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Biomedical subjects

J A Johnson

Publications and source records attributed to J A Johnson.

At least 73 records · Page 4Linked to original sources
PubMed2001

Ligamentous stabilizers against posterolateral rotatory instability of the elbow.

BACKGROUND: The lateral ulnar collateral ligament, the entire lateral collateral ligament complex, and the overlying extensor muscles have all been suggested as key stabilizers against posterolateral rotatory instability of the elbow. The purpose of this investigation was to determine whether either an intact radial collateral ligament alone or an intact lateral ulnar collateral ligament alone is sufficient to prevent posterolateral rotatory instability when the annular ligament is intact. METHODS: Sequential sectioning of the radial collateral and lateral ulnar collateral ligaments was performed in twelve fresh-frozen cadaveric upper extremities. At each stage of the sectioning protocol, a pivot shift test was performed with the arm in a vertical position. Passive elbow flexion was performed with the forearm maintained in either pronation or supination and the arm in the varus and valgus gravity-loaded orientations. An electromagnetic tracking device was used to quantify the internal-external rotation and varus-valgus angulation of the ulna with respect to the humerus. RESULTS: Compared with the intact elbow, no differences in the magnitude of internal-external rotation or maximum varus-valgus laxity of the ulna were detected with only the radial collateral or lateral ulnar collateral ligament intact (p > 0.05). However, once the entire lateral collateral ligament was transected, significant increases in internal-external rotation (p = 0.0007) and maximum varus-valgus laxity (p < 0.0001) were measured. None of the pivot shift tests had a clinically positive result until the entire lateral collateral ligament was sectioned. CONCLUSIONS: This study suggests that, when the annular ligament is intact, either the radial collateral ligament or the lateral ulnar collateral ligament can be transected without inducing posterolateral rotatory instability of the elbow.

Aged↗
PubMed2001

Underutilisation of ACE inhibitors in patients with congestive heart failure.

Congestive heart failure (CHF) is associated with substantial morbidity and mortality, and is the only major cardiovascular disease increasing in prevalence. Despite abundant evidence to support their efficacy and cost-effectiveness, angiotensin-converting enzyme (ACE) inhibitors are sub-optimally used in patients with CHF. This paper reviews the evidence for the sub-optimal use of ACE inhibitors in patients with CHF, the factors contributing to this, and its implications for health systems. A systematic review of all articles assessing practice patterns (specifically the use of ACE inhibitors in CHF) identified by MEDLINE, search of bibliographies, and contact with content experts was undertaken. 37 studies have documented the use of ACE inhibitors in patients with CHF. Studies assessing use among all patients with CHF document 33% to 67% (median 51%) of all patients discharged from hospital and 10% to 36% (median 26%) of community dwelling patients were prescribed ACE inhibitors. Rates of ACE inhibitor use range from 43% to 90% (median of 71%) amongst those discharged from hospital having known systolic dysfunction, and from 67% to 95% (median of 86%) for those monitored in specialty clinics. Moreover, the dosages used in the 'real world' are substantially lower than those proven efficacious in randomised, controlled trials, with evaluations reporting only a minority of patients achieving target doses and/or an overall mean dose achieved to be less than one-half of the target dose. Factors predicting the use and optimal dose administration of ACE inhibitors are identified, and include variables relating to the setting (previous hospitalisation, specialty clinic follow-up), the physician (cardiology specialty versus family practitioner or general internist, board certification), the patient (increased severity of symptoms, male, younger), and the drug (lower frequency of administration). In light of the substantial evidence for reductions in morbidity and mortality, clearly, the prescription of ACE inhibitors is sub-optimal. Wide variability in ACE inhibitor use is noted, with higher rates consistently reported among patients having systolic dysfunction confirmed by an objective assessment--an apparent minority of the those having CHF. Optimisation of the prescription of proven efficacious therapies has the potential to confer a substantial reduction in the total cost of care for patients with CHF by reducing hospitalisations and lengths of hospital stays. It is likely that only multifaceted programs targeted toward the population at large will yield benefits to the healthcare system, given the widespread nature of the sub-optimal prescription of therapies proven effective in the management of patients with CHF.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2001

Drug target pharmacogenomics: an overview.

