Biomedical subjects

J A Johnson

Publications and source records attributed to J A Johnson.

At least 55 records · Page 3Linked to original sources

PubMed2001

INVEST substudies: design and patient characteristics.

The INternational VErapamil SR/trandolapril STudy (INVEST) will provide a large database of information. Proposed substudies for analysis include ambulatory blood pressure monitoring (ABPM), depression, genotyping, atrial fibrillation, electrocardiogram (ECG), echocardiography, renal dysfunction, diabetes, and cardiac care cost estimate. This paper reviews the design and status of several of the INVEST substudies. The ABPM substudy will obtain objective blood pressure recordings during daily life masked to both the patient and the investigator. Ambulatory blood pressure monitoring is an especially useful technology because of the role of nocturnal hypertension and circadian blood pressure irregularities in the development of hypertensive disease. The depression substudy, which enrolled 2,393 patients in the United States, will report quality-of-life (QOL) data, including information regarding energy and fatigue. The genotyping substudy will provide genomic DNA samples from approximately 15,000 patients in the United States, including Puerto Rico. Many candidate genes will be examined for polymorphisms that may predict outcomes and/or responses to various treatments.

Blood Pressure Monitoring, Ambulatory↗

PubMed2001

Simulated active control produces repeatable motion pathways of the elbow in an in vitro testing system.

The purpose of this study was to determine if the repeatability and pattern of elbow kinematics are affected by changing the relative magnitudes of loads applied to muscles around the elbow in vitro. In eight cadaveric upper extremities, passive and three methods of simulated active elbow flexion were tested with the forearm maintained in both pronation and supination. Passive flexion involved moving the elbow manually through a full arc of motion. Simulated active flexion used a custom designed loading system to generate elbow motion by applying loads to various tendons via pneumatic actuators. Three different simulated active loading protocols, with loading ratios based on muscle activity and physiologic cross-sectional area, were tested. Testing was performed initially on an intact elbow, and then an unstable elbow model created by transection of the lateral collateral ligament (i.e. the radial and lateral ulnar collateral ligaments). An electromagnetic tracking device was used to measure rotation of the ulna relative to the humerus. Varus-valgus angulation and internal-external rotation were less repeatable during passive flexion than simulated active flexion, regardless of the loading ratio used, in both the intact (p<0.05) and unstable (p<0.05) elbows. Throughout the arc of flexion, the motion pathways were similar for the three simulated active motion protocols employed in this study (p>0.05). The pathways followed during passive motion were different from those generated with simulated active motion, especially in the unstable elbow with the forearm supinated (p<0.001). These results suggest that using simulated active motion rather than manual passive motion can improve the repeatability of elbow kinematics generated in the laboratory, and that a wide range of muscle loading ratios may produce similar kinematic output.

Aged↗

PubMed2001

Preferential expression of antioxidant response element mediated gene expression in astrocytes.

Transcriptional control of target genes by antioxidant/electrophile response elements has been well described in peripheral tissues. Genes that are regulated by this mechanism include the antioxidant enzymes NAD(P)H:quinone oxidoreductase, gamma-glutamyl cystine synthetase and glutathione-S-transferase. Antioxidant/electrophile response elements within a gene's promoter confer induction by low-molecular-weight electrophilic compounds such as tert-butylhydroquinone and dimethyl fumarate. We have now examined the ability of antioxidant/electrophile response elements to elicit gene expression in neurons and astrocytes in both brain slices and primary cultures using transient transfection of promoter reporter constructs. Our results using a heat-stable human placental alkaline phosphatase reporter indicate that antioxidant/electrophile response element mediated gene expression is largely restricted to astrocyte cell populations. Placental alkaline phosphatase expression was significantly elevated in astrocytes treated with the antioxidant/electrophile response element inducer dimethyl fumarate. Mutant constructs lacking a functional antioxidant/electrophile response element abolished all placental alkaline phosphatase expression in astrocytes. We suggest that astrocytic metabolic processes that normally aid and/or protect neurons may be controlled via this inducible system.

Animals↗

PubMed2001

Ilizarov hybrid external fixation for fractures of the distal radius: Part II. Internal fixation versus Ilizarov hybrid external fixation: Stability as assessed by cadaveric simulated motion testing.

