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Biomedical subjects

R W Evans

Publications and source records attributed to R W Evans.

At least 19 recordsLinked to original sources

Prospective association between lipid soluble antioxidants and coronary heart disease in men. The Multiple Risk Factor Intervention Trial.

A nested case-control study was performed using participants enrolled in the Multiple Risk Factor Intervention Trial (MRFIT). The cases involved nonfatal myocardial infarction or death from coronary heart disease. Serum samples (n = 734) obtained at baseline and frozen for approximately 20 years were analyzed for the antioxidants, carotenoids, retinol, and alpha-, gamma-, and total tocopherol. The concentrations of antioxidants were in the expected range and their association with low density lipoprotein (LDL) cholesterol reflected their absorption and transport mechanisms. Among nonsmokers, the odds ratios (95% confidence intervals (CI)) for quartile IV versus quartile I were 1.40 (0.40-4.89), 0.77 (0.20-2.96), 1.45 (0.38-5.56), 2.34 (0.56-9.81), and 2.40 (0.52-11.07) for retinol, total carotenoids, and alpha-, gamma-, and total tocopherol, respectively. The equivalent odds ratios (95% CI) for smokers were 0.90 (0.34-2.41), 0.66 (0.23-1.84), 0.67 (0.21-2.13), 2.04 (0.88-4.73), and 0.52 (0.16-1.67), respectively. This analysis of antioxidant concentrations by quartiles indicated no significant association of antioxidant levels with the risk of coronary disease death or nonfatal myocardial infarction.

Adult

An economic analysis of kidney transplantation.

Kidney transplantation is the most cost-effective treatment modality for end-stage renal disease (ESRD). Nonetheless, in keeping with the managed care mandate, expense has become an increasingly significant issue. Over $11 billion is now spent each year on ESRD treatment. Medicare per capita annual payments exceed $36,000 per beneficiary. Transplant procedure charges and outcomes vary dramatically across the United States. The average charge for a kidney transplant is approximately $82,000. Graft and patient survival rates are highly variable, even among the most active programs in the US. Individual transplant programs must implement approaches to contain their costs and assure quality. At the Mayo Clinic, our mean charge for a kidney transplant ($53,510) in 1996 was 27.2% below expected, given national medical inflation over the past decade. Unfortunately, the net operating income associated with our kidney transplant program has been severely eroded in an increasingly brutal economic environment.

Cost Control

Complications of lumbar puncture.

This article reviews historical aspects and the following complications of lumbar puncture: cerebral and spinal herniation, postdural puncture headache, cranial neuropathies, nerve root irritation, low back pain, stylet associated problems, infections, and bleeding complications. The incidence of postdural puncture headache can be greatly reduced by pointing the face of the bevel in the direction of the patient's side, replacing the stylet and rotating the needle 90;dg before withdrawing the needle, and using the Sprotte atraumatic needle, especially in high risk patients.

History, 19th Century

Structure-function relationship of antibacterial synthetic peptides homologous to a helical surface region on human lactoferrin against Escherichia coli serotype O111.

Lactoferricin includes an 11-amino-acid amphipathic alpha-helical region which is exhibited on the outer surface of the amino-terminal lobe of lactoferrin. Synthetic peptides homologous to this region exhibited potent antibacterial activity against a selected range of both gram-negative and gram-positive bacteria. An analog synthesized with methionine substituted for proline at position 26, which is predicted to disrupt the helical region, abolished antibacterial activity against Escherichia coli and considerably reduced antibacterial activity against Staphylococcus aureus and an Acinetobacter strain. The mode of action of human lactoferrin peptide (HLP) 2 against E. coli serotype O111 (NCTC 8007) was established by using flow cytometry, surface plasmon resonance, and transmission electron microscopy. Flow cytometry was used to monitor membrane potential, membrane integrity, and metabolic processes by using the fluorescent probes bis-1,3-(dibutylbarbituric acid)-trimethine oxonol, propidium iodide, and carbonyl cyanide m-chlorophenylhydrazone, respectively. HLP 2 was found to act at the cell membrane, causing complete loss of membrane potential after 10 min and of membrane integrity within 30 min, with irreversible damage to the cell as shown by rapid loss of viability. The number of particles, measured by light scatter on the flow cytometer, dropped significantly, showing that bacterial lysis resulted. The peptide was shown to bind to E. coli O111 lipopolysaccharide by using surface plasmon resonance. Transmission electron microscopy revealed bacterial distortion, with the outer membrane becoming detached from the inner cytoplasmic membrane. We conclude that HLP 2 causes membrane disruption of the outer membrane, resulting in lysis, and that structural considerations are important for antibacterial activity.