Pharmacogenomics is a field aimed at understanding the genetic contribution to variability in drug efficacy and toxicity. The goal is to be able to select the drugs with the greatest likelihood of benefit and the least likelihood of harm in individual patients, based on their genetic make-up. Pharmacogenetics has historically been a field focused primarily on genetic polymorphisms in drug metabolizing enzymes and their impact on drug efficacy and toxicity. More recently, investigators have begun to study the relationship between drug target polymorphisms and drug efficacy and toxicity. There are now numerous examples in the literature of associations between drug target polymorphisms and drug effect. Drug targets can be broken into three main categories: the direct protein target of the drug, signal transduction cascades or downstream proteins, and disease pathogenesis proteins. While the drug target pharmacogenetics literature provides 'proof of concept' that genetic variability contributes to the variability in drug response, the data are not to the point of being clinically useful in most cases. Specific problems to date include the inability of a single polymorphism to be highly predictive of response, and inconsistencies across studies of the same polymorphism. It seems likely that an important factor in the above limitations is the approach of focusing on a single polymorphism in a single gene. Given that most drug responses involve a large number of proteins, all of whose genes could have several polymorphisms, it seems unlikely that a single polymorphism in a single gene would explain a high degree of drug response variability in a consistent fashion. Thus, it seems that a polygenic, or genomic approach will be more appropriate. Candidate gene and genome scanning approaches to pharmacogenomics have shown promise in relating drug target polymorphisms to response or toxicity, and pharmacogenomic strategies for drug discovery and drug development are now being implemented by most major pharmaceutical companies. Pharmacogenomics has the potential to significantly enhance the ability of clinicians to use medications in a safe and effective manner and, as such, represents an exciting field with tremendous clinical potential.

Drug Design↗
PubMed2001

Determination of human beta(2)-adrenoceptor haplotypes by denaturation selective amplification and subtractive genotyping.

OBJECTIVE: beta(2)-Adrenoceptor haplotype may be better associated with asthma severity and drug response than a polymorphic variant at any single site. Because present methods of haplotype determination are time consuming and impractical for large population studies, we sought to develop a simple and efficient method of determining haplotype of 3 common polymorphisms at codons -19 (Arg/Cys), 16 (Arg/Gly) and 27 (Glu/Gln). DESIGN: Preliminary studies showed that the C/G base pair of the Arg(-19) allele increases the local melting temperature over the T/A base pair of the Cys(-19) allele by 3.6 degrees C and establishes a new local maximum denaturation temperature. By choosing a suitable denaturation temperature and appropriate primers and coupling them with restriction fragment length polymorphism (RFLP) analysis, we hypothesized that the genotype of one separately amplified allele followed by subtraction from the combined genotype of two alleles would yield the beta(2) haplotype in > 99% of the population. RESULTS: Haplotype determined by our method was in complete agreement with haplotype determined by cloning and sequencing in 29 samples. The frequencies of haplotype pairs in 78 healthy adults, according to our method, were in agreement with published values that were inferred, and were: RGE/CRQ, 26.9%; CRQ/CRQ, 25.6%; RGE/CGQ, 16.7%; CRQ/CGQ, 10.3%; RGE/RGE, 11.5%; CGQ/CGQ, 7.7%. The haplotype pair in one individual was RRE/CRQ (1.3%). CONCLUSION: Our method of determining beta(2)-adrenoceptor haplotype is simple, accurate and cost effective for haplotyping large populations.

DNA Primers↗
PubMed2001

Productivity losses associated with diabetes in the US.

