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Biomedical subjects

K Robinson

Publications and source records attributed to K Robinson.

At least 91 records · Page 5Linked to original sources

Mucosal delivery of murine interleukin-2 (IL-2) and IL-6 by recombinant strains of Lactococcus lactis coexpressing antigen and cytokine.

Lactococcus lactis is a nonpathogenic and noncolonizing bacterium which is being developed as a vaccine delivery vehicle for immunization by mucosal routes. To determine whether lactococci can also deliver cytokines to the immune system, we have constructed novel constitutive expression strains of L. lactis which accumulate a test antigen, tetanus toxin fragment C (TTFC), within the cytoplasmic compartment and also secrete either murine interleukin-2 (IL-2) or IL-6. When mice were immunized intranasally with various different expression strains of L. lactis, the anti-TTFC antibody titers increased more rapidly and were substantially higher in mice immunized with the bacterial strains which secreted IL-2 or IL-6 in addition to their production of TTFC. This adjuvant effect was lost when the recombinant strains of L. lactis were killed by pretreatment with mitomycin C and could therefore be attributed to the secretion of IL-2 or IL-6 by the recombinant lactococci. These results provide the first example of the use of a cytokine-secreting, noninvasive experimental bacterial vaccine vector to enhance immune responses to a coexpressed heterologous antigen and point the way to experiments which will test the possible therapeutic efficacy of this mode of cytokine delivery.

Administration, Intranasal↗

Systematic analysis of snoring in women.

Nineteen percent of women are habitual snorers, yet most snoring studies report only on male snorers. The aim of this study was to identify the factors responsible for habitual snoring in women. Twenty-four snorers and 16 controls were studied prospectively in a special snoring clinic. Snorers were shorter (p = .005) and heavier (p = .001), and with greater body mass index (BMI: p < .001), collar size (p = .002), and submental skinfold thickness (p = .001) than controls. The area of the posterior pharyngeal wall visible on oral examination was smaller in snorers (p = .005). Acoustic rhinometry areas and volumes were similar in the two groups. Nasal flow-volume loops showed reduced expiratory (p = .01) and inspiratory (p = .07) flow in snorers. Inspiratory flow correlated inversely with nasal symptoms (p < .05). The factors that best predict habitual snoring in women are a high BMI, a high nasal symptom score, and heavy weight. Of these, BMI is the most powerful.

Adolescent↗

Vitamins C and E inhibit O2- production in the pig coronary artery.

BACKGROUND: We previously found in a pig coronary balloon injury model that vitamins C and E as well as probucol had beneficial effects on the vessel response to injury measured by morphometry These effects correlated with an inhibition in the ability to oxidize LDLs ex vivo, suggesting that the morphological response was due to the antioxidant effect of the treatments. METHODS AND RESULTS: In the present study, the production of O2- by vessels 14 days after balloon injury was determined and correlated with circulating and tissue levels of vitamins C and E. Twenty-five domestic pigs were divided into four groups: control (n=7), vitamin C (500 mg/d, group C, n=6), vitamin E (1000 IU/d, group E, n=6), and vitamins C and E (500 mg/d and 1000 IU/d, group C+E, n=6). Vitamins were administered 7 days before oversized balloon injury of the left anterior descending coronary artery (LAD) and continued for 14 days after injury. Vitamin C and E concentrations were determined in plasma and lymphocytes as an index for tissue levels. Vessels were harvested after animals were killed, and O2- production was measured by lucigenin chemiluminescence. O2- production by the injured LAD was 2.5-fold greater than O2- production by the uninjured LAD or right coronary artery (RCA). The increase in O2- was caused primarily by cells present in the media and neointima. All vitamin-treated groups showed significantly decreased O2- production in both the RCA and LAD (approximately 45% inhibition) relative to vessels in the control, untreated group. There was a significant correlation between LAD O2- production and lymphocyte vitamin E levels. CONCLUSIONS: The present study is the first to show increased O2- production in injured vessels and to demonstrate that antioxidant vitamins reduce O2- production. These results suggest that beneficial effects of antioxidant vitamins in coronary artery disease are related, in part, to alterations in vessel redox state.

