Statistical methods for assessing observer variability in clinical measures.
Explore the source record for details and available documents.
Arthritis↗
Biomedical subjects
P Brennan
Publications and source records attributed to P Brennan.
Timing of pregnancy in relation to the onset of rheumatoid arthritis.
The interval between the onset of rheumatoid arthritis (RA) and the most recent pregnancy prior to RA onset in 88 women was determined. These data were compared with data obtained from a group of 144 age-matched normal women (controls) who had been assigned a "dummy date for RA onset" for the purposes of analysis. The frequency of disease onset during 3 time intervals within the period from conception to 1 year postpartum was compared with the frequency of disease onset outside this period. There was a reduction in the incidence of disease onset during pregnancy (adjusted odds ratio [OR] 0.30, 95% confidence interval [CI] 0.04-2.6) and a numerically greater increased risk of RA onset during the first 3 months postpartum (OR 5.6, 95% CI 1.8-17.6), which persisted for the subsequent 9 months (OR 2.6, 95% CI 0.8-7.9). A reduction in the incidence of disease onset was seen during all pregnancies; in contrast, the postpartum increase was greater in those with RA onset after the first pregnancy. The reduced incidence of RA onset during pregnancy, with the increased risk postpartum, mirrors the previously described suppression of disease activity during pregnancy and the subsequent flare postpartum in women with established RA. In addition, the increased postpartum risk after the first pregnancy might suggest that in susceptible women, either the hormonal changes or the exposure to the fetus's paternal HLA might represent a risk factor for disease causation.
Adult↗
Do current regimes of hormone replacement therapy protect against subsequent fractures?
It is now accepted that unopposed oestrogen therapy reduces osteoporotic fractures by about 50%. Although current regimes with added progestogens are thought to act similarly to unopposed oestrogens, no study has yet demonstrated an effect on fractures with the former. Using a retrospective cohort design we studied fracture rates in women attending a menopause clinic for hormone replacement therapy (HRT) and compared them with women derived from the general population. Data were analysed from 1075 women exposed to HRT and 1741 non-exposed postmenopausal women. In all 226 fractures were reported between 1977 and 1986, the commonest site being the distal radius, occurring in 28 of the HRT women and in 37 of the non-exposed women. The incidence density rate for fracture of the distal radius is 3.5/1000 woman-years (wy) in non-exposed women. This was similar to the rate in the HRT women prior to HRT use, the rate falling by 30% after exposure from 3.2 to 2.2/1000 wy. The protective effect on osteoporotic fractures increased progressively with duration of use. After 5 years of use the relative risk fell to 0.5 (95% confidence interval, 0.2-1.2) for all osteoporotic fractures and for the distal radius to 0.18 (95% confidence interval, 0.05-1.3). No similar changes were seen for non-osteoporotic fractures. There were 6 (0.6/1000 wy) reported fractures of the hip in the non-exposed group compared with none in the HRT group (when 1.7 were expected based on non-exposed rates) (p = 0.15).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Reliability of skin involvement measures in scleroderma. The UK Scleroderma Study Group.
Two methods have been proposed to quantify the extent of skin involvement in scleroderma. These are (1) a scoring system which quantifies and summates this severity rating in 17 areas of skin surface and (2) a method estimating the percentage of skin involvement using a shaded manikin. We report on a study comparing the inter-observer reliability of these two approaches using the ratings of six clinicians on 12 patients. Systematic bias between observers was noted with both methods, but inter-observer agreement, as-assessed by the intraclass correlation coefficient (ICC), was higher with the score method. The manikin method resulted in a greater degree of disagreement between the observers, as well as a higher amount of random error, reflecting the difficulty of defining the bounds of abnormal skin. Despite the presence of bias, the score method is the preferred method for assessing the level of skin involvement.
Analysis of Variance↗
Reproductive function prior to disease onset in women with scleroderma.
