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Biomedical subjects

M M Johnson

Publications and source records attributed to M M Johnson.

At least 19 recordsLinked to original sources

Effective antigen-specific immunotherapy in the marmoset model of multiple sclerosis.

Mature T cells initially respond to Ag by activation and expansion, but high and repeated doses of Ag cause programmed cell death and can suppress T cell-mediated diseases in rodents. We evaluated repeated systemic Ag administration in a marmoset model of experimental allergic encephalomyelitis that closely resembles the human disease multiple sclerosis. We found that treatment with MP4, a chimeric, recombinant polypeptide containing human myelin basic protein and human proteolipid protein epitopes, prevented clinical symptoms and did not exacerbate disease. CNS lesions were also reduced as assessed in vivo by magnetic resonance imaging. Thus, specific Ag-directed therapy can be effective and nontoxic in primates.

Animals↗

Urban-rural differences in a memory disorders clinical population.

OBJECTIVES: To compare patient characteristics and family perceptions of patient function at one urban and one rural memory disorders clinic. DESIGN: Secondary, cross-sectional data analyses of an extant clinical database. SETTING/PARTICIPANTS: First time visits (n = 956) at two memory disorders clinics. MEASUREMENTS: Patient and family-member demographics and assessment results for the Mini-Mental State Examination (MMSE), instrumental activities of daily living (IADLs), activities of daily living (ADLs), the Memory Change and Personality Change components of the Blessed Dementia Rating Scale, and the Revised Memory and Behavior Problems Checklist. RESULTS: In both clinics, patients and family members were more likely female. The typical urban clinic patient was significantly more likely to be living in a facility and more educated than the typical rural patient. Urban and rural patients did not show significant differences in age- and education-adjusted MMSE scores or raw ADL/IADL ratings, but the urban family members reported more memory problems, twice as many personality changes, more-frequent behavior problems, and more adverse reactions to problems. CONCLUSION: Physicians who practice in both urban and rural areas can anticipate differences between patients, and their families, who seek a diagnosis of memory disorders. Our most important finding is that despite similarities in reported functional abilities, urban families appear to be more sensitive to and more distressed by patients' cognitive and behavioral symptoms than rural families. These differences may reflect different underlying needs, and should be explored in further research.

Activities of Daily Living↗

Diversity in medical school: perceptions of first-year students at four southeastern U.S. medical schools.

PURPOSE: To assess students' perceptions of the extent of diversity in their classes, the role of diversity in their first-year curriculum, and their predictions of the amount of diversity in their future patient populations. METHOD: In 1998, students at four southeastern U.S. medical schools that had distinct demographics and differing institutional missions completed a questionnaire on diversity at the end of the first year. In the instrument, diversity was defined according to nine population characteristics: age, sex, race, ethnic background, physical disability, religious affiliation, sexual orientation, socioeconomic status, and rural background (growing up in a community of less than 5,000). Responses were compared according to students' institution, sex, and race. RESULTS: Questionnaires were returned by 349 of 474 students (74%). Students at the school with the most diverse first-year class placed the greatest value on the contributions of diversity to the learning environment. Women students placed more value on the inclusion of diversity issues in the curriculum than did men students, and they placed greater value on understanding diversity issues in their future medical practices than did men. Compared with Asian American, Hispanic, and white students, African American students were the least likely to think that the curriculum contained adequate information about diversity. CONCLUSIONS: The results indicate that perceptions of diversity were influenced by the students' own demographic characteristics and those of their medical school. The more diverse the class, the more comfortable the students were with diversity and the more they valued its contribution to their medical education.

Curriculum↗

Artifacts and the visualization of fetal distal extremities using three-dimensional ultrasound.

