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Biomedical subjects

R Mulligan

Publications and source records attributed to R Mulligan.

At least 19 recordsLinked to original sources
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

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↗
PubMed1999

Detecting anxiety and depression in hospitalised elderly patients using a brief inventory.

This study validated a French language version of an inventory designed to detect symptoms of depression and anxiety [Goldberg et al, 1987] in a sample of elderly French-speaking inpatients at risk for one of these disorders. Latent trait analysis was used to replicate the structure of the symptoms in the inventory, and receiver operating characteristic analysis was used to assess the performance of the inventory as a screening measure for Major Depressive Episode and Generalised Anxiety Disorder according to DSM-IV criteria. Reflecting the ascertainment of individuals in the sample as being at risk for a disorder, prevalence of individual symptoms was high although the general structure of the inventory was found to be comparable to that found in samples of both community elderly and younger medical patients. ROC analyses showed that the subscales of inventory performed satisfactorily as screening measures for anxiety or depression but lacked specificity for each disorder. In addition to providing further evidence for the utility of this inventory to detect general psychiatric distress in elderly persons, this study provides a valid means of detecting symptoms of depression and anxiety in French speaking groups.

Aged↗
PubMed1999

Tumor metastasis biopsy as a surrogate marker of response to melanoma immunotherapy.

In patients undergoing immunotherapy for metastatic melanoma, the clinical response in immunotherapeutic trials may be partial or difficult to detect. Tumor metastasis biopsy allows direct characterisation of an anti-tumor immunological response. During a phase I/II trial of granulocyte macrophage colony stimulating factor (GM-CSF) transduced autologous melanoma immunotherapy, the cellular response was examined by immunohistochemical analysis in a limited number of tumor biopsies taken from patients who either responded or progressed. Clinical response was associated with tumor infiltration by CD4+ and CD8+ T-cells, macrophages and differentiated dendritic cells (DC), and expression of HLA-DR by the tumor cells. This tumor infiltration was associated with increased melanoma-specific peripheral blood precursor cytotoxic T-lymphocyte (pCTL) and the ability to obtain tumor-infiltrating lymphocytes in vitro. In contrast, progression or a lack of clinical response was associated with a lack of T-cell and DC infiltration into the tumor tissue in all such biopsies. Macrophages and eosinophils infiltrated these tumors, while T-cells and DC were present at some distance from the tumor. These preliminary data strongly suggest that the location and extent of T-cell and DC infiltration, as well as the expression of HLA-DR by tumor cells are associated with a clinical response in this form of melanoma immunotherapy.

Adult↗
PubMed1999

The future of dental care for the elderly population.

The U.S. population is aging, and the elderly are maintaining many of their natural teeth. Studies have shown that if older people have teeth, they tend to utilize dental services to a similar extent as younger cohorts. Geriatric dental care is the diagnosis, treatment, and prevention of dental and oral diseases for all older adults. A functional categorization of the aging population is more useful in dentistry than a chronological one, and 70 percent of this population, or 23.2 million people, is able to visit a dentist in his or her office. The oral health care of older adults has become more challenging because they will no longer accept extraction and dentures as a solution to complex restorative needs. This paper discusses these issues and looks at the future of geriatric dental care.

Aged↗
PubMed1998

In vivo and in vitro modulation of immune stimulatory capacity of primary dendritic cells by adenovirus-mediated gene transduction.

