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Biomedical subjects

R M McKinney

Publications and source records attributed to R M McKinney.

At least 19 recordsLinked to original sources

Growth velocity assessment in paediatric AIDS: smoothing, penalized quantile regression and the definition of growth failure.

The analysis of growth records in paediatric anti-HIV clinical trials plays an important role in trial evaluation. Growth failure may be a manifestation of progressive disease or treatment toxicity, and is commonly specified as a major trial outcome event indicating poor treatment performance. Despite new therapeutic advances against HIV proliferation in infected patients, accurate monitoring and interpretation of somatic growth in paediatric AIDS remains clinically important, in light of uncertainties regarding relationship between viral load reductions and achievement of favourable somatic growth profiles. Our aim in this paper is to construct a criterion for growth failure that discriminates patients whose risk of death subsequent to growth failure is elevated to a clinically significant degree. To construct the criterion, individual growth curves and velocities are modelled using loess smoothing, penalized likelihood quantile regressions are fit to model age-specific growth velocity distributions for gender-stratified cohorts, and proportional hazards model selection is conducted to identify features of velocity series that are informative on the survival distribution. The resulting growth-failure criterion is expected to be useful for disease staging in resource-limited medical environments where T-cell counts and viral load measures are unavailable.

Adolescent↗

Pricing of hospital services: issues and some propositions.

Pricing in relation to tangible products has been studied at great lengths by both economists and marketers. The pricing of services has received less attention. Only a few studies concerning pricing in the health care area have been conducted. A review of relevant pricing issues concerning services, and particularly health care, is presented. Several limitations of an existing pricing model for hospitals are discussed. Improvements are proposed.

Economic Competition↗

Community-acquired Legionnaires' disease associated with a cooling tower: evidence for longer-distance transport of Legionella pneumophila.

In the period August 10-29, 1986, 29 confirmed cases of Legionnaires' disease occurred in Sheboygan, Wisconsin; two cases were fatal. No common source of indoor exposure was identified. Water specimens were obtained from all known cooling tower units in Sheboygan; Legionella pneumophila serogroup 1 was isolated at 1 x 10(6) colony-forming units per liter from a specimen obtained August 27 at plant A. This isolate was identical to the only clinical isolate by monoclonal antibody and isoenzyme subgrouping. Of 29 persons with Legionnaires' disease, 21 lived or worked within one mile (1.6 km) of plant A; seven of the remaining eight visited within one to two miles (1.6 to 3.2 km) of plant A from three to seven days before onset of illness. Attack rates were highest for persons living within 0.5 mile (0.8 km) of plant A. These findings associate a cooling tower with community-acquired Legionnaires' disease and suggest that dissemination of Legionella may occur over longer than previously recognized distances.

Adult↗

Antigenic and genetic variation in Legionella pneumophila serogroup 6.

Legionella pneumophila subsp. pneumophila serogroup 6 is second in importance only to L. pneumophila serogroup 1 as a cause of legionellosis. Monoclonal antibody (MAb) reactivity and multilocus enzyme electrophoretic analyses were used to subtype serogroup 6 isolates as a potential aid for epidemiologic and virulence studies. Forty-eight serogroup 6 isolates submitted to the Centers for Disease Control from 1980 to 1985 were examined by these methods. The isolates were divided into two groups based on differential reactivity with two MAbs. Thirty-two of the isolates were of a single electrophoretic type (ET) and were reactive with both MAbs. The remaining 16 isolates were distributed among 10 ETs and were reactive with one or both MAbs. The mean genetic diversity for serogroup 6, as determined from the degree of variability at 20 enzyme loci, was found to be essentially the same as that for L. pneumophila subsp. pneumophila as a whole. The ETs of serogroup 6 isolates were unique but closely related genetically to the ETs of L. pneumophila subsp. pneumophila serogroups 1 to 5, 7, and 8. The range of serogroup 6 subtypes distinguished by MAbs and enzyme electrophoresis suggests that the combination of these two methods can be useful as a typing system.

Animals↗

Two-site monoclonal antibody quantitative ELISA for toxic shock syndrome toxin-1.