Amino Acid Sequence

Expression of acute otitis media after receptor blockade of platelet activating factor, thromboxane, and leukotrienes in the chinchilla.

To determine the role of inflammatory products of phospholipid metabolism in acute otitis media (AOM), we infected 128 chinchillas with Streptococcus pneumoniae and randomly assigned them to one of four equal-sized treatment groups receiving intramuscular ampicillin sodium (control) or intramuscular ampicillin plus receptor blockers of platelet activating factor (WEB 2086, 5 mg/d orally), of leukotriene (MK 571, 0.5 mg/d orally), or of thromboxaneA2 (GR 32191B, 5 mg/d orally). All treatments were begun on day 2 postinoculation and continued for 10 days. On days 3, 6, 9, and 12, 8 animals from each group were sacrificed. Effusions were recovered for biochemical assay, and the right middle ears were prepared for histologic study. Differences among groups in the number of ears with effusion or in effusion volume were not statistically significant. In comparison to the control group, mucosal thickness and the number of ears with histopathologic signs of inflammation were significantly less in the GR and WEB treatment groups, but not the MK group. Also, effusion concentrations of free fatty acids, protease, and hydrolytic enzymes were significantly less in those groups. These results show that the addition of a receptor blocker for either platelet activating factor and/or thromboxane to ampicillin in the treatment of AOM reduces mucosal inflammation and decreases the production of other inflammatory chemicals. The failure of a receptor blocker of leukotrienes to moderate disease expression suggests either a less important role for these chemicals in AOM or an insufficient bioavailability of the specific MK 571 inhibitor. These results confirm that platelet activating factor and thromboxane are active mediators of inflammation in AOM.

6-Ketoprostaglandin F1 alpha

Cost-effectiveness of 6 and 12 months of interferon-alpha therapy for chronic hepatitis C.

BACKGROUND: Interferon-alpha is effective in only a small number of patients with chronic hepatitis C, although prolonged treatment may increase the response rate. There is concern that the expense of interferon-alpha therapy may not be justified by the low response rates and uncertain long-term benefit. OBJECTIVE: To compare clinical and economic outcomes after 6 months and 12 months of interferon-alpha therapy for chronic hepatitis C. DESIGN: A Markov model depicting the natural progression of chronic hepatitis C. On the basis of this model, a simulated trial compared no therapy with 6 and 12 months of interferon-alpha therapy at standard doses (3 million U three times weekly). PATIENTS: Four age-specific cohorts (30, 40, 50, and 60 years of age) with chronic hepatitis C. MEASUREMENTS: Number of deaths from liver disease, total costs, and cumulative quality-adjusted life-years (QALYs). RESULTS: Six and 12 months of interferon-alpha treatment gained 0.25 QALYs at an incremental cost of $1000 and 0.37 QALYs at an incremental cost of $1900, respectively. Thus, although 6 months of interferon-alpha therapy was less efficacious than 12 months of therapy, it was more cost-effective ($4000 per QALY gained compared with $5000 per QALY gained). Nonetheless, in patients younger than 60 years of age, both 6 and 12 months of therapy compared favorably with other established medical interventions, such as screening mammography and cholesterol reduction programs. Important variables affecting the cost-effectiveness of interferon-alpha treatment included the cost and efficacy of interferon-alpha, the cost of treatment for decompensated cirrhosis, and quality of life in patients with chronic hepatitis C. CONCLUSION: From the standpoint of cost-effectiveness, interferon-alpha therapy for 6 or 12 months may be justified in patients with chronic hepatitis C. The possible exception is patients older than 60 years of age.