OBJECTIVES: To demonstrate that acoustic shadowing in 3D US may give rise to artifacts simulating limb defects and provide a solution to eliminate its occurrence. METHODS: Twenty second trimester fetuses (gestational age 15-24 weeks) were scanned with three-dimensional ultrasound (3D US) using a sagittal acquisition plane. Fetal tibia/fibula and radius/ulna pairs were assessed for completeness of imaging. A further 20 fetuses (gestational age 20-26 weeks) were scanned in both axial and sagittal planes and the results compared to verify clear visualization of both bones. RESULTS: Shadowing from adjacent structures produced an apparent limb defect in 55% of the first 20 fetuses imaged only sagittally (18% of limb pairs). Acquiring data from more than one orientation avoided this artifact. CONCLUSIONS: The 3D US is subject to the same artifacts as two-dimensional (2D US) in terms of acoustic shadowing, although their presentation may be different. Awareness of this fact is essential for correct interpretation of 3D US studies. Three-dimensional scanning protocols should be modified to ensure that fetal structures are adequately visualized by acquiring volume data in more than one acquisition orientation.

Artifacts↗

Addition of eicosapentaenoic acid to gamma-linolenic acid-supplemented diets prevents serum arachidonic acid accumulation in humans.

Previous studies reveal that supplementation of human diets with gamma-linolenic acid (GLA) reduces the generation of lipid mediators of inflammation and attenuates clinical symptoms of chronic inflammatory disorders such as rheumatoid arthritis. However, we have shown that supplementation with this same fatty acid also causes a marked increase in serum arachidonate (AA) levels, a potentially harmful side effect. The objective of this study was to design a supplementation strategy that maintained the capacity of GLA to reduce lipid mediators without causing elevations in serum AA levels. Initial in vitro studies utilizing HEP-G2 liver cells revealed that addition of eicosapentaenoic acid (EPA) blocked Delta-5-desaturase activity, the terminal enzymatic step in AA synthesis. To test the in vivo effects of a GLA and EPA combination in humans, adult volunteers consuming controlled diets supplemented these diets with 3.0 g/d of GLA and EPA. This supplementation strategy significantly increased serum levels of EPA, but did not increase AA levels. EPA and the elongation product of GLA, dihomo-gamma-linolenic acid (DGLA) levels in neutrophil glycerolipids increased significantly during the 3-wk supplementation period. Neutrophils isolated from volunteers fed diets supplemented with GLA and EPA released similar quantities of AA, but synthesized significantly lower quantities of leukotrienes compared with their neutrophils before supplementation. This study revealed that a GLA and EPA supplement combination may be utilized to reduce the synthesis of proinflammatory AA metabolites, and importantly, not induce potentially harmful increases in serum AA levels.

Adult↗

Acquired thermotolerance and expression of the HSP100/ClpB genes of lima bean.

Acquired thermotolerance (AT) is the ability of cells to survive a normally lethal temperature treatment as a consequence of pretreatment at an elevated but sublethal temperature. In yeast and cyanobacteria, the expression of the HSP100/ClpB protein is required for the AT response. To determine whether the HSP100/ClpB protein is associated with this response in lima bean (Phaseolus lunatus), we have cloned an HSP100/ClpB homolog and assessed expression of the two gene copies under heat stress conditions, which induce AT. Transcription of the cytoplasmically localized HSP100/ClpB protein genes is stringently controlled by heat stress in both of the laboratory and field heat stress conditions. From a heat-induced cDNA library, we identified a clone of a putative chloroplast-targeted (cp) HSP100/ClpB protein gene sequence. The cp HSP100/ClpB protein genes are constitutively expressed, but transcript levels increase post-heat stress in laboratory heat stress experiments. In field conditions the genes for the cp HSP100/ClpB are constitutively expressed. Although we were unable to correlate differences in the timing of AT response with the expression or genetic structure of the HSP100/ClpB genes in heat-tolerant or -sensitive varieties of lima bean, we clearly demonstrate the association of expression of HSP100/ClpB proteins with heat response in this species.

Amino Acid Sequence↗

Determinant spreading associated with demyelination in a nonhuman primate model of multiple sclerosis.