The in vitro stability of an Ilizarov hybrid external fixator was compared with that of a dorsal 3.5-mm AO T-plate in 8 unpaired, fresh-frozen upper extremities. A specially designed testing device that used computer-controlled pneumatic actuators was used to simulate active finger, wrist, and forearm motions by applying loads to relevant tendons. A comminuted extra-articular distal radius fracture was modelled using a dorsally based wedge osteotomy. Fracture stability was assessed using an electromagnetic tracking device to measure motion across the fracture site after randomized application of the plate and the hybrid fixator. During simulated finger and wrist motions with the forearm pronated or supinated, motion of the distal fragment with the hybrid fixator applied was comparable to or statistically less than with the AO plate applied. During simulated forearm rotation, the stability provided by the 2 fixation types was similar, although the plate allowed statistically less radial-ulnar deviation of the fragment. In this model of a 2-part extra-articular distal radius fracture, the clinically meaningful stability of the Ilizarov hybrid external fixator was comparable to that of the dorsal AO plate.

Aged↗

PubMed2001

The effect of flexor tendon repair bulk on tendon gliding during simulated active motion: an in vitro comparison of two-strand and six-strand techniques.

The gliding function of 2-strand (Tajima) and 6-strand (Savage) techniques of flexor tendon repair were compared in an in vitro biomechanical model. Stainless steel beads were inserted directly into the metacarpals, phalanges, and flexor digitorum profundus tendons of 22 human cadaver specimens. The FDP tendons were loaded from 5 to 25 N using a pneumatic actuator. The angular rotation and tendon excursion of the cadaver specimens were measured radiographically. The gliding function of the repairs was compared with core suture only, core suture plus epitenon repair, and sheath repair. There was no significant difference in angular rotation or linear excursion between the 2-strand and 6-strand techniques of flexor tendon repair. The addition of the epitendinous suture to the core suture improved the angular rotation and linear excursion for the 2-strand technique. Although the 6-strand repair tended to increase the repair site bulk more than the conventional 2-strand technique, the gliding function of the repair techniques was equivalent.

Aged↗

PubMed2001

An anthropometric study of the radial head: implications in the design of a prosthesis.

The dimensions of the native radial head were measured in 28 cadaveric upper extremities and radiographs of the contralateral elbows of 40 patients who had received a radial head replacement. The mean difference between the maximum and minimum radial head diameters was 1.7 +/- 0.7 mm (range, 0.12-3.27 mm). This variability suggests that although the native radial head is not circular, it does not have a consistently elliptic shape. The native radial head also is variably offset from the axis of the neck (4.2 +/- 2.5 mm), suggesting that a radial head hemiarthroplasty that precisely replicates normal anatomy would be difficult to achieve. There was a poor correlation between the radial head diameter and the medullary canal of the radial neck, suggesting that a modular implant system should be considered.

Aged↗

PubMed2001

A biomechanical analysis of intrascaphoid compression using the 3.00 mm Synthes cannulated screw and threaded washer: an in vitro cadaveric study.

This study evaluated the compressive capabilities of the 3.0 mm Synthes cannulated screw and threaded washer. A transverse osteotomy was performed at the waist of eight cadaveric scaphoids and a custom-designed load cell was inserted before internal fixion with a 3.0 mm cannulated screw and threaded washer. The mean intrascaphoid compression achieved was 108 (SD, 60) N. This compressive force is comparable to that produced by standard cortical screws.

Aged↗

PubMed2001

An episodic outbreak of genetically related Burkholderia cepacia among non-cystic fibrosis patients at a university hospital.

OBJECTIVE: To investigate an outbreak of Burkholderia cepacia. DESIGN: Observational study and chart review. PATIENTS: Adult non-cystic fibrosis (CF) patients. SETTING: Intensive care units (ICUs) at a university-affiliated teaching hospital. METHODS: As part of the epidemiological investigation, we conducted a chart review and collected environmental samples. A review of work schedules of healthcare workers also was performed. We used B. cepacia selective agar for preliminary screening for all isolates, which subsequently were confirmed as members of the B. cepacia complex by polyphasic analysis employing conventional biochemical reactions and genus- and species-specific polymerase chain reaction assays. Pulsed-field gel electrophoresis, randomly amplified polymorphic DNA typing, and automated ribotyping were used to genotype the isolates. As part of the intervention, contact isolation precautions were initiated for all patients identified as having had a culture positive for B. cepacia. RESULTS: Between September 1997 and September 1999, B. cepacia was isolated from 31 adult patients without CF in ICUs at a university-affiliated teaching hospital. Based on geographic clustering and genotypic analysis, three distinct clusters were observed involving 20 patients. Isolates from 17 of these patients were available for testing and were found to be of the same strain (outbreak strain). Further taxonomic analysis indicated that the outbreak strain was B. cepacia complex genomovar III. Twelve (71%) of the 17 patients were judged to be infected, and 5 (29%) were colonized with this strain. Six of 200 environmental cultures from multiple sources in the hospital's ICUs yielded B. cepacia. Two of these isolates, both recovered from rooms of colonized patients, were the same genotype as the outbreak strain recovered from patients. CONCLUSION: Despite an extensive investigation, the source of the B. cepacia clone involved in this outbreak remains unknown. The spatial and temporal pattern of cases suggests that cross-transmission of a genetically related strain contributed to clustering among patients. The initiation of contact isolation may have limited the extent of this transmission. Additional studies are needed to elucidate better the epidemiology of nosocomial B. cepacia infection among non-CF adult patients.

