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Biomedical subjects

C Donnelly

Publications and source records attributed to C Donnelly.

At least 19 recordsLinked to original sources
PubMed2006

Human immunodeficiency virus (HIV) antibody avidity testing to identify recent infection in newly diagnosed HIV type 1 (HIV-1)-seropositive persons infected with diverse HIV-1 subtypes.

A guanidine-based antibody avidity assay for the identification of recently acquired human immunodeficiency virus type 1 (HIV-1) infection was evaluated. The kinetics of maturation of antibody avidity were determined prospectively in 23 persons undergoing acute seroconversion followed for up to 1,075 days. Avidity indices (AI) of <or=0.75 and <or=0.80 reproducibly identified seroconversion within the previous 125 (95% confidence interval [CI], 85 to 164) and 142 (95% CI, 101 to 183) days, respectively. To validate the assay, 432 serum samples from newly diagnosed patients were tested by both the avidity assay and the detuned assay. Results were highly concordant (kappa value for agreement, 0.85). The avidity assay was subsequently used to screen 134 consecutive newly diagnosed patients, including 55/134 (41%) infected with non-B subtypes (A, C, D, G, CRF01, CRF02, CRF06, CRF13, and CRF16). In this cohort, 25/79 (32%) persons with the B subtype and 7/55 (13%) with non-B subtypes showed an AI of <or=0.75, and there were 16/25 (64%) and 3/7 (43%) persons, respectively, with a documented history of acute seroconversion illness within the predicted seroconversion interval. An AI of <or=0.75 was also observed for four patients (three with the B subtype and one with a non-B subtype) who presented with AIDS-defining conditions. In multivariate analysis, an AI of <or=0.75 was associated with younger age, higher HIV-1 plasma RNA load, and being born in the United Kingdom or Ireland rather than in Africa but not with gender, ethnicity, risk group, HIV-1 subtype, or CD4 counts. In conclusion, HIV antibody avidity testing provides a reliable method for identifying recently acquired HIV-1 infection. Results are affected by advanced disease and should therefore be interpreted in the context of other clinical parameters.

Adult↗
PubMed2006

Utilization, access and satisfaction with primary care among people with spinal cord injuries: a comparison of three countries.

STUDY DESIGN: Cross-sectional; survey. OBJECTIVES: To describe the utilization, accessibility and satisfaction of primary and preventive health-care services to individuals with long-term spinal cord injuries, and compare results among three countries: the United States, Canada and the United Kingdom. SETTING: The Canadian sample was obtained from the Canadian Paraplegic Association-Ontario and Manitoba Divisions. The British sample was recruited from the Northwest Regional Spinal Injuries Centre in Southport and National Spinal Injuries Centre at Stoke Mandeville Hospital in Aylesbury. The American sample was recruited through Craig Hospital in Englewood, CO, USA. METHOD: A total sample of 373 individuals aging with a spinal cord injury participated in a mailed survey. The Health Care Questionnaire was used to measure utilization, access and satisfaction with primary care and preventive services. RESULTS: In total, 93% of individuals reported having a family doctor, 63% had a spinal injuries specialist and 56% had both a family doctor and spinal injuries specialist. Considerable duplication of services occurred for general medical and preventive services, although lifestyle and emotional issues were not addressed for over 75% of the participants. Significant differences were found in utilization among Canada, US and UK, with Canadians most likely to receive health care from family physicians and Americans most likely to receive care from specialists. Access to and satisfaction with health services was not significantly different among countries. CONCLUSION: People with long-standing spinal cord injuries develop complex maps by which they seek out appropriate primary health-care and preventive services. Given the differences among countries, it is clear that the health delivery model plays an important role in how and where individuals receive health services.

Adult↗
PubMed2005

Pain following spinal cord injury: the impact on community reintegration.

