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Biomedical subjects

D Campbell

Publications and source records attributed to D Campbell.

At least 109 records · Page 6Linked to original sources

Cytomegalovirus seropositivity is associated with the expansion of CD4+CD28- and CD8+CD28- T cells in rheumatoid arthritis.

OBJECTIVE: Previous researchers have found expansion of CD4+CD28- T cells in patients with rheumatoid arthritis (RA) compared to age matched controls, and have identified expanded clones of autoreactive cells within this population. We examine the association of prior cytomegalovirus (CMV) infection (positive serum anti-CMV IgG) with the percentage of CD4+CD28- T cells and CD8+CD28- T cells in patients with RA. METHODS: A total of 45 patients (36 women, 9 men), mean age of 59 years, with definite RA were studied. RESULTS: In this group 28 patients were seropositive for CMV and 17 seronegative. Seropositive and seronegative subjects did not differ significantly in age, sex, medication use, or severity of disease. Joint count, Health Assessment Questionnaire, pain score, patient global assessment, physician global assessment, and presence of extraarticular disease served to assess disease severity. Expression of CD4/CD28/CD57 and CD8/CD28/CD57 on lymphocytes was determined by 3 color flow cytometry. (CD28 and CD57 are reciprocally related.) CD4+CD28-CD57+ T cells were expanded only in CMV seropositive patients. CONCLUSION: The "carrier" phenotype that has been hypothesized based on a 2 population model for the distribution of CD4+CD28- T cells in RA can be explained by prior infection with CMV.

Arthritis, Rheumatoid↗

Sulfur isotopic composition of cenozoic seawater sulfate

A continuous seawater sulfate sulfur isotope curve for the Cenozoic with a resolution of approximately 1 million years was generated using marine barite. The sulfur isotopic composition decreased from 19 to 17 per mil between 65 and 55 million years ago, increased abruptly from 17 to 22 per mil between 55 and 45 million years ago, remained nearly constant from 35 to approximately 2 million years ago, and has decreased by 0.8 per mil during the past 2 million years. A comparison between seawater sulfate and marine carbonate carbon isotope records reveals no clear systematic coupling between the sulfur and carbon cycles over one to several millions of years, indicating that changes in the burial rate of pyrite sulfur and organic carbon did not singularly control the atmospheric oxygen content over short time intervals in the Cenozoic. This finding has implications for the modeling of controls on atmospheric oxygen concentration.

Journal Article↗

Mechanism of rhinovirus-induced changes in airway smooth muscle responsiveness.

An important interplay exists between specific viral respiratory infections and altered airway responsiveness in the development and exacerbations of asthma. However, the mechanistic basis of this interplay remains to be identified. This study addressed the hypothesis that rhinovirus (RV), the most common viral respiratory pathogen associated with acute asthma attacks, directly affects airway smooth muscle (ASM) to produce proasthmatic changes in receptor-coupled ASM responsiveness. Isolated rabbit and human ASM tissue and cultured ASM cells were inoculated with human RV (serotype 16) or adenovirus, each for 6 or 24 h. In contrast to adenovirus, which had no effect, inoculation of ASM tissue with RV induced heightened ASM tissue constrictor responsiveness to acetylcholine and attenuated the dose-dependent relaxation of ASM to beta-adrenoceptor stimulation with isoproterenol. These RV-induced changes in ASM responsiveness were largely prevented by pretreating the tissues with pertussis toxin or with a monoclonal blocking antibody to intercellular adhesion molecule-1 (ICAM-1), the principal endogenous receptor for most RVs. In extended studies, we found that the RV-induced changes in ASM responsiveness were associated with diminished cAMP accumulation in response to dose-dependent administration of isoproterenol, and this effect was accompanied by autologously upregulated expression of the Gi protein subtype, Gialpha3, in the ASM. Finally, in separate experiments, we found that the RV-induced effects on ASM responsiveness were also accompanied by autologously induced upregulated mRNA and cell surface protein expression of ICAM-1. Taken together, these findings provide new evidence that RV directly induces proasthmatic phenotypic changes in ASM responsiveness, that this effect is triggered by binding of RV to its ICAM-1 receptor in ASM, and that this binding is associated with the induced endogenously upregulated expression of ICAM-1 and enhanced expression and activation of Gi protein in the RV-infected ASM.

