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Biomedical subjects

M A Richardson

Publications and source records attributed to M A Richardson.

At least 19 recordsLinked to original sources
PubMed1992

Enhancing protein C interaction with thrombin results in a clot-activated anticoagulant.

Human protein C is a vitamin K-dependent plasma glycoprotein that circulates as an inactive zymogen. At the endothelial cell surface, thrombin in complex with the integral membrane protein thrombomodulin converts protein C to its active form by specific cleavage of an activation peptide. The activated form of protein C has potent anticoagulant activity as a feedback regulator of thrombin generation (reviewed in refs 4-6), and also has profibrinolytic, anti-ischaemic and anti-inflammatory properties. Protein C is effective in the treatment of model and human thrombotic diseases but, except when it has been used to treat genetic or acquired deficiencies and microvascular thrombosis, it is administered as the activated enzyme, which has a short biological half-life. We have altered two putative inhibitory acidic residues near the thrombin cleavage site, which results in a 30-fold increase in substrate utilization by alpha-thrombin. We combined these changes with a genetically altered glycoform to generate a zymogen protein C with a 60-fold increased cleavage rate by free alpha-thrombin, independent of its cofactor thrombomodulin. We show that this 'proform' of protein C, unlike the natural circulating zymogen, can be activated by thrombin generated in clotting human plasma, resulting in an inhibition of further clot formation. Our data therefore show that we have engineered a site-activated agent, which only has anticoagulant activity when significant amounts of thrombin are being generated.

Amino Acid Sequence↗
PubMed1992

Vertically fused tracheal cartilage. An underrecognized anomaly.

Anterior vertical fusion of the tracheal cartilages with normal pars membranacea is a rarely described tracheal anomaly. We report four cases of this anomaly, three associated with craniosynostosis syndromes and one with Goldenhar's syndrome. The anomaly was documented at postmortem examination in one case, both endoscopically and at tracheotomy in two cases, and endoscopically in one case. Documentation from gross postmortem photographs, photomicrographs, and intraoperative endoscopic photographs is presented so that the anatomical aspects of this anomaly can be thoroughly understood and recognized. All four newborn patients developed recurrent lower respiratory tract infections, reactive airway disease, and chronically retained secretions attributable to this anomaly. Neither tracheal stenosis nor stridor was encountered. In the three surviving patients, the infections grew less frequent and less severe in later childhood. These observations suggest that this tracheobronchial anomaly may be associated with a variety of craniofacial syndromes and may alter airflow dynamics in a way that predisposes to retained secretions and chronic pulmonary disease.

Abnormalities, Multiple↗
PubMed1992

Acute-phase reactants and acute bacterial otitis media.

OBJECTIVE: To determine if the erythrocyte sedimentation rate and C-reactive protein level are elevated in uncomplicated acute bacterial otitis media. DESIGN: Investigator-blinded, antibiotic efficacy trial. SETTING: The emergency department of an urban regional children's hospital with 24,000 annual visits. PARTICIPANTS: Thirty-one children with symptoms of acute bacterial otitis media of 7 days' duration or less. SELECTION PROCEDURE: Volunteer sample. INTERVENTIONS: Tympanocentesis, oral antibiotics for 10 days, and three follow-up visits in the next 30 days. MEASUREMENTS/RESULTS: The erythrocyte sedimentation rate and C-reactive protein level were obtained at time of entry into the antibiotic study. Seventeen patients (55%; 95% confidence interval, 37% to 72%) had either an erythrocyte sedimentation rate above 20 mm/h or a C-reactive protein level above 8 mg/L. Eleven patients (35%) had a recurrent episode of acute bacterial otitis media during the follow-up period. The relative risk of recurrence of otitis media given an elevated erythrocyte sedimentation rate or C-reactive protein level was 8.24 (95% confidence interval, 1.20 to 56.74; Fisher's Exact Test; P = .007). CONCLUSIONS: Clinicians who use elevated acute-phase reactants as possible indicators of invasive bacterial infections should be aware that an elevated erythrocyte sedimentation rate or C-reactive protein level is also consistent with acute bacterial otitis media. An elevated erythrocyte sedimentation rate or C-reactive protein level also appears to be associated with an increased risk of recurrence of acute bacterial otitis media. If these findings can be confirmed in a larger study, the erythrocyte sedimentation rate or C-reactive protein level could be used to assess the risk of recurrent otitis media.

Acute Disease↗
PubMed1992

Parental and family predictors of behavior problems in inner-city black children.