Dendritic cells (DCs) are potent antigen-presenting cells which are key leukocytes in the initiation of cell-mediated organ graft rejection, antiviral immunity, and antitumor responses. In this study we demonstrate that genetic modification of primary human and mouse DCs by adenoviral gene transfer is an effective means of induction and modulation of antigen presentation by DCs. An adenovirus vector (AdLacZ) was used to express an intracellular model antigen beta-galactosidase (beta-gal) in DCs. Our results show that 30-40% of precursor dendritic cells (PDCs) derived from human umbilical cord blood and circulating mature blood DCs express high levels beta-galactosidase (beta-gal) after infection with AdLacZ with no cytopathic effect observed. In vitro, AdLacZ transduced PDCs and DCs demonstrated a 10- to 20-fold higher mixed lymphocyte reaction (MLR) stimulatory capacity as compared to that of monocytes. In vivo, immunization with AdLacZ transduced mouse DCs resulted in more potent cytotoxic T lymphocyte (CTL) responses against the predicted H-2 restricted beta-gal epitope as compared to CTL responses obtained by beta-gal peptide pulsed DCs. Modulations of the MLR stimulatory capacity of DCs were examined by expression of mouse B7 and CTLA-4Ig. The results show that expression of mouse B7 by a recombinant adenoviral vector (Ad7) significantly enhances the MLR stimulatory capacity of human DCs. In contrast, expression of CTLA-4Ig (AdCTLA-4Ig) reduces the MLR stimulatory capacity of the transduced cells. We conclude that recombinant adenovirus can readily be used for genetic modulation DC-induced immune responses in vivo and in vitro. DCs targeted for induction of specific antigen responses or for modulation of the immune stimulatory capacity may have a potential use in the control of transplantation rejection or viral infections.

Adenoviridae↗
PubMed1998

Combining cognitive testing and informant report to increase accuracy in screening for dementia.

OBJECTIVE: Cognitive testing and an informant report questionnaire were combined to determine whether their use in combination could improve accuracy in screening for the diagnosis of dementia over either test used alone. Methods of combining test scores that can be readily applied in clinical settings were developed and assessed. METHOD: The subjects were 106 patients admitted to the geriatric hospital or outpatients assessed at the memory clinic of the university hospital system in Geneva, Switzerland. The instruments used were the Mini-Mental State and the short form of the Informant Questionnaire on Cognitive Decline in the Elderly. The diagnosis of dementia was made according to DSM-IV criteria. RESULTS: Logistic regression demonstrated that the combination of the Mini-Mental State and the Informant Questionnaire on Cognitive Decline in the Elderly resulted in more accurate prediction of caseness than either test alone. The performance of logical "or" and "and" combinations of test results and a weighted sum of scores on the two tests as screens for dementia were investigated by using receiver operating characteristic analysis. By using suitable cutoff points, both the "or" rule and the weighted sum were shown to be capable of improving performance over that of either test used alone. CONCLUSIONS: This study shows that informant report can be formally incorporated into assessment for dementia in such a way as to increase the accuracy of detection of cases and noncases. A graphical method was developed that enables the most robust approach to be applied to individual cases without any calculation.

Aged↗
PubMed1998

5-HT2A receptor blockade in patients with schizophrenia treated with risperidone or clozapine. A SPET study using the novel 5-HT2A ligand 123I-5-I-R-91150.

BACKGROUND: 5-HT2A receptor antagonism may be crucial to the action of atypical antipsychotics. Previous work has related 5-HT2A receptor blockade to clinical efficacy and protection from extrapyramidal side-effects. METHOD: We developed a SPET imaging protocol for assessing 5-HT2A receptor binding using the selective ligand 123I-5-I-R91150. Six healthy volunteers, five clozapine- and five risperidone-treated subjects with DSM-IV schizophrenia were studied. Multi-slice SPET was performed on each subject. RESULTS: Cortex:cerebellum ratios were significantly lower in both clozapine- and risperidone-treated subjects compared with the healthy volunteers in all cortical regions. There was no difference in occupancy between the two drug-treated groups. No correlation was found between the percentage change in the Global Assessment Scale (GAS) and 5-HT2A receptor binding indices in the drug-treated groups. CONCLUSIONS: Clozapine and risperidone potently block 5-HT2A receptors in vivo. The lack of relationship between receptor binding indices and change in GAS suggests that 5-HT2A receptor blockade may be unrelated to clinical improvement. Future studies will substantiate this finding by studying 5-HT2A receptor binding in large groups of patients treated with both typical and novel atypical antipsychotics.

Adult↗
PubMed1998

Subtyping analysis of Fanconi anemia by immunoblotting and retroviral gene transfer.

