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Biomedical subjects

C Power

Publications and source records attributed to C Power.

At least 37 records · Page 2Linked to original sources

Neurocognitive symptoms and impairment in an HIV community clinic.

BACKGROUND: Neurocognitive impairment is a frequent complication of HIV infection and heralds a poor survival prognosis. With the availability of highly active antiretroviral therapy (HAART), survival times for HIV-infected patients have markedly increased although the effects of HAART on the prevalence of neurocognitive impairment remain uncertain. OBJECTIVE: To determine the relationship between self-reported neurocognitive symptoms and neuropsychological (NP) performance together with the impact of HAART among HIV-infected patients. METHODS: A cross-sectional study was performed in which patients without previously documented neurocognitive impairment attending an HIV community clinic were questioned about neurocognitive symptoms and a NP test battery was administered. RESULTS: Of the eighty-three patients examined, neurocognitive symptoms were reported by 34% of patients and were associated with a shorter duration of HAART and higher viral loads. Patients reporting neurocognitive symptoms were also more likely to exhibit impaired NP performance (p<0.005) with NP impairment being detected in 46% of all patients examined (12% with HIV-associated dementia). Neuropsychological impairment was directly correlated with age (p<0.001), plasma viral load (p<0.005) and inversely correlated with the number of prescribed antiretroviral drugs (p<0.01). CONCLUSIONS: These results suggest that neurocognitive symptoms are predictive of impaired NP performance and that NP impairment remains a frequent finding among older patients with higher viral loads. An increased number of antiretroviral drugs may be neuroprotective.

Adult↗

Encephalopathy with staphylococcal endocarditis: multiple neuropathological findings.

BACKGROUND: Infective endocarditis is associated with serious neurological sequelae. OBJECTIVE: Here, we report a patient with Staphylococcus aureus endocarditis, secondary to congenital heart disease, with subacute onset of multiple neurological complications. RESULTS: Despite prompt antibiotic treatment with rapid sterilization of blood cultures, the patient died with brain herniation within 96 hours of admission. Neuropathological examination showed intraparenchymal hemorrhages, mycotic aneurysms, micro-abscesses and septic arteritis with accompanying infarction. Immunocytochemical studies revealed enhanced CD45 and GFAP immunoreactivity, together with adenosine A1 receptor detection on macrophages and microglia. CONCLUSIONS: Infective endocarditis is associated with multiple neuropathological lesions, which may contribute to its poor clinical outcome and activation of cells of monocyte-microglial lineage throughout the brain.

Adult↗

A case for a neonatal, low-dose BCG vaccination trial.

The rational design of a successful vaccination strategy against tuberculosis requires certain kinds of information and must take account of several considerations: (i) the nature of the immune response that protects the large majority of individuals infected by Mycobacterium tuberculosis, designated as healthy contacts, must be defined and distinguished from that in tuberculosis patients, whose immune system must have failed; (ii) the vaccination strategy must incorporate a way of priming the immune system to guarantee in all individuals this protective response, normally generated in healthy contacts, upon natural infection by M. tuberculosis; (iii) the strategy must incorporate a mechanism for ensuring that the effectiveness of this priming is not abrogated by exposure to environmental mycobacteria; and (iv) the strategy must take account of the fact that the vaccinated population is genetically heterogeneous, and that individuals will therefore respond variably to most standard vaccination protocols. We describe a tentative proposal for how these interrelated problems might be solved and discuss predictions of this tentative vaccination strategy. Critical testing of the neonatal, low-dose BCG vaccination strategy can only be achieved by a field trial and we outline the considerations underlying this proposal.

Animals↗

Family social class, maternal body mass index, childhood body mass index, and age at menarche as predictors of adult obesity.

