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Biomedical subjects

M Roberts

Publications and source records attributed to M Roberts.

At least 73 records · Page 4Linked to original sources

Effect of smoking cessation on exercise performance in female smokers participating in exercise training.

We evaluated in a randomized prospective trial the possible effect of smoking cessation on exercise performance in middle-aged female smokers who underwent vigorous exercise training as an adjunct to a cognitive-behavioral smoking cessation treatment program. A total of 109 subjects met the criteria for this substudy; of these, 51 were in the contact control (nonexercising) group and 58 were in the exercise training group. Both groups had a graded maximal exercise stress test performed on a bicycle ergometer before and after 12 weeks of treatment. All subjects participated in a 12-session, group-based, cognitive-behavioral treatment program for nicotine dependence. Subjects in the contact condition participated in 3 supervised health education lectures per week but did not engage in regular exercise. Subjects in the exercise group trained 3 times a week, averaging 83% of maximum heart rate achieved on their baseline exercise test. On the 12-week exercise stress test, the exercise group did significantly better than control in all aspects of exercise performance. Those who quit showed a further increase in their exercise test duration (p <0.001) and had a greater increase in calculated peak oxygen consumption expressed as fat-free weight (p = 0.031). In conclusion, women who undergo a vigorous exercise training program and quit smoking demonstrate improved exercise performance over those who continue to smoke.

Adult↗

Routine protein energy supplementation in adults: systematic review.

OBJECTIVES: To determine whether routine oral and enteral nutritional supplementation can improve the weight, anthropometry, and survival of adult patients. DESIGN: Systematic review of randomised controlled trials of oral or enteral protein supplementation in adults. Trials were identified from Medline (Silver Platter 3.11, 1966-96), reference lists of identified studies and review articles, and communication with feed manufacturers. SUBJECTS: Randomised controlled trials comparing oral or enteral protein supplementation with no routine supplementation. All trials of adult subjects were included except those addressing nutrition in pregnancy. MAIN OUTCOME MEASURES: Change in body weight and anthropometry (mid-arm muscle circumference), and all cause case fatality recorded at the end of scheduled follow up. Body weight and anthropometry were analysed as the weighted mean difference and 95% confidence intervals of the percentage change in these variables. Case fatality was analysed with odds ratio and 95% confidence intervals. RESULTS: 32 eligible reports (2286 randomised patients) published between February 1979 and July 1996 were identified, of which 30 (93.8%) (2062 randomised patients) reported outcomes of interest. Case fatality data were available for 1670 (81%) patients, and continuous variable data for up to 1607 (78%) patients. The treatment group receiving routine nutritional supplementation showed consistently improved changes in body weight and anthropometry compared with controls; weighted mean difference 2.06% (95% confidence interval 1.63% to 2.49%) and 3.16% (2.43% to 3.89%) respectively. The pooled odds ratio for death in the treatment group was 0.66 (0.48 to 0.91, 2P<0.01). Apparent benefits were observed in several prespecified subgroups of patients, treatment settings, and interventions, but were not evident if trials with less robust methodology were excluded. CONCLUSIONS: Routine oral or enteral supplementation seems to improve the nutritional indices of adult patients, but there are insufficient data in trials which meet strict methodological criteria to be certain if mortality is reduced. Benefits were not restricted to particular patient groups. Further large pragmatic randomised controlled trials of routine nutritional supplementation are justified.

Administration, Oral↗

Effect of arsenite on induction of CYP1A and CYP2H in primary cultures of chick hepatocytes.

In earlier studies, treatment with sodium arsenite was shown to decrease total hepatic CYP in rats. A concomitant increase in heme oxygenase, the rate-limiting step in heme degradation to biliverdin, was considered responsible for the decrease in CYP. Here we investigated the effect of sodium arsenite on induction of CYP2H, CYP1A, and heme oxygenase in primary cultures of chicken embryo hepatocytes. When added simultaneously with inducer, arsenite inhibited phenobarbital-mediated increases in CYP2H and 3-methylcholanthrene-mediated increases in CYP1A, as measured enzymatically and immunochemically. Near maximal decreases were observed in these forms of CYP at a concentration of 2.5 microM sodium arsenite. The concentration-dependent decreases in CYP2H and CYP1A by sodium arsenite were concomitant with increases in heme oxygenase. Sodium arsenite was not toxic at concentrations as high as 10 microM, as indicated by protein synthesis and the reduction of MTT by intact cells. Sodium arsenite had no effect on induction of CYP2H1 mRNA, suggesting that the decreases in this form of CYP occurred post-transcriptionally. Treatment of cells with tin mesoporphyrin (SnMeso), an inhibitor of heme oxygenase, resulted in inhibition of arsenite-induced heme oxygenase. However, SnMeso did not alter the effect of arsenite to prevent phenobarbital-mediated increases in CYP2H protein. SnMeso alone inhibited phenobarbital-mediated increases in CYP2H. Inclusion of 2 or 5 microM exogenous heme with arsenite did not prevent the arsenite-mediated decrease in CYP2H. Combined treatment with heme and phenobarbital induced heme oxygenase to the same extent as treatment with heme, arsenite, and phenobarbital. However, CYP2H activity was decreased only when the treatment included arsenite. These results suggest that elevated levels of heme oxygenase alone are not responsible for arsenite-mediated decreases in CYP2H.