Animals↗

The cyanobacterium Synechococcus resists UV-B by exchanging photosystem II reaction-center D1 proteins.

Current ambient UV-B levels can significantly depress productivity in aquatic habitats, largely because UV-B inhibits several steps of photosynthesis, including the photooxidation of water catalyzed by photosystem II. We show that upon UV-B exposure the cyanobacterium Synechococcus sp. PCC 7942 rapidly changes the expression of a family of three psbA genes encoding photosystem II D1 proteins. In wild-type cells the psbAI gene is expressed constitutively, but strong accumulations of psbAII and psbAIII transcripts are induced within 15 min of moderate UV-B exposure (0.4 W/m2). This transcriptional response causes an exchange of two distinct photosystem II D1 proteins. D1:1 is encoded by psbAI, but on UV-B exposure, it is largely replaced by the alternate D1:2 form, encoded by both psbAII and psbAIII. The total content of D1 and other photosystem II reaction center protein, D2, remained unchanged throughout the UV exposure, as did the content and composition of the phycobilisome. Wild-type cells suffered only slight transient inhibition of photosystem II function under UV-B exposure. In marked contrast, under the same UV-B treatment, a mutant strain expressing only psbAI suffered severe (40%) and sustained inhibition of photosystem II function. Another mutant strain with constitutive expression of psbAII and psbAIII was almost completely resistant to the UV-B treatment, showing no inhibition of photosystem II function and only a slight drop in electron transport. In Synechococcus the rapid exchange of alternate D1 forms, therefore, accounts for much of the cellular resistance to UV-B inhibition of photosystem II activity and photosynthetic electron transport. This molecular plasticity may be an important element in community-level responses to UV-B, where susceptibility to UV-B inhibition of photosynthesis changes diurnally.

Bacterial Proteins↗

A genome-wide screen for susceptibility loci in ankylosing spondylitis.

OBJECTIVE: To localize the regions containing genes that determine susceptibility to ankylosing spondylitis (AS). METHODS: One hundred five white British families with 121 affected sibling pairs with AS were recruited, largely from the Royal National Hospital for Rheumatic Diseases AS database. A genome-wide linkage screen was undertaken using 254 highly polymorphic microsatellite markers from the Medical Research Council (UK) (MRC) set. The major histocompatibility complex (MHC) region was studied more intensively using 5 microsatellites lying within the HLA class III region and HLA-DRB1 typing. The Analyze package was used for 2-point analysis, and GeneHunter for multipoint analysis. RESULTS: When only the MRC set was considered, 11 markers in 7 regions achieved a P value of < or =0.01. The maximum logarithm of odds score obtained was 3.8 (P = 1.4 x 10(-5)) using marker D6S273, which lies in the HLA class III region. A further marker used in mapping of the MHC class III region achieved a LOD score of 8.1 (P = 1 x 10(-9)). Nine of 118 affected sibling pairs (7.6%) did not share parental haplotypes identical by descent across the MHC, suggesting that only 31% of the susceptibility to AS is coded by genes linked to the MHC. The maximum non-MHC LOD score obtained was 2.6 (P = 0.0003) for marker D16S422. CONCLUSION: The results of this study confirm the strong linkage of the MHC with AS, and provide suggestive evidence regarding the presence and location of non-MHC genes influencing susceptibility to the disease.

Chromosome Mapping↗

Obstetric events leading to anal sphincter damage.