BACKGROUND: Obesity is an increasingly prevalent nutritional disorder throughout the world and is a risk factor for many chronic diseases. The prevalence of obesity increases with age. OBJECTIVE: The objective was to evaluate the associations between BMI at 31 y of age and family social class during early childhood, maternal body mass index (BMI) before pregnancy, BMI at birth and at 1 and 14 y of age, and age at menarche. DESIGN: This was a longitudinal study of the northern Finland birth cohort for 1966. Subjects were measured at birth and at 1, 14, and 31 y of age. The analysis was restricted to individuals for whom BMI data were available for all measurement points (n = 2876 males and 3404 females). RESULTS: The mean BMI at birth was highest in offspring from the highest social classes, but BMI was inversely related to social class at 1 y. BMI, the waist-to-hip ratio, and the proportion of obese subjects were inversely related to social class at 31 y. The heavier the mother, the heavier the offspring from birth to 31 y. The paired analyses between maternal BMI and daughter's BMI at 31 y showed no significant difference in BMI after adjustment for the age difference. BMI at 14 y was the most important predictor of BMI at 31 y. Early menarche in females was associated with a higher BMI at 14 and 31 y. CONCLUSIONS: Differences in BMI by social class are formed at least partly during early childhood. Low social class of the child's family, a high maternal BMI before pregnancy, a high BMI during adolescence, and early menarche are predictors of obesity in adulthood.

Adolescent↗

Physical and psychological effects of injury. Data from the 1958 British birth cohort study.

BACKGROUND: There is only scant evidence for the long-term health effects of road traffic injuries. We therefore assessed the extent to which motor vehicle driver injuries influence limiting long-standing illness and psychological distress using data from a nationwide study (the 1958 British birth cohort) in early adulthood. METHODS: Information was obtained on driver injuries occurring between ages 23 and 33 years and limiting illnesses and psychological distress at age 33 years. The risks of injury-related adverse consequences were derived using logistic regression and expressed as odds ratios (ORs) and 95% confidence intervals. RESULTS: A single injury was associated with limiting illness (OR = 2.01 and 95% CI: 1.38-2.94). The association between a single injury and psychological distress was strong for a recent injury occurring between ages 30 and 33 years (OR = 1.86 and 95% CI: 1.24-2.81), but not for injuries occurring earlier on. The population attributable fraction for limiting illness with one injury was 3.8% (range 1.7-5.3%) and with two or more injuries was 1.0% (range 0.5-1.3%). After controlling for potential confounding factors the corresponding figures were 4.2% (range 2.2-5.6%) and 1.1% (range 0.5-1.3%) respectively. CONCLUSIONS: Driver injuries are associated with a substantial increase in disability and, also in the short term, with increases in psychological distress. These results highlight the need for identifying effective strategies for the prevention of road traffic injuries as well as more effective approaches for rehabilitation of the injured.

Accidents, Traffic↗

Self-rated health and limiting longstanding illness: inter-relationships with morbidity in early adulthood.

BACKGROUND: Self-rated health and limiting longstanding illness are both widely used global measures of health, but understanding is poor of their meaning and validity at younger ages. METHODS: We examined the association between self-rated health and limiting longstanding illness and specific health problems at two ages (23 and 33 years), and assessed change over the 10-year period for each health measure relative to another. Longitudinal data were taken from the nationally representative British birth cohort for which health measures were obtained at ages 23 and 33. RESULTS: Self-rated health and limiting longstanding illness were strongly associated with each other as well as with specific health problems, particularly with serious conditions (e.g. epilepsy, cancer, diabetes) and more weakly with less serious conditions (e.g. eczema and hay fever). Rating of overall health and limiting longstanding illness was highly stable during the 10-year period with most, but not all, health change reflecting a deterioration in health status. Deterioration in limiting illness corresponded to an even greater health decline in specific conditions. CONCLUSIONS: Self-rated health and limiting longstanding illness are valid health measures appropriate for use in general health surveys.

Adult↗

Proinflammatory effects of bacterial lipoprotein on human neutrophil activation status, function and cytotoxic potential in vitro.