STUDY DESIGN: Prospective, correlational. OBJECTIVES: (1) Describe how pain changes over recovery from admission to spinal cord injury (SCI) rehabilitation, discharge and after 6 months of community living and (2) examine the relationship between pain and community integration at 6 months of community living. SETTING: Tertiary rehabilitation centre, SCI unit, Vancouver, Canada. METHODS: Subjects from 66 consecutive admissions to the SCI Program of a tertiary rehabilitation centre for the treatment of a traumatic SCI during the years 2000-2002 were followed using data from the National Rehabilitation Reporting System (NRS). Information was obtained from NRRS standardized assessments performed on admission, discharge and 6 months of community living. Early community living was defined as 6 months postdischarge. Community reintegration was assessed by the Reintegration to Normal Living Index (RNL). Pain presence, pain impact and pain intensity were assessed using single item Likhert-type scales. RESULTS: In all, 86% of individuals with a SCI reported pain at 6 months postdischarge, with 27% of these individuals reporting pain that impacted on many or most activities. Pain impact and pain intensity were related to the community reintegration (r = -0.39 and -0.55, P < 0.001), with pain intensity accounting for 25% of the variance in RNL scores. CONCLUSIONS: Pain is a major consequence of a SCI, impacting on an individual's activities and perception of how well they are integrated into the community. The results of this study highlight the need to address pain during both the rehabilitation phase of treatment and the early transition into the community.

Activities of Daily Living↗
PubMed2004

Client-centred assessment and the identification of meaningful treatment goals for individuals with a spinal cord injury.

STUDY DESIGN: Retrospective analysis. OBJECTIVES: (1) Describe the self-care, productivity and leisure problems identified by individuals with a spinal cord injury (SCI) during rehabilitation, (2) describe the perceived level of satisfaction and performance with self-care, productivity and leisure activities following an SCI, (3) quantify the relationship between the Canadian occupational performance measure (COPM), a client-centred, individualized measure of function, and the functional independence measure (FIM). SETTING: Tertiary rehabilitation centre, spinal cord injury unit, GF Strong Rehabilitation Centre, Vancouver, Canada. METHODS: Health records from 41 individuals with an SCI admitted between 2000 and 2002 were reviewed. Information was obtained from assessments performed on admission and discharge. Self-care, productivity and leisure problems identified by individuals with an SCI were described and their perceived level of performance and satisfaction was calculated. The relationship between the COPM and the FIM was measured by the Pearson product correlation. RESULTS: Self-care goals were identified most frequently (79%) followed by productivity (12%) and leisure (9%) goals. The top three problems identified by individuals with an SCI were functional mobility (including transfers and wheelchair use), dressing and grooming. A fair relationship was found between the COPM and the FIM (r between 0.351 and 0.514, P<0.05). CONCLUSIONS: The results highlight the importance of including a client-centred outcome measure in the assessment of individuals with an SCI. Initial support is provided for use of the COPM in individuals with an SCI.

Activities of Daily Living↗
PubMed2002

Clients' perceptions of the benefits of reflexology on their quality of life.

Awareness has increased among health-care professionals, patients and the general public of the importance of an holistic approach to cancer care. Psychosocial interventions, including complementary therapies, may help to improve the quality of life (QoL) of people with cancer by helping to reduce the distress associated with the diagnosis and treatment of cancer and by facilitating improved psychological adjustment to the experience of cancer. The following article presents anecdotal findings at ARC Cancer Support Centre Dublin, Ireland, of clients' perceptions of the benefits of reflexology interventions on their QoL. Reflexology interventions were perceived to impact positively upon clients' levels of impairment and functional status, including physical and psychological function, with implications for general health perceptions. The paper discusses how these findings might form the basis of further, more rigourous evaluation of the benefits of reflexology for people with cancer at ARC Cancer Support Centre.

Adaptation, Psychological↗
PubMed2001

Single-nucleotide polymorphism alleles in the insulin receptor gene are associated with typical migraine.

We have identified a migraine locus on chromosome 19p13.3/2 using linkage and association analysis. We isolated 48 single-nucleotide polymorphisms within the locus, of which we genotyped 24 in a Caucasian population comprising 827 unrelated cases and 765 controls. Five single-nucleotide polymorphisms within the insulin receptor gene showed significant association with migraine. This association was independently replicated in a case-control population collected separately. We used experiments with insulin receptor RNA and protein to investigate functionality for the migraine-associated single-nucleotide polymorphisms. We suggest possible functions for the insulin receptor in migraine pathogenesis.

Alleles↗
PubMed2001

Lack of association between atopic eczema and the genetic variants of interleukin-4 and the interleukin-4 receptor alpha chain gene: heterogeneity of genetic backgrounds on immunoglobulin E production in atopic eczema patients.