Definition of the immune process that causes demyelination in multiple sclerosis is essential to determine the feasibility of Ag-directed immunotherapy. Using the nonhuman primate, Callithrix jacchus jacchus (common marmoset), we show that immunization with myelin basic protein and proteolipid protein determinants results in clinical disease with significant demyelination. Demyelination was associated with spreading to myelin oligodendrocyte glycoprotein (MOG) determinants that generated anti-MOG serum Abs and Ig deposition in central nervous system white matter lesions. These data associate intermolecular "determinant spreading" with clinical autoimmune disease in primates and raise important issues for the pathogenesis and treatment of multiple sclerosis.

Adjuvants, Immunologic↗

Venous air embolism from central venous catheterization: a need for increased physician awareness.

OBJECTIVES: To report a series of patients with clinically diagnosed venous air embolism (VAE) and major sequelae as a complication of the use of central venous catheters (CVCs), to survey health care professionals' practices regarding CVCs, and to implement an educational intervention for optimizing approaches to CVC insertion and removal. SETTING: Tertiary care, university-based 806-bed medical center. INTERVENTIONS: We surveyed 140 physicians and 53 critical care nurses to appraise their awareness of the proper management and complications of CVCs. We then designed, delivered, and measured the effects of a multidisciplinary educational intervention given to 106 incoming house officers. MEASUREMENTS AND MAIN RESULTS: Although most physicians (127, 91%) chose the Trendelenburg position for CVC insertion, only 42 physicians (30%) reported concern for VAE. On CVC removal, only 36 physicians (26%) cited concern for VAE. Some physicians (13, 9%) reported elevating the head of the bed during CVC removal, possibly increasing the risk of VAE. Awareness of VAE or its prevention did not correlate with the level of physician training, experience, or specialty. After the educational intervention, concern for and awareness of proper methods of prevention of VAE improved (p < .001). At 6-month follow-up, reported use of the Trendelenburg position continued, but concern cited for VAE had returned to baseline. CONCLUSIONS: There is inadequate awareness of VAE as a complication of CVC use. Focused instruction can improve appreciation of this potentially fatal complication and knowledge of its prevention, but the effect declines rapidly. To achieve a more sustained improvement, a more intensive, hands-on, periodic educational program will likely be necessary, as well as reinforcement through enhanced supervision of CVC insertion and removal practices.

Academic Medical Centers↗

Effect of carbon dioxide on testing of susceptibilities of respiratory tract pathogens to macrolide and azalide antimicrobial agents.

The in vitro activities of erythromycin, azithromycin, and clarithromycin against 178 clinical isolates from the lower respiratory tract of patients with chronic obstructive pulmonary disease were determined by an agar dilution method. The plates were incubated in air alone or in 5% carbon dioxide. The MICs measured in air alone were lower for most isolates than those measured in 5% carbon dioxide, illustrating the "pH effect" of incubation in carbon dioxide. Testing of isolates in 5% carbon dioxide on pH-adjusted medium (pH 8.4) resulted in MICs of one or two doubling dilutions lower than those obtained on agar with a neutral pH. A bioassay of the three agents incubated in air and in 5% carbon dioxide resulted in a significant loss of activity of all three agents in the carbon dioxide-enriched atmosphere. However, this loss-of-activity effect was significantly reduced when the bioassay medium was adjusted to pH 8.4 prior to incubation in 5% carbon dioxide.

Anti-Bacterial Agents↗

Role of arachidonyl triglycerides within lipid bodies in eicosanoid formation by human polymorphonuclear cells.