Animals↗

Bacterial meningitis in the United States in 1995. Active Surveillance Team.

BACKGROUND: Before the introduction of the conjugate vaccines, Haemophilus influenzae type b was the major cause of bacterial meningitis in the United States, and meningitis was primarily a disease of infants and young children. We describe the epidemiologic features of bacterial meningitis five years after the H. influenzae type b conjugate vaccines were licensed for routine immunization of infants. METHODS: Data were collected from active, population-based surveillance for culture-confirmed meningitis and other invasive bacterial disease during 1995 in laboratories serving all the acute care hospitals in 22 counties of four states (total population, more than 10 million). The rates were compared with those for 1986 obtained by similar surveillance. RESULTS: On the basis of 248 cases of bacterial meningitis in the surveillance areas, the rates of meningitis (per 100,000) for the major pathogens in 1995 were Streptococcus pneumoniae, 1.1; Neisseria meningitidis, 0.6; group B streptococcus, 0.3; Listeria monocytogenes, 0.2; and H. influenzae, 0.2. Group B streptococcus was the predominant pathogen among newborns, N. meningitidis among children 2 to 18 years old, and S. pneumoniae among adults. Pneumococcal meningitis had the highest case fatality rate (21 percent) and in 36 percent of cases was caused by organisms that were not susceptible to penicillin. From these data, we estimate that 5755 cases of bacterial meningitis were caused by these five pathogens in the United States in 1995, as compared with 12,920 cases in 1986, a reduction of 55 percent. The median age of persons with bacterial meningitis increased greatly, from 15 months in 1986 to 25 years in 1995, largely as a result of a 94 percent reduction in the number of cases of H. influenzae meningitis. CONCLUSIONS: Because of the vaccine-related decline in meningitis due to H. influenzae type b, bacterial meningitis in the United States is now a disease predominantly of adults rather than of infants and young children.

Adolescent↗

Plasma homocysteine as a risk factor for vascular disease. The European Concerted Action Project.

CONTEXT: Elevated plasma homocysteine is a known risk factor for atherosclerotic vascular disease, but the strength of the relationship and the interaction of plasma homocysteine with other risk factors are unclear. OBJECTIVE: To establish the magnitude of the vascular disease risk associated with an increased plasma homocysteine level and to examine interaction effects between elevated plasma homocysteine level and conventional risk factors. DESIGN: Case-control study. SETTING: Nineteen centers in 9 European countries. PATIENTS: A total of 750 cases of atherosclerotic vascular disease (cardiac, cerebral, and peripheral) and 800 controls of both sexes younger than 60 years. MEASUREMENTS: Plasma total homocysteine was measured while subjects were fasting and after a standardized methionine-loading test, which involves the administration of 100 mg of methionine per kilogram and stresses the metabolic pathway responsible for the irreversible degradation of homocysteine. Plasma cobalamin, pyridoxal 5'-phosphate, red blood cell folate, serum cholesterol, smoking, and blood pressure were also measured. RESULTS: The relative risk for vascular disease in the top fifth compared with the bottom four fifths of the control fasting total homocysteine distribution was 2.2 (95% confidence interval, 1.6-2.9). Methionine loading identified an additional 27% of at-risk cases. A dose-response effect was noted between total homocysteine level and risk. The risk was similar to and independent of that of other risk factors, but interaction effects were noted between homocysteine and these risk factors; for both sexes combined, an increased fasting homocysteine level showed a more than multiplicative effect on risk in smokers and in hypertensive subjects. Red blood cell folate, cobalamin, and pyridoxal phosphate, all of which modulate homocysteine metabolism, were inversely related to total homocysteine levels. Compared with nonusers of vitamin supplements, the small number of subjects taking such vitamins appeared to have a substantially lower risk of vascular disease, a proportion of which was attributable to lower plasma homocysteine levels. CONCLUSIONS: An increased plasma total homocysteine level confers an independent risk of vascular disease similar to that of smoking or hyperlipidemia. It powerfully increases the risk associated with smoking and hypertension. It is time to undertake randomized controlled trials of the effect of vitamins that reduce plasma homocysteine levels on vascular disease risk.