BACKGROUND: The genetic background of atopic eczema might be heterogeneous and there is a possibility that immunoglobulin (Ig)E responsiveness in patients with atopic eczema is controlled separately from the development of atopic eczema. Although both interleukin (IL)-4 and the IL-4 receptor alpha chain have an important role for IgE production and are therefore possible candidate genes for atopy, it has not been clarified whether these genes play any roles in atopic eczema patients who have normal IgE productivity. OBJECTIVE: We aimed to assess whether the polymorphisms of the IL-4 gene and the IL-4 receptor alpha chain gene play any roles in atopic eczema patients, particularly in patients who have normal IgE productivity. METHOD: We determined the genotype with regard to polymorphisms in the genes for IL-4 and the IL-4 receptor alpha chain (- 589C/T of IL-4; Ile50Val, Ala375Glu and Arg551Gln of IL-4 receptor alpha chain) in patients with atopic eczema using the fluorogenic 5' nuclease assay. RESULTS: IL-4 and the IL-4 receptor alpha chain genotypes were not significantly associated with either total patients with atopic eczema or atopic eczema patients who had normal IgE productivity. The distribution of genotypes of IL-4-589C/T differed by the serum IgE levels in patients with atopic eczema. CONCLUSION: These results suggest that the polymorphisms in the IL-4 gene and the IL-4 receptor alpha chain gene play no role in the development of atopic eczema in patients who have normal IgE productivity.

Adolescent↗
PubMed2000

The health of enrolled and non enrolled children of school age in Tanga, Tanzania.

The health of 227 children enrolled at primary school was compared with that of 214 non enrolled children living in rural Tanga, Tanzania. No consistent difference was observed with respect to prevalence and intensity of parasitic infection (hookworm, T. trichiura, A. lumbricoides, S. haematobium and P. falciparum). Since enrolled children were as commonly and as heavily infected as non enrolled children, treatment of enrolled children would be effective in reducing transmission throughout the total population. Non enrolled children were more stunted (P=0.0001) and wasted (P=0.0001) than enrolled children and also tended to be more anaemic (P=0.080) showing that poor nutrition is not only associated with delayed enrolment but continues to be associated with non enrolment throughout the school age years. Given that treatment has the greatest impact on the most malnourished children, additional measures to extend treatment to non enrolled children would be justified.

Animals↗
PubMed1999

Acquired immunity and postnatal clinical protection in childhood cerebral malaria.

By analysing data on the age distribution of cerebral malaria among sites of different transmission intensities, we conclude that the most plausible explanation for the epidemiological patterns seen is that (i) cerebral malaria is caused by a distinct set of Plasmodium falciparum antigenic types; (ii) these antigenic types or 'CM strains' are very common and induce strong strain-specific immunity; and (iii) the postnatal period of protection against cerebral malaria is much longer than the period of protection against other forms of severe disease. The alternative hypothesis that cerebral malaria may be caused by any 'strain' of P. falciparum is compatible with the data only if a single exposure is sufficient to protect against further episodes. This is not consistent with observations on the history of exposure of patients with cerebral malaria. Finally, it is clear that although the delayed peak in incidence of cerebral malaria (with age) can be generated by assuming that subsequent exposures carry a higher risk of disease, such an explanation is not compatible with the observation that severe disease rates are low among infants and young children in areas of high transmissibility.

Africa South of the Sahara↗
PubMed1999

Multiplex polymerase chain reaction for the simultaneous detection of Mycoplasma pneumoniae, Chlamydia pneumoniae, and Chlamydia psittaci in respiratory samples.

AIMS: To develop a multiplex polymerase chain reaction (PCR) for the simultaneous detection of Mycoplasma pneumoniae, Chlamydia pneumoniae, and Chlamydia psittaci in respiratory samples. METHODS: Oligonucleotide primers for the amplification of the DNA of these three organisms were optimised for use in combination in the same reaction. PCR products were detected by hybridisation with pooled internal probes using an enzyme linked immunosorbent assay. Those with positive signals were further differentiated using species specific probes. Quality of DNA extraction and PCR inhibition were controlled by amplification of a human mitochondrial gene. A panel of 53 respiratory samples with known results was evaluated blindly. This was followed by a retrospective study on sputa collected from 244 patients with suspected community acquired pneumonia. RESULTS: The multiplex assay had a lower sensitivity than PCR with individual primers by about one log. The resultant sensitivity was considered acceptable for diagnostic use. Of the panel of 53 samples, nine of 11 M pneumoniae, 11 of 11 C pneumoniae, six of seven C psittaci, and 24 of 24 negative samples were correctly identified. Of the 244 patients with pneumonia, seven (2.9%) had detectable M pneumoniae, six (2.5%) had C pneumoniae, and one (0.4%) had C psittaci. The case notes from 11 patients were studied. The PCR finding was of possible significance in at least eight of these patients. CONCLUSIONS: This multiplex PCR assay has the potential to be used as a diagnostic and epidemiological tool. Further prospective studies are needed to establish its clinical value.

