PubMed Health⌕ Search

Biomedical subjects

R Cotton

Publications and source records attributed to R Cotton.

At least 19 recordsLinked to original sources
PubMed1991

A controlled trial of synthetic surfactant in infants weighing 1250 g or more with respiratory distress syndrome. The American Exosurf Neonatal Study Group I, and the Canadian Exosurf Neonatal Study Group.

BACKGROUND: Surfactant-replacement therapy is now recognized as a life-saving and safe intervention in small premature infants, but there is little evidence concerning its risks and benefits in larger premature infants. METHODS: We conducted a placebo-controlled, blinded trial in 1237 infants with respiratory distress who were enrolled at 23 hospitals in the United States and 13 hospitals in Canada. At entry all the infants weighed at least 1250 g, were receiving mechanical ventilation, and had a ratio of arterial to alveolar oxygen tension below 0.22. The initial dose of either the synthetic surfactant (Exosurf, 5 ml per kilogram of body weight) or air (the placebo) was administered less than 24 hours after birth, with a second dose given 12 hours later. A total of 614 infants were assigned to receive surfactant, and 623 to receive placebo. RESULTS: Fewer infants in the surfactant group than in the placebo group died before 28 days of age or survived at 28 days with bronchopulmonary dysplasia (7 percent vs. 12 percent, P = 0.002). In the first 28 days of life, there were fewer deaths due to respiratory distress syndrome in the surfactant group (1 percent vs. 3 percent, P = 0.043), lower overall neonatal mortality (4 percent vs. 7 percent, P = 0.04), and a lower incidence of bronchopulmonary dysplasia (3 percent vs. 6 percent, P = 0.008). There was also a significantly lower incidence of pulmonary air leaks, intraventricular hemorrhage, patent ductus arteriosus, seizures, hypotension, and pulmonary hypertension in the surfactant group. The infants treated with surfactant were weaned from oxygen and mechanical ventilation significantly sooner than those given placebo, and they less often required high-frequency ventilation or extracorporeal membrane oxygenation. The primary side effect observed more frequently among the infants who received surfactant treatment was pulmonary hemorrhage (six infants vs. one infant, P = 0.055). CONCLUSIONS: In infants weighing at least 1250 g at birth who have respiratory distress syndrome, treatment with two doses of synthetic surfactant improves survival and reduces perinatal morbidity.

Birth Weight↗
PubMed1990

Structural similarities among enzyme pterin binding sites as demonstrated by a monoclonal anti-idiotypic antibody.

BALB/c mice were immunized with a synthetic co-factor of the aromatic amino acid hydroxylases, 6,7-dimethyl-5,6,7,8-tetrahydropterin, conjugated to albumin. Hybridoma cell lines isolated from the immunized mice secreted monoclonal antibodies reacting specifically with the pterin molecule and monoclonal antibodies which were found to bind phenylalanine hydroxylase. Several lines of evidence were consistent with the anti-phenylalanine hydroxylase antibodies being anti-idiotype antibodies mimicking the pterin molecule and binding to the pterin binding site of phenylalanine hydroxylase. (a) An anti-idiotype monoclonal antibody, NS7, when reimmunized into mice produced anti-pterin antibodies consistent with NS7 being an internal image anti-idiotypic antibody. (b) NS7 antibody was prevented from binding to phenylalanine hydroxylase when a competitive inhibitor of phenylalanine hydroxylase enzyme activity, 6,7-dimethyl-7,8-dihydropterin, was bound to phenylalanine hydroxylase. (c) NS7 antibody was shown to bind to a wide range of pterin-requiring enzymes: phenylalanine, tyrosine and tryptophan hydroxylases, dihydropteridine reductase, dihydrofolate reductase, and sepiapterin reductase. Thus the NS7 antibody has successfully mimicked a common portion of the pterin cofactors utilized by these enzymes and demonstrated structure homology in their pterin binding sites despite their diverse function and little amino acid sequence homology except among the three aromatic amino acid hydroxylases.

Adrenal Glands↗
PubMed1990

Subglottic cysts in the premature infant.

