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K M Edwards

Publications and source records attributed to K M Edwards.

At least 55 records · Page 3Linked to original sources
PubMed1999

Productive working relationships in the midst of change in health care.

Traditional lines of authority that once provided identity and meaning in health care are blurring as delivery organizations adapt to the challenges of controlling cost and providing quality service. Teams and committees tackle work that was once the realm of individual managers. Men and women at different levels of authority in the organization now work together to make decisions. Previous lines of authority in the health administration education setting are also blurring as colleges and universities, under pressure, respond to customer needs. Academia is increasingly drawing upon adjunct and non-tenure-eligible professionals to streamline departments and save money. Within the structure of a department, workers in these temporary positions have less authority than tenured and tenure-track faculty. They have less authority in the classroom as well. In both the health care industry and academia, women endure these changes more than their male counterparts, since women often assume the variety of flexible roles required by these strategies. Changes in traditional academic authority produce anxiety and stress for everyone involved. However, faculty can teach students a flexible paradigm to navigate and find meaning in these situations to ensure successful and productive working relationships between men and women in the changing workplace. This paper identifies the pertinent components of this paradigm and its application in the health administration classroom.

Competency-Based Education↗
PubMed1998

Haemophilus influenzae type b vaccines: history, choice and comparisons.

The conjugate Haemophilus influenzae type b (Hib) vaccines are safe and far more immunogenic among infants and young children than is the unconjugated H. influenzae type b polysaccharide. The vaccines differ in their immunogenicity when used for primary immunization of infants, and these differences appear to be predictive of efficacy, such that some vaccines might be more suitable than others in certain populations.

Antibody Formation↗
PubMed1998

Recombinant expression and characterization of the major beta-lactamase of Mycobacterium tuberculosis.

New antibiotic regimens are needed for the treatment of multidrug-resistant tuberculosis. Mycobacterium tuberculosis has a thick peptidoglycan layer, and the penicillin-binding proteins involved in its biosynthesis are inhibited by clinically relevant concentrations of beta-lactam antibiotics. beta-Lactamase production appears to be the major mechanism by which M. tuberculosis expresses beta-lactam resistance. beta-Lactamases from the broth supernatant of 3- to 4-week-old cultures of M. tuberculosis H37Ra were partially purified by sequential gel filtration chromatography and chromatofocusing. Three peaks of beta-lactamase activity with pI values of 5.1, 4.9, and 4.5, respectively, and which accounted for 10, 78, and 12% of the total postchromatofocusing beta-lactamase activity, respectively, were identified. The beta-lactamases with pI values of 5.1 and 4.9 were kinetically indistinguishable and exhibited predominant penicillinase activity. In contrast, the beta-lactamase with a pI value of 4.5 showed relatively greater cephalosporinase activity. An open reading frame in cosmid Y49 of the DNA library of M. tuberculosis H37Rv with homology to known class A beta-lactamases was amplified from chromosomal DNA of M. tuberculosis H37Ra by PCR and was overexpressed in Escherichia coli. The recombinant enzyme was kinetically similar to the pI 5.1 and 4.9 enzymes purified directly from M. tuberculosis. It exhibited predominant penicillinase activity and was especially active against azlocillin. It was inhibited by clavulanic acid and m-aminophenylboronic acid but not by EDTA. We conclude that the major beta-lactamase of M. tuberculosis is a class A beta-lactamase with predominant penicillinase activity. A second, minor beta-lactamase with relatively greater cephalosporinase activity is also present.

Drug Resistance, Multiple↗
PubMed1998

Safety and immunogenicity of heptavalent pneumococcal vaccine conjugated to CRM197 in United States infants.