A two-site monoclonal antibody (MAB) quantitative enzyme-linked immunosorbent assay (ELISA) was developed that enables quantitation of toxic shock syndrome toxin-1 (TSST-1) down to 0.25 ng/ml and detection of TSST-1 to 0.06 ng/ml. Interference by Staphylococcus protein A was eliminated by incorporating normal rabbit serum into the test sample diluent. In the process of selecting an MAB pair for a two-site 'sandwich'-type ELISA, the MABs were screened for inhibition or common epitope binding. Some MABs that reacted with antigen that was adsorbed to a polystyrene well would not bind to antigen that was presented in a more natural configuration, as in the case of antigen immobilized by trapping antibody. Conversely, MABs that reacted with antigen that was immobilized by another antibody did not all function as trapping antibodies when adsorbed directly to a polystyrene surface. ELISAs that used polyclonal antibodies in the capture mode and MAB conjugate as the second antibody were generally more sensitive than were those that used polyclonal antibodies for both capture and indicator functions. MAB screening and selection schemes should be carefully designed to evaluate MABs in the mode in which they will be used in the final assay.

Animals↗

Monoclonal antibody reactivity as a virulence marker for Legionella pneumophila serogroup 1 strains.

Using a panel of nine monoclonal antibodies, we subgrouped 85 environmental and 129 clinical Legionella pneumophila serogroup 1 isolates from Paris, France. Patients were unlikely to be epidemiologically linked either with each other or with the 44 sampled environmental sites (14 air conditioning systems and 30 buildings) that were selected at random in the Paris area. According to their monoclonal antibody patterns, isolates belonged to 14 subgroups. Monoclonal antibody 2 recognized 121 (93.8%) of 129 clinical isolates and 30 (35.3%) of 85 environmental isolates (P less than 10(-9)). Of the eight patients infected with L. pneumophila not recognized with monoclonal antibody 2, seven were immunocompromised; only 46.3% of the 121 patients infected with L. pneumophila reactive with monoclonal antibody 2 were immunocompromised (P = .02). We conclude that monoclonal antibody 2 can be used as a marker for the more virulent strains of L. pneumophila serogroup 1.

Antibodies, Monoclonal↗

Multilocus enzyme analysis of Legionella dumoffii.

Variability among 29 clinical and environmental strains of Legionella dumoffii was investigated by multilocus enzyme analysis by use of starch gel electrophoresis. Based on results of analysis at 20 enzyme loci, the strains were separated into five closely related electrophoretic types (ETs), which were clearly distinguished from 53 strains representing 53 ETs of L. pneumophila. DNA hybridization results (hydroxyapatite method, 60 and 75 degrees C) for representative strains confirmed that all L. dumoffii ETs were a single genetic species. Although multilocus enzyme analysis indicated that L. dumoffii was genetically a quite uniform species, sufficient variability existed to warrant electromorph fingerprinting for epidemiologic studies.

DNA, Bacterial↗

Legionella pneumophila serogroup Lansing 3 isolated from a patient with fatal pneumonia, and descriptions of L. pneumophila subsp. pneumophila subsp. nov., L. pneumophila subsp. fraseri subsp. nov., and L. pneumophila subsp. pascullei subsp. nov.

Previous DNA relatedness and enzyme electrophoretic mobility studies indicated heterogeneity among strains of Legionella pneumophila serogroups 1, 4, 5, and Lansing 3 (a new, as yet unnumbered serogroup). In this study 60 L. pneumophila strains were studied by DNA hybridization (hydroxyapatite method) to assess their genomic relatedness. These strains were also studied biochemically and serologically to determine whether they formed one or more phenotypic groups. DNA relatedness studies identified three groups. DNA group 1 contained the type strain Philadelphia 1 and strains from serogroups 1 through 14 of L. pneumophila. The average relatedness of DNA group 1 strains was 88% at 60 degrees C with 1.1% divergence in related sequences and 85% at 75 degrees C. DNA group 2 contained strain Los Angeles 1, the reference strain of serogroup 4, and strains of serogroups 1, 4, 5, and Lansing 3, an unnumbered serogroup. Average relatedness of DNA group 2 strains was 84% at 60 degrees C with 0.7% divergence and 87% at 75 degrees C. Reciprocal relatedness of DNA groups 1 and 2 was approximately 67% at 60 degrees C with 6.0% divergence and 48% at 75 degrees C. DNA group 3 strains were in serogroup 5. They were 98% related at 60 degrees C with 0.5% divergence and 97% related at 75 degrees C. Reciprocal relatedness of DNA group 3 and DNA group 1 was approximately 74% at 60 degrees C with 5.3% divergence and 43% at 75 degrees C, and reciprocal relatedness of DNA groups 3 and 2 was 66% at 60 degrees C with 5.7% divergence and 55% at 75 degrees C. The DNA groups could not be separated biochemically or serologically or by cell wall fatty acid and isoprenoid quinone composition. Three subspecies of L. pneumophila are proposed to accommodate the three DNA groups: L. pneumophila subsp. pneumophila subsp. nov. for DNA group 1, L. pneumophila subsp. fraseri subsp. nov. for DNA group 2, and pneumophila subsp. pascullei subsp. nov. for DNA group 3.