OBJECTIVE: The objective of this study was to estimate the cost of productivity losses in the U.S. attributable to diabetes, with regard to specific demographic and disease-related characteristics in the U.S.. RESEARCH DESIGN AND METHODS: We used the 1989 National Health Interview Survey, a random survey of individuals in the U.S. that included a diabetes supplement. Data on individuals were obtained for labor force participation, hours of work, demographic and occupational characteristics, self-reported health status, and several variables that indicated the presence, duration, and severity (complications) of diabetes. Using multivariate regression analyses, we estimated the association of independent variables (e.g., demographics, health, and diabetes status) with labor force participation, hours of work lost, and the economic value of lost work attributable to diabetes and its complications and duration. RESULTS: In general, the presence of diabetes and complications were found to be related to workforce participation variables. The magnitude of the lost-productivity costs depended on personal characteristics and on the presence and status of diabetes. In general, the loss of yearly earnings amounted to about a one-third reduction in earnings and ranged from $3,700 to $8,700 per annum. CONCLUSIONS: Diabetes has a considerable net effect on earnings, and the complications and duration of diabetes have compound effects. Our findings have implications for the cost-effectiveness of diabetes control; the presence of complicating factors is the single most important predictive factor in lost productivity costs attributable to diabetes, and thus the avoidance or retardation of complications will have an impact on indirect health-related costs.

Adult↗
PubMed2001

Fisetin induces transcription of NADPH:quinone oxidoreductase gene through an antioxidant responsive element-involved activation.

Induction of phase II enzymes such as NADPH:quinone oxidoreductase (QR) can reduce carcinogen-induced mutagenesis and tumor formation. In our search for novel dietary anticarcinogens, fisetin, a flavonol widely distributed in fruits and vegetables was found to induce QR activity in murine hepatoma 1c1c7 cells. The cells were treated with various concentrations of fisetin, and then were assessed for cell growth, QR activity, QR mRNA expression and transcription activation of the QR gene. The results showed that fisetin induced QR activity in time- and dose-dependent manner in the concentration range of 0.1 to 10 microM, and the activity induction was associated with QR mRNA expression as detected by reverse transcription-PCR. Furthermore, transfection studies using a human QR antioxidant/electrophile-response element (ARE/EpRE) reporter construct demonstrated that fisetin activated the ARE/EpRE. These results show that fisetin increases QR activity by transcriptional activation of the ARE/EpRE, suggesting a novel mechanism by which dietary fisetin may be implicated in cancer chemoprevention.

Animals↗
PubMed2001

Acute confusion in terminally ill hospitalized patients.

Knowledge about acute confusion (AC) has grown rapidly during the past decade, but very few studies have focused specifically on AC episodes associated with the end of life. Although experienced oncology clinicians accept that AC is common near the end of life, little is known about the frequency, nature, course, and timing of AC during this critical stage of life in patients with terminal cancer. Data suggest patients with advanced cancer have reversible causes of delirium, where appropriate treatment can result in improved outcomes. The data for this article are drawn from a larger study investigating the incidence, prevalence, behaviors, and outcomes of AC in acutely ill medical patients. The diagnosis of AC was ascertained using the NEECHAM Confusion Scale. Of the 117 participants included in the larger study, 16 developed delirium (cumulative incidence estimate, 14%) and 10 died within 1 year of the index hospitalization. These 10 cases were categorized in two groups: those with a cancer-related diagnosis (n = 6) and those without cancer (n = 4). To further describe the nature of AC near the end of life, two case studies are presented. Because all previous studies were conducted using samples consisting of patients with cancer, it is unknown whether the findings reported in previous studies hold for other terminal illnesses, such as chronic obstructive pulmonary disease or heart failure. The data presented in this article suggest there are differences in baseline vulnerability (e.g., cognitive status) and the timing of AC in relation to death. These differences need to be explored in a larger sample of individuals both with and without a diagnosis of cancer. The severity and course of AC in the terminally ill population needs to be described to gain a better understanding of end-of-life AC phenomenology (e.g., signs, patterns, subtypes). Armed with this information, health care providers will then be able to develop and test AC-specific treatments of patients, as well as counsel and support family members of patients experiencing AC.

Acute Disease↗
PubMed2001

The Doctor of Health Administration: an educational innovation for healthcare executives.

This article describes the development and implementation of an innovative doctoral program designed to enhance the knowledge and skills of healthcare executives. The program is a Doctor of Health Administration (D.H.A.) Degree with a specific focus on leadership. This sets the program at the Medical University of South Carolina apart from all others in being the first D.H.A. offered in the United States and the only program at the time to place its primary emphasis on leadership.