OBJECTIVE: To identify the obstetric factors relating to anal sphincter injury at first vaginal delivery by prospective cohort study of primiparous women. METHODS: We compared the results of a bowel function questionnaire and anal vector manometry before and 6 weeks after delivery in 184 primiparous women. Postpartum, pudendal nerve conduction latency was measured in all women, and anal endosonography was performed in 81 with altered fecal continence or abnormal physiology. RESULTS: Sixteen (9%) women, none of whom had altered fecal continence, were delivered by cesarean. After vaginal delivery, 42 of 168 (25%) women had impairment of fecal continence and 76 of 168 (45%) women had abnormal anal physiology. Instrumental vaginal delivery was associated with an 8.1-fold (95% confidence interval [CI] 2.7, 24.0; P < .001) risk of anal sphincter injury and a 7.2-fold (95% CI 2.8, 18.6; P < .001) risk of symptoms. Duration of the second stage of labor beyond 60 minutes led to a 1.7-fold (95% CI 1.14, 2.48; P;< .01) risk of anal sphincter injury and a 1.6-fold (95% CI 1.03, 2.6, P = .01) risk of symptoms. Epidural analgesia, used in 58% of vaginal deliveries, prolonged the second stage of labor (P = .004; odds ratio [OR] 7.7; 95% CI 4.0, 14.7) and was associated with increased risk of sphincter injury (P = .02; OR 2.1; 95% CI 1.1, 4.0) and of symptoms (P = .02; OR 2.0; 95% CI 1.1, 3.7). CONCLUSION: Instrumental delivery and a second stage of labor prolonged by epidural analgesia are the obstetric factors that pose the greatest risk of injury to the anal sphincter mechanism in primiparous vaginal delivery.

Anal Canal↗

Apical extent of rotary canal instrumentation with an apex-locating handpiece in vitro.

PROBLEM: The Tri Auto ZX (J. Morita Co., Kyoto, Japan) is a cordless endodontic handpiece with a built-in apex locator that is programmed to reverse the direction of rotation when the file reaches a predetermined apical level or when torque becomes excessive. OBJECTIVE: The purpose of this investigation was to examine the apical extent of rotary canal instrumentation and the ability to maintain apical constriction with the Tri Auto ZX at different automated settings. STUDY DESIGN: In 60 extracted teeth, canals were measured to the apical constriction, first visually and then electronically with the Tri Auto ZX; then they were instrumented with nickel titanium rotary files. For the instrumentation, the automatic apical reverse mechanism of the handpiece was set to 1, 1.5, or 2; these settings correspond to different distances from the apical foramen. Instrumentation was carried out apically until rotation was reversed by the automatic apical reverse function; the instrumented length was then measured, and the canal was filled with gutta-percha and sealer. The integrity of the apical constriction was assessed by exposing the apical 4 mm of the canal and observing the dentin-cementum junction. Paired t-tests were used to compare the visually measured length, the electronically measured length, and the instrumented length for each tooth. RESULTS: On average, the electronically measured length was 0.54 mm shorter than the visually measured length (p < 0.05). When the automatic apical reverse mechanism's setting was 1, the instrumented length was 0.1 mm shorter than the electronically measured length; when the setting was 1.5, the instrumented length was 0.36 mm shorter than the electronically measured length (p < 0.01). Results were inconsistent when the setting was 2. CONCLUSION: Instrumentation with the automatic apical reverse feature set at 1 consistently approximated the apical constriction; however, the constriction was frequently enlarged.

Dental Alloys↗

Double-blind comparison of lansoprazole 15 mg, lansoprazole 30 mg, and placebo in the maintenance of healed gastric ulcer.

Our purpose was to compare the safety and efficacy of lansoprazole 15 mg and 30 mg with placebo in preventing recurrence in 49 patients with a history of gastric ulcer. Within one month, 40% of patients receiving placebo experienced ulcer recurrence compared to 0% and 7% of patients receiving lansoprazole 15 mg and 30 mg, respectively. All placebo patients became symptomatic, experienced ulcer recurrence or withdrew from the study by month 9. As compared to placebo, a significantly (P < 0.001) higher percentage of patients treated with lansoprazole 15 mg (83%) and lansoprazole 30 mg (93%) with healed gastric ulcer disease remained healed at month 12. Of patients asymptomatic at baseline, 100% and 59% of those treated with lansoprazole 15 mg and 30 mg, respectively, remained asymptomatic at month 12. The incidence of adverse events was comparable among the treatment groups. Lansoprazole safely and effectively reduces ulcer recurrence in patients with a history of gastric ulcer disease.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Cultures of sexual adventurism as markers of HIV seroconversion: a case control study in a cohort of Sydney gay men.

A case control analysis within an ongoing cohort study was used to examine differences between seroconverters and men who remained HIV-negative. The cases were interviewed within one to 13 months prior to their seroconversion. Their responses to a structured questionnaire were compared with those of HIV-negative controls drawn from the same time period and from the same longitudinal study, Sydney Men and Sexual Health. Data collected from both cases and controls included: demographic and contextual variables, knowledge of HIV transmission, sexual practices, drug and alcohol use and attitudinal factors. The aim was to compare the sexual behaviours, and the social and cultural contexts of such behaviours, of men prior to their HIV seroconversion with men who did not seroconvert. Twenty-three men had seroconverted within the cohort. Cases were identified by a positive HIV antibody test or self-report of positive HIV status following a previous negative HIV test. Three-hundred-and-sixty-nine controls were selected on the basis of being HIV negative at interview in 1994, and having at least one subsequent medically-confirmed negative HIV antibody test. Univariate predictors of seroconversion were: being in a regular relationship with a known HIV-positive partner, drug use, and engaging in a range of anal and esoteric sexual practices. Practices commonly used to enhance sexual pleasure, such as group sex, watching and being watched having sex, the use of sex toys and dressing up/fantasy, were engaged in more frequently by seroconverters. Engaging in these esoteric sexual practices was highly correlated with drug use, involvement in the gay community and engagement in a wide range of anal practices. In the multivariate analysis independent predictors of seroconversion were: younger age; being in a regular relationship with a known HIV-positive partner; believing withdrawal to be safe with regard to HIV transmission; and range of esoteric practices. These results indicate the importance of the social and cultural contexts of particular sexual practices and consequent HIV transmission. Sexually adventurous men may be at increased risk for HIV because they seek sex within particular sexual sub-cultures.

Adult↗

Chlorophyll fluorescence analysis of cyanobacterial photosynthesis and acclimation.

Cyanobacteria are ecologically important photosynthetic prokaryotes that also serve as popular model organisms for studies of photosynthesis and gene regulation. Both molecular and ecological studies of cyanobacteria benefit from real-time information on photosynthesis and acclimation. Monitoring in vivo chlorophyll fluorescence can provide noninvasive measures of photosynthetic physiology in a wide range of cyanobacteria and cyanolichens and requires only small samples. Cyanobacterial fluorescence patterns are distinct from those of plants, because of key structural and functional properties of cyanobacteria. These include significant fluorescence emission from the light-harvesting phycobiliproteins; large and rapid changes in fluorescence yield (state transitions) which depend on metabolic and environmental conditions; and flexible, overlapping respiratory and photosynthetic electron transport chains. The fluorescence parameters FV/FM, FV'/FM',qp,qN, NPQ, and phiPS II were originally developed to extract information from the fluorescence signals of higher plants. In this review, we consider how the special properties of cyanobacteria can be accommodated and used to extract biologically useful information from cyanobacterial in vivo chlorophyll fluorescence signals. We describe how the pattern of fluorescence yield versus light intensity can be used to predict the acclimated light level for a cyanobacterial population, giving information valuable for both laboratory and field studies of acclimation processes. The size of the change in fluorescence yield during dark-to-light transitions can provide information on respiration and the iron status of the cyanobacteria. Finally, fluorescence parameters can be used to estimate the electron transport rate at the acclimated growth light intensity.

Acclimatization↗

Increase in exhaled nitric oxide levels in patients with difficult asthma and correlation with symptoms and disease severity despite treatment with oral and inhaled corticosteroids. Asthma and Allergy Group.

BACKGROUND: Patients with difficult asthma suffer chronic moderate to severe persistent asthma symptoms despite high doses of inhaled and oral corticosteroid therapy. These patients suffer a high level of treatment and disease related morbidity but little is known about the degree of airway inflammation in these patients. METHODS: Fifty two patients were examined to assess levels of exhaled nitric oxide (NO) as a surrogate marker of inflammatory activity in this condition. From this group, 26 patients were defined with severe symptoms and current physiological evidence of reversible airway obstruction requiring high dose inhaled (> or = 2000 micrograms beclomethasone dipropionate (BDP) equivalent) or oral steroid therapy to maintain disease control. RESULTS: Exhaled NO levels were higher in subjects with difficult asthma (mean 13.9 ppb, 95% CI 9.3 to 18.5) than in normal controls (7.4 ppb, 95% CI 6.9 to 7.8; p < 0.002), but lower than levels in steroid naive mild asthmatics (36.9 ppb, 95% CI 34.6 to 39.3; p < 0.001). Prednisolone treated patients had higher exhaled NO levels than patients only requiring inhaled corticosteroids (17.5 ppb, 95% CI 11.1 to 24.0 versus 7.2 ppb, 95% CI 4.6 to 9.8; p = 0.016), suggesting greater disease severity in this group. Non-compliance with prednisolone treatment was observed in 20% of patients but this did not explain the difference between the treatment groups. Exhaled NO levels were closely correlated with symptom frequency (p = 0.03) and with rescue beta agonist use (p < 0.002), but they did not correlate with lung function. CONCLUSIONS: Exhaled NO may serve as a useful complement to lung function and symptomatology in the assessment of patients with chronic severe asthma, and in the control and rationalisation of steroid therapy in these patients.

Administration, Inhalation↗

Evaluating critical thinking skills in a scenario-based community health course.

This study evaluated the influence of a scenario-based community health course on the ability of senior nursing students (N = 54) to address complex problems seen in the community health setting. In addition, we examined whether students' scores on the Watson-Glaser Critical Thinking Appraisal (WGCTA) questionnaire would differ depending on the size of the educational institution they attended before enrollment in a school of nursing and whether the types of electives (liberal arts or science) previously taken would influence the scores. Sign ficant improvements were seen on the Interpretation and Evaluation subscales and on the total critical thinking score from pretest to posttest for students who completed the course. Also students who completed nursing prerequisites in midsized, 4-year universities (10,000 to 30,000 students) had higher pretest mean scores on the majority of WGCTA subscales than did other students.

Adult↗

Gay men who engage repeatedly in unprotected anal intercourse with casual partners: the Sydney Men and Sexual Health Study.

We set out to determine the frequency and correlates of gay men's repeated unprotected anal intercourse with casual partners (UAI-C), defined as UAI-C reported at each of 3 annual interviews. By May 1997, 659 men had completed 3 annual interviews for the Sydney Men and Sexual Health (SMASH) cohort study. For the 3 6-month periods prior to each interview, 127 men reported UAI-C during one period only; 45 reported it during 2 periods; and 20 men reported it during all 3 periods. These 20 men who had repeated UAI-C were compared with 497 men who had anal intercourse with casual partners but did not report on all 3 occasions that they had UAI-C. Logistic regression revealed that repeated UAI-C was associated with HIV-positive status, more casual partners, less favourable attitudes toward condoms and greater recreational drug use. Few gay men have repeated UAI-C but those who do run greater risk of HIV transmission.

Adult↗

Needy children.

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California↗

Effects of daunomycin implants on filtering surgery outcomes in rabbits.

PURPOSE: To evaluate the effects of a novel daunomycin (DM) implant on intraocular pressure (IOP), bleb survival, and anterior segment complications when administered during filtering surgery on New Zealand White rabbits. METHODS: Implants were prepared by covalent coupling of DM to a high molecular weight hyaluronic acid (HA) and fabricated into solid implants containing 250, 65, and 25 microg of DM. Full thickness sclerostomies were performed, and rabbits received no implant (control), placebo implant containing HA, or an implant containing HA-DM conjugate at the time of surgery. Rabbits were then followed for 30 days to assess change in IOP, bleb survival, and anterior segment associated complications. RESULTS: In vitro, the release of DM from the implants was a first order process with a half-life of 51 h. In control rabbits, rabbits receiving placebo implant, and rabbits receiving HADM (250 microg) implants, the mean IOPs on day 3 were 11.1 +/-1.6, 10.8 +/- 2.7, and 14 +/- 0.98 mm of Hg, respectively. On days 5 through 9, IOP in the control and placebo-implanted groups returned to preoperative levels. However, in rabbits receiving 250 microg of conjugated DM, mean IOP on day 7 was reduced from preoperative levels by 11.8 +/- 3.2 mm of Hg (P < 0.05). This reduction in IOP was significantly different (P < 0.05) from both control and placebo implant groups, and IOPs remained at these levels until studies were terminated on day 30. In control and placebo-implanted rabbits, bleb size started decreasing on day 1, and by day 7, no blebs were observed. In rabbits receiving 250 microg HA-DM implants, mean bleb survival time was greater than 30 days. The DM-induced reduction in IOP and enhanced bleb survival was dose-dependent. In rabbits receiving 65 microg of conjugated DM, lOPs were significantly reduced through day 30; however, at times beyond day 19 there was a gradual rise in mean IOP as filtering procedures in individual animals began to fail. Mean bleb survival time was greater than 30 days for implants containing 65 microg of conjugated DM. In rabbits receiving HA-DM implant containing 25 microg of DM, IOPs were not significantly different from preoperative levels beyond day 9, and no significant enhancement in bleb survival was observed in these animals. Comparison of HA-DM conjugated implants to those containing equal doses of free DM demonstrated that the mean IOP change at 30 days were similar; however, there was a reduction in anterior segment complications associated with the use of HA-DM conjugated implants. CONCLUSIONS: This study provides evidence that the controlled release of DM when conjugated to HA can significantly improve the success of filtering procedures. The maintenance of ocular hypotension and bleb survival along with the reduction in anterior segment complications supports the idea that HA-DM conjugate will be more efficacious than the use of free DM in improving the success rate of filtering surgery.

Animals↗

Pulmonary dysfunction and reduced exercise capacity in patients with myelomeningocele.

OBJECTIVE: To evaluate pulmonary function and exercise capacity in children with myelomeningocele. STUDY DESIGN: Prospective evaluation in a randomly selected cohort of 12 subjects (10 to 17 years of age) with myelomeningocele and 12 control subjects matched for age, sex, and arm span. METHODS: Spirometry, lung volumes, maximum respiratory pressures, maximum oxygen expenditure during arm ergometry, and anaerobic threshold were measured. RESULTS: Mean total lung capacity and fractional lung volumes were significantly lower in case subjects than control subjects. Eleven subjects (92%) had a reduced forced vital capacity; seven (58%) had restrictive disease as evidenced by reductions in total lung capacity with normal or increased forced expiratory volume in 1 second/forced vital capacity ratio. Nine subjects (75%) had respiratory muscle weakness as evidenced by reduced maximum respiratory pressures or a low maximum voluntary ventilation. Exercise capacity was reduced as evidenced by a lower maximum oxygen consumption at peak exercise (13.8 +/- 4.8 vs 21.3 +/- 7.5 ml/min per kilogram of body weight; p < 0.02) and a lower anaerobic threshold (12.4 +/- 5.1 vs 17.3 +/- 4.2 ml/min per kilogram; p < 0.01) than the control group. Though the majority of subjects with myelomeningocele had a significant degree of restrictive disease, respiratory muscle weakness, or both, only one subject had pulmonary symptoms during exercise. CONCLUSIONS: Though most subjects with myelomeningocele had a significant degree of restrictive lung disease, respiratory muscle weakness, or both, exercise capacity was mostly limited by arm weakness. Skeletal muscle weakness may mask the symptoms of an underlying pulmonary abnormality, which may not be evident unless a pathologic cause of increased ventilation is present. Pulmonary function testing is suggested to screen for these abnormalities.

Adolescent↗