Supraglottic cysts in the newborn are a well-recognized entity, but subglottic cysts have been rarely reported. Over the past 6 years we have observed subglottic cysts in nine patients with relatively long intubations from the neonatal intensive care unit of two university hospitals. Most frequently the patients were extubated and did well for weeks or months, but then they had progressive biphasic stridor. On endoscopy the patients had a subglottic stenosis that was irregular but with a smooth mucosal lining. Usually the cysts were apparent, but in two patients the mucosa was thickened and the patients were treated as a subglottic stenosis with tracheostomy. These subglottic cysts were recognized at the time of laryngotracheoplasty. In six patients the cysts were managed either by marsupialization with cup forceps, endoscopic diathermy, or carbon dioxide laser without recurrence. It is our belief that this condition is most likely due to scarring and obstruction of mucus glands of the subglottic area from prolonged intubation. This entity should be recognized and looked for in the neonate who has an acquired subglottic stenosis and should first be treated conservatively with endoscopic marsupialization.

Child, Preschool↗
PubMed1990

Identification of Pneumocystis carinii chromosomes and mapping of five genes.

Pulsed field gel electrophoresis was used to identify the chromosome-size DNA of Pneumocystis carinii, a major pathogen of immunocompromised patients. Thirteen chromosomes of rodent Pneumocystis carinii, ranging in size from 300 to 700 kilobases (kb), were identified. The minimum genome size for P. carinii, estimated on the basis of the sizes of chromosomes, is 7,000 kb. Genetic heterogeneity among different P. carinii isolates was documented by demonstration of chromosomal size variability. By hybridization studies, the genes for topoisomerase I, dihydrofolate reductase, rRNA, actin, and thymidylate synthase were mapped to single chromosomes of approximately 650, 590, 550, 460, and 350 kb, respectively. Hybridization studies further confirmed the genetic heterogeneity of P. carinii.

Actins↗
PubMed1990

Antagonists of bombesin/gastrin releasing peptide based on [D-Ala24]GRP(20-26)-heptapeptide. Modifications leading to potent analogues with prolonged duration of action.

Analogues of gastrin releasing peptide (GRP) and bombesin based on His-Trp-Ala-Val-D-Ala-His-Leu, the 20-26 heptapeptide sequence of [D-Ala24]GRP, have been synthesized and tested in vitro for their ability to inhibit GRP (18-27)-induced mitogenesis in Swiss 3T3 cells. Compounds identified as potent antagonists in this test system were also tested in vivo for their ability to inhibit bombesin-induced amylase secretion in rats. The Trp-Ala-Val sequence was found to be a very important feature of the antagonist activity; most substitutions in this region led either to much less potent or inactive analogues. In contrast, amino acid replacements in other parts of the molecule were more tolerated and sometimes led to marked increases in the in vitro and in vivo activity. The most potent analogues were obtained by replacing Leu26 by MeLeu and His25 by Lys(X) where X = Z, PhCO, PhCH2CO or Ph(CH2)2CO. Thus 4-pyridylcarbonyl-His-Trp-Ala-Val-D-Ala-Lys(CO-CH2-CH2-Ph)-Leu- NHMe (86) and 4-pyridylcarbonyl-His-Trp-Ala-Val-D-Ala-Lys(Z)-MeLeu-OMe (87) had IC50 values of less than 20 micrograms/kg s.c. in vivo, and their effects lasted for more than 3 hr.

Amino Acid Sequence↗
PubMed1989

N-isobutyryl-His-Trp-Ala-Val-D-Ala-His-Leu-NHMe (ICI 216140) a potent in vivo antaconist analogue of bombesin/gastrin releasing peptide (BN/GRP) derived from the C-terminal sequence lacking the final methionine residue.

The GRP receptor mediated growth response in Swiss 3T3 cells has been used to identify BN/GRP antagonists. Analysis of bombesin antagonism by substance P analogues and by truncated GRP analogues revealed that deletion of the C-terminal methionine residue was important for antagonism. Des-Met analogues showing potent antagonist activity in the in vitro 3T3 system (IC50 approximately 2nM) were synthesized. Further structural modification of these peptides led to the identification of (CH3)2CHCO-His-Trp-Ala-Val-D-Ala-His-Leu-NHCH3 (ICI 216140) which reduced bombesin-stimulated rat pancreatic amylase secretion to basal levels when administered subcutaneously at 2.0 mg per kg.