Studied contributions of maternal psychological distress, family stress load, maternal and family risk factors, and family coping strategies in predicting behavior problems in 441 inner-city black primary-grade children. Results indicated maternal psychological distress and high family stress load were associated with high child behavior problems. Family coping strategies offered no protection against risk, while coping with life difficulties by reframing them was detrimental to child behavioral adjustment. Active help-seeking strategies (i.e., family mobilization, acquiring social supports) served to moderate the effects of maternal psychological distress and family risk attributes for boys, but exacerbated the effects of dysfunctional maternal social and psychiatric histories for girls. Implications for understanding vulnerability and resilience in inner-city black children and recommendations for future research are discussed.

Adaptation, Psychological↗
PubMed1992

Impact of sinusitis in cystic fibrosis.

The cause of cystic fibrosis has been determined to be faulty ionic transport of chloride across the apical membrane of epithelial cells lining exocrine glands. The subnormal ionic transport leads to dehydration of extra cellular fluids and the development of thickened inspissated mucous secretions. The vast majority of patients with cystic fibrosis develop sinus disease with panopacification of the sinuses present in 90% to 100% of patients older than 8 months of age. Indications for surgical management of sinusitis in children with cystic fibrosis include (1) chronic nasal obstruction with mouth breathing, (2) chronic purulent draining nasal secretions unresponsive to medical treatment, and (3) persistent headaches thought to be related to sinusitis. Operative therapy is based on computerized tomographic scan findings and can be performed endoscopically. Postoperative management is critical for ensuring successful surgical results. Antibiotics, topical steroids, and cleansing of the surgical fields must be performed on a regular basis to ensure adequate healing. The impact of sinusitis on the cystic fibrosis population is significant. Approximately 20% of patients will eventually require surgical treatment of their sinuses. Chronic sinusitis may cause deformities of the external nasal skeleton, a loss of the sense of smell, and headaches.

Cystic Fibrosis↗
PubMed1992

Lidocaine effects on the laryngeal chemoreflex, mechanoreflex, and afferent electrical stimulation reflex.

The use of lidocaine hydrochloride as either a topical or intravenous agent has become a common practice for minimizing laryngospasm and the reflex cardiovascular effects resulting from upper airway manipulation. The efficacy and mechanism of action of lidocaine for this purpose remain unclear. We evaluated the effect of lidocaine on the laryngeal chemoreflex (LCR), mechanoreflex (LMR), and superior laryngeal nerve electrical stimulation adductor reflex (SLN-ESAR) in piglets. Cardiopulmonary responses were used to assess LCR and LMR. Latency following SLN stimulation was used to assess SLN-ESAR. Intravenous lidocaine hydrochloride at 3 mg/kg produced no suppression of the LCR, LMR, or latency (SLN-ESAR onset latency before lidocaine 11.7 +/- 0.7 milliseconds, after lidocaine 12.2 +/- 0.5 milliseconds; peak latency before lidocaine 13.2 +/- 0.2 milliseconds, after lidocaine 13.4 +/- 0.4 milliseconds). Topically applied lidocaine at the same dose eliminated both LCR and LMR responses in all animals, with return of reflex responses 15 minutes after application. No effect on the SLN-ESAR was seen with application of topical lidocaine. This study supports topical lidocaine as a suppressant of laryngeal mucosal neuroreceptors without central neural reflex effects. Intravenous lidocaine did not affect peripheral neuroreceptors, nor did it significantly affect the latency of the SLN-ESAR neural reflex arc. Intravenous and topical lidocaine differ in mechanism of action and efficacy with regard to modulation of reflex effects induced by laryngeal stimulation.

Administration, Topical↗
PubMed1991

Plasmid cloning vectors that integrate site-specifically in Streptomyces spp.

Cloning vectors based on the Streptomyces ambofaciens plasmid pSAM2 and the streptomycete phage phi C31 were developed for use in Streptomyces spp. These vectors replicate in Escherichia coli but integrate by site-specific recombination in Streptomyces spp. Both pSAM2-based and phi C31-based vectors transformed a number of different Streptomyces spp; however, the phi C31-based vectors consistently transformed at higher frequencies than pSAM2-based vectors. Southern analysis indicated that the phi C31-based vectors integrated at a unique site in the S. ambofaciens chromosome, while the pSAM2-based vectors gave complex patterns which could indicate structural instability or use of multiple loci. Both types of vectors utilize the apramycin (Am)-resistance gene which can be selected in E. coli and Streptomyces spp. with either Am or the commercially available antibiotic Geneticin (G418).

Blotting, Southern↗
PubMed1991

Cervicofacial cystic hygroma. Patterns of recurrence and management of the difficult case.