DNA, Bacterial↗

Public service announcements: their effect on smoking.

The reasons for choosing the two-stage hierarchy of effects model in Table 5 and the process model of commitment in Table 6 to test are twofold. First, the two-stage hierarchy of effects model allows for reconsideration of the decision once it is made. Secondly, the process model of commitment seemed to be most appropriate in this context, since few commitment models have been specifically applied to marketing and the process model suggested offered the most complete description of commitment of those offered. Other models, such as the EKB model, would be more difficult to operationalize and would not allow for focused attention on commitment in relation to awareness, attitude, etc. The EKB model would also bring in other factors that may or may not be applicable, but the study of which would be made more meaningful in terms of cessation of smoking once the concept of commitment has been investigated in this context. The importance of investigating this decision making process is to give insight not only to health officials attempting to curb smoking in society but for firms marketing products and services that aid in this pursuit to be more effective in their advertising. An understanding of how commitment fits into the decision process to stop smoking would allow for the development of advertisements aimed specifically at boosting commitment to the decision to quit, as well as informing people about what to expect once they start the process of quitting the habit. These models may also find applicability in other areas, such as alcoholism treatment, drug rehabilitation, and the treatment of the mentally ill. In terms of the applications aforementioned, the issue of forced treatment or rehabilitation by the judicial system may need to be more specifically addressed since this was not a major issue in terms of smoking, though some employers are forcing workers to quit smoking or face being fired, this issue is not of the magnitude to be specifically addressed, though one would assume that this would initially serve to increase commitment to quit smoking. The applicability of these models to public service announcements are many. It is not enough to make individuals aware of the dangers of smoking but to create an unfavorable image and attitude towards smoking that leads an individual to action.(ABSTRACT TRUNCATED AT 400 WORDS)

Health Behavior↗

A community hospital outbreak of legionellosis. Transmission by potable hot water.

Seven cases of nosocomial legionellosis occurred between February and September 1982 in a small community hospital in Upstate New York. All seven were cases of Legionella pneumophila serogroup 1; six were hospital patients and one a hospital employee. None of the cases died. During the peak of the outbreak, the incidence of nosocomial legionellosis was 1.2 cases per 100 patient discharges. An epidemiologic comparison of the six patient cases with 21 matched patient controls suggested that longer hospital stay (chi 1(2) = 24.2, p less than 0.001) and the proximity of patients' rooms to ward showers (chi 1(2) = 4.4, p less than 0.04) were significant risk factors for acquiring legionellosis. An environmental investigation demonstrated that the ward showers and the hospital hot water system were contaminated with L. pneumophila serogroup 1. Monoclonal antibody subtyping performed on isolates obtained during the outbreak investigation confirmed that the hot water system and patient isolates had an identical pattern of reactivity. The outbreak demonstrates that legionellosis can be a significant cause of nosocomial pneumonia in a community hospital and that transmission can occur from contaminated potable hot water sources, potentially via shower aerosols.

Aged↗

Molecular epidemiology of Legionella species by restriction endonuclease and alloenzyme analysis.

As part of an ongoing investigation into nosocomial Legionella infections at Stanford University Medical Center (SUMC), we applied the technique of restriction endonuclease analysis (REA) to determine strain differences among three species, including Legionella pneumophila, Legionella dumoffii, and Legionella micdadei. A total of 26 human and environmental water isolates from SUMC were selected for REA and compared with control strains that were not epidemiologically linked to SUMC. REA results were compared with results of alloenzyme typing, typing by monoclonal antibodies, and plasmid fingerprinting in all but L. micdadei strains. REA and alloenzyme typing showed that SUMC patient isolates were derived from distinct strains of three species. L. pneumophila strains from SUMC patients were genotypically identical to those isolated from potable water. REA was especially useful in proving that SUMC L. dumoffii patient isolates were derived from a single strain and that patients may have been exposed to a common source(s). REA typing correlated well with alloenzyme typing. These methods complement serologic typing of L. pneumophila and provide discriminating capability between strains of other Legionella species such as L. dumoffii, for which serologic types have not been identified. In addition, REA typing is somewhat easier to perform than alloenzyme typing and can be done in clinical laboratories.

DNA Restriction Enzymes↗

Production and characterization of monoclonal antibodies to toxic shock syndrome toxin 1 and use of a monoclonal antibody in a rapid, one-step enzyme-linked immunosorbent assay for detection of picogram quantities of toxic shock syndrome toxin 1.