Adult↗

Local drug delivery.

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Cardiac Catheterization↗

Shoulder rotator torque and wheelchair dependence differences of National Wheelchair Basketball Association players.

OBJECTIVE: Shoulder rotator muscle imbalances can contribute to subacromial impingement. The forces and movement patterns of wheelchair locomotion may contribute to these imbalances. This study attempted to determine whether National Wheelchair Basketball Association players of differing classifications had significant differences (p < or = .05) in concentric isokinetic peak shoulder rotator torque and torque ratios, and wheelchair locomotion dependence. DESIGN: Fifty-seven (class 1 = 12, class 2 = 24, class 3 = 21) of 117 total tournament participants (class 1 = 25, class 2 = 49, class 3 = 43) served as the convenience sample of volunteers for the survey portion, and 33 of these subjects (class 1 = 11, class 2 = 12, class 3 = 10) also entered the isokinetic portion of this study. SETTING: National wheelchair basketball tournament. RESULTS: Class 1 and 2 players had greater wheelchair dependence than class 3 players (p < or = .05). Peak torque or torque ratios generally did not differ among player classifications or with other populations. Class 1 players had weaker nondominant shoulder external rotator torque production at 60 degrees/sec (p < or = .03) compared with other classes and at 180 degrees/sec compared with class 3 players (p = .02), suggesting an inability to develop the "attenuation of dominance" noted among other groups. Diminished torque-producing capacity at 60 degrees/sec related to greater wheelchair dependence among class 1 players (p = .034). CONCLUSIONS: Class 1 players failed to demonstrate the acquired shoulder external rotator torque symmetry evident among class 2 and 3 players (with specific weakness of the nondominant shoulder external rotators). This torque symmetry difference was related to their greater dependence on wheelchair locomotion.

Adult↗

Oral vaccination of mice against tetanus with recombinant Lactococcus lactis.

To determine whether a protective immune response could be elicited by oral delivery of a recombinant bacterial vaccine, tetanus toxin fragment C (TTFC) was expressed constitutively in Lactococcus lactis and administered orally to C57 BL/6 mice. The antibody titers elicited were lower than those following intranasal immunization (a route already known to result in high-level systemic anti-TTFC immune responses) but the protective efficacy was the same order of magnitude. The serum antibody isotypes elicited were predominantly IgG1 and IgG2a. TTFC-specific fecal IgA responses could be detected following oral or intranasal immunization. Chemically killed lactococci administered via the intranasal route were also able to elicit serum antibody responses of similar levels and kinetics to those induced by live bacteria.

Administration, Intranasal↗

Patient-reported problems associated with dysphonia.

In the UK there has been little assessment of the efficacy of therapy for patients with dysphonia. Current objective assessment methods (e.g. acoustical analysis) do not correlate well with patient symptoms. Existing subjective measures are based on clinical impression. To date, no measure has been based on the patient's experience and the aim of this study was to explore the difficulties that patients encounter as a consequence of their illness or disability. One hundred and thirty-three dysphonic patients completed an open-ended questionnaire where they were asked to make a list of the problems they experienced due to their voice disorder. Responses were categorized using the WHO International Classification of Impairments, Disabilities and Handicaps. A total number of 467 problems were listed: 60% impairments, 26% disabilities and 14% were handicap related. The six major impairments related to altered voice and throat symptoms. Although the majority of disabilities resulted from lack of projection and clarity, the most frequently reported was singing. Reported handicaps encompassed psychological, emotional and employment-related difficulties and effects on family and friends. People with dysphonia experience social, lifestyle and employment difficulties as a consequence of their voice disorder. Responses to the open-ended questionnaire have considerable practical applications in targeting more comprehensive treatment strategies.

