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R Mulligan

Publications and source records attributed to R Mulligan.

At least 19 recordsLinked to original sources
PubMed2004

Comparison of methodologies for the in vivo assessment of 18FLT utilisation in colorectal cancer.

Fluorine-18 3'-deoxy-3'-fluorothymidine (18FLT) is a tissue proliferation marker which has been suggested as a new tumour-specific imaging tracer in positron emission tomography (PET). The objectives of this study were to investigate the pharmacokinetics of 18FLT in patients with colorectal cancer, defining methodologies for the quantitative analysis of the in vivo 18FLT uptake and subsequently assessing the accuracy of semi-quantitative measures. Dynamic acquisitions over a single field of view of interest identified by computed tomography were carried out for up to 60 min following injection of 18FLT (360 +/- 25 MBq). Dynamic arterial blood sampling was carried out in order to provide a blood input function. Simultaneous venous samples were also taken in order to investigate their potential utilisation in deriving a hybrid input function. Arterial and venous blood samples at 5, 15, 30, 60 and 90 min p.i. were used for metabolite analysis. Eleven patients with primary and/or metastatic colorectal cancer were studied on a lesion by lesion basis (n = 21). All acquired images were reconstructed using ordered subsets expectation maximisation and segmented attenuation correction. Time-activity curves were derived by image region of interest (ROI) analysis and image-based input functions were obtained using abdominal or thoracic aorta ROIs. Standardised uptake values (SUVs) were calculated to provide semi-quantitative indices of uptake, while non-linear regression (NLR) methodology in association with a three-compartment model and Patlak analysis were carried out to derive the net influx constant Ki. The metabolite analysis revealed two radioactive metabolites, with the parent compound representing approximately 80% of the total radioactivity in the 30-min plasma sample. In the case of NLR, better fits were obtained with a 3k model (i.e. k4 = 0) for both lesion and bone marrow time-activity curves. For the same lesions, a high correlation was observed between the Ki derived from either Patlak analysis or NLR(3k) and the corresponding SUVs. Our results also suggest that the quantitative behaviour of 18FLT in vivo (up to 60 min p.i.) may be characterised using a 3k model or Patlak analysis in combination with image-derived input functions. The good correlation found between the SUVs (at 60 min) and Ki values supports the use of semi-quantitative indices to assess the proliferation rate of colorectal cancer lesions in vivo with 18FLT.

Aged↗
PubMed2004

Incidence of oral lesions in HIV-1-infected women: reduction with HAART.

Few studies assess the effectiveness of HAART on reducing the incidence and recurrence of oral lesions. We investigated such changes among 503 HIV+ women over six years in the Women's Interagency HIV Study. The incidence of erythematous candidiasis (EC), pseudomembranous candidiasis (PC), hairy leukoplakia (HL), and warts was computed over follow-up visits after HAART initiation compared with before HAART initiation. Analysis of our data demonstrates a strong decrease in candidiasis after HAART initiation. The incidence of EC fell to 2.99% from 5.48% (RR 0.545); PC fell to 2.85% from 6.70% (RR 0.425); and EC or PC fell to 3.43% from 7.35% (RR 0.466). No changes were seen in HL or warts. Higher HIV-RNA was associated with greater incidence of candidiasis and HL, but not warts. Analysis of these data indicates that recurrence and incidence of candidiasis are reduced by HAART, and that recurrence is reduced independently of CD4 and HIV-RNA.

Anti-HIV Agents↗
PubMed2004

Dental caries in HIV-seropositive women.

Reports that compare dental caries indices in HIV-seropositive (HIV+) subjects with HIV-seronegative (HIV-) subjects are rare. The objective of this study was to determine if there was an association between HIV infection and dental caries among women enrolled in the Women's Interagency HIV Study. Subjects included 538 HIV+ and 141 HIV- women at baseline and 242 HIV+ and 66 HIV- women at year 5. Caries indices included DMFS and DFS (coronal caries) and DFSrc (root caries). Cross-sectional analysis of coronal caries data revealed a 1.2-fold-higher caries prevalence among HIV+ women compared with HIV- women. Longitudinally, DMFS increased with increasing age and lower average stimulated salivary volume. Root caries results were not significant except for an overall increased DFSrc associated with smoking. Anti-retroviral therapy was not identified as a risk factor for dental caries.

