillary gland morphology and ultrastructure.

Extract: Submaxillary glands of rats treated with reserpine for 7 days showed striking morphologic changes when studied by light and electron microscopy. Grossly, the glands from treated animals were smaller and firmer than those from untreated controls. There was a marked accumulation of periodic acid-Schiff (PAS)-positive material in acinar cells and in the lumen of intralobular ducts, which appeared to be obstructed and distended by the precipitated material. In the acinar cells, this material occurred in discrete globules that coalesced at times, filling the acinar cytoplasm almost entirely and pushing the nuclei towards the periphery of the cell. The duct cells showed increased numbers of dark, discrete granules which did not stain with PAS, but colored with toluidine blue. In electron micrographs, the PAS-positive material that accumulated in acinar cells had a fibrillar appearance and there was a decrease in perinuclear rough endoplasmic reticulum in affected secretory cells. The increased mucopolysaccharide material is probably secretory material, as stimulation of the gland results in its partial disappearance. The observed changes were progressive and first became evident after 3 days of treatment with the drug. By the 7th day, the changes described were full blown and generalized. A similar obstructive exocrinopathy has been described in the submaxillary gland of patients with cystic fibrosis. These findings suggest that the chronically reserpinized rat may be a potentially useful model in evaluating the pathogenesis of cystic fibrosis.Speculation: Reserpine treatment for several days results in morphologic changes in the submaxillary glands of rats which are similar to the obstructive exocrinopathy reported in cystic fibrosis. These and other observations suggest that the reserpinized rat may be a useful model for the study of disorders of the mucus-producing glands.

Symptom outcome after functional endoscopic sinus surgery in patients with cystic fibrosis: A prospective study ☆ ☆☆ ★ ★★

Twenty-nine consecutive patients with cystic fibrosis were offered functional endoscopic sinus surgery. Twenty-six of these patients underwent surgery. A symptom questionnaire was obtained from the patient or parent before surgery. At the end of the study this symptom questionnaire was again administered to the same individual, and 21 completed it. There were 14 male and 7 female patients, with a mean age of 12.3 years and a median age of 8.7 years. Mean follow-up was 34.3 months. Results for the following symptoms were significant: nasal airway obstruction was improved (p < 0.0002), olfactory function was improved (p < 0.0037), purulent nasal discharge was decreased (p < 0.001), and activity level was increased (p < 0.001). Other parameters are also reported in the text. In summary, this study prospectively studies the effects of functional endoscopic sinus surgery on symptoms in patients with cystic fibrosis. The study points out several significant areas of symptom improvement and supports the selective use of functional endoscopic sinus surgery in patients with cystic fibrosis. Indications for surgery are provided.

A placebo‐controlled, double‐blind trial of the long‐term effects of albuterol administration in patients with cystic fibrosis

This placebo‐controlled study was designed to confirm a previously performed open label study that showed significant improvement in spirometry on maintenance therapy with albuterol for 1 year. In a double‐blind, cross‐over trial, albuterol (by metered dose inhaler) 180 μg b.i.d. or placebo were given for 6 months each. Spirometry was monitored at the start, and 3 and 6 months following initiation of each arm of the study. Peak expiratory flow rate (PEFR) was measured twice daily at home before and after study drug administration. Only patients with clinically detectable lung disease were enrolled.

Structural analysis of monosulfated side-chain oligosaccharides isolated from human tracheobronchial mucous glycoproteins.

To determine the location of some sulfate esters on respiratory mucins, an unambiguous sequencing strategy was developed for a crude, monosulfated oligosaccharide fraction derived from tracheobronchial mucous glycoproteins, isolated from sputum from a patient with cystic fibrosis, and which possessed Ricinus communis-I lectin affinity. Employing fractionation by Bio-Gel P-2 chromatography and high-voltage paper electrophoresis of the pool, eighteen branched and four straight-chained monosulfated oligosaccharides, each possessing at least one neutral D-galactose residue at a nonreducing terminus, were purified. Desulfated analogs of each sulfated oligosaccharide were then produced. Elucidation of their structures and sulfate ester locations was accomplished through a parallel comparative sequencing approach for the sulfated oligosaccharide and its desulfated analog. The method was based on their carbohydrate composition and parallel analysis by sequential exoglycosidase degradations, endoglycosidase digestion, permethylation analyses, and specific lectin affinities. Key to this approach was the inability for specific exoglycosidases and lectins to cleave or bind to, respectively, carbohydrates of their specificity which occupied nonreducing termini and possessed a sulfate ester. Herein we report the structures of twenty-two novel sulfated oligosaccharides. Oligosaccharides ranged from trisaccharides to heptasaccharides, were branched and unbranched, and each possessed a single sulfate ester on either C-6 of a terminal or an internal D-galactose residue or on C-6 of an internal residue of 2-acetamido-2-deoxy-D-glucose (N-acetyl-D-glucosamine).

Paranasal Sinus Mucoceles in Cystic Fibrosis

Six patients between the ages of 6 and 22 years old with cystic fibrosis were found to have mucoceles of the paranasal sinuses. Four were male and two were female. They experienced nasal obstruction, purulent rhinorrhea, and anosmia, but none had fever or pain. Nasal endoscopy and coronal computerized tomography scans revealed the lateral nasal wall to be displaced medially against the septum. Functional endoscopic sinus surgery revealed large cystic spaces filled with thick yellow-green mucus. Postoperatively most patients are able to smell and breathe through their noses. The mucocele probably begins as an obstructed anterior ethmoid cell, which then enlarges and obstructs the osteomeatal complex, which further impairs drainage of the other sinuses into this area.