Curriculum↗
PubMed2000

Program participation, exercise adherence, cardiovascular outcomes, and program cost of traditional versus modified cardiac rehabilitation.

Common concerns with the traditional protocol (TP) for cardiac rehabilitation include suboptimal program participation, poor facilitation of independent exercise, the use of costly continuous electrocardiographic (ECG) monitoring, and lack of insurance reimbursement. To address these concerns, a reduced cost-modified protocol (MP) was developed to promote independent exercise. Eighty low- to moderate-risk cardiac patients were randomized to a TP (n = 42) or a MP (n = 38) and were compared over 6 months on program participation, exercise adherence, cardiovascular outcomes, and program costs. During month 1, patients followed identical regimens, including 3 ECG-monitored exercise sessions/week, with encouragement to achieve >/=5 thirty-minute sessions/week. In week 5, the TP continued with a facility-based regimen including 3 exercise sessions/week for 6 months and used ECG monitoring the initial 3 months. The MP discontinued ECG monitoring in week 5 and were gradually weaned to an off-site exercise regimen that was complemented with educational support meetings and telephone follow-up. Compared with TP patients, MP patients had higher rates of off-site exercise over 6 months (p = 0.05), and total exercise (on site + off site) during the final 3 months (p = 0.03). Also, MP patients were less likely to drop out (p = 0.05). Both protocols promoted comparable improvements in maximal oxygen uptake (p <0.05), blood lipids (p <0.001), and hemodynamic measurements (p <0.002). The MP cost $738 less/patient than the TP and required 30% less staff (full-time equivalents). These results suggest that a reduced cost MP was as effective as an established TP in improving physiologic outcomes while demonstrating higher rates of exercise adherence and program participation. Thus, the MP or a similar protocol has applicability to hospitals with large capitated or managed care populations to provide cost-effective cardiovascular risk reduction to patients.

Adult↗
PubMed2000

Simple method for determination of terbutaline plasma concentration by high-performance liquid chromatography.

A method is described in which low nanomolar concentrations of terbutaline in plasma can be quantitated by use of a standard isocratic high-performance liquid chromatography system with electrochemical detection. Samples were prepared for injection by solid-phase extraction and preserved from degradation by addition of glutathione. Terbutaline and internal standard metaproterenol were resolved from plasma constituents on a single C(18) column by ion-pairing chromatography. The method is precise and accurate for measurement of freebase concentrations as low as 4.4 nmol/l (1 ng/ml).

Bronchodilator Agents↗
PubMed2000

Comparative tracking error analysis of five different optical tracking systems.

OBJECTIVE: Effective utilization of an optical tracking system for image-based surgical guidance requires optimal placement of the dynamic reference frame (DRF) with respect to the tracking camera. Unlike other studies that measure the overall accuracy of a particular navigation system, this study investigates the precision of one component of the navigation system: the optical tracking system (OTS). The precision of OTS measurements is quantified as jitter. By measuring jitter, one can better understand how system inaccuracies depend on the position of the DRF with respect to the camera. MATERIALS AND METHODS: Both FlashPointtrade mark (Image Guided Technologies, Inc., Boulder, Colorado) and Polaristrade mark (Northern Digital Inc., Ontario, Canada) optical tracking systems were tested in five different camera and DRF configurations. A linear testing apparatus with a software interface was designed to facilitate data collection. Jitter measurements were collected over a single quadrant within the camera viewing volume, as symmetry was assumed about the horizontal and vertical axes. RESULTS: Excluding the highest 5% of jitter, the FlashPoint cameras had an RMS jitter range of 0.028 +/- 0.012 mm for the 300 mm model, 0.051 +/- 0.038 mm for the 580 mm model, and 0.059 +/- 0.047 mm for the 1 m model. The Polaris camera had an RMS jitter range of 0.058 +/- 0.037 mm with an active DRF and 0.115 +/- 0.075 mm with a passive DRF. CONCLUSION: Both FlashPoint and Polaris have jitter less than 0.11 mm, although the error distributions differ significantly. Total jitter for all systems is dominated by the component measured in the axis directed away from the camera.

Surgical Procedures, Operative↗
PubMed2000

Effect of in vitro testing over extended periods on the low-load mechanical behaviour of dense connective tissues.

