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Biomedical subjects

J A Johnson

Publications and source records attributed to J A Johnson.

At least 127 records · Page 7Linked to original sources

Cost of care for individuals with cystic fibrosis: a regression approach to determining the impact of recombinant human DNase.

We estimated direct medical costs of care and important determinants of the costs in patients with cystic fibrosis (CF), including therapy with recombinant human DNase (rhDNase). Costs were estimated with resource use data from the Epidemiologic Study of Cystic Fibrosis. Ordinary least squares regression was used to determine the effect of clinical and demographic variables on individual cost of care. The estimated cost of caring for 303 patients in Alberta was $2,279,801 in 1996. The mean cost of care was $7524 (range $386-92,376)/patient. Regression results indicated that age and forced expiratory volume predicted had a negative association with costs. Being female, receiving rhDNase, and having Pseudomonas aeruginosa or Burkholderia cepacia were all associated with high costs. Our estimates indicated large interindividual variation in cost of care for patients with CF.

Adult↗

Effects of gender and race on albuterol pharmacokinetics.

We evaluated the effects of race and gender on albuterol pharmacokinetics in 30 patients with moderate asthma (15 blacks, 15 whites, 16 men, 14 women). Subjects received a single dose of albuterol 8 mg oral solution and had blood samples collected at various times for 12 hours after the dose. Albuterol plasma concentrations were determined by HPLC with fluorescence detection, and pharmacokinetics were determined by compartmental analysis. The apparent volume of distribution of albuterol was significantly higher in men than in women (631+/-171 and 510+/-109 L, respectively, p<0.05). Consequently, the maximum concentration was lower in men than women (10.3+/-2.1 and 12.0+/-1.9 ng/ml, respectively, p<0.05). Elimination rates were 0.136+/-0.008 and 0.160+0.012 hour(-1), respectively (p<0.10). When corrected for ideal body weight, apparent volume of distribution was not different by gender. No differences between blacks and whites other than lag time were noted in albuterol kinetics. The greater apparent volume of distribution in men is likely explained by differences in ideal body weight or lean body mass.

Adolescent↗

Measuring quality of life in paediatric patients.

The purpose of this paper is to highlight important considerations in the measurement of health-related quality of life (HR-QOL) in paediatric populations. Considerations specific to the evaluation of HR-QOL in children include children's understanding of the questions being asked, their understanding of their own disease, using parents as proxies, time perception problems and simply the fact that children are continually changing. We provide a review of the currently available literature regarding paediatric HR-QOL assessments to examine the different instruments and approaches taken to assess HR-QOL in paediatrics. Asthma-specific measures are discussed as examples of condition-specific HR-QOL instruments because of the considerable amount of methodological and developmental work that has been conducted in this disease. Our search strategy revealed 15 main generic and 5 main asthma-specific instruments that met our criteria for inclusion. The main points high-lighted for each instrument are the description of domains, respondent (i.e. the child, parent or clinician), age group, number of items, format of instrument (usually self-administered or by interview), original country and language, and the existence of translations. For the various studies in which the different instruments are used, the issues of patient population tested, sample size, reliability and validity are addressed. Although this paper does not attempt to be an exhaustive study of paediatric HR-QOL instruments, we provide an overview of the main generic and asthma-specific instruments, as well as an examination of the different methods used in assessing paediatric HR-QOL. Many challenges exist in the measurement of HR-QOL in paediatric patients. With increased attention to the considerations high-lighted, the field will continue to grow, and the usefulness and application of HR-QOL measures in paediatric patients is likely to improve.

Child↗

Intranasal DDAVP induced increases in plasma von Willebrand factor alter the pharmacokinetics of high-purity factor VIII concentrates in severe haemophilia A patients.