OBJECTIVE: To determine the safety and immunogenicity of heptavalent pneumococcal saccharide vaccine (serotypes 4, 6B, 9V, 14, 18C, 19F, 23F) individually conjugated to CRM197 (PNCRM7), administered at 2, 4, 6, and 12 to 15 months of age. DESIGN: Two hundred twelve healthy 2-month-old infants were equally randomized to receive four consecutive doses of PNCRM7 or an investigational meningococcal group C conjugate vaccine, which served as a control. Concomitantly administered routine vaccines were oral polio vaccine and combined diphtheria toxoid, tetanus toxoid, and whole cell pertussis vaccine/Haemophilus influenzae type b vaccine consisting of capsular oligosaccharides conjugated to CRM197 (DTP/HbOC) at 2, 4, and 6 months, and either measles-mumps-rubella vaccine or HbOC at 12 to 15 months. Active safety surveillance was conducted for 3 days after each dose. Antibody concentrations to each of the 7 pneumococcal serotypes were measured by enzyme-linked immunosorbent assay prevaccination, after doses two and three, prebooster, and postbooster. RESULTS: Significantly fewer children experienced local reactions at the PNCRM7 injection site than at the DTP/HbOC site. There was no increase in the incidence or severity of local reactions at the PNCRM7 site with increasing doses of vaccine. Mild to moderate postvaccination fever was common in both the PNCRM7 and control vaccine groups, however DTP/HbOC was administered concurrently. All 7 vaccine serotypes were immunogenic. The kinetics of the immune responses were serotype-specific. After three doses of PNCRM7, between 92% to 100% of children had >/=0.15 microg/mL of antibody, and 51% to 90% achieved a level of >/=1 microg/mL against specific serotypes. A booster dose of PNCRM7 resulted in a brisk anamnestic response to all 7 vaccine serotypes, demonstrating effective stimulation of T-cell memory by the primary series of vaccinations. CONCLUSION: Primary immunization followed by a booster dose of PNCRM7 seemed to be acceptably safe and resulted in significant rises in antibody to all 7 serotypes. Implications. Studies to assess vaccine efficacy of PNCRM7 for prevention of systemic disease, nasopharyngeal colonization, and acute otitis media are in progress. If PNCRM7 proves to be protective, there is the potential to prevent up to 85% of invasive pneumococcal disease occurring in US children.

Antibodies, Bacterial↗
PubMed1998

Varicella-zoster.

Explore the source record for details and available documents.

Chickenpox↗
PubMed1997

Combination vaccines consisting of acellular pertussis vaccines.

Combination vaccines consisting of multiple vaccine antigens delivered in a single injection simplify vaccine administration. Combining multiple antigens into one injection, however, presupposes that the administration of multiple vaccines in combination will not reduce the safety and immunogenicity of the component vaccines. New generation vaccines seek to combine many more antigens from multiple, different pathogens, making them difficult to study in controlled, double blind, randomized clinical trials because of the number of study arms required for complete evaluation. Methods to simplify studies of combination vaccines include building on the framework of earlier studies to calculate sample size and reduce the number of control arms, standardizing serologic assays and assessment of adverse reactions and determining serologic correlates of protection to minimize the need for multiple efficacy studies and to facilitate evaluation of immunogenicity studies. Preliminary data indicate that immune responses to combination vaccines including diphtheria-tetanus-acellular pertussis, hepatitis B and inactivated poliovirus are comparable with those seen when the vaccines are administered separately. In contrast studies of combination vaccines that include Haemophilus influenzae type b Hib antigens show a diminished Hib antibody response, although the clinical relevance of this lowered antibody response has not yet been determined. Numerous small safety studies of combined vaccines have not found evidence of increased adverse reactions.

Clinical Trials as Topic↗
PubMed1997

Prevalence of positive serology for acute Chlamydia pneumoniae infection in emergency department patients with persistent cough.

OBJECTIVE: To determine the prevalence of acute Chlamydia pneumoniae infection in ED patients presenting with a persistent cough. METHODS: This was a case series consisting of a convenience sample of 65 patients > or = 18 years of age who presented with a chief complaint of a cough lasting > or = 2 weeks. Patients were treated in the ED of an urban university hospital. Patients with immunosuppression, lung disease, pneumonia, or a cough lasting > or = 3 months were excluded. Acute and convalescent sera were assayed for antibody to C. pneumoniae. Subjects with C. pneumoniae antibody titers showing a fourfold rise in either immunoglobin M (IgM) or immunoglobin G (IgG) antibody, an IgM titer of > or = 16, or an IgG titer of > or = 512 were considered to have evidence of acute C. pneumoniae infection. RESULTS: Thirteen (20%; 95% CI, 11% to 32%) of the 65 subjects had serologic evidence of acute C. pneumoniae infection. Except for an increased rate of fever, clinical signs and symptoms and laboratory studies did not differentiate those who had C. pneumoniae from those who did not have the disease. Patients diagnosed as having Bordetella pertussis or Mycoplasma pneumoniae infection did not have serologic evidence of concurrent C. pneumoniae infection. CONCLUSIONS: C. pneumoniae infection appears to be associated with a persistent cough in ED patients. Clinicians should consider this organism when evaluating these patients. It is unclear whether antibiotic therapy is indicated for these patients. If antibiotics are used, a tetracycline or macrolide antibiotic would be most appropriate.

Adolescent↗
PubMed1997

Expression of an antisense hla fragment in Staphylococcus aureus reduces alpha-toxin production in vitro and attenuates lethal activity in a murine model.