Bacterial lipoprotein (BLP) is the most abundant protein in gram-negative bacterial cell walls, heavily outweighing lipopolysaccharide (LPS). Herein we present findings demonstrating the potent in vitro effects of BLP on neutrophil (PMN) activation status, function, and capacity to transmigrate an endothelial monolayer. PMNs are the principal effectors of the initial host response to injury or infection and constitute a significant threat to invading bacterial pathogens. The systemic inflammatory response syndrome (SIRS) is characterised by significant host tissue injury mediated, in part, by uncontrolled regulation of PMN cytotoxic activity. We found that BLP-activated human PMN as evidenced by increased CD11b/CD18 (Mac-1) expression. Up-regulation of PMN Mac-1 in response to BLP occurred independently of membrane-bound CD14 (mCD14). A similar up-regulation of intercellular adhesion molecule-1 (ICAM-1) on endothelial cells was observed whilst E-Selectin expression was unaffected. PMN transmigration across a human umbilical vein endothelial cell (HUVEC) monolayer was markedly increased after treating either PMN's or HUVEC independently with BLP. This increased transmigration did not occur as a result of any direct effect of BLP on HUVEC monolayer permeability, assessed objectively using the passage of FITC-labeled Dextran-70. BLP primed PMN for enhanced respiratory burst and superoxide anion production in response to PMA, but did not influence phagocytosis of opsonized Escherichia coli. BLP far exceeds LPS as a gram-negative bacterial wall component, these findings therefore implicate BLP as an additional putative mediator of SIRS arising from gram-negative infection.

Antigens, CD↗

Antisense oligodeoxynucleotide inhibition of tumor necrosis factor-alpha expression is neuroprotective after intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Tumor necrosis factor-alpha (TNF-alpha) expression is increased in brain after cerebral ischemia, although little is known about its abundance and role in intracerebral hemorrhage (ICH). A TNF-alpha-specific antisense oligodeoxynucleotide (ORF4-PE) was used to study the extent to which TNF-alpha expression influenced neurobehavioral outcomes and brain damage in a collagenase-induced ICH model in rat. METHODS: Male Sprague-Dawley rats were anesthetized, and ICH was induced by intrastriatal administration of heparin and collagenase. Immediately before or 3 hours after ICH induction, ORF4-PE was administered directly into the site of ICH. TNF-alpha mRNA and protein levels were measured by reverse transcriptase-polymerase chain reaction and immunoblot analyses. Cell death was measured by terminal deoxynucleotidyl transferase-mediated uridine 5'triphosphate-biotin nick end labeling (TUNEL). Neurobehavioral deficits were measured for 4 weeks after ICH. RESULTS: ICH induction (n=6) elevated TNF-alpha mRNA and protein levels (P:<0.01) at 24 hours after the onset of injury compared with sham controls (n=6). Immunohistochemical labeling indicated that ICH was accompanied by elevated expression of TNF-alpha in neutrophils, macrophages, and microglia. Administration of ORF4-PE (2.0 nmol) directly into striatal parenchyma, 15 minutes before (n=4) or 3 hours after (n=6) ICH, decreased levels of TNF-alpha mRNA (P:<0.001) and protein (P:<0. 01) in the brain tissue surrounding the hematoma compared with animals treated with saline alone (n=6). Mean+/-SEM striatal cell death (cells per high-powered field) was also reduced in animals receiving ORF4-PE (34.1+/-5.0) compared with the saline-treated ICH group (80.3+/-7.50) (P:<0.001). ORF4-PE treatment improved neurobehavioral deficits observed at 24 hours (P:<0.001) after induction of ICH (n=6) compared with the untreated ICH group (n=6). This improvement was maintained at 28 days after hemorrhage induction (P:<0.001). CONCLUSIONS: These results indicate a pathogenic role for TNF-alpha during ICH and demonstrate that reducing TNF-alpha expression using antisense oligodeoxynucleotides is neuroprotective.

Animals↗

Predictors of low back pain onset in a prospective British study.