Because native circulating factor VIII (FVIII) is maximally stabilized when it is bound to von Willebrand factor (vWf), increased plasma vWf levels may enhance the infused FVIII concentrate intravascular survival and efficacy in severe haemophiliacs. To assess whether the kinetic characteristics and recovery of high purity, plasma-derived (Monoclate-P, Centeon) and recombinant (Bioclate , Centeon) FVIII concentrates are enhanced by increased plasma vWf concentrations, we compared the pharmacokinetic response to a bolus of FVIII infused alone with the response to a bolus infused 2 h after the intranasal delivery of 300 microg of desmopressin acetate (DDAVP) High Concentration Nasal Spray (Stimate, Centeon) in 10 adult severe haemophiliacs. FVIII activity was determined using a one-stage clotting assay on cryopreserved plasma specimens obtained at baseline and at 14 distinct time points (0.25-48 h) following the FVIII infusions. Ristocetin co-factor activity (RCoFA) and vWf antigen levels were assayed at baseline and 2 h after Stimate. FVIII kinetic parameters were calculated using standard, noncompartmental kinetic methods. Statistical analysis was performed using a paired t-test with 95% confidence limits. The mean rises in RCoFA (0.65+/-0.44 IU mL(-1)) and vWf antigen (0.19+/-0.07 IU mL-1) induced by Stimate were significant (P<0.01 and P<0.0001, respectively). The mean increases in the volume of distribution at steady state (Vss) (13.2+/-9.3 dL) and mean residence time (MRT) (4.4+/-3.9 h) between the FVIII-only arm and the FVIII plus Stimate arm were highly significant (P = 0.0015 and P = 0. 0059, respectively). The mean differences in recovery, area under the curve (AUC), half-life, and clearance (Cl) were not significantly altered. Subgroup analysis revealed statistically significant increases in Vss and MRT (P = 0.025 and P = 0.012, respectively) following the administration of intranasal DDAVP in the Monoclate-P cohort, but not in the Bioclate group. These data suggest that even modest pharmacologically induced increases in plasma vWf can favourably affect the kinetics of high-purity, plasma-derived FVIII concentrates in severe haemophiliacs.

Administration, Intranasal↗

Health status and satisfaction with pharmacy services.

OBJECTIVE: To evaluate the relationship between self-reported health status and satisfaction with pharmacy services. STUDY DESIGN: Secondary analysis of data previously collected via a computer-assisted telephone interview system. PATIENTS AND METHODS: Survey respondents were enrollees in a large managed care organization who were recent patrons of either traditional or mail pharmacy services. Satisfaction data were gathered using an existing satisfaction with pharmacy services survey. Health status was measured using the Medical Outcome Study's Short-Form 12-Item Health Survey. The relationships between satisfaction with pharmacy services and health status were analyzed using structural equation modeling. RESULTS: A significant positive relationship between mental health status and satisfaction with pharmacy services was hypothesized and confirmed. The correlations between mental health status and satisfaction, however, were not strong (r = .10 to .18). No relationship between physical health status and satisfaction with pharmacy services was observed. Similar results were observed in patrons of both traditional and mail pharmacy services. CONCLUSION: This investigation offers evidence that satisfaction with healthcare services is more closely related to mental health status than to physical health status. This has important implications for case-mix adjustments in the measurement of satisfaction with care.

Computer Communication Networks↗

Club foot, an adverse outcome of early amniocentesis: disruption or deformation? CEMAT. Canadian Early and Mid-Trimester Amniocentesis Trial.

An association between the occurrence of club foot and early amniocentesis has been reported. The largest of these randomised studies was the Canadian Early and Mid-Trimester Amniocentesis Trial. Data describing the neonatal outcome, focusing on this association, are presented. Possible mechanisms for the association and the implications for the development of club foot are discussed.

Adult↗

Metallic radial head arthroplasty improves valgus stability of the elbow.

The stabilizing influence of radial head arthroplasty was studied in eight medial collateral ligament deficient anatomic specimen elbows. An elbow testing apparatus, which used computer controlled pneumatic actuators to apply tendon loading, was used to simulate active elbow flexion. The motion pathways of the elbow were measured using an electromagnetic tracking device, with the forearm in supination and pronation. As a measure of stability, the maximum varus to valgus laxity over the range of elbow flexion was determined from the difference between varus and valgus gravity loaded motion pathways. After transection of the medial collateral ligament, the radial head was excised and replaced with either a silicone or one of three metallic radial head prostheses. Medial collateral ligament transection caused a significant increase in the maximum varus to valgus laxity to 18.0 degrees +/- 3.2 degrees. After radial head excision, this laxity increased to 35.6 degrees +/- 10.3 degrees. The silicone implant conferred no increase in elbow stability, with a maximum varus to valgus laxity of 32.5 degrees +/- 15.5 degrees. All three metallic implants improved the valgus stability of the medial collateral ligament deficient elbow, providing stability similar to the intact radial head. The use of silicone arthroplasty to replace the radial head in the medial collateral ligament deficient elbow must be questioned. Metallic radial head arthroplasty provides improved valgus stability, approaching that of an intact radial head.