Adult

Identification of potential ferric binding residues in the iron-binding protein of pathogenic Neisseria meningitidis through structure-based multiple sequence alignments.

The ferric iron-binding proteins of pathogenic Neisseria display structural and metal-binding properties characteristic of the transferrin family. In the absence of structural data for the ferric iron-binding proteins, spacial folding templates have been derived for the meningococcal protein from complete and partial structure-based multiple sequence alignments with structurally related proteins. The templates have been used to identify a number of potential iron-binding residues. These include four residues that are identical with the iron coordinating ligands of transferrin, but only two reside within equivalent structural elements.

Bacterial Outer Membrane Proteins

Characterisation of the meningococcal transferrin binding protein complex by photon correlation spectroscopy.

Photon correlation spectroscopy demonstrated for the first time that co-purified meningococcal TbpA+B form a complex in solution. This structure bound hTf and the resultant species underwent partial dissociation after exposure to additional hTf or following prolonged incubation. Purified TbpA and TbpB had similar apparent sizes but showed distinctive size profiles suggesting that TbpA forms a largely homogeneous population while TbpB may produce more variable particle sizes under these conditions.

Bacterial Outer Membrane Proteins

Identification of potential ferric binding residues in the iron-binding protein of pathogenic Neisseria meningitidis through structure-based multiple sequence alignments.

The ferric iron-binding proteins of pathogenic Neisseria display structural and metal-binding properties characteristic of the transferrin family. In the absence of structural data for the ferric iron-binding proteins, spacial folding templates have been derived for the meningococcal protein from complete and partial structure-based multiple sequence alignments with structurally related proteins. The templates have been used to identify a number of potential iron-binding residues. These include four residues that are identical with the iron coordinating ligands of transferrin, but only two reside within equivalent structural elements.

Amino Acid Sequence

Expression of recombinant human ceruloplasmin--an absolute requirement for splicing signals in the expression cassette.

We report the successful expression of recombinant human ceruloplasmin which was made possible by inclusion of splicing signals in the expression vector. Ceruloplasmin cDNA expressed from the vector pNUT in baby hamster kidney cells gave protein yields of 0.03 mg/l which increased to 15 mg/l with splicing signals present. The defect in expression from the intronless cDNA is due to complete retention of ceruloplasmin mRNA in cell nuclei. The block to cytoplasmic export is alleviated by splicing signals, allowing full expression of the mRNA.

Animals

Postacute neurorehabilitation: roles and responsibilities within a national information system.

The definition of a "postacute neurorehabilitation provider" has broadened considerably in the last 10 years. The postacute domain, once the purview of community re-entry (aka transitional) programs now includes hospital-based day and outpatient services, home health agencies, assisted living programs, subacute programs, and employment agencies to name but a few. Consequently, a range of outcome variables are considered, in large part as related to the clinical and/or business missions of the providers. This article reviews the postacute neurorehabilitation outcome literature with an eye toward establishing a concensus as to what outcomes are germane to these providers, with the patients and payers as the preferred primary consumers of the outcome-related information.

Brain Injuries

Cost-effectiveness of treating nicotine dependence: the Mayo Clinic experience.