Increasing evidence suggests that the subcellular and glycerolipid localization of esterified arachidonic acid (AA) is a key factor in regulating its availability to lipases. The goal of the current study was to determine the potential of AA stored in triglycerides (TG) to serve as a substrate for lipases and 5-lipoxygenase during neutrophil (polymorphonuclear leukocytes, PMN) activation. PMN containing high concentrations of AA in TG were generated by culturing PMN in vitro with high concentrations of exogenous AA (eAA) for 12 h. Cellular AA increased 2- and 4-fold in PMNs incubated with 5 and 20 microM AA, respectively, and this increase was almost exclusively observed in neutral lipids (NL). Further analysis revealed that 88% of the AA in the NL fraction was associated with TG. Subsequent experiments were designed to determine whether this AA in TG could be mobilized and metabolized to eicosanoids during cell activation. TG pools of AA were increased as previously described and then PMN were stimulated with ionophore, A23187. In contrast to the 43-fold increase in TG AA after eAA loading (20 microM), free AA increased by only 1.9-fold after cell stimulation. Similarly, leukotriene (LT)B(4) production increased only 2-fold after loading TG with large quantities of AA. The magnitude of increase in free AA released and in LTB(4) formation was similar to the magnitude of increase in AA mass in phospholipase (PL), suggesting that PL, and not TG, served as the source of released AA and subsequent product generation. To confirm that AA in TG did not serve as a source for eicosanoid production, cellular pools of AA were differentially labeled with [(14)C]AA and [(3)H]AA, and the [(3)H]AA-to-[(14)C]AA ratio of LTB(4) and 20-hydroxyl LTB(4) produced during cell stimulation was measured. The [(3)H]AA/[(14)C]AA ratios of LTs were markedly different from the ratios in TG, thus providing further evidence that AA pools in TG are not a major source of AA for LT generation.

Arachidonic Acids↗

Physicians and clergy as facilitators of formal services for older adults.

Researchers have sought to understand the determinants of the use of in-home and community-based services in order to better serve the needs of older adults. One component frequently included in formal service utilization models is the role of individuals who exert an influence on the service use process. An analysis of in-depth interviews conducted with 115 older adults revealed the important facilitating role that physicians and religious leaders play in encouraging the use of these services. The sample, which included African-American and white adults age 65+ from rural and urban environments, described various ways in which these "facilitators" influence the use of formal services. These ways include: (1) supplying instrumental support either by "ordering" a particular program for or linking the elder with the program and (2) providing informational and affective support, including advising or recommending the use of a program, conveying necessary background on formal services, and legitimizing the use of formal services. Regardless of personal characteristics (such as ethnicity and residence), a majority of elders in the sample recognized the important role played by physicians, and clergy. The acknowledgement of the role played by these facilitators should be viewed as an opportunity for physicians and clergy to enhance the knowledge and appropriate use of needed formal services for elders. In addition, these findings have policy implications for the current provision of aging services.

Aged↗

Radiographic assessment of hyperinflation: correlation with objective chest radiographic measurements and mechanical ventilator parameters.