Adolescent↗
PubMed2003

Can diagnostic triage by general practitioners or rheumatology nurses improve the positive predictive value of referrals to early arthritis clinics?

OBJECTIVES: To determine whether diagnostic triage by general practitioners (GPs) or rheumatology nurses (RNs) can improve the positive predictive value of referrals to early arthritis clinics (EACs). METHODS: Four GPs and two RNs were trained in the assessment of early inflammatory arthritis (IA) by four visits to an EAC supervised by hospital rheumatologists. Patients referred to one of three EACs were recruited for study and assessed independently by a GP, an RN and one of six rheumatologists. Each assessor was asked to record their clinical findings and whether they considered the patient to have IA. Each was then asked to judge the appropriateness of the referral according to predetermined guidelines. The rheumatologists had been shown previously to have a satisfactory level of agreement in the assessment of IA. RESULTS: Ninety-six patients were approached and all consented to take part in the study. In 49 cases (51%), the rheumatologist judged that the patient had IA and that the referral was appropriate. The assessments of GPs and RNs were compared with those of the rheumatologists. Levels of agreement were measured using the kappa value, where 1.0 represents total unanimity. The kappa value was 0.77 for the GPs when compared with the rheumatologists and 0.79 for the RNs. Significant stiffness in the morning or after rest and objective joint swelling were the most important clinical features enabling the GPs and RNs to discriminate between IA and non-IA conditions. CONCLUSION: Diagnostic triage by GPs or RNs improved the positive predictive value of referrals to an EAC with a degree of accuracy approaching that of a group of experienced rheumatologists.

Arthritis, Rheumatoid↗
PubMed2001

The Psychogeriatric Assessment Scales (PAS): psychometric properties in French and German speaking populations.

OBJECTIVES: To investigate the structure and measurement properties of the Psychogeriatric Assessment Scales (PAS) in a community sample, to study the performance of French and German translations of the PAS, and to determine the power of PAS scales to discriminate dementia and depression diagnosed to DSM-IV criteria. Design and measures The measures were gathered as part of a large community survey. Responses to PAS items were obtained in the course of the administration of the 'Canberra Interview for the Elderly'. Demographic variables, the mini-mental state examination and measures of premorbid intelligence robust to current intellectual impairment were also gathered in the course of the survey. SETTING: A community survey in the cities of Zurich and Geneva, Switzerland. PARTICIPANTS: Subjects were residents of the two cities aged 65 years or older. There were 465 participants from Zurich and 456 from Geneva. Interviews with an informant who knew the subject well were also obtained. Subjects from Zurich were interviewed in German, subjects from Geneva in French. RESULTS: Confirmatory factor analyses of PAS scales showed close agreement between sites and with results obtained in the sample used to construct the instrument. Correlations with demographic and validating variables also showed this pattern. The PAS cognitive impairment and cognitive decline scales were shown to be good discriminators of DSM-IV dementia while the depression scale discriminated DSM-IV major depressive episode. CONCLUSIONS: This study supports the PAS as a valid and reliable summary of the status of older persons with respect to the impairments, changes and symptomatology that lie at the core of dementing and depressive disorders. This study not only supports the results found in the original development sample, but demonstrates that it performs well against DSM-IV diagnostic criteria and amongst speakers of French and German.

Aged↗
PubMed2001

Economic considerations of Alzheimer's disease and related disorders.

Economic analyses of geriatric syndromes are seldom performed. However, demographic and epidemiological imperatives have led to significant interest in the evaluation of AD-related costs. Over 300 papers devoted to economic considerations of Alzheimer's disease have been published in peer-reviewed journals, within the last five years. In these papers, the chosen perspective (costs to society or to specific payers) is important. Analytical methods are still evolving and remain complex. Unresolved methodological issues will need to be addressed to further our understanding of long-term economic consequences. At present, it is clear that diagnostic and drug costs are low compared to the major cost of institutionalization. Thus, directing efforts at early diagnosis and delaying nursing home placement are two key cost-containment interventions. In this respect, the need to support informal care should not be underestimated.