OBJECTIVES: This study examined predictors of low back pain onset in a British birth cohort. METHODS: Univariate and multivariate analyses focused on individuals who experienced onset of low back pain at 32 to 33 years of age (n= 571) and individuals who were pain free (n = 5210). Participants were members of the 1958 British birth cohort. RESULTS: Incident pain was elevated among those with psychological distress at 23 years of age (adjusted odds ratio [OR] = 2.52, 95% confidence interval [CI] = 1.65, 3.86) and among persistent moderate or heavy smokers (adjusted OR = 1.63, 95% CI = 1.23, 2.17). Significant univariate associations involving other factors (e.g., social class, childhood emotional status, body mass index, job satisfaction) did not persist in multivariate analyses. CONCLUSIONS: This prospectively studied cohort provides evidence that psychological distress more than doubles later risk of low back pain, with smoking having a modest independent effect. Other prospective studies are needed to confirm these findings before implications for low back pain prevention can be assessed.

Adult↗

Very low prevalence of bovine immunodeficiency virus infection in western Canadian cattle.

Bovine immunodeficiency virus (BIV) is a lentivirus that causes disease in cattle. Despite the large cattle industry in western Canada, the presence of BIV has not been examined to date. Genomic DNA, derived from semen and buffy coat samples, was analyzed by nested polymerase chain reaction (PCR) using specific primers for the gag, pol, and env genes of BIV. Despite utilizing a procedure that detected a minimum of 10 proviral copies, BIV sequences were not amplified in any of 317 buffy coat and 50 semen samples that were obtained from an archive that included 27 cattle breeds, collected from different sources in Alberta (1980-1999). In the 367 DNA samples examined, there was no evidence of BIV infection, suggesting that the prevalence of BIV infection was very low.

Alberta↗

Seroprevalence of infection with Mycobacterium avium subspecies paratuberculosis, bovine leukemia virus, and bovine viral diarrhea virus in maritime Canada dairy cattle.

The purpose of this study was to survey the seroprevalence of infection with the agents of production-limiting diseases in dairy cattle in New Brunswick, Nova Scotia, and Prince Edward Island. In 30 randomly selected herds per province, 30 cattle per herd were randomly selected and tested for antibodies to bovine leukemia virus (BLV) and Mycobacterium avium subspecies paratuberculosis (M. paratuberculosis), while 5 unvaccinated cattle over 6 months of age were tested for antibodies to bovine viral diarrhea virus (BVDV). For BLV, 20.8% (15.8% to 27.0%) of cows were positive, and 70.0% (60.3% to 79.7%) of herds had at least one positive cow. In BLV-positive herds, the average BLV prevalence was 30.9% (24.8% to 37.2%). For M. paratuberculosis, 2.6% (1.8% to 3.9%) of cows were positive, and 16.7% (8.8% to 24.5%) of herds had at least 2 M. paratuberculosis-positive cows. In M. paratuberculosis-positive herds, the average M. paratuberculosis prevalence was 8.5% (6.9% to 10.1%). For BVDV, 46.1% (35.5% to 56.7%) of herds had at least 1 BVDV-positive animal with a titer greater than or equal to 1:64.

Acute Disease↗

Diminished adenosine A1 receptor expression on macrophages in brain and blood of patients with multiple sclerosis.