Many biomechanical studies are performed on dense connective tissues in the laboratory over a substantial time period; however, the effect of the in vitro testing environment on the cyclic load-relaxation behaviour of these structures is not well established. This study evaluated the effect of long duration of testing on ligament viscoelastic behaviour, using the rabbit femur-medial collateral ligament-tibia complex as a model. Dissected rabbit knee joints were mounted on a materials testing machine, and isolated ligament complexes were cycled at a frequency of one cycle/min to a fixed displacement of 0.7 mm for an 18-hour period. After an initial period of exponential load relaxation, the cyclic peak loads slowly decreased over the 18-hour period. The average decrease in the cyclic peak load between 0.5 and 18.0 hours was 0.26% (of the original peak load) per hour (r2 = 0.934), or a total of 8.6+/-4.6% over this period (p < 0.0001). Thus, low-load testing of dense connective tissues in the laboratory over extended periods significantly alters their biomechanical behaviour, and these changes should be considered in long-term laboratory-based studies of dense connective tissues.

Animals↗
PubMed2000

Importance of beta(2)adrenergic receptor genotype, gender and race on albuterol-evoked bronchodilation in asthmatics.

To determine whether race and gender affect beta(2)receptor-stimulated bronchodilation, we quantified FEV(1)and plasma concentrations of albuterol at various times following the oral administration of a single 8-mg dose of albuterol in 15 black and 15 white male and female asthmatics. No important racial or gender differences in albuterol-evoked FEV(1)or percent-predicted FEV(1)were evident, although females tended to be more sensitive compared to males. Pharmacodynamic (PD) models were fitted to data in 19 patients (63%); FEV(1)was too erratic to fit in three, and a clockwise hysteresis in the FEV(1)vs. albuterol concentration relationship was observed in eight asthmatics. Mean +/- SD baseline (E(0)), maximal FEV(1)(E(max)) and C(50)were: 3.18 + 1.03 l, 4.00 +/- 1.12 l, 7.84 +/- 10.2 microg/l, respectively. beta(2)receptor genotype was determined in 16 patients. All Arg 16 homozygotes exhibited proportional FEV(1)response vs. plasma albuterol concentration relationships, and thus were fitted by PD models. All those having a poor FEV(1)vs. albuterol concentration relationship carried the Gly 16 allele. We conclude that receptor genotype, but not race or gender, is an important determinant of albuterol pharmacodynamics.

Adolescent↗
PubMed2000

Simulation of elbow and forearm motion in vitro using a load controlled testing apparatus.

The purpose of this study was to compare passive to active testing on the kinematics of the elbow and forearm using a load-controlled testing apparatus that simulates muscle loading. Ten fresh-frozen upper extremities were tested. Active control was achieved by employing computer-controlled pneumatic actuators attached to the tendons of the brachialis, biceps, triceps, brachioradialis and pronator teres. Motion of the radius and ulna relative to the humerus was measured with an electromagnetic tracking system. Active elbow flexion produced more repeatable motion of the radius and ulna than when tested passively (p<0.05). The decrease in variability, as determined from the standard deviation of five successive trials in each specimen, was 76.5 and 58.0% for the varus-valgus and internal-external motions respectively (of the ulna relative to the humerus). The variability in flexion during simulated active forearm supination was 30.6% less than during passive testing. Thus under passive control, in the absence of stability provided by muscular loading across the joint, these uncontrolled motions produce increased variability amongst trials. The smooth and repeatable motions resulting from active control, that probably model more closely the physiologic state, appear to be beneficial in the evaluation of unconstrained kinematics of the intact elbow and forearm.

Aged↗
PubMed2000

The effect of cement restrictors on the occlusion of the humeral canal: an in vitro comparative study of 2 devices.