Twenty-six hybridoma cell lines that produced monoclonal antibodies to toxic shock syndrome toxin 1 (TSST-1) were generated by immunizing mice with a highly purified preparation of TSST-1 and fusing their splenic lymphocytes with SP2/0-Ag-14 cells. One monoclonal antibody of the immunoglobulin G1 isotype, designated as PEC-1 10-2SCH, was selected for extensive study. The specificity of this antibody was determined by testing spent culture fluid filtrates of TSST-1- and non-TSST-1-producing strains of Staphylococcus aureus by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and enzyme-linked immunoelectrotransfer blot techniques. Monoclonal antibody PEC-1-10-2SCH was specific for TSST-1-producing strains of S. aureus, reacting with TSST-1 and two other proteins which appear to be unique to S. aureus strains that produce TSST-1. Monoclonal antibody PEC-1-10-2SCH was used in conjunction with polyclonal rabbit antibodies to TSST-1 in a rapid, one-step, sensitive, specific, and quantitative enzyme-linked immunosorbent assay. This assay was shown to be more sensitive, faster, and simpler to perform than previously described isoelectric focusing, immunodiffusion, and solid-phase radioimmunoassays for TSST-1. Monoclonal antibody PEC-1-10-2SCH was not reactive with Staphylococcus protein A under the conditions of the test.

Antibodies, Monoclonal↗

Development of a standardized subgrouping scheme for Legionella pneumophila serogroup 1 using monoclonal antibodies.

A panel of monoclonal antibodies to Legionella pneumophila serogroup 1 and a subclassification scheme were developed in a collaborative project among three laboratories. The seven most useful monoclonal antibodies were selected from three previously developed panels on the basis of indirect fluorescent antibody patterns with 83 strains of L. pneumophila serogroup 1 that were obtained from widely distributed geographic locations. The isolates were divided into 10 major subgroups on the basis of reactivity patterns that can be readily reproduced in any laboratory and are not subject to major inconsistencies of interpretation of staining intensity. A standard protocol for the indirect fluorescent antibody procedure was also developed.

Antibodies, Bacterial↗

Enzyme-linked immunosorbent assay with major outer membrane proteins of Brucella melitensis to measure immune response to Brucella species.

We developed an enzyme-linked immunosorbent assay (ELISA) system to measure human immunoglobulin G (IgG) and IgM response to the major outer membrane proteins of Brucella melitensis. The ELISA was more sensitive in detecting antibody than a standard microagglutination (MA) test with B. abortus antigen. Of 101 sera from persons with suspected brucellosis, 79 (78.2%) gave ELISA IgM titers greater than or equal to the B. abortus MA titer without 2-mercaptoethanol (2ME), which measures both IgM and IgG. Of the 101 sera, 97% gave ELISA IgG titers greater than or equal to the MA with 2ME titer. A total of 58 sera, drawn from 11 human patients from 1 to 29 weeks after onset of brucellosis, gave higher geometric mean titers for the ELISA IgG test than for the MA with 2ME test. These 58 sera also gave ELISA IgM geometric mean titers that were greater than or within one doubling dilution of the geometric mean titers of MA without 2ME. In addition to detecting antibody response to B. abortus, B. melitensis, and B. suis, the ELISA was sensitive to antibody response to human and canine infections with B. canis. The B. canis antibody response is not detected by the MA test with B. abortus antigen. The ELISA, with a standard preparation of major outer membrane proteins of B. melitensis as antigen, appears to be useful in measuring antibody response in humans to infections by all species of Brucella known to infect humans.

Agglutination Tests↗

Nosocomial legionellosis, Paris, France. Evidence for transmission by potable water.

During a five-week period in 1981, six cases of legionellosis due to Legionella pneumophila serogroup 1 were recognized in a hospital in Paris, France. Four cases were clearly nosocomial in origin. There was a direct association between development of disease and exposure to potable hot water (p = 0.003). The entire hot water system was contaminated with L. pneumophila serogroup 1; monoclonal antibody testing demonstrated that the case isolate and the potable water isolates belonged to the same subgroup. Although serogroup 1 was isolated from both the cooling tower and its drift, the cooling tower isolate was antigenically distant from the case isolate. In other nosocomial outbreaks of legionellosis, multiple sources have been found within the hospital environment, but an epidemiologic association of disease with potable water had not been shown. The significant association of cases with exposure to the potable hot water supply, and the identification of case and potable water isolates of the same subtype, suggest that the potable hot water was responsible for transmission of disease in this outbreak.

Adult↗