Isogeneic bacterial strains that differ only in the production of a single microbial factor have been invaluable in studying the pathogenesis of bacterial infections. The targeted, intentional inactivation of a gene encoding a potential virulence determinant generally requires homologous recombination to replace the gene with an inactivated allele. To determine whether the insertion and expression of a fragment of a bacterial gene in an antisense orientation could be used as a rapid alternative to allelic inactivation for producing paired isogeneic isolates, we inverted a 600-bp fragment of the Staphylococcus aureus gene encoding alpha-toxin, hla, behind its native promoter on an Escherichia coli-S. aureus shuttle vector. A transformant of an S. aureus strain carrying the antisense hla fragment produced antisense hla RNA and made 16-fold less alpha-toxin than either its parent or an isogeneic transformant containing vector DNA without hla. Also, intraperitoneal injection of 1.5 x 10(9) CFU of the antisense hla-containing transformant was significantly less lethal in a murine model than that of the parent (1 of 10 versus 7 of 10 mice expired [P < 0.02]) or the transformant without hla (1 of 10 versus 7 of 7 mice expired [P < 0.001]). We conclude that the expression of a fragment of hla in an antisense orientation in S. aureus on a plasmid vector reduces alpha-toxin production and the lethal activity of the strain in a murine model. The antisense strategy for creating isogeneic strains of bacteria may facilitate molecular investigations into the pathogenesis of infection. It also may be useful in creating novel live-attenuated strains of bacteria for use as vaccine candidates.

Animals↗
PubMed1997

A safety and immunogenicity comparison of 12 acellular pertussis vaccines and one whole-cell pertussis vaccine given as a fourth dose in 15- to 20-month-old children.

OBJECTIVE: To compare the safety and immunogenicity of 12 different acellular pertussis vaccines combined with diphtheria and tetanus toxoids (DTaP) with one licensed diphtheria, tetanus, and whole-cell pertussis vaccine (DTwP) as a fourth-dose booster in children who had previously received DTaP or DTwP primary vaccinations. METHODS: Healthy 15- to 20-month-old children were enrolled at six National Institutes of Health Vaccine Treatment and Evaluation Units. All had been randomly assigned to receive three primary doses of DTaP or DTwP at 2, 4, and 6 months of age as part of an earlier National Institutes of Health multicenter trial of DTaP vaccines in the same Vaccine Treatment and Evaluation Units. Parents recorded the occurrence and magnitude of fever; irritability; and injection site redness, swelling, and pain for 3 days after vaccination. Sera obtained before and 1 month after the booster vaccination were analyzed for antibody to pertussis toxin (PT), filamentous hemagglutinin (FHA), fimbriae (FIM), and pertactin (PRN). Diphtheria and tetanus toxoid as well as PT neutralizing (Chinese hamster ovary cell) and whole-cell agglutinating antibodies were measured on a subset of sera. RESULTS: A total of 1293 children contributed fourth-dose reaction data. Reactions were less frequent after DTaP than after DTwP. For children vaccinated with a fourth dose of DTaP, which was the same DTaP as received in the primary series, fever and injection site redness, swelling, and pain increased in prevalence compared with the third dose in the primary series. For children receiving DTaP as a fourth dose, injection site redness and swelling occurred more frequently in DTaP-primed than in DTwP-primed children. Variation in the occurrence of reactions among DTaP vaccines was observed. A total of 1160 paired pre- and postvaccination sera were available for analysis. Serum antibody concentrations before boosting were lower than those obtained 1 month after the primary immunization. After the fourth dose, significant increases in antibodies directed against the included antigens were observed for all vaccines; postbooster vaccination antibody titers differed significantly among the DTaP vaccines. For children primed and boosted with the same DTaP, antibody levels were not directly related to the quantity of antigen included for PT, FHA, and FIM; for PRN, there was a closer relationship. Some DTaP vaccines given as fourth-dose boosters elicited antibody to PRN or FIM in some vaccinees, although the DTaP vaccines were not reported to contain these antigens; these responses were observed more frequently in DTwP-primed children. Agglutinin antibody rises were observed in all groups immunized with four doses of a DTaP vaccine containing FHA or PRN, regardless of whether the vaccine included FIM. Diphtheria and tetanus antibody levels exceeded the presumed protective concentration (0.1 IU/mL for diphtheria and 0.01 IU/mL for tetanus) after the fourth dose for all vaccinees. CONCLUSION: Although differences were observed in reaction rates among the DTaP vaccines given as a fourth dose, the DTaP vaccines were, in general, associated with fewer adverse events than a US-licensed DTwP. For DTaP vaccines, fever; irritability; and injection site pain, redness, and swelling occurred more frequently after the fourth dose than after the third dose of the same vaccine in the primary series. No DTaP was consistently most or least reactogenic or immunogenic. Although serologic correlates of pertussis immunity are not defined, it is clear that most DTaP vaccines can stimulate comparable or higher serum antibody responses than DTwP for those antigens contained in the vaccine.