Adult↗

PubMed2001

Muscle forces and pronation stabilize the lateral ligament deficient elbow.

The influence of muscle activity and forearm position on the stability of the lateral collateral ligament deficient elbow was investigated in vitro, using a custom testing apparatus to simulate active and passive elbow flexion. Rotation of the ulna relative to the humerus was measured before and after sectioning of the joint capsule, and the radial and lateral ulnar collateral ligaments from the lateral epicondyle. Gross instability was present after lateral collateral ligament transection during passive elbow flexion with the arm in the varus orientation. In the vertical orientation during passive elbow flexion, stability of the lateral collateral ligament deficient elbow was similar to the intact elbow with the forearm held in pronation, but not similar to the intact elbow when maintained in supination. This instability with the forearm supinated was reduced significantly when simulated active flexion was done. The stabilizing effect of muscle activity suggests physical therapy of the lateral collateral ligament deficient elbow should focus on active rather than passive mobilization, while avoiding shoulder abduction to minimize varus elbow stress. Passive mobilization should be done with the forearm maintained in pronation.

Collateral Ligaments↗

PubMed2001

Design and validation of an unconstrained loading system to measure the envelope of motion in the rabbit knee joint.

An unconstrained loading system was developed to measure the passive envelope of joint motion in an animal model commonly used to study ligament healing and joint arthritis. The design of the five-degree-of-freedom system allowed for unconstrained knee joint loading throughout flexion with repeated removal and reapplication of the device to a specimen. Seven New Zealand White rabbit knees were subjected to varus, valgus, internal and external loads, and the resulting envelopes of motion were recorded using an electromagnetic tracking device. Intra-specimen reproducibility was excellent when measured in one specimen, with maximal rotational differences of 0.6 and 0.3 deg between the fourth and fifth testing cycles for the varus (VR) and valgus (VL) envelopes, respectively. Similarly, the maximal internal (INT) and external (EXT) envelope differences were 0.5 and 0.4 deg, respectively, between the fourth and fifth cycles. Good inter-animal envelope reproducibility was also observed with consistent motion pathways for each loading condition. A maximal VR-VL laxity of 17.9 +/- 2.3 deg was recorded at 95 deg flexion for the seven knees tested. The maximal INT-EXT laxity of 75.2 +/- 4.8 deg occurred at 50 deg flexion. Studies on measurement reproducibility of re-applying individual testing components demonstrated a maximal error of 1.2 +/- 0.7 deg. Serial removal and re-application (test-retest) of the complete measuring system to one cadaveric knee demonstrated maximal envelope differences of less than 0.7 deg for VR-VL rotation and 2.1 deg for INT-EXT rotation. Our results demonstrate that the measuring system is reproducible and capable of accurate evaluation of knee joint motion. Baseline in vitro data were generated on normal joint kinematics for future in-vivo studies with this system, evaluating ligament healing and disease progression in arthritis models.

Animals↗

PubMed2001

Salmonella enterica serovar Typhimurium DT104 displays a rugose phenotype.

Rugose phenotypes, such as those observed in Vibrio cholerae, have increased resistance to chlorine, oxidative stress, and complement-mediated killing. In this study we identified and defined a rugose phenotype in Salmonella enterica serovar Typhimurium DT104 and showed induction only on certain media at 25 degrees C after 3 days of incubation. Incubation at 37 degrees C resulted in the appearance of the smooth phenotype. Observation of the ultrastructure of the rugose form and a stable smooth variant (Stv), which was isolated following a series of passages of the rugose cells, revealed extracellular substances only in cells from the rugose colony. Observation of the extracellular substance by scanning electron microscopy (SEM) was correlated with the appearance of corrugation during development of rugose colony morphology over a 4-day incubation period at 25 degrees C. In addition, the cells also formed a pellicle in liquid broth, which was associated with the appearance of interlacing slime and fibrillar structures, as observed by SEM. The pellicle-forming cells were completely surrounded by capsular material, which bound cationic ferritin, thus indicating the presence of an extracellular anionic component. The rugose cells, in contrast to Stv, showed resistance to low pH and hydrogen peroxide and an ability to form biofilms. Based on these results and analogy to the rugose phenotype in V. cholerae, we propose a possible role for the rugose phenotype in the survival of S. enterica serovar Typhimurium DT104.