Aged↗
PubMed2001

In vivo 5-HT2A receptor blockade by quetiapine: an R91150 single photon emission tomography study.

BACKGROUND: Atypical antipsychotic drugs are thought to show a high degree of 5-HT2A receptor blockade, which may prevent the emergence of extrapyramidal symptoms. METHOD: 5-HT2A binding was estimated using 123I-5-I-R91150 and single photon emission tomography (SPET) in six schizophrenic subjects treated with quetiapine at a mean (+/-SD) daily dose of 350+/-123 mg for at least 5 weeks and a matched sample of six healthy volunteers. Clinical and side-effect ratings were performed at baseline and at the time of SPET scanning. The reference region approach was used to define a 5-HT2A binding index in the frontal and temporal cortex. RESULTS: Quetiapine treatment resulted in a significant decline in 5-HT2A receptor availability in the frontal cortex (mean 0.98+/-0.09) relative to healthy volunteers (mean 1.33+/-0.16). All patients showed improvements in clinical symptom or side-effect ratings. The mean frontal cortex:cerebellum ratio after quetiapine treatment was significantly negatively correlated with reduction in the Abnormal Involuntary Rating scale and Simpson-Angus scores (P<0.05 Bonferroni corrected), but not with the reduction in the scores from the scale for the assessment of positive symptoms, the scale for the assessment of negative symptoms, the Montgomery-Asberg depression rating scale or patient age. CONCLUSION: Quetiapine treatment results in significant in vivo blockade of cortical 5-HT2A, similar to other atypical antipsychotic drugs. This effect may contribute to its placebo level extrapyramidal side-effect profile.

Adult↗
PubMed2001

Accuracy of diagnoses of HIV-related oral lesions by medical clinicians. Findings from the Women's Interagency HIV Study.

OBJECTIVE: To determine if medical clinicians are as accurate as dental clinicians in recognizing diagnostic characteristics of HIV-related oral lesions. METHODS: In 355 HIV-infected participants at five Women's Interagency HIV Study sites, we paired oral examinations conducted within 7 days of each other by dental and medical clinicians. We used the former as a gold standard against which to evaluate the accuracy of the latter. We assessed the accuracy of the medical clinicians' findings based both on their observations of abnormalities and on their descriptions of these abnormalities. RESULTS: Dental clinicians diagnosed some oral abnormality in 38% of participants. When "abnormality" was used as the medical clinicians' outcome, sensitivities were 75% for pseudomembranous candidiasis and 58% for erythematous candidiasis, but only 40% for hairy leukoplakia. When a precise description of the abnormality was used as their outcome, sensitivities were 19%, 12% and 20%, respectively. CONCLUSIONS: Medical clinicians recognize that HIV-related oral abnormalities are present in 40-75% of cases, but less often describe them accurately. Low sensitivity implies that the true associations of specific oral lesions with other HIV phenomena, such as time until AIDS, must be stronger than the literature suggests.

AIDS-Related Opportunistic Infections↗
PubMed2001

HIV risk assessment: building on dentistry's history of promoting health.

Dentists have demonstrated a willingness to look beyond the mouth and consider the patient's overall presentation in a number of health-related areas. The HIV pandemic is another opportunity to involve the dentist in overall health issues through identification of those individuals at risk for acquiring HIV. This risk assessment activity can be facilitated through the use of a structured risk assessment algorithm that is presented in detail. The purpose of this algorithm is to encourage dentists--when they notice specific conditions or become aware of risky behaviors--to talk with their patients about HIV/AIDS and how the patient may be at risk. The historic success dentists have achieved in conveying information about the prevention of disease and promotion of health should bolster their resolve to expand their discussions with patients to include an HIV risk assessment.

Algorithms↗
PubMed2000

Oral mucosal lesions and HIV viral load in the Women's Interagency HIV Study (WIHS).