Animals↗

Allergic bronchopulmonary mycosis to Fusarium vasinfectum in a child.

BACKGROUND: A 12-year-old boy with asthma and 6 years of recurrent pneumonias who had normal serum immunoglobulin concentrations was suspected of having allergic bronchopulmonary aspergillosis (ABPA). OBJECTIVE: To search for and secure a fungal etiology for a child who did not have ABPA but was suspected of having an allergic bronchopulmonary mycosis. METHODS: Immediate skin testing with fungal extracts, high resolution computerized tomography, and establishment of an ELISA procedure to detect serum IgE and IgG antibodies to Fusarium vasinfectum. RESULTS: Immediate skin reactivity was present for Fusarium, Cladosporium, Helminthosporium, and Aspergillus fumigatus. The ELISA demonstrated serum IgE and IgG antibodies to Fusarium vasinfectum 8.5 and 5.6 times nonatopic control sera. CONCLUSIONS: This 12-year-old with asthma has sufficient criteria for a diagnosis of allergic bronchopulmonary mycosis (ABPM) to Fusarium vasinfectum. Bronchiectasis was not present despite recurrent pneumonias and hemoptysis. This case appears to be the first pediatric example of ABPM to Fusarium species, a fungus more recognized for causing rotting of tomatoes and melons than human disease.

Antibodies, Fungal↗

Regulation of host immune responses by modification of Salmonella virulence genes.

Modifying bacterial virulence genes to probe the nature of host immunity is mostly unexplored. Here we investigate whether host immune responses can be regulated by modification of bacterial virulence genes. In mice, attenuated Salmonella mutant strains with clinical relevance elicited differential host immune responses. Oral administration of a mutant strain with a PhoP-null phenotype promoted potent innate immune responses of macrophages that were sufficient for host defense. In contrast, administration of an Aro- mutant strain elicited stronger specific antibody and T-helper (Th)-cell responses, wherein Th1-type cells were required for clearance. Thus, genetic manipulation of bacteria may be used to broadly alter immune mechanisms that regulate attenuation within the host and to tailor host immunity to specific bacterial pathogens.

Animals↗

Human IgE responses to rSm22.6 are associated with infection intensity rather than age per se, in a recently established focus of Schistomiasis mansoni.

In studies of schistosomasis mansoni-endemic communities, individuals with IgE responses to a 22 kD adult worm antigen (rSm22.6) suffered lower intensities of reinfection after treatment. It is of interest to define the factors that lead to the production of rSm22.6-specific IgE because it is a marker for resistant individuals and it may be involved in the development of resistance to reinfection. In endemic populations rSm22.6-specific IgE increases linearly with age. However, it is not possible to distinguish between age per se and 'history of infection' in endemic populations because individuals are exposed to the parasite at an early age. We have, therefore, quantified pre- and post-treatment isotype responses to rSm22.6 in a comparatively 'epidemic' Senegalese community where the patients were infected at different ages and where pre-treatment intensity of infection can be taken as a reasonable measure of antigen exposure. Post-treatment isotype responses to rSm22.6 correlated positively with pre-treatment intensities of infection but were not shown to be related to age. IgG1, IgG4 and IgE responses to rSm22.6 were significantly higher after treatment with the difference increasing with the pre-treatment level of infection. These results from a recently established focus of infection suggest that isotype responses to rSm22.6 are antigen-exposure dependent rather than dependent on age per se.

Adolescent↗

Oral vaccination against tetanus: comparison of the immunogenicities of Salmonella strains expressing fragment C from the nirB and htrA promoters.