OBJECTIVE: To estimate the cost-effectiveness of treating nicotine dependence, expressed as cost per net year of life gained by smoking cessation. DESIGN: A cost-effectiveness analysis was conducted of a cohort of consecutive adult patients treated for nicotine dependence from April 1988 through December 1992 at the Mayo Clinic Nicotine Dependence Center (NDC). MATERIAL AND METHODS: The study cohort consisted of 5,544 patients (50.8% female; mean age, 47.8 years) with a mean baseline smoking rate of 25.4 cigarettes per day. After an initial consultation, a nonphysician counselor developed an individual nicotine dependence treatment plan, which could include follow-up counseling, nicotine replacement therapy (patches or gum), group therapy, or an inpatient program. A relapse-prevention program included telephone calls and a series of letters to the patient. We computed the years of life gained for each person specific to age, gender, smoking rate at entry, and 6-month smoking status by using published mortality rates for current and former cigarette smokers. The 6-month smoking status was assumed to be applicable at 1 year. For subsequent determinations, we modeled by computer simulation the year-by-year (to age 100) smoking status by using published relapse and late cessation rates. Coupled with treatment costs, this information allowed the expression of cost per net year of life gained by stopping smoking. Net years of life gained, discounted 0, 3, and 5%, were computed with use of cessation and relapse rates expected for patients not seen in the NDC. Treatment costs were based on 1993 rates for the intervention services but did not include any tobacco product cost savings associated with smoking cessation. RESULTS: The 1-year smoking-cessation rate was 22.2%. With all NDC patients included, the estimated net years of life gained, with use of a 5% rate of discount for benefits, was 0.058, and the corresponding cost was $6,828 per net year of life gained. CONCLUSION: In comparison with the cost-effectiveness of other medical services, the cost of $6,828 per net year of life gained by treatment of nicotine dependence is relatively inexpensive. Such cost-outcome data are important as economic considerations are applied for optimal allocation of limited health-care resources. Nonphysician health-care professionals can assume a key role in the provision of cost-effective nicotine dependence intervention.

Adult

Factors associated with work outcome after anterior temporal lobectomy for intractable epilepsy.

PURPOSE: Whereas the effect of anterior temporal lobectomy on seizure frequency is well recognized, less is known about its impact on work status. METHODS: One hundred thirty-four of 190 consecutive patients with temporal lobectomy participated in this study. Eligibility criteria were developed to ensure that only patients with the potential of achieving specific outcomes were included in the corresponding analyses. RESULTS: After surgery, significantly more patients were independent in activities of daily living (p < 0.001) or able to drive (p < 0.001). Income from work also increased (p < 0.01). Nearly one fifth of the patients who were eligible for analysis had either a gain (8%) or a loss (11%) of full- or of part-time work. Univariate analyses revealed the following factors to be associated with full-time work after surgery: student or full-time work within a year before surgery, full-time work experience before surgery, full- or part-time employment experience before surgery, no disability benefits before surgery, low postsurgical seizure frequency, improved postsurgical seizure control, excellent postsurgical seizure control, driving after surgery, and further education after surgery (p < 0.05). Significant factors on multivariate analysis were being a student or having full-time work within a year before surgery [odds ratio, 16.2 (95% CI, 4.3-60.5)], driving after surgery [15.2 (3.2-72.0)], and obtaining further education after surgery [9.2 (2.2-53.0)]. CONCLUSIONS: Anterior temporal lobectomy for intractable epilepsy improves activities of daily living and the ability to drive. Work outcome of this surgery is influenced by presurgical work experience, successful postsurgical seizure control especially to allow driving, and obtaining further education after surgery.

Activities of Daily Living

Homocyst(e)ine and risk of cardiovascular disease in the Multiple Risk Factor Intervention Trial.

A nested case-control study was undertaken involving men participating in the Multiple Risk Factor Intervention Trial (MRFIT). Serum samples from 712 men, stored for up to 20 years, were analyzed for homocyst(e)ine. Cases involved nonfatal myocardial infarctions (MIs), identified through the active phase of the study, which ended on February 28, 1982, and deaths due to coronary heart disease (CHD), monitored through 1990. The nonfatal MIs occurred within 7 years of sample collection, whereas the majority of CHD deaths occurred more than 11 years after sample collection. Mean homocyst(e)ine concentrations were in the expected range and did not differ significantly between case patients and control subjects: MI cases, 12.6 mumol/L; MI controls, 13.1 mumol/L; CHD death cases, 12.8 mumol/L; and CHD controls, 12.7 mumol/L. Odds ratios versus quartile 1 for CHD deaths and MIs combined were as follows: quartile 2, 1.03; quartile 3, 0.84; and quartile 4, 0.92. Thus, in this prospective study, no association of homocyst(e)ine concentration with heart disease was detected. Homocyst(e)ine levels were weakly associated with the acute-phase protein (C-reactive protein). These results are discussed with respect to the suggestion that homocyst(e)ine is an independent risk factor for heart disease.

Adult