The prevalence of oral lesions was assessed in a five-center subset of the Women's Interagency HIV Study (WIHS) and correlated with other features of HIV disease. Oral examinations were performed by dental examiners on 729 women (577 HIV-positive and 152 HIV-negative) during baseline examination. Significant differences between the groups were found for the following oral lesions: pseudomembranous candidiasis, 6.1% and 2.0%, respectively; erythematous candidiasis, 6.41% and 0.7%, respectively; all oral candidiasis, pseudomembranous and/or erythematous, 13.7% and 3.3%, respectively. Hairy leukoplakia was observed in 6.1% of HIV-positive women. No significant differences were found for recurrent aphthous ulcers, herpes simplex lesions, or papillomas. Kaposi's sarcoma was seen in 0.5% of HIV-positive and 0% of HIV-negative women. Using multiple logistic regression models controlling for use of antiretrovirals and antifungals, in HIV-positive women the presence of oral candidiasis was associated with a CD4 count <200 cells/microl, cigarette smoking, and heroin/methadone use; the presence of hairy leukoplakia was not related to CD4 count but was associated with high viral load. Oral candidiasis and hairy leukoplakia are confirmed as being common features of HIV infection in women and appear to be associated with HIV viral load, immunosuppression, and various other behaviorally determined variables.

AIDS-Related Opportunistic Infections↗
PubMed2000

Salivary gland disease in human immunodeficiency virus-positive women from the WIHS study. Women's Interagency HIV Study.

OBJECTIVE: To determine the prevalence of enlargement, tenderness, and absence of saliva on palpation as indicators of salivary gland disease in women who are human immunodeficiency virus (HIV)-positive. STUDY DESIGN: The study subjects are participants in the Women's Interagency HIV Study (WIHS), a multicenter study examining HIV-seropositive women and at-risk HIV-seronegative women. A total of 576 HIV-positive women and 152 HIV-negative women were examined at their baseline oral visit for clinical markers of salivary gland disease. Viral load levels, CD4 counts, and CD8 counts were obtained as part of the related core study. RESULTS: HIV-positive women had higher rates of salivary gland enlargement (4.3%), tenderness (6.9%), and absence of saliva on palpation (26.6%) compared with HIV-negative women, who had rates of 1.3%, 4.6%, and 13.2%, respectively. Absence of saliva was significantly different (P =. 001) between the 2 groups. When 2 of the 3 clinical findings were combined, comparisons between the HIV-positive women and HIV-negative women became significant at the P <.05 level for every combination, except for enlargement/tenderness for the submandibular/sublingual gland. For the HIV-positive women, the viral load was significantly related to enlargement (P =.019) and enlargement/absence of saliva on palpation (P =.037) for the parotids and enlargement (P =.046), absence of saliva (P =.043), and enlargement/absence of saliva (P =.022) for the submandibular/sublingual glands. Significant linear trends were found for increasing viral load and enlargement (P =.013) and enlargement/tenderness (P =.024) for the submandibular/sublingual glands. Significance was present for submandibular/sublingual absence of saliva and tenderness/absence of saliva for CD4 and CD8 medians. CONCLUSIONS: Serostatus is related to salivary gland disease as assessed by glandular enlargement, tenderness, and absence of saliva on palpation. Furthermore, our findings indicate that a multidimensional approach to gland assessment may provide a more complete and perhaps more adequate description of glandular involvement with HIV infection.

Adolescent↗
PubMed2000

The prevalence of xerostomia and salivary gland hypofunction in a cohort of HIV-positive and at-risk women.