Aged↗

Participation of upstream stimulator factor (USF) in cadmium-induction of the mouse metallothionein-I gene.

The roles of the bHLH-Zip protein, upstream stimulatory factor (USF), in mouse metallothionein-I (MT-I) gene expression were examined. The promoter contains a putative USF binding site which overlaps an antioxidant response element (ARE) located at -101 bp relative to the transcription start point. The USF/ARE composite element increases basal expression of the mouse MT-I gene, and partly mediates response to oxidative stress. However, other functions of this composite element and the in vivo roles for USF in MT-I promoter functions have not been examined. We report studies which indicate that USF participates via the USF/ARE element in cadmium responsiveness of the mouse MT-I promoter. During the course of these studies a second, higher affinity USF binding site at -223 bp was identified. Stable and transient transfection assays in mouse hepatoma cells, using the USF/ARE in the context of a minimal promoter and site-directed and truncation mutants of the MT-I promoter, revealed that the USF and the ARE sites contribute to cadmium (2-30 microM) but not zinc responsiveness, and to basal promoter activity. Overexpression of dominant-negative (dn)USF in co-transfection assays significantly attenuated cadmium induction of the USF/ARE in the context of a minimal promoter, and attenuated cadmium, but not zinc, induction of the intact MT-I promoter. A consensus E-box (CACATG) at -223 bp in the MT-I promoter was also found to bind USF in vitro , and to be constitutively footprinted in vivo . The interaction of USF with E-box1 was apparently 10-fold stronger than that with the USF/ARE. However, in contrast, E-box1 was not a strong basal promoter element nor was it metal ions responsive in mouse Hepa cells. In conclusion, these studies demonstrate a role for USF in cadmium-specific induction of the mouse MT-I gene, but bring into question an obligate role for USF in regulating basal activity of this gene. The data further suggest that USF interacts with ARE-binding proteins to influence MT-I gene expression.

Animals↗

A Vibrio cholerae pathogenicity island associated with epidemic and pandemic strains.

The bacterial species Vibrio cholerae includes harmless aquatic strains as well as strains capable of causing epidemics and global pandemics of cholera. While investigating the relationship between pathogenic and nonpathogenic strains, we identified a chromosomal pathogenicity island (PAI) that is present in epidemic and pandemic strains but absent from nonpathogenic strains. Initially, two ToxR-regulated genes (aldA and tagA) were studied and were found to be associated with epidemic and pandemic strains but absent in nontoxigenic strains. The region containing aldA and tagA comprises 13 kb of previously unidentified DNA and is part of a PAI that contains a regulator of virulence genes (ToxT) and a gene cluster encoding an essential colonization factor and the cholera toxin phage receptor (toxin-coregulated pilus; TCP). The PAI is 39.5 kb in size, has low %G+C (35%), contains putative integrase and transposase genes, is flanked by att sites, and inserts near a 10Sa RNA gene (ssrA), suggesting it may be of bacteriophage origin. We found this PAI in two clinical non-O1/non-O139 cholera toxin-positive strains, suggesting that it can be transferred within V. cholerae. The sequence within this PAI includes an ORF with homology to a gene associated with the type IV pilus gene cluster of enteropathogenic Escherichia coli, a transposase from Vibrio anguillarum, and several ORFs with no known homology. As the PAI contains the CTXPhi receptor, it may represent the initial genetic factor required for the emergence of epidemic and pandemic cholera. We propose to call this island VPI (V. cholerae pathogenicity island).

Aldehyde Dehydrogenase↗

Effect of age on protein conservation during very-low-energy diet in obese Sprague-Dawley rats.