The nucleoside adenosine has been shown to control the production of proinflammatory molecules through its actions on cell surface purine receptors. Previously, we have reported that the adenosine A1 receptor (A1AR) regulates tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) expression and exhibits diminished function in patients with multiple sclerosis (MS; Mayne et al., Ann Neurol 1999;45:633-639). In the present study, A1AR expression in both brain and peripheral blood mononuclear cells (PBMC) from MS and control groups was characterized by fluorescence-activated cell sorting (FACS), reverse transcriptase-polymerase chain reaction (RT-PCR), and immunohistochemical analyses. FACS analyses of PBMC revealed that A1AR expression was chiefly detectable on CD14-positive cells and was reduced by 53.1% (p < 0.01) in MS patients compared to controls. A1AR mRNA levels were reduced by 43.1% (p < 0.001) in the brains of MS patients compared to patients with other neurological diseases and controls. A1AR protein expression in brain was detected primarily in CD45-positive glial cells and was markedly diminished in MS patients. The analysis of A1AR transcripts in the brain revealed that the A1AR-beta transcript was diminished (49.2%) in MS patients compared to controls (p < 0.002). These results indicate that the A1AR, expressed principally on cells of monocyte/macrophage lineage in both brain and blood, is selectively diminished in MS patients. Reduction of the A1AR-beta transcript in MS patients suggests that dysregulated splicing may influence A1AR protein levels, potentially leading to increased macrophage activation and central nervous system inflammation.

Brain↗

Autopsy study of HIV-1-positive and HIV-1-negative adult medical patients in Nairobi, Kenya.

HIV infection has now been consistently identified as the major cause of death in young Africans in both urban and rural areas. In Africa, several studies have defined the clinical presentation of HIV disease but there have only been a limited number of autopsy studies. Because of the scarcity of autopsy data and the possibility of differing type and frequency of opportunistic infections between different geographic locations we set out to study consecutive new adult medical admissions to a tertiary referral hospital in Nairobi and perform autopsies on a sample of HIV-1-positive and HIV-1-negative patients who died in the hospital ward. Basic demographic data were collected on all patients admitted to two acute medical wards over an 11-month period. Final outcome and final clinical diagnoses were recorded at discharge or death. An autopsy examination was requested if the patient died in the ward. Autopsy examination was performed in 75 HIV-1-positive (40 men, 35 women) and 47 HIV-1-negative (28 men, 19 women) adults who died in the hospital. This represented 48.4% of all HIV-1-positive deaths and 33.3% of all HIV-1-negative deaths. Tuberculosis (TB) and bacterial and interstitial bronchopneumonia accounted for 96% of the major pathology in patients found to be HIV-1-positive at autopsy. TB was present in half the HIV-1-positive autopsy patients and was disseminated in over 80% of cases. Meningeal involvement was present in 26% of those with disseminated TB. By contrast, TB was much less common in the HIV-1-negative patients at autopsy in whom bacterial bronchopneumonia and malignancies were the most common pathologies. The type pathology found in the HIV-1-positive autopsy patients was not different than that found in other areas in Africa so far studied.

AIDS-Related Opportunistic Infections↗

Back pain and obesity in the 1958 British birth cohort. cause or effect?

An association between obesity and back pain has been observed, but the underlying causal direction is uncertain. We examined the temporal sequence among back pain, BMI, and weight gain using data from the 1958 British birth cohort followed to age 33 (4395 men and 4468 women). Heights and weights were measured at ages 7 and 33, and self-reported at age 23. Back pain was classified as: chronic, incident, early onset but recovered, and never. Those with chronic pain gained more weight between ages 23 and 33 than those with no pain, significantly for women (7.39 kg vs. 6.29 kg). Women who were obese at age 23 years had an elevated risk of subsequent back pain onset (32-33 years) (adjusted OR = 1.78). No significant relationships were found for men. The risk of pain onset among women was evident in relation to BMI at baseline (age 23) and cannot therefore be explained by an effect of back pain on adiposity.

Adult↗

AIDS- and non-AIDS-related PML association with distinct p53 polymorphism.

A population-based analysis of progressive multifocal leukoencephalopathy (PML) showed PML frequencies of 5.1% among patients with AIDS and 0.07% among patients with hematologic malignancies, but similar clinical features of PML in both groups. Sequencing of the p53 gene, exon 4, showed heterozygosity (Arg-Pro) at codon 72 in five of six PML patients. These findings indicate that frequencies of non-AIDS- and AIDS-related PML differ markedly but p53 polymorphisms may influence the occurrence of PML in both groups.

Acquired Immunodeficiency Syndrome↗