Cystic hygromas usually present in infancy or early childhood as compressible masses that may rapidly and intermittently enlarge. While they may arise in any anatomic location, hygromas of the head and neck are especially difficult to manage since enlargement may cause serious sequela such as airway obstruction, feeding difficulties, and speech pathology. Complete extirpation of these lesions is often impossible, and recurrence rates are accordingly high. We reviewed our 10-year experience in treating cervicofacial cystic hygromas. Of 34 patients, 21 had lesions cephalad to the hyoid and 13 had lesions caudal to the hyoid. While none of the 13 children with infrahyoid lesions demonstrated feeding or respiratory difficulties, eight of 21 children with suprahyoid involvement presented with dysphagia or airway compromise. The recurrence rates for infrahyoid and suprahyoid lesions were 15% and 81%, respectively. Those children with suprahyoid hygromas also experienced an increased operative complication rate compared with patients with infrahyoid involvement. Principles of management for suprahyoid and infrahyoid lesions are described, including the specific management of lingual, submandibular, parotid, and parotofacial hygromas.

Adolescent↗
PubMed1991

A comparison of anterior cricoid split with and without costal cartilage graft for acquired subglottic stenosis.

The use of the anterior cricoid split has allowed the extubation of multiple children who would otherwise require tracheostomy. Success, however, has been variable and difficult postoperative complications have occurred. Since 1981, 22 children at the Children's Hospital and Medical Center in Seattle, Washington have failed extubation because of subglottic disease as defined previously by Cotton and Seid. Two approaches have been used in managing the extubation of these children, one employing the anterior cricoid split and one employing the anterior cricoid split with immediate tracheoplasty using costal cartilage grafting. Immediate costal cartilage grafting resulted in fewer complications and a higher success rate in extubating patients with acquired subglottic stenosis.

Cartilage↗
PubMed1991

Neuroleptic use, parkinsonian symptoms, tardive dyskinesia, and associated factors in child and adolescent psychiatric patients.

OBJECTIVE: The authors' goal was to determine the prevalence of and risk factors for neuroleptic-induced movement disorders in a group of psychiatrically hospitalized children and adolescents. METHOD: They evaluated the presence or absence of parkinsonism, tardive dyskinesia, and akathisia in 104 children and adolescents who were in residence in or admitted over a 6-month period to a state-operated child psychiatric center. They applied a standardized, structured assessment procedure used in research on adult and geriatric psychiatric patients and the mentally retarded. RESULTS: The prevalence of parkinsonism among the 61 subjects at risk was 34% and was significantly associated with longer neuroleptic treatment periods immediately before evaluation. The prevalence of treatment-emergent tardive dyskinesia among the 41 subjects at risk was 12% and showed no association with quantitative neuroleptic treatment variables. However, patients with tardive dyskinesia were significantly more likely to have a family history of mental illness and significantly less likely to have a history of assaultive behavior. A pattern of complex pharmacological responses for parkinsonism and tardive dyskinesia, some of which are not typical of those most commonly reported in adults, was seen in this group of young patients. CONCLUSIONS: The study data highlight the acute sensitivity of the neuroleptic-treated child and adolescent to the development of parkinsonism, the possible role of certain patient characteristics in the vulnerability to develop tardive dyskinesia, and the possibility that neuroleptic-induced side effects experienced by children and adolescents differ in some ways from those experienced by adults. The data further strongly support the need for systematic monitoring of neuroleptic-treated child and adolescent patients for a full range of side effects.

Adolescent↗
PubMed1991

Behavioral audiometry.

Behavioral audiometry is based on observation of overt responses to controlled auditory stimuli, as contrasted with electrophysiologic procedures, which involve electrophysiologic monitoring or direct recording of the bioelectric correlates of the original signal. When reinforcement is added to the behavioral procedures, the infant or young child provides highly reliable responses, and it is possible to test most infants 6 months of age and older with these procedures. The combination of both behavioral and electrophysiologic procedures can resolve most clinical questions regarding the auditory function of young infants and children.

Acoustic Stimulation↗
PubMed1990

The social competence of children born prematurely: effects of medical complications and parent behaviors.

36-month-old, full-term children (n = 21) and low-birthweight (LBW) children of high (n = 25) and low (n = 23) medical risk status were observed in interactions with mothers in teaching and social context. Child compliance, self-directed behaviors, and problem behaviors were evaluated as well as associations among aspects of children's social competence, mothers' behaviors, and context factors. Degree of medical risk was associated with impairments in children's self-directed behavior and quality of response to maternal directives. Mothers of LBW children showed a smaller proportion of behaviors that provided choices compared to mothers of full-term children. Medical complications, children's cognitive status, and mothers' interactive behaviors were significantly associated with LBW children's social competence. Results of regression analyses suggested that mothers and LBW children influence each others' behavior in ways similar to mothers and full-term children in both teaching and social contexts.