OBJECTIVE: To examine the effect of age on body protein losses occurring during severe energy restriction in obesity. RESEARCH METHODS AND PROCEDURES: Weanling (young) Sprague-Dawley rats (YR) were fed a high fat (35% energy) diet (HFD) until mean body weight approached that of a group of chow-fed retired breeder (aged) rats (AR). Both groups were then fed HFD for an additional 2 weeks, after which selected controls from YR and AR groups were killed for baseline carcass analysis. Remaining rats were fed a very-low-energy diet (VLED, 33% kcal of HFD) for 3 weeks and then killed for carcass analysis. RESULTS: YR had greater fat stores before VLED, and lost proportionately more fat and less protein during VLED than did AR. Weight loss composition during VLED was 66.7% fat, 11.1% protein, and 22.2% water in YR, and 39.4% fat, 26.2% protein, and 34.3% water in AR. Greater YR fat loss during VLED (70.6+/-30.4 vs. 32.6+/-29.1 g in AR; mean+/-SD) was paralleled by significantly larger decreases in epididymal and retroperitoneal fat pad weights, mean adipocyte size, and lipoprotein lipase activity. Greater protein loss in AR (21.6+/-13.9 g vs. 11.8+/-10.7 g in YR) coincided with larger decreases in visceral organ weights and serum thyroxine and triiodothyronine. Energy expenditure changes during VLED were similar between groups. DISCUSSION: Dietary obese young rats appear better able than aged rats to conserve body protein while losing body fat during severe energy restriction.

Adipocytes↗

German women in chemistry, 1895-1925 (Part I).

The paper traces the entrance of German women into the chemistry profession from the 1890s to 1925, examining how they first overcame social and cultural conservatism to obtain access to opportunities for a chemical education during the later Kaiserreich, then began to seek academic and industrial careers and to establish a professional organization in the face of resistance from the established Verein Deutscher Chemiker. The paper examines the effect of World War I and the advent of the Weimar Republic in completing the process whereby German women achieved a small but significant role in the profession of chemistry, in science as well as industry. Finally, it discusses the considerable limitations on women's full and equal participation that still remained by 1925.

Chemistry↗

A biomechanical analysis of intrascaphoid compression using the Herbert scaphoid screw system. An in vitro cadaveric study.

The purpose of this study was to evaluate the compressive capabilities of the Herbert scaphoid screw system. A transverse osteotomy was performed at the waist of eight scaphoids removing a 3 mm wafer of bone. A custom-designed load washer was inserted within this defect to measure intrascaphoid compression during Huene guide application, during screw insertion, after screw insertion and after guide release. The intrascaphoid compression was noted to peak during screw insertion; however it dramatically decreased without any clinical subjective evidence of decreased insertional torque by the surgeon. The average final compression as a percentage of maximal compression was 38 (SD 26) %.

Aged↗

Load relaxation and forces with activity in Hoffman external fixators: a clinical study in patients with Colles' fractures.

A small-frame Hoffman external fixation bar instrumented with strain gauges to quantify bending and torsional forces was applied to 4 patients with a displaced metaphyseal fracture of the distal radius. Measurements were taken during surgery as well as at 1, 3, and 6 weeks after surgery during activities of daily living and hand therapy mobilization. Radiographs also were taken before and after reduction and at each subsequent visit. Force decay occurred after reduction of the fracture, averaging only 26% of the initial distraction forces by 5 minutes. These forces plateaued and did not significantly change over the subsequent 40-minute observation period. There was no correlation between carpal height index and the forces measured in the external fixator. Significant changes in external fixator forces were measured during activities of daily living and hand therapy mobilization, but these returned to baseline after the activities were performed. The most provocative activities studied were twisting a doorknob and lifting heavy objects. These activities should be performed with caution by patients with unstable distal radial fractures.

Activities of Daily Living↗

Comparison of the EQ-5D and SF-12 in an adult US sample.

The purpose of this paper is to discuss the results of a direct comparison of two instruments, the SF-12 health survey and the EuroQol Group's EQ-5D, in a sample drawn from the adult US population. The data were collected via a survey instrument mailed to 1,800 subjects in the USA. The instrument contained the EQ-5D valuation questionnaire and the items of the SF-12. In addition, the subjects were asked to provide demographic information, complete a depression screening item and to indicate if they had any of seven common chronic conditions. The usable response rate was 23.7%. Patients indicating a health problem on the EQ-5D had significantly lower mean SF-12 component scores (i.e. MCS-12 and PCS-12) for all dimensions. As was expected, the relationships were stronger between the EQ-5D functional dimensions and the PCS-12 and between the MCS-12 and the EQ-5D anxiety/depression dimension. The EQ-5D visual analogue scale (VAS) scores were positively correlated with both component scores; r = 0.55 for PCS-12 and r = 0.41 for MCS-12. The results of this investigation provide support for the validity of both the EQ-5D and the SF-12 as descriptive measures of health status. The measurements by both instruments behaved in patterns that were consistent with recognized sociodemographic differences in health status. The limitations of the dimensional structure of the EQ-5D were somewhat overcome by the use of the VAS, which may also be possible with a constructed index score based on explicit values derived from a general population. The SF-12 appeared to be more sensitive to differences associated with less severe morbidity.