Adolescent↗
PubMed1998

The dependence of amino acid pair correlations on structural environment.

A statistical analysis was performed to determine to what extent an amino acid determines the identity of its neighbors and to what extent this is determined by the structural environment. Log-linear analysis was used to discriminate chance occurrence from statistically meaningful correlations. The classification of structures was arbitrary, but was also tested for significance. A list of statistically significant interaction types was selected and then ranked according to apparent importance for applications such as protein design. This showed that, in general, nonlocal, through-space interactions were more important than those between residues near in the protein sequence. The highest ranked nonlocal interactions involved residues in beta-sheet structures. Of the local interactions, those between residues i and i + 2 were the most important in both alpha-helices and beta-strands. Some surprisingly strong correlations were discovered within beta-sheets between residues and sites sequentially near to their bridging partners. The results have a clear bearing on protein engineering studies, but also have implications for the construction of knowledge-based force fields.

Amino Acids↗
PubMed1997

The role of ranitidine bismuth citrate in significantly reducing the emergence of Helicobacter pylori strains resistant to antibiotics.

BACKGROUND: This study was carried out to investigate the clinical observation that the emergence of antibiotic resistance can be reduced in Helicobacter pylori if agents are administered in combination with bismuth salts. MATERIALS AND METHODS: Two H. pylori clinical isolates were grown on chocolate Columbia agar containing either ranitidine bismuth citrate (RBC) at one-half lethal concentration (8 micrograms/ml) or no drug control for 22 subcultures. After 1, 5, 8, 14, 17, and 22 subcultures, the emergence of antibiotic resistance to metronidazole, clarithromycin, and streptomycin was calculated and statistically analyzed. RESULTS: Acquisition of resistance to metronidazole was reduced significantly for both strains (p = .007 and 0.014) and for one strain against clarithromycin (p = .037). However, spontaneous emergence of resistance to streptomycin was not altered significantly. In an analysis of the effect of long-term exposure of the isolates to RBC, susceptibility to bismuth was unaltered in one strain and had risen by only twofold in the other at experiment termination. CONCLUSION: RBC significantly decreased resistance acquisition in an inherently sensitive strain and also decreased resistance emergence in a strain that readily became metronidazole-resistant.

Anti-Bacterial Agents↗
PubMed1997

Lowering the cut off value of an automated chlamydia enzyme immunoassay and confirmation by PCR and direct immunofluorescent antibody test.

AIMS: To increase the sensitivity of an automated chlamydia enzyme immunoassay by significantly lowering its cut off value, and to maintain specificity by confirmation with polymerase chain reaction (PCR) and direct immunofluorescent antibody test (DFA). METHODS: Over five months, the cut off value of the enzyme immunoassay used to screen urogenital samples for chlamydia antigen was reduced from 80 to 10. Samples with a test value of 10 or above were further tested with a commercial PCR assay. All samples during the first three months and discrepant samples during the last two months of the study were also tested with the DFA. RESULTS: 3250 urogenital swabs (1246 urethral, 1335 endocervical, 669 pooled urethral/endocervical) from 1246 males and 2004 females were processed. Using the manufacturer's recommended cut off of 80, the enzyme immunoassay identified chlamydia antigen in 134 samples (4.1%). Using the lower cut off value of 10 and either PCR or DFA as the confirmatory test, Chlamydia trachomatis was identified in 178 samples (5.5%). Thus, 45 additional positive samples were identified and the confirmed detection rate was increased by 33.8% (45/133). Excluding equivocal PCR results, the concordance between DFA and PCR was 91.8%. This strategy increased the detection rate by 2.1% in men and 0.9% in women (significant only in men). In female patients, pooled urethral/endocervical swabs as a specimen gave a significantly higher yield than endocervical swabs regardless of whether the lower cut off strategy was used. CONCLUSIONS: This strategy of significantly lowering the cut off test value with confirmation on the same specimen by either PCR or DFA is feasible and cost effective. The use of pooled urethral/ endocervical specimens in females should be considered routinely as detection rate was significantly improved.