Bacterial Capsules↗

PubMed2001

High-frequency recovery of quinupristin-dalfopristin-resistant Enterococcus faecium isolates from the poultry production environment.

The occurrence of resistance to the streptogramin quinupristin-dalfopristin in Enterococcus faecium isolates from chickens on the Eastern Seaboard, was evaluated. Quinupristin-dalfopristin resistance was found in 51 to 78% of E. faecium isolates from the food production environment. The high level of resistance in this organism suggests that this reservoir of resistance may compromise the therapeutic potential of quinupristin-dalfopristin.

Animal Husbandry↗

PubMed2001

Characterization of endogenous avian leukosis viruses in chicken embryonic fibroblast substrates used in production of measles and mumps vaccines.

Previous findings of low levels of reverse transcriptase (RT) activity in chick cell-derived measles and mumps vaccines showed this activity to be associated with virus particles containing RNA of both subgroup E endogenous avian leukosis viruses (ALV-E) and endogenous avian viruses (EAV). These particles originate from chicken embryonic fibroblast (CEF) substrates used for propagating vaccine strains. To better characterize vaccine-associated ALV-E, we examined the endogenous ALV proviruses (ev loci) present in a White Leghorn CEF substrate pool by restriction fragment length polymorphism. Five ev loci were detected, ev-1, ev-3, ev-6, ev-18, andev-19. Both ev-18 and ev-19 can express infectious ALV-E, while ev-1, ev-3, and ev-6 are defective. We analyzed the full-length sequence of ev-1 and identified an adenosine insertion within the pol RT-beta region at position 5026, which results in a truncated RT-beta and integrase. We defined the 1,692-bp deletion in the gag-pol region of ev-3, and we found that in ev-6, sequences from the 5' long terminal repeat to the 5' pol region were absent. Based on the sequences of the ev loci, RT-PCR assays were developed to examine expression of ALV-E particles (EV) in CEF supernatants. Both ev-1- and ev-3-like RNA sequences were identified, as well as two other RNA sequences with intact pol regions, presumably of ev-18 and ev-19 origin. Inoculation of susceptible quail fibroblasts with CEF culture supernatants from both 5-azacytidine-induced and noninduced CEF led to ALV infection, confirming the presence of infectious ALV-E. Our data demonstrate that both defective and nondefective ev loci can be present in CEF vaccine substrates and suggest that both ev classes may contribute to the ALV present in vaccines.

Animals↗

PubMed2001

Pharmacogenomics: the inherited basis for interindividual differences in drug response.

It is well recognized that most medications exhibit wide interpatient variability in their efficacy and toxicity. For many medications, these interindividual differences are due in part to polymorphisms in genes encoding drug metabolizing enzymes, drug transporters, and/or drug targets (e.g., receptors, enzymes). Pharmacogenomics is a burgeoning field aimed at elucidating the genetic basis for differences in drug efficacy and toxicity, and it uses genome-wide approaches to identify the network of genes that govern an individual's response to drug therapy. For some genetic polymorphisms (e.g., thiopurine S-methyltransferase), monogenic traits have a marked effect on pharmacokinetics (e.g., drug metabolism), such that individuals who inherit an enzyme deficiency must be treated with markedly different doses of the affected medications (e.g., 5%-10% of the standard thiopurine dose). Likewise, polymorphisms in drug targets (e.g., beta adrenergic receptor) can alter the sensitivity of patients to treatment (e.g., beta-agonists), changing the pharmacodynamics of drug response. Recognizing that most drug effects are determined by the interplay of several gene products that govern the pharmacokinetics and pharmacodynamics of medications, pharmacogenomics research aims to elucidate these polygenic determinants of drug effects. The ultimate goal is to provide new strategies for optimizing drug therapy based on each patient's genetic determinants of drug efficacy and toxicity. This chapter provides an overview of the current pharmacogenomics literature and offers insights for the potential impact of this field on the safe and effective use of medications.

Cytochrome P-450 Enzyme System↗

PubMed2001

Impaired insulin action in subcutaneous adipocytes from women with visceral obesity.