We tested in a retrospective study the hypothesis that women with scleroderma have an increased risk, before disease presentation, of problems in pregnancy. Reproductive history, as reported from a validated postal questionnaire, was obtained from 204 women with scleroderma [mean year of birth (yob) 1942] and compared to that reported by 233 women with primary Raynaud's phenomenon (mean yob 1948) and 189 healthy women from a population register (mean yob 1950). Only pregnancies occurring before symptom onset in the scleroderma group were considered for analysis. All analyses were adjusted for job, social class, age at first pregnancy, smoking habit, and where relevant, parity. The results are expressed as odds ratios (OR) [with 95% confidence limits (CL)] giving the risk of developing scleroderma, with previous exposure to each of the specific reproductive variables analyzed, relative to the 2 comparison groups. The women with scleroderma were more likely than the population women to have had a delay in conception (> or = 12 months): OR 2.6 (1.1, 5.7) or be infertile: OR 2.3 (0.7, 7.2). These differences were not apparent when the scleroderma group was compared to the women with Raynaud's: OR's 0.7 and 1.1, respectively. Similarly there was a greater self report of maternal ill health in pregnancy in the group with scleroderma compared to the population women: OR 2.1 (1.2, 3.5) but not compared to the women with Raynaud's: OR 1.0 (0.7, 1.6).(ABSTRACT TRUNCATED AT 250 WORDS)
Female↗
Researcher develops computer networks for AIDS and Alzheimer patients.
Explore the source record for details and available documents.
Acquired Immunodeficiency Syndrome↗
Dermal absorption of niclosamide in rats and minipigs.
The dermal absorption of niclosamide, a drug shown to prevent Schistosomiasis by blocking the dermal penetration of cercariae, has been examined in Sinclair minipigs and rats. Radioactivity in the urine and feces collected daily for 7 days after application of 14C-niclosamide accounted for less than 2 per cent and 10 per cent of the labelled compound applied to pig and rat skin, respectively. Approximately 20 per cent of the radioactivity from the dose solution was recovered on the skin excised from the area of application in both minipigs and rats. No radioactivity was detected in organs removed from the pig 7 days after application of radiolabelled drug while less than 6 per cent of the dose could be accounted for in the rat organs/carcass. Radioactivity in swine blood, removed 0.5, 1, 2, 4 and at 24 h intervals after dosing, was at or below three times background in all of the samples. Total recovery of the applied radioactivity was 78 per cent in pigs and 57 per cent in rats. These studies indicate that niclosamide is very poorly absorbed after dermal application. The results are consistent with earlier comparative studies showing that dermal penetration of xenobiotics in rats is generally higher than in swine.
Administration, Cutaneous↗
Does estrogen replacement therapy protect against rheumatoid arthritis?
The incidence of rheumatoid arthritis (RA) was compared in 2 cohorts of women aged 35-64. One consisted of 1,075 estrogen replacement therapy (ERT) users and the other was 3,251 women from general practice registers. Screening detected 32 cases; 8 postmenopausal control and 6 ERT women developed RA during the study period 1982-1986. This produced incidence rates of 19.7/10,000 and 12.3/10,000 years of observation for ERT and controls, respectively. The relative risks for ERT was 1.62 (95% CI 0.56-4.74) and reduced towards unity after adjustment for potential confounders. Despite the wide confidence interval, our data do not support the previous observation of a 4-fold reduction in RA incidence in ERT users. Indeed the incidence rate in the exposed group in this study exceeded current population estimates of RA incidence in postmenopausal women. We believe that the high incidence rates could be best explained by the self-selection for estrogen therapy at the menopause of those with undiagnosed joint symptoms. These findings underscore the difficulties in elucidating the relationship between ERT and RA.
Adult↗
An integrated informatics curriculum in a baccalaureate nursing program.
As health care requirements change, nurses will not only have to process and communicate more information, but the nature and types of this information will dramatically change as well. It is imperative that nurses understand the potential information technologies offer to assist the nurse in this expanded role. This paper describes an innovative endeavor to incorporate information technology with its undergraduate nursing program. The challenge was to design a program that would help develop the students' skills to critically appraise their information needs and conceptually evaluate the utility of gathering information in providing patient care. After completing the first nursing informatics course, there was an increase in the students' perception and understanding of the uses of information technology to support the nursing process in providing patient care.