The association of xerostomia and salivary gland hypofunction with HIV infection has been established for men but not for women. We investigated the prevalence of these conditions in a national cohort (n = 733) of HIV-positive and at-risk HIV-negative women. Participants in this prospective cross-sectional study were recruited from the Women's Interagency HIV Study (WIHS) at five outpatient USA clinics. Xerostomia was assessed based on "yes" responses to a dry-mouth questionnaire. Samples of unstimulated whole and chewing-stimulated whole saliva were collected under standardized conditions. The major salivary glands were also evaluated clinically. The prevalence of dry-mouth complaint, the absence of saliva upon palpation, and zero unstimulated whole saliva (flow rate = 0 mL/min) were significantly (p = 0.001) higher in HIV-positive women. Adjusted odds of zero unstimulated whole saliva were significantly (p = 0.02) higher in HIV-positive women vs. HIV-negative women (OR = 2.86; 95% CI, 1.23 to 6.63). Significant (p = 0.03) univariate association was found between zero unstimulated whole saliva and CD4 counts. Adjusted odds of zero unstimulated whole saliva were significantly (p = 0.02) higher for HIV-positive women with CD4 < 200 compared with those with CD4 > 500 (OR = 2.61; 95% CI, 1.17 to 5.85). Chewing-stimulated flow rates were not significantly different between seropositive and seronegative women. The prevalence of xerostomia and salivary gland hypofunction appears to be significantly higher in HIV-positive women relative to a comparable group of at-risk seronegative women. Immunosuppression levels measured by CD4 cell counts are significantly associated with xerostomia and salivary gland hypofunction in a population of HIV-positive women.

Adolescent↗
PubMed2000

Ultrastructural localization of the vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) receptor-2 (FLK-1, KDR) in normal mouse kidney and in the hyperpermeable vessels induced by VPF/VEGF-expressing tumors and adenoviral vectors.

Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) interacts with two high-affinity tyrosine kinase receptors, VEGFR-1 and VEGFR-2, to increase microvascular permeability and induce angiogenesis. Both receptors are selectively expressed by vascular endothelial cells and are strikingly increased in tumor vessels. We used a specific antibody to localize VEGFR-2 (FLK-1, KDR) in microvascular endothelium of normal mouse kidneys and in the microvessels induced by the TA3/St mammary tumor or by infection with an adenoviral vector engineered to express VPF/VEGF. A pre-embedding method was employed at the light and electron microscopic levels using either nanogold or peroxidase as reporters. Equivalent staining was observed on both the luminal and abluminal surfaces of tumor- and adenovirus-induced vascular endothelium, but plasma membranes at interendothelial junctions were spared except at sites connected to vesiculovacuolar organelles (VVOs). VEGFR-2 was also localized to the membranes and stomatal diaphragms of some VVOs. This staining distribution is consistent with a model in which VPF/VEGF increases microvascular permeability by opening VVOs to allow the transendothelial cell passage of plasma and plasma proteins.

Adenoviridae↗
PubMed2000

Interactions of CRH, AVP and cortisol in the secretion of ACTH from perifused equine anterior pituitary cells: "permissive" roles for cortisol and CRH.

To further elucidate the interaction of CRH, AVP and cortisol in the control of ACTH secretion, we used an in vitro perifusion model with dispersed equine anterior pituitary cells. To approximate the in vivo milieu in the horse, CRH was perifused continuously (at 0, 2 and 20 pmol/L) and 5-min pulses of AVP (0, 1, 3 and 10 nmol/L) were given every 30 min in the presence of 0 or 100 nmol/L cortisol. Total (baseline + incremental) ACTH secretion increased as both the CRH (p<0.001) and the AVP (p<0.001) concentration increased and interaction between CRH and AVP was significant (p=0.042). Cortisol reduced total ACTH secretion in the presence of 2 pmol CRH/L (p=0.001) but not 0 or 20 pmol CRH/L. For incremental ACTH there was interaction between CRH and AVP (p<0.0001), with increased secretion at higher concentrations, and no significant main effect of cortisol. There was significant (p=0.001) interaction between cortisol and CRH, with cortisol attenuating ACTH release at 0 pmol CRH/L (p=0.008), having no effect at 2 pmol CRH/L and potentiating it at 20 pmol CRH/L (p=0.026). We conclude that (1) CRH at high physiological levels has a "permissive" role in preventing the cortisol inhibition of the ACTH response to AVP, and (2) basal cortisol levels have a "permissive" action in priming the HPA axis for maximal responsiveness to stimulated levels of CRH and AVP.

Adrenocorticotropic Hormone↗