Attention↗
PubMed1990

Cloning of spiramycin biosynthetic genes and their use in constructing Streptomyces ambofaciens mutants defective in spiramycin biosynthesis.

Several cosmid clones from Streptomyces ambofaciens containing the spiramycin resistance gene srmB were introduced into S. fradiae PM73, a mutant defective in tylosin synthesis, resulting in tylosin synthesis. The DNA responsible for this complementation was localized to a 10.5-kilobase EcoRI fragment. A 32-kilobase DNA segment which included the srmB spiramycin resistance gene and DNA which complemented the defect in strain PM73 were mutagenized in vivo with Tn10 carrying the gene for Nmr (which is expressed in Streptomyces spp.) or in vitro by insertional mutagenesis with a drug resistance gene (Nmr) cassette. When these mutagenized DNA segments were crossed into the S. ambofaciens chromosome, three mutant classes blocked in spiramycin synthesis were obtained. One mutant accumulated two precursors of spiramycin, platenolide I and platenolide II. Two mutants, when cofermented with the platenolide-accumulating mutant, produced spiramycin. Tylactone supplementation of these two mutants resulted in the synthesis of a group of compounds exhibiting antibiotic activity. Two other mutants failed to coferment with any of the other mutants or to respond to tylactone supplementation.

Chromosomes, Bacterial↗
PubMed1990

School performance, academic aspirations, and drug use among children and adolescents.

The relationship between drug use, school performance, and academic aspirations among 446 Anglo and Hispanic youths, age nine to seventeen, is explored. Two groups of subjects--current substance users and non-users--were interviewed. Subjects in each comparison group were similar in age, ethnicity, and gender. Overall results, consistent with prior research, indicate a significant relationship between current school performance, future educational aspirations, and drug use. No difference was noted between substance use groups on indicators of general interest in school work or probability of dropping out of school. Important differences in response patterns occurring with age, ethnicity, and gender were found.

Achievement↗
PubMed1990

Noma and noma neonatorum.

Noma and noma neonatorum are rare gangrenous diseases that result in mutilating loss of tissue in the oronasal region. Noma usually occurs in patients between the ages of 2 and 5 years who are malnourished, have suffered a precedent illness, or are in some way immunodeficient, or all of the above. The gangrenous slough is thought to be caused by a mixed infection of oral bacterial pathogens. The disease may be fatal when it occurs in a severely debilitated patient. Noma neonatorum produces somewhat similar appearing lesions in the neonate. The infectious organism is usually Pseudomonas and the disease is generally accompanied by a life-threatening pseudomonal sepsis. Both diseases are rare in North America. Patients with noma and noma neonatorum were treated at the Children's Hospital and Medical Center, Seattle, WA. We present these cases and a literature review.

Bacterial Infections↗
PubMed1989

Lack of platelet monoamine oxidase activity in Cebus monkeys (Cebus albifrons).

1. Recent evidence suggests that monoamine oxidase (MAO) plays an important role modulating the extrapyramidal syndromes produced by neuroleptic drugs in both human and nonhuman primates. 2. To evaluate the possibility of using peripheral blood platelet MAO-B levels as indices of central nervous system MAO-B effects, we measured platelet MAO-B levels in Cebus monkeys that were previously tested with neuroleptics (N = 36) or drug naive (N = 6). 3. No platelet MAO-B was consistently detectable in these blood samples. 4. Thus platelet measures of MAO-B do not reliably reflect brain MAO-B function in nonhuman primates and do not offer a useful model for studying blood-brain MAO-B relationships.

Animals↗
PubMed1989

Site-specific integration in Streptomyces ambofaciens: localization of integration functions in S. ambofaciens plasmid pSAM2.

In Streptomyces ambofaciens ATCC 15154, an 11.1-kilobase element, pSAM2, exists as a single integrated copy in the chromosome. In S. ambofaciens 3212 (a derivative of ATCC 15154), pSAM2 exists as a free, circular plasmid as well as an integrated element. BclI fragments from the free form of pSAM2 were cloned into an Escherichia coli plasmid vector. By using gene transplacement methods, the chromosomally integrated form of pSAM2 was marked with a gene coding for apramycin resistance. This enabled us to isolate both a segregant that had lost the integrated pSAM2 element and a cosmid clone containing integrated pSAM2 along with the flanking chromosomal sequences. One of the BclI fragments derived from free pSAM2 was shown to contain all the plasmid-specified information required to direct site-specific recombination in a derivative of S. ambofaciens lacking the resident pSAM2 element as well as in a number of other Streptomyces strains. The attachment sites used by the plasmid and the chromosome in site-specific recombination and the junctions created after integration were cloned and sequenced. Certain structural features in common with other integrating elements in actinomycetes were noted.

Base Sequence↗