Visceral obesity is associated with resistance to the antilipolytic effect of insulin in vivo. We investigated whether subcutaneous abdominal and gluteal adipocytes from viscerally obese women exhibit insulin resistance in vitro. Subjects were obese black and white premenopausal nondiabetic women matched for visceral adipose tissue (VAT), total adiposity, and age. Independently of race and adipocyte size, increased VAT was associated with decreased sensitivity to insulin's antilipolytic effect in subcutaneous abdominal and gluteal adipocytes. Absolute lipolytic rates at physiologically relevant concentrations of insulin or the adenosine receptor agonist N(6)-(phenylisopropyl)adenosine were higher in subjects with the highest vs. lowest VAT area. Independently of cell size, abdominal adipocytes were less sensitive to the antilipolytic effect of insulin than gluteal adipocytes, which may partly explain increased nonesterified fatty acid fluxes in upper vs. lower body obese women. Moreover, increased VAT was associated with decreased responsiveness, but not decreased sensitivity, to insulin's stimulatory effect on glucose transport in abdominal adipocytes. These data suggest that insulin resistance of subcutaneous abdominal and, to a lesser extent, gluteal adipocytes may contribute to increased systemic lipolysis in both black and white viscerally obese women.

Abdomen↗

PubMed2001

High-fat hypocaloric diet modifies carbohydrate utilization of obese rats during weight loss.

The effects of fat content in the hypocaloric diet on whole body glucose oxidation and adipocyte glucose transport were investigated in two animal-feeding experiments. Diet-induced obese rats were food restricted to 75% of their previous energy intakes with either a high (45% by calorie) or a low (12% by calorie) corn oil diet for 9 wk (experiment 1) or 10 days (experiment 2). The losses of body weight (P < 0.05) and adipose depot weight (P < 0.05) were less in the 45% compared with the 12% fat group. During the dynamic phase of weight loss (day 10 of food restriction), plasma glucose and insulin concentrations were higher (P < 0.05) in the 45% than those in the 12% fat group. Whole body carbohydrate oxidation rate in response to an oral load of glucose was increased (P < 0.001) by food restriction in both dietary groups; however, carbohydrate oxidation rates were lower (P < 0.01) in the 45% than in the 12% fat-fed rats during the weight loss period. Adipocyte glucose transport was greater (P < 0.02) in the 45% than in the 12% fat group in an intra-abdominal adipose depot but not in subcutaneous fat. These data suggest that dietary fat content modifies whole body glucose oxidation and intra-abdominal adipocyte glucose uptake during weight loss.

Adipocytes↗

PubMed2001

Economic impact of community pharmacist intervention in cholesterol risk management: an evaluation of the study of cardiovascular risk intervention by pharmacists.

The Study of Cardiovascular Risk Intervention by Pharmacists, a randomized, controlled trial in over 50 community pharmacies in Alberta and Saskatchewan, Canada, demonstrated that a pharmacist intervention program improved cholesterol risk management in patients at high risk for cardiovascular disease. In a substudy, costs and consequences were analyzed to describe the economic impact of the program. Two perspectives were taken: a government-funded health care system and a pharmacy manager. Costs were reported in 1999 Canadian dollars. Incremental costs to a government payor and community pharmacy manager were $6.40/patient and $21.76/patient, respectively, during the 4-month follow-up period. The community pharmacy manager had an initial investment of $683.50. The change in Framingham risk function for the intervention group from baseline also was reported. The 10-year risk of cardiovascular disease decreased from 17.3% to 16.4% (p<0.0001) during the 4 months. The intervention program in this study led to a significant reduction in cardiovascular risk in the intervention group during the 4-month follow-up period. The incremental cost to provide the program appeared minimal from both government and pharmacy manager perspectives. It is hoped that these results could support negotiations for reimbursement of clinical pharmacy services with payors.

Aged↗

PubMed2001

Practice-based research: lessons from community pharmacist participants.

We designed this project to determine community pharmacists' opinions regarding the challenges and motivations of their recent participation in a pharmacy practice-based research study At the conclusion of a randomized, multicenter study, 87 community pharmacist-investigators were sent a questionnaire that explored four areas: motivating factors to participate, barriers to participation, communication tools used by study coordinators, and design issues for future studies. Fifty-eight (67%) completed questionnaires were returned. Key factors motivating participation in the study were desire to improve the profession and opportunity to learn. Time was the greatest barrier to participation. Pharmacy practice-based research has two distinct advantages. First, it translates clinical knowledge into direct application in the community. Second, it provides needed data to demonstrate the value of enhanced pharmacy practice. Thorough understanding of pharmacists' opinions is necessary to optimize the design of future studies.

Attitude of Health Personnel↗