Antibodies, Bacterial↗
PubMed1997

Twenty years of outpatient respiratory syncytial virus infection: a framework for vaccine efficacy trials.

BACKGROUND: Respiratory syncytial virus (RSV) is the most important viral respiratory pathogen of infancy and childhood. Much has been written about inpatients with severe disease. Inpatients, however, represent only a minority of RSV-infected children. We studied the characteristics of symptomatic outpatient RSV infection in healthy children to gain a better understanding of RSV disease and to provide a background for the testing of intervention strategies in children without high-risk conditions. METHODS: A total of 1113 children were followed during 20 consecutive RSV seasons. Signs and symptoms of respiratory infection were monitored. Cultures were obtained for febrile upper respiratory infection, acute otitis media, and lower respiratory infection (LRI). Rates of febrile upper respiratory infection, acute otitis media, LRI, and hospitalization were calculated. Given those rates, numbers of children needed to demonstrate efficacy of a vaccine product were calculated. RESULTS: Mild disease from RSV infection lacked some of the classic features of RSV infection seen in hospitalized children. Involvement of the lower respiratory tract was, however, noted to be much higher in RSV infection than it was in infection with other viral respiratory pathogens. LRI was, therefore, considered the best candidate endpoint for vaccine trials. A product with 60% efficacy could be proven, with a power of 0.8, to be efficacious with as few as 1500 infants. CONCLUSIONS: RSV infection is common and often involves the lower respiratory tract, even in outpatients. Our 20-year study of RSV infection provides a basis for calculation of sample sizes to be used in trials of vaccine candidates.

Ambulatory Care Facilities↗
PubMed1997

Comparison of serological results in the NIAID Multicenter Acellular Pertussis Trial with recent efficacy trials.

Comparison of the serological results from the NIAID-funded Multicenter Acellular Pertussis Trial (MAPT) and the efficacy trials are complicated by differences in assay methods, immunization schedules, vaccine lots and populations immunized. In spite of these differences, serological results closely approximating those obtained in the MAPT were found for most or all of the assayed antibodies in the Mainz and Erlangen studies. Serological results for some of the antigens included in the vaccines used in the Italian and Stockholm trials were similar to the MAPT results, while significant differences were noted with other antigens. Differences in immunization schedules and serological assay methods made comparisons between MAPT and the Gothenburg and Senegal trials more difficult. Our understanding of the efficacy trial results, and our ability to apply those results to the U.S. population, would be enhanced markedly by simultaneous re-analysis of stored sera from MAPT and selected efficacy trials. This goal should be given priority by the study organizers and sponsors.

Clinical Trials as Topic↗
PubMed1996

Prevalence and incidence of adult pertussis in an urban population.

OBJECTIVES: To determine the prevalence of Bordetella pertussis infection among adults who have prolonged cough for 2 weeks or longer and to estimate the incidence of B pertussis infection in adults in a defined urban population. DESIGN: A prospective clinical study. SETTING: Kaiser Permanente, San Francisco (Calif) Medical Center. PARTICIPANTS: One hundred fifty-three referred and participating health plan members 18 years old or older with the complaint of cough persisting for 2 weeks or longer and 154 health plan members 18 years old or older with no cough for the past 3 months (controls) were enrolled. Medical records for an additional 100 patients randomly sampled from 676 patients 18 years old or older with an ambulatory diagnosis of cough (60 with prolonged cough) were also reviewed. MAIN OUTCOME MEASURES: Prevalence of adult pertussis as determined by enzyme-linked immunosorbent assay IgG antibody levels to pertussis toxin in individuals with prolonged cough for 2 weeks or longer and the incidence of adult pertussis in San Francisco Kaiser health plan members. RESULTS: The prevalence of adult pertussis was 12.4% of the participating referrals. The incidence of adult pertussis was estimated to be 176 cases per 100 000 person-years (95% confidence interval, 97 to 255 cases). CONCLUSIONS: Adult pertussis is a significantly greater public health threat than previously suspected. Booster doses of acellular pertussis vaccine after 7 years of age may be an effective approach to minimize transmission and infection.

Adult↗