We have found the in vivo-regulated nirB promoter (PnirB) to be effective for directing expression of a number of antigens in salmonella in vivo. We wished to determine if other in vivo-regulated promoters have utility for antigen expression in salmonella and to compare the effectiveness of these promoters with that of PnirB. To this end, we have devised a scheme that allows the promoter element of the PnirB-fragment C plasmid pTETnir15 to be swapped with other promoters of interest. We demonstrate the usefulness of this system by replacing PnirB with PhtrA to create plasmid pTEThtrA1. htrA is a stress response gene that is required for virulence of salmonella in mice and survival within macrophages. Expression of fragment C in Salmonella typhimurium BRD509 (aroA aroD) harboring pTEThtrA1 (strain BRD937) correlated with growth temperature in vitro. A comparison was made of the immune responses to fragment C elicited in mice immunized orally with BRD937 or BRD847 (BRD509/pTETnir15) or subcutaneously with purified fragment C plus alhydrogel. High levels of anti-fragment C antibodies that persisted for at least 12 weeks were present in all groups of mice. Vaccination with BRD937 was the most effective means of immunization: the serum immunoglobulin G (IgG), IgA, and IgM anti-fragment C titers were higher in the BRD937-immunized mice throughout the duration of the study than in mice in the other groups. The kinetics of the serum anti-fragment C responses were different in different groups. The response was most rapid in the BRD937 group, with the titers almost at peak levels at 2 weeks postimmunization. Only the mice immunized with BRD937 or BRD847 developed an intestinal IgA response to fragment C. Again, the response was superior in the BRD937 group. The peak of the intestinal response was delayed with respect to the serum response. Analysis of the IgG subtype response to fragment C revealed a dominant IgG2a response in the salmonella-immunized mice, indicating a type 1 helper T-cell response to fragment C, whereas the major subtype in the group parenterally immunized with fragment C plus alhydrogel was IgG1. The IgG1/IgG2a ratio was much higher in sera of BRD937-immunized mice than in sera of BRD847-immunized mice. At 15 to 20 weeks after immunization, the mice immunized with BRD937 or BRD847 were solidly immune to tetanus toxin and salmonella. The immune responses to fragment C seen in mice immunized with BRD937 are the strongest we have observed and indicate that the htrA promoter may be very useful for expressing foreign antigens in salmonella vaccine strains.

Administration, Oral↗

Susceptibility to Salmonella typhimurium infection and effectiveness of vaccination in mice deficient in the tumor necrosis factor alpha p55 receptor.

Mice defective in the ability to produce the tumor necrosis factor alpha p55 receptor (TNFalphap55R) were orally challenged with a number of Salmonella typhimurium HWSH derivatives that differ in virulence. In comparison to TNFalphap55R+/+ mice, TNFalphap55R-/- mice succumbed earlier to challenge with wild-type S. typhimurium HWSH and S. typhimurium HWSH purE. In contrast, TNFalphap55R-/- mice were able to control an S. typhimurium HWSH aroA challenge, although greater numbers of Salmonella organisms were present in the tissues for a longer time period than was observed with TNFalphap55R+/+ mice. Vaccination of normal and TNFalphap55R knockout animals with S. typhimurium HWSH aroA showed that TNFalphap55R-/- mice, unlike TNFalphap55R+/+ mice, were not protected against a virulent S. typhimurium HWSH challenge. Splenocytes from TNFalphap55R-/- mice exhibited a reduced ability to proliferate in the presence of S. typhimurium antigen compared to TNFalphap55R+/+ mice. Thus, TNFalphap55R is essential for controlling Salmonella growth in tissues and for recall of immunity in murine salmonellosis.

Animals↗

"Saturday night fever": ecstasy related problems in a London accident and emergency department.

OBJECTIVES: To report on the extent and nature of acute MDMA (ecstasy) related problems presenting to a large London hospital's accident and emergency (A&E) department. METHOD: The computerised attendance records for all patients attending the A&E department over a 15 month period were retrospectively screened. Potential cases thus identified had their case notes systematically reviewed to confirm the history of MDMA use and to extract other relevant data. RESULTS: Forty eight consecutive MDMA related cases were identified. All were in the 15-30 year age group with the majority presenting in the early hours at weekends and having consumed the drug at a night club. The mean number of tablets consumed was two and almost 40% had taken MDMA before. Polydrug use was common with half of the sample having concurrently taken another illicit substance--most commonly other stimulants (amphetamines and cocaine). A wide range of adverse clinical features was found. The most common symptoms were vague and non-specific such as feeling strange or unwell, however many patients had collapsed or lost consciousness. The most common signs elicited were related to sympathetic overactivity, agitation/disturbed behaviour, and increased temperature. The more serious complications of delirium, seizures, and profound unconsciousness (coma) were commoner when MDMA was used in combination with other substances. CONCLUSIONS: For young adults presenting late at night at weekends and exhibiting symptoms of sympathetic overactivity, disturbed behaviour, and increased temperature ("Saturday night fever") the use of stimulant dance drugs especially MDMA should be suspected. As MDMA use does not appear to occur in isolation, the clinical picture is likely to be complicated by multiple rather than single drug ingestion. This poses increased diagnostic and management challenges for A&E staff who typically represent the front line response to dance drug related problems.