Adolescent↗

Hyperhomocysteinemia: detection, risk assessment, and treatment.

Homocysteine is formed by the demethylation of methionine in the course of its normal metabolism. Hyperhomocysteinemia is an independent risk factor for vascular disease. It develops most commonly from folate deficiency, genetic abnormalities, and chronic renal failure. Current models favor direct angiotoxicity involving endothelial and vascular smooth muscle cells, and impaired thrombolysis. Folic acid reduces hyperhomocysteinemia and thus provides an opportunity for risk-factor modification.

Animals↗

Constraints on the cerebral basis for semantic processing from neuroimaging studies of Alzheimer's disease.

OBJECTIVE: Functional activation studies of semantic processing in healthy adults have yielded conflicting results. The purpose was to evaluate the relative role of the brain regions implicated in semantic processing with converging evidence from imaging studies of patients with impaired semantic processing. METHODS: Semantic memory was assessed in patients with Alzheimer's disease using two measures, and these performance patterns were related to profiles of reduced cerebral functioning obtained with high resolution single photon emission computed tomography (SPECT). Patients with frontotemporal degeneration were similarly evaluated as a control group. RESULTS: Reduced relative cerebral perfusion was seen in parietal and posterior temporal brain regions of patients with Alzheimer's disease but not patients with frontotemporal degeneration. Impairments on semantically guided category membership decision tasks were also seen in patients with Alzheimer's disease but not those with frontotemporal degeneration. Performance on the semantic measures correlated with relative cerebral perfusion in inferior parietal and superior temporal regions of the left hemisphere only in Alzheimer's disease. Relative perfusion was significantly lower in these regions in patients with Alzheimer's disease with semantic difficulty compared with patients with Alzheimer's disease with relatively preserved semantic processing. CONCLUSION: These findings provide converging evidence to support the contribution of superior temporal and inferior parietal regions of the left hemisphere to semantic processing.

Aged↗

A European perspective on pediatric cochlear implantation, rehabilitation services, and their educational implications.

OBJECTIVE: To assess the educational implications of pediatric cochlear implantation from the perspective of the implant team. METHODS: Coordinators of pediatric cochlear implant teams throughout Europe took part in a survey using forced-choice questions. Fifty-four centers were originally sent the questionnaire; 41 centers replied. RESULTS: Of 504 children planned to receive cochlear implants in Europe during 1996, 54% (273/504) were aged 2-5 years and 12% (60/504) aged 0-2 years, indicating a trend toward pediatric implantation in younger children. There is a strong commitment to rehabilitation in the teams; 66% (27/41) employ a teacher of the deaf, the ratio of medical/audiological to rehabilitation personnel is 1:2, and 76% (31/41) of the implant teams visit local educators. Of all the children receiving implants to the date of this report, 23% were considered to be in unfavorable educational environments; these were environments where children were taught with an emphasis on sign language and little expectation from audition, and mainstream provision without support from experienced teachers of the deaf. CONCLUSION: There is a high staff input to children with cochlear implants from implant rehabilitation personnel over and above the input received in the educational environment. Hence, it is important for the school and the implant team to mutually agree on their shared responsibilities. Moreover, as the provision of service is variable and inconsistent, the development of guidelines for practice in each country should ensure consistency of rehabilitative and educational support to children with cochlear implants.

Adolescent↗

Managing vancomycin-resistant enterococci. A winning team approach.

Antibiotics have been the treatment of choice for a broad range of bacterial infections for decades. In recent years, however, concern has been growing over the increasing incidence of infections that are resistant to known antibiotics. A 1995 outbreak of ampicillin- and vancomycin-resistant enterococci (VRE) at the 3Y site of the McMaster University Medical Centre brought this concern home to us and resulted in the development of outbreak-management guidelines for VRE.

Ampicillin Resistance↗