Chlamydia Infections↗
PubMed1996

Effect of estrogen withdrawal on blood pressure and insulin resistance in sucrose-fed juvenile rats.

We have previously shown that juvenile Sprague-Dawley rats, fed a diet in which complex carbohydrates are replaced by sucrose, develop insulin resistance and hypertension. These conditions develop despite the absence of genetic predisposition to either. When studied with the euglycemic hyperinsulinemic clamp technique, these rats have reduced insulin-stimulated glucose utilization, but normal suppression of hepatic glucose output. In the young sucrose-fed rats, it was noted that the degree of blood pressure elevation was greater in males than in females. The purpose of this study was to test the hypothesis that estrogen withdrawal increases insulin resistance and hypertension. Female rats were randomized at weaning (3 weeks of life) to receive control diet or sucrose diet. Animals were assessed with weekly weight and indirect tail-cuff blood pressure. At 8 weeks of life, the sucrose-fed rats were randomized to receive bilateral oophorectomy or sham surgery (anesthesia and uterine horn exposure without removal of the ovaries). At 13 to 14 weeks of life, all animals were fasted overnight, and had an oral glucose tolerance test while conscious. Weight and weight gain were not different among the groups over the 11 week study period. Animals fed the sucrose diet developed significantly higher blood pressure than animals fed the control diet; oophorectomized animals had higher blood pressure than sham-operated animals (P <.0001). Sucrose-fed oophorectomized animals developed fasting and glucose-stimulated hyperinsulinemia. Estrogen withdrawal augments blood pressure in juvenile rats made insulin resistant and hypertensive with a sucrose diet. Estrogen withdrawal in these animals also induces fasting and glucose-stimulated hyperinsulinemia, which are signs of worsening insulin resistance. Androgen:estrogen imbalance increases metabolic dysfunction and worsens hypertension in this animal model.

Animals↗
PubMed1996

The use of a rapid Salmonella latex serogrouping test (Spectate) to assist in the confirmation of ELISA-based rapid Salmonella screening tests.

Spectate, a 10 min, simple, latex-based agglutination test for serogrouping of salmonellae, has been investigated as a tool to assist in the confirmation of ELISA presumptive positive broth samples when screening for salmonellae in foods. When obtaining a combined ELISA and Spectate positive result, there was a 90% (27/30) confidence limit of a genuine positive result, some one or two working days quicker than the traditional methods. Of the 10% (3/30) that were not confirmed as salmonellas, two gave a Spectate result which is advised as being a possible Citrobacter spp. and one sample gave a positive confirmation by Spectate only, which suggested a failure of the traditional confirmation process, a finding confirmed at other sites. Extensive studies performed at several food company microbiology laboratories showed Spectate to be a useful additional tool in the confirmation process of ELISA screening techniques for salmonellae in food. Additionally the concept of a "false positive' may need to be refined to that of a "not culturally' positive, given the apparent possible failure of the traditional confirmation methods.

Enzyme-Linked Immunosorbent Assay↗
PubMed1993

Comparison of transmission rates of HIV-1 and HIV-2 in a cohort of prostitutes in Senegal.

To explore the biological similarities and differences between the HIV-1 and HIV-2 viruses, we model the probability of male-to-female transmission of either HIV virus as a function of the number of sexual partners, the prevalence of the viruses and the infectivity per contact. Using maximum likelihood estimation theory and data from a prospective study of registered female prostitutes in Dakar, Senegal, we estimate and compare the infectivities of HIV-1 and HIV-2. Graphical goodness-of-fit methods are used to show that our model fits the data well. We find that in male-to-female transmission HIV-1 is significantly more infectious than HIV-2. This finding is consistent with other data from laboratory and epidemiologic studies comparing the biology of HIV-1 and HIV-2.

Acquired Immunodeficiency Syndrome↗