Adolescent↗

Hypersensitivity pneumonitis due to humidifier disease: seek and ye shall find.

STUDY OBJECTIVES: This study reports a classic case of hypersensitivity pneumonitis (HP) with classic histologic changes in lung tissue and the research used to identify the causative antigens. DESIGN: A patient with clinical, radiographic, pulmonary function abnormalities and a lung biopsy consistent with HP had no identifiable antigen exposure. SETTING: Evaluation of the patient's activities provided no suggestion of antigen exposure. Her home was evaluated. It was found that her humidifier ran continually without being cleaned but water was added periodically. MEASUREMENTS: Serologic analysis demonstrated precipitating antibodies against her humidifier water and ten antigens in the hypersensitivity lung disease serologic panel. CONCLUSION: Removal of the humidifier, cleaning of the house, and a course of prednisone resulted in the return of the patient to a normal state.

Aged↗

IPS Empress: a standard of excellence.

For 10 years, clinicians have been able to provide patients with a proven aesthetic and functional restoration that exhibits wear-compatibility, durability, and marginal integrity. This leucite-reinforced, pressed ceramic (IPS Empress, Ivoclar Williams, Amherst, NY) presents to patients and dentists the option of a metal-free alternative which retains the functional advantages of a porcelain-fused-to-metal restoration. This article illustrates the importance of sound laboratory communication in the utilization of this restorative material, focusing upon three aspects: midline and incisal edge inclination, elimination of open gingival embrasures, and incisal edge translucency. Techniques are also presented in order to efficiently communicate details of each case presented to the laboratory.

Aluminum Silicates↗

Salmonella typhimurium infections in mice deficient in interleukin-4 production: role of IL-4 in infection-associated pathology.

Mice harboring mutations in the IL-4 gene (IL-4(-/-)) were infected with a range of Salmonella typhimurium HWSH derivatives using different routes of infection. Compared with IL-4(+/+) mice, IL-4(-/-) mice exhibited a delayed time to death following infection with wild-type S. typhimurium HWSH. Groups of IL-4(+/+) mice infected with S. typhimurium HWSH purE, a less virulent derivative, showed sporadic deaths and harbored micro- or macroabscesses in their tissues, particularly associated with the liver. However, IL-4(-/-) mice infected with similar doses of S. typhimurium HWSH purE bacteria were resistant to killing and failed to develop detectable abscesses. Abscess formation in IL-4(-/-) mice could be induced by i.v. administration of rIL-4 during the S. typhimurium HWSH purE infection. The immune response in both IL-4(-/-) and IL-4(+/+) mice was of the Th1-type. Viable salmonella bacteria could be found associated with abscesses. Both IL-4(-/-) and IL-4(+/+) mice were resistant to killing by S. typhimurium aroA.

Animals↗

Centromeric sites and cereal chromosome evolution.

Comparative genome analysis enables the sites of centromeres, telomeres and nucleolar organiser regions to be aligned with borders that define the sets of linked genes conserved across the cereal genomes. This provides a basis for studying cereal genome evolution.

Biological Evolution↗

Immunization of mice with DNA encoding fragment C of tetanus toxin.

Immunization of mice with Fragment C protein, the non-toxic C-terminal domain of tetanus toxin, will protect mice against lethal challenge with tetanus toxin. A plasmid, pcDNA3/tetC, which encodes a synthetic tetC gene expressed under the control of the human cytomegalovirus major intermediate early promoter/enhancer region, was constructed. Fragment C expression was observed in Chinese hamster ovary cells following transfection with pcDNA3/tetC. The immune response induced by intramuscular immunization with pure pcDNA3/tetC DNA was evaluated in a murine model. Anti-Fragment C serum immunoglobulin and proliferative responses in splenocytes were observed following two immunizations with pcDNA3/tetC. The major IgG subclass that recognized Fragment C was IgG2a and the stimulated splenocytes secreted high levels of interferon-gamma. Sufficient anti-Fragment C serum immunoglobulins were induced by DNA-mediated immunization to protect mice against lethal challenge with tetanus toxin.

Animals↗