Attitude to Computers↗
Inhibition of protein kinase C activation by low concentrations of aluminium.
An extract of rat brain protein kinase C was fully activated at a total calcium concentration 3 x 10(-4) mol/l (Ca2+ 10(-4) mol/l) in the presence of non-limiting concentrations of phosphatidylserine. Available aluminium (ionised plus soluble hydrolysed) at a median value of 2 x 10(-8) mol/l inhibited enzyme activation by 90% at this non-limiting calcium concentration. Literature values for tissue aluminium concentrations suggest that interference with this key intracellular regulatory protein might occur in vivo.
Aluminum↗
Olfactory recognition: a simple memory system.
Mice have an olfactory (pheromone) recognition memory located at the first relay in the sensory system. It is acquired with one-trial learning, contingent upon norepinephrine activation at mating, and lasts for several weeks. The mechanism involves Hebbian (association-dependent) changes in synaptic efficacy at dendrodendritic synapses in the accessory olfactory bulb. As a result of this memory, males made familiar by mating are recognized by the females, thereby mitigating pregnancy block. Such a memory function is biologically important to the female, as it is required to sustain pregnancy in the presence of her stud male's odors.
Amygdala↗
Prevalence of symptoms of Raynaud's phenomenon in general practice.
OBJECTIVE: To investigate the prevalence of Raynaud's phenomenon in the populations of five general practices. DESIGN: Two populations studied. A questionnaire was given to all new patients attending five general practices over four weeks, and the same questionnaire was sent by post to a random sample of adults from two of the practices. SETTING: General practices in inner London, Merseyside, and Cheshire. SUBJECTS: 1532 Patients who completed questionnaires (1119 who attended the surgeries (response rate unknown) and 413 respondents to the postal survey (response rate 69%)). MAIN OUTCOME MEASURES: Response to questionnaire on symptoms of Raynaud's phenomenon: patients were regarded as having the disease if they had episodes of blanching of the fingers that were precipitated by cold and accompanied by sensory symptoms (pins and needles or numbness). Subsequent interview and clinical appraisal of patients with the disease according to their responses to the questionnaire. RESULTS: The prevalence of Raynaud's phenomenon was 11% (26/231) and 19% (34/182) respectively in men and women who completed the postal questionnaire and 16% (56/357) and 21% (157/762) respectively in those who completed the questionnaire when attending their general practice. Thus the overall rates were slightly higher in women, but there was no effect of age even after adjustment of the rates for practice and method of survey. CONCLUSION: The prevalence of Raynaud's phenomenon is high compared with the low number of patients who seek treatment for the disease.
Adolescent↗
Recognition of a peptide antigen by heat shock--reactive gamma delta T lymphocytes.
Small synthetic peptides that correspond to different portions of the 65-kilodalton mycobacterial heat shock protein (Hsp65) were used to identify a putative antigenic epitope for gamma delta cells. Weaker gamma delta responses to the equivalent portion of the autologous homolog, mouse Hsp63, were also seen. The stimulatory epitope overlaps with an epitope recognized by arthritogenic alpha beta T cell clones. The data suggest that gamma delta cells have a role in autoimmune disorders and imply that these cells recognize ligands by a mechanism similar to that of alpha beta T lymphocytes, that is, in the form of small processed protein fragments bound to antigen-presenting molecules.
Amino Acid Sequence↗
Recognition of heat shock proteins and gamma delta cell function.
Recently evidence has accumulated suggesting that gamma delta cells may participate in the immune response to mycobacteria and other infectious organisms. Many mouse gamma delta cells are stimulated by the 65 kDa heat shock protein of M. bovis and human gamma delta cell lines reactive with this mycobacterial protein have also been isolated. Indirect evidence further suggests that gamma delta cells can recognize autologous heat shock proteins. In this article, Willi Born and colleagues focus on these and other recent findings and speculate on their importance to gamma delta cell function in vivo.