BACKGROUND: Pulmonary barotrauma is a potentially fatal complication of positive pressure ventilation. We previously found that barotrauma occurred in patients with radiographic hyperinflation, but few objective data define the relationships among hyperinflation, objective chest radiograph (CXR) measurements, ventilator parameters, and development of barotrauma. OBJECTIVES: We sought (1) to assess the relationships among hyperinflation, objective CXR findings, mechanical ventilator parameters, and development of barotrauma. (2) To compare radiographic hyperinflation, ventilator parameters, and incidence of barotrauma in a current group of ICU patients with historical control subjects. SETTING: Medical and surgical ICU patients in a university hospital. DESIGN: Prospective blinded observational study; comparison of current series with historical control subjects. METHODS: One hundred two prospectively enrolled mechanically ventilated medical and surgical ICU patients each received portable supine CXRs that were reviewed independently by three radiologists who made objective measurements and subjectively determined the likelihood of hyperinflation. Ventilator parameters were recorded at the bedside at the time each CXR was obtained. CXR measurements and ventilator parameters were then related to the development of barotrauma during the course of ventilation and compared with findings of a prospective study at our institution 1 year earlier. RESULTS: Radiographically recognizable hyperinflation occurred in 18 of 102 mechanically ventilated ICU patients (18%) and correlated with lung length (24.7 vs 19.8 cm; p<0.05) and the anterior rib number that intersects the hemidiaphragm (5.4 vs 4.7; p<0.05). Patients with hyperinflation were ventilated at higher tidal volume per kilogram (VT/kg) (11.0 vs 9.4; p=0.0081), but peak airway pressure, plateau pressure, and positive end-expiratory pressure were similar. There were significant decreases in VT (810 vs 739 mL; p=0.015) and VT/kg (11.0 vs 10.1 mL/kg; p<0.001) in these mechanically ventilated ICU patients in comparison to hospital control subjects evaluated during the previous year. Paralleling these changes was a decrease in the frequency of CXR hyperinflation (p=0.003) and the incidence of ventilator-associated barotrauma (6.5% vs 0.98%; p=0.048). CONCLUSIONS: Ventilation at higher VT/kg is associated with a higher incidence of CXR hyperinflation. Radiographic hyperinflation is associated with lung length > or =24.7 cm and visualization of the sixth anterior rib. Patients with hyperinflation may be at greater risk for developing barotrauma or volutrauma. Ventilatory strategies utilizing lower volumes are associated with a lower incidence of such trauma in the current sample as compared with historical control subjects.

Adolescent↗

Dietary supplementation with gamma-linolenic acid alters fatty acid content and eicosanoid production in healthy humans.

To understand the in vivo metabolism of dietary gamma-linolenic acid (GLA), we supplemented the diets of 29 volunteers with GLA in doses of 1.5-6.0 g/d. Twenty-four subjects ate controlled eucaloric diets consisting of 25% fat; the remaining subjects maintained their typical Western diets. GLA and dihomo-gamma-linolenic acid (DGLA) increased in serum lipids of subjects supplemented with 3.0 and 6.0 g/d; serum arachidonic acid increased in all subjects. GLA supplementation with 3.0 and 6.0 g/d also resulted in an enrichment of DGLA in neutrophil phospholipids but no change in GLA or AA levels. Before supplementation, DGLA was associated primarily with phosphatidylethanolamine (PE) of neutrophil glycerolipids, and DGLA increased significantly in PE and neutral lipids after GLA supplementation. Extending the supplementation to 12 wk did not consistently change the magnitude of increase in either serum or neutrophil lipids in subjects receiving 3.0 g/d. After GLA supplementation, A23187-stimulated neutrophils released significantly more DGLA, but AA release did not change. Neutrophils obtained from subjects after 3 wk of supplementation with 3.0 g/d GLA synthesized less leukotriene B4 (P < 0.05) and platelet-activating factor. Together, these data reveal that DGLA, the elongase product of GLA, but not AA accumulates in neutrophil glycerolipids after GLA supplementation. The increase in DGLA relative to AA within inflammatory cells such as the neutrophil may attenuate the biosynthesis of AA metabolites and may represent a mechanism by which dietary GLA exerts an anti-inflammatory effect.

8,11,14-Eicosatrienoic Acid↗

A comparison of specialty choices, residency training, and practice locations of early-decision and regular-admission graduates.

PURPOSE: Early-decision (ED) medical school applicants express a clear preference for attending a particular medical school. The present study assessed whether ED graduates would demonstrate similar geographic preferences in their choices of undergraduate institutions and selections of in-state residency sites and practice locations. METHOD: The study was conducted at the University of Kentucky College of Medicine. Uniform academic and nonacademic criteria were used to evaluate the applications of ED and regular-admission students who matriculated from 1974-75 to 1984-85. The student variables assessed were class year, gender, age, county of residence, and undergraduate college, as well as undergraduate science and cumulative grade-point averages (GPAs) and Medical College Admission Test (MCAT) scores. Specialty choice and locations of residency programs were obtained from the medical school's commencement programs. Specialty types and practice locations were obtained from practicing physician records maintained by the alumni office. RESULTS: Of the 1,243 matriculants, 193 (15.5%) gained admission to the school through the ED plan. The ED graduates were significantly more likely to have completed their undergraduate studies at the University of Kentucky than at other public or private schools, in state or out of state, and had significantly higher GPAs and MCAT scores. As a group, the ED graduates were somewhat (though not significantly) more likely than the regular-admission graduates to remain in state for their residencies and practice in state. CONCLUSION: The authors suggest that medical schools should work closely with their undergraduate admission offices to attract academically outstanding high school students. Such students are likely to stay in state for the eight-year span of their undergraduate and medical educations and may have a greater tendency to practice in state.