Amino Acid Sequence↗
PubMed1985

The use of [3H]-[D-Pen2,D-Pen5]enkephalin as a highly selective ligand for the delta-binding site.

The characteristics of the binding of [3H]-[D-Pen2,D-Pen5]enkephalin were determined in homogenates of guinea-pig and rat brain. In the guinea-pig, the maximum binding capacity for [3H]-[D-Pen2,D-Pen5]enkephalin was 4.19 pmol g-1 and the KD 1.61 nM. In the rat, the corresponding values were 2.47 pmol g-1 and 5.42 nM. In both species, the maximum binding capacity and the affinity were not altered when mu-binding was suppressed with [D-Ala2,MePhe4,Gly-ol5]enkephalin. The mu-agonists, [D-Ala2,MePhe4,Gly-ol5]enkephalin and morphine, displaced a small portion of the binding of [3H]-[D-Pen2,D-Pen5]enkephalin with high affinities.

Animals↗
PubMed1978

Carotid artery rupture. Management and prevention of delayed neurologic sequelae with low-dose heparin.

Carotid artery ligation, whether elective or an emergency, is an operation that most head and neck surgeons do with some trepidation because of the possible neurologic consequences. Of 440 major head and neck operations for cancer in which the carotid artery was exposed, 20 (4.5%) patients suffered a carotid rupture or had the vessel ligated just prior to rupture. We describe the typical patient and his management. Of these 20 patients, five died as a direct result of rupture or ligation, ten survived rupture and/or ligation with neurologic sequelae, and five survived rupture and/or ligation without neurologica sequelae. Of the ten patients with neurologic problems, four had immediate strokes, and six had delayed strokes, ie, these occurred greater than eight hours after ligation. Seven patients who required carotid artery ligation, separate from the previously mentioned group, received 5,000 units of heparin sodium subcutaneously every 12 hours in a prospective study. Of these seven patients, one died immediately postoperatively, and six survived without any neurologic sequelae. We discuss the cause of delayed neurologic problems and the rationale for the use of low-dose heparin.

Carotid Artery Diseases↗
PubMed1978

Middle ear ciliary defect in Kartagener's syndrome.

Patients with Kartagener's syndrome have shown electron photomicrographic abnormalities of nasal or bronchial cilia in addition to functional defects of mucociliary transport (immotile cilia syndrome). This report describes a boy with Kartagener's syndrome and chronic otitis media who demonstrates electron photomicrographic abnormalities of middle ear cilia, confirming the important role of cilia in providing protection against infection of the middle ear.

Child↗
PubMedDate not supplied

Distal tracheal compression.

The consultants concur that distal tracheal stenosis is a challenging problem in the pediatric patient but don't all agree on the presentation or management. Drs. Cotton and Crysdale agree that these children are usually seen with biphasic stridor. Dr. Parsons believes that biphasic stridor is not particularly common but inspiratory stridor is. The experts divide the differential diagnosis into intrinsic and extrinsic categories. Dr. Cotton lists tracheomalacia, complete tracheal rings and masses, such as an isolated hemangioma or granuloma. The usual extrinsic lesion is a vascular anomaly, the most common being an innominate artery. Dr. Crysdale's differential diagnosis includes tracheal stenosis, either congenital or acquired, and tracheomalacia. Vascular compression is most common as an extrinsic cause. Dr. Parsons includes tracheomalacia, complete tracheal rings, segmental tracheal stenosis, isolated masses, and vascular anomalies, such as an aberrant innominate artery. He also states that a tracheoesophageal fistula must be considered. Dr. Cotton prefers MRI and possibly a barium swallow for assessing vascular architecture. Even finding an air bronchogram on a chest x-ray can pinpoint an area of stenosis. The best test is direct laryngoscopy with video-photography. While Drs. Parsons and Crysdale agree that direct laryngoscopy is the best, Dr. Crysdale also suggests MRI or CT and adds that a contrast bronchogram is a most useful test.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Obstruction↗