Fanconi anemia (FA) is an autosomal recessive cancer susceptibility syndrome with at least eight complementation groups (A-H). Two of the FA genes (FAA and FAC) have been cloned, and mutations in these genes account for approximately 80% of FA patients. Subtyping of FA patients is an important first step toward identifying candidates for FA gene therapy. In the current study, we analyzed a reference group of 26 FA patients of known subtype. Most of the patients (18/26) were confirmed as either type A or type C by immunoblot analysis with anti-FAA and anti-FAC antisera. In order to resolve the subtype of the remaining patients, we generated retroviral constructs expressing FAA and FAC for transduction of FA cell lines (pMMP-FAA and pMMP-FAC). The pMMP-FAA construct specifically complemented the abnormal phenotype of cell lines from FA-A patients, while pMMP-FAC complemented FA-C cells. In summary, the combination of immunoblot analysis and retroviral-mediated phenotypic correction of FA cells allows a rapid method of FA subtyping.

Amino Acid Sequence↗
PubMed1997

[Non-drug alternatives in Alzheimer disease].

Profiles of cognitive deficits in Alzheimer patients are often heterogenous and can vary considerably from one patient to another. Studies published in the last 10 years have shown that improvement of cognitive functioning is possible in these patients. A detailed neuropsychological exam is necessary to evaluate not only disturbed functions but also preserved areas and factors which could help to improve performance. These elements, which are also part of the diagnostic procedure, are necessary to put the deficit into its context, and to propose specific methods of therapy. The aim of this therapy is to insure optimal performances at each stage of the disease. The strategies employed vary and have to be adapted to each patient and the therapy goals but they almost always make the involvement of a family member necessary, to ensure that the acquired strategies are used systematically in everyday life. In view of the importance of the social problems connected with dementia, more research is necessary to develop techniques of intervention which lead to an improvement of impaired cognitive functioning.

Activities of Daily Living↗
PubMed1997

Initial evaluation of 123I-5-I-R91150, a selective 5-HT2A ligand for single-photon emission tomography, in healthy human subjects.

The mapping of 5-HT2 receptors in the brain using functional imaging techniques has been limited by a relative lack of selective radioligands. Iodine-123 labelled 4-amino-N-[1-[3-(4-fluorophenoxy)propyl]-4-methyl-4-piperidinyl]-5-io do-2-methoxybenzamide (123I-5-I-R91150 or 123I-R93274) is a new ligand for single-photon emission tomography (SPET), with high affinity and selectivity for 5-HT2A receptors. This study reports on preliminary 123I-5-I-R91150 SPET, whole-body and blood distribution findings in five healthy human volunteers. Maximal brain uptake was approximately 2% of total body counts at 180 min post injection (p.i. ). Dynamic SPET sequences were acquired with the brain-dedicated, single-slice multi-detector system SME-810 over 200 min p.i. Early peak uptake (at 5 min p.i.) was seen in the cerebellum, a region free from 5HT2A receptors. In contrast, radioligand binding in the frontal cortex increased steadily over time, up to a peak at approximately 100-120 min p.i. Frontal cortex-cerebellum activity ratios reached values of 1.4, and remained stable from approximately 100 min p.i. onwards. Multi-slice SPET sequences showed a pattern of regional variation of binding compatible with the autoradiographic data on the distribution of 5-HT2A receptors in humans (cerebral cortex>striatum>cerebellum). These findings suggest that 123I-5-I-R91150 may be used for the imaging of 5-HT2A receptors in the living human brain with SPET.

Adult↗
PubMed1997

Sensitivity and specificity of newly proposed clinical criteria for possible vascular dementia.

The objective of this study was to determine the sensitivity and specificity of clinical criteria for possible vascular dementia (VaD) recently developed independently by two groups: the State of California Alzheimer's Disease Diagnostic and Treatment Centers (ADDTC) and the National Institute for Neurological Disorders and Stroke with the Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS-AIREN). We also wished to compare the performance of the new