Academic Medical Centers↗

The effect of a rolling admission policy on a medical school's selection of applicants.

PURPOSE: As the University of Kentucky College of Medicine (UKCM) employs a rolling admission policy, this study was designed to determine (1) whether the month during which applicants were considered by the UKCM admission committee was associated with admission status, (2) whether applicants considered early in the process differed in selected academic and noncognitive pre-admission characteristics in comparison with later applicants, and (3) what the importance of the month of the applicant's consideration was relative to other predictors of admission to UKCM. METHOD: The application files and admission committee's minutes regarding 302 applicants who received interviews during the 1993-94 application cycle were examined. Data reviewed included each applicant's gender, age, geographic origin, undergraduate science and non-science grade-point averages, and Medical College Admission Test scores; the date of consideration by the committee; interviewers' ratings; the initial motion on the applicant; and the final admission status. RESULTS: The findings indicate that the applicants considered earlier were significantly more likely to gain admission. However, upon assigning the applicants to three groups according to the month of consideration, no difference in academic qualifications was found. Regression analyses revealed that despite the effect of time of consideration, noncognitive characteristics related to UKCM's mission also predicted admission decisions. CONCLUSION: This study provides useful information to admission committees reviewing the effect of a rolling admission policy, as well as to applicants and premedical advisors, who should be aware of the potential importance of submitting applications in a timely manner.

Adult↗

Effect on the duration of mechanical ventilation of identifying patients capable of breathing spontaneously.

BACKGROUND: Prompt recognition of the reversal of respiratory failure may permit earlier discontinuation of mechanical ventilation, without harm to the patient. METHODS: We conducted a randomized, controlled trial in 300 adult patients receiving mechanical ventilation in medical and coronary intensive care units. In the intervention group, patients underwent daily screening of respiratory function by physicians, respiratory therapists, and nurses to identify those possibly capable of breathing spontaneously; successful tests were followed by two-hour trials of spontaneous breathing in those who met the criteria. Physicians were notified when their patients successfully completed the trials of spontaneous breathing. The control subjects had daily screening but no other interventions. In both groups, all clinical decisions, including the decision to discontinue mechanical ventilation, were made by the attending physicians. RESULTS: Although the 149 patients randomly assigned to the intervention group had more severe disease, they received mechanical ventilation for a median of 4.5 days, as compared with 6 days in the 151 patients in the control group (P=0.003). The median interval between the time a patient met the screening criteria and the discontinuation of mechanical ventilation was one day in the intervention group and three days in the control group (P<0.001). Complications -- removal of the breathing tube by the patient, reintubation, tracheostomy, and mechanical ventilation for more than 21 days -- occurred in 20 percent of the intervention group and 41 percent of the control group (P=0.001). The number of days of intensive care and hospital care was similar in the two groups. Total costs for the intensive care unit were lower in the intervention group (median, $15,740, vs. $20,890 in the controls, P=0.03); hospital costs were lower, though not significantly so (median, $26,229 and $29,048, respectively; P=0.3). CONCLUSIONS: Daily screening of the respiratory function of adults receiving mechanical ventilation, followed by trials of spontaneous breathing in appropriate patients and notification of their physicians when the trials were successful, can reduce the duration of mechanical ventilation and the cost of intensive care and is associated with fewer complications than usual care.

Adult↗