An in vitro study investigated the efficacy of cement restrictor devices on cement containment and penetration within the humerus. Eight pairs of preserved humeri were prepared using advanced cementing technique followed by insertion of 1 of 2 cement restrictors. Low-viscosity cement was injected followed by sham humeral stem insertion. Each specimen was sectioned into transverse 10-mm slices. Slices were photographed and digitized to quantify the cement/stem and canal cross-sectional area. Cement penetration was determined from the ratio of cement area to canal area. A significant increase in cement penetration was observed among slices from distal to proximal for both restrictors (P = .02). There was no significant difference in cement penetration, leakage, or migration between restrictors. Five of the 8 specimens migrated, with means of 21.5 +/- 25.0 mm and 24.0 +/- 36.0 mm for the polyethylene and silicone restrictors. Leakage or migration resulted in a significant decrease in cement penetration with the polyethylene restrictors (P = .001). In the silicone restrictor group, migration resulted in decreased cement penetration (P = .04). When using advanced cementing techniques, intramedullary restrictors allow improved cement penetration; however, they do not ensure cement containment.

Arthroplasty, Replacement↗
PubMed2000

Rehabilitation of the medial collateral ligament-deficient elbow: an in vitro biomechanical study.

The purpose of this study was to determine the relative contribution of muscle activity and the effect of forearm position on the stability of the medial collateral ligament (MCL)-deficient elbow. Simulated active and passive elbow flexion with the forearm in both supination and pronation was performed using a custom elbow testing apparatus. Testing was first performed on intact specimens, then on MCL-deficient specimens. Elbow instability was quantified using an electromagnetic tracking device by measuring internal-external rotation and varus-valgus laxity of the ulna relative to the humerus. Compared with the intact elbow, transection of the MCL, with the arm in a vertical orientation, caused a significant increase in internal-external rotation during passive elbow flexion with the forearm in pronation, but forearm supination reduced this instability. Overall, following MCL transection the elbow was more stable with the forearm in supination than pronation during passive flexion. In the pronated forearm position simulated active flexion also reduced the instability detected during passive flexion, with the arm in a varus and valgus gravity-loaded orientation. The maximum varus-valgus laxity was significantly increased with MCL transection regardless of forearm position during passive flexion. We concluded that active mobilization of the elbow with the arm in vertical orientation during rehabilitation is safe in the setting of an MCL-deficient elbow with the forearm in a fully supinated and pronated position. Splinting and passive mobilization of the MCL-deficient elbow with the forearm in supination should minimize instability and valgus elbow stresses should be avoided throughout the rehabilitation period.

Aged↗
PubMed2000

Use of health status measures in patients with low back pain in clinical settings. Comparison of specific, generic and preference-based instruments.

OBJECTIVE: To evaluate the discriminative performance over time of specific, generic and preference-based instruments in patients with low back pain (LBP) in clinical settings. METHODS: Forty-six consecutive patients with LBP participated in the study. Self-response questionnaires were administered at baseline and 3 and 6 months, including the following instruments: Oswestry (specific for LBP), SF-36 (generic), EuroQol (EQ-5D) and Health Utilities Index (HUI) (preference-based). EQ-5D and HUI weights were derived from previously published evaluations in the general population. Patients were asked to compare their health status with their baseline health and were categorized on the basis of an ordinal scale as: (a) improved; (b) stable; or (c) worse. Changes in the instruments were evaluated by rescaling the instruments over the same scale interval and by estimating standardized effect sizes between two time points for the three categories of change. RESULTS: Thirty-seven patients (80%) completed both the baseline and the 3-month questionnaire and 34 the baseline and 6-month questionnaires (74%). Overall, at both time points, approximately half of the patients reported no changes in their health status. Correlations between instruments were generally low, suggesting that they measure different health domains. The scales which discriminated best between patients who improved and those who deteriorated at 3 months were the Oswestry, the HUI, the EQ-5D and the SF-36 bodily pain and emotional role subscales. The SF-36 subscales appeared to have a floor effect for those patients who had deteriorated. CONCLUSIONS: Most SF-36 subscales did not adequately reflect changes in the health status of patients with LBP, mostly for those who reported deterioration. Preference-derived quality-of-life scores appeared to discriminate among patients who improved and those who deteriorated, although not as consistently as the disease-specific measure (Oswestry). Additional research is needed to evaluate the role of generic measures of quality of life in the assessment of patients with LBP before they can be widely implemented in clinical settings or outcomes research.

Data Collection↗