Adult↗

The structure of satisfaction with pharmacy services.

OBJECTIVES: The objectives of this investigation were to evaluate the dimensional structure of satisfaction with pharmacy services, to determine whether satisfaction is best viewed as a unidimensional or multidimensional construct, and to determine the degree of correspondence between a general satisfaction scale and satisfaction with specific aspects of pharmacy services. METHODS: Data was collected via telephone interviews of 509 patrons of traditional retail pharmacies and analyzed using structural equation modeling techniques. RESULTS: The hypothesized, multidimensional measurement model fit the observed data reasonably well. However, correlations between the latent dimensions of satisfaction with pharmacy services indicated that some dimensions were empirically indistinguishable. CONCLUSIONS: Considering item content and theoretical considerations, modifications to the structure of previously used measures of satisfaction with pharmacy services were suggested. The data also support the hypothesis of a hierarchical model in which general satisfaction could be simultaneously represented as both an overall domain and as a set of distinct dimensions tapping unique aspects of satisfaction with pharmacy services. Depending on the purpose of the measurement, either or both levels of analysis may be useful.

Adult↗

Sonchus yellow net rhabdovirus nuclear viroplasms contain polymerase-associated proteins.

We have initiated a study of the cytopathology of nucleorhabdoviruses by analyzing the subcellular localization of sonchus yellow net virus (SYNV) genomic and antigenomic RNAs and the encoded polymerase proteins. In situ hybridizations demonstrated that the minus-strand genomic RNA sequences are restricted to the nuclei of infected cells, while the complementary plus-strand antigenomic RNA sequences are present in both the nuclei and the cytoplasm. Immunofluorescence and immunogold labeling experiments also revealed that the nucleocapsid (N) protein and phosphoprotein (M2) are primarily localized to discrete regions within the nuclei and in virus particles that accumulate in perinuclear spaces. The N protein antiserum specifically labeled the nuclear viroplasms, whereas the M2 antiserum was more generally distributed throughout the nuclei. Antibody detection also indicated that the polymerase (L) protein is present in small amounts in the viroplasm. When the N and M2 proteins were expressed individually from the heterologous potato virus X (PVX) vector, both proteins preferentially accumulated in the nuclei. In addition, viroplasm-like inclusions formed in the nuclei of cells infected with the PVX vector containing the N gene. Fusions of the carboxy terminus of beta-glucuronidase to N and M2 resulted in staining of the nuclei of infected cells following expression from the PVX vector. Deletion analyses suggested that multiple regions of the N protein contain signals that are important for nuclear localization.

Cell Nucleus↗

Valuation of EuroQOL (EQ-5D) health states in an adult US sample.

While the EuroQOL instrument (EQ-5D) is being considered and used in clinical trials in the United States and Canada, and in large international multicentre studies, population weights for the instrument have never been established in North America. The primary purpose of this investigation was to derive a set of US-based population weights for the standard set of health states described in the EQ-5D health questionnaire. Valuations for EQ-5D health states were obtained via a postal survey using the visual analogue scale (VAS) format. A sample of 3,500 adults from the continental US were surveyed. A response rate of 25.8% was obtained. Mean and median valuations for 45 distinct health states, including dead and unconscious, were calculated. An ordinary least squares (OLS) regression-based weighting scheme was constructed to impute scores for states not directly valued in the questionnaire formats. Valuations for the standard EQ-5D health states displayed similar characteristics to VAS valuations obtained in previous investigations in European countries. The OLS model fit the observed data relatively well, achieving an adjusted R2 of 0.42. However, the diagnostic testing indicated that the initial model was misspecified. Subsequent alternative models alleviated some, but not all, of the problems of misspecification. The EQ-5D valuations from adult Americans in this sample appeared to behave in much the same fashion as in previous valuation studies. However, the generalisability of results to the entire adult American population may be limited. Violations of assumptions of the OLS regression model indicate the need for further investigation into the modelling technique used in deriving a single index score.

Adult↗