Animals↗
Pediatric problems in a suburban shelter for homeless families.
The experience of an affiliation between a hospital-based clinic and a family shelter is presented. The medical implications of family shelter residence include special issues related to the spread of infectious diseases, particularly to the neonate. Preentry medical evaluation revealed that a large proportion of children and their parents had one or more medical problems. Of 67 children screened before entrance, 13% [corrected] had Giardia lamblia detected in the stool. In addition to carriage of enteric pathogens, the range of pediatric problems encountered included a variety of acute and chronic medical conditions, unmet primary care needs, and developmental and school difficulties. Fifty-eight percent of shelter residents were found to be "medically homeless." Formal liaison between a hospital-based clinic and a family shelter was found to be an effective way to promote a healthy environment in the family shelter and to provide needed medical services to shelter families.
Adolescent↗
Microbial glycolipids: possible virulence factors that scavenge oxygen radicals.
Two important pathogens of developing countries, Mycobacterium leprae, the etiologic agent of leprosy, and Leishmania donovani, the protozoal parasite that causes kalaazar, persist in the human host primarily in mononuclear phagocytes. The mechanisms by which they survive in these otherwise highly cytocidal cells are presently unknown. Since the best understood cytocidal mechanism of these cells is the oxygen-dependent system that provides lethal oxidants including the superoxide anion (O2-), hydrogen peroxide (H2O2), hydroxyl radical (OH), and singlet oxygen (1O2), we sought specific microbial products of these organisms that might enable them to elude oxidative cytocidal mechanisms. Phenolic glycolipid I of M. leprae and lipophosphoglycan of L. donovani are unique cell-wall-associated glycolipids produced in large amounts by the organisms. In this study, phenolic glycolipid I derivatives and lipophosphoglycan were examined for their ability to scavenge potentially cytocidal oxygen metabolites in vitro. Electron spin resonance and spin-trapping indicate that phenolic glycolipid I derivatives and lipophosphoglycan are highly effective in scavenging hydroxyl radicals and superoxide anions. The results suggest that complex glycolipids and carbohydrates of intracellular pathogens that can scavenge oxygen radicals may contribute to their pathogenicity and virulence.
Animals↗
Vaccine development. On relating immunology to the Third World: some studies on leprosy.
Leprosy is of interest to immunologists because the varied clinical manifestations of the disease correlate closely with the immunological spectrum. Resistance to infection is dependent on appropriate cell-mediated immunity, but patients with the lepromatous form fail to respond to antigens of M. leprae. In vitro studies have revealed the existence of T-suppressor cells of the phenotype CD8+, CD3+, HLA-DR+, FcR+, 9.3-, which are restricted by major histocompatibility complex (MHC) class II antigens. Several new candidate vaccines against leprosy have been effective in breaking immunological unresponsiveness and engendering cell-mediated immunity in lepromatous leprosy patients, including the combination of BCG+ killed M. leprae. Because BCG has unique adjuvant properties, we have begun to use molecular genetic approaches to develop BCG into a multivaccine vehicle capable of immunizing simultaneously against several pathogens. Both phage-based and plasmid-based strategies have been successfully developed for introducing selectable markers into BCG for the first time.
Bacterial Vaccines↗
Postcopulatory genital grooming in male rats: prevention of sexually transmitted infections.
Prevention of postcopulatory genital grooming in male rats increased the likelihood that they would be genitally infected with a marker microorganism (Staphylococcus aureus) inoculated previously into the vagina of female rats. Male as well as female rat saliva was found to have very minimal bactericidal effects on the marker organism indicating that physical washing during postcopulatory grooming can prevent the transmission of infectious organisms. Saliva of both male and female rats, however, was found to have bactericidal effects on 2 murine pathogens (Pasteurella pneumotropica and Mycoplasma pulmonis) that infect the genitalia of males and females, revealing that the physical washing effect can be enhanced by specific antibacterial properties of saliva for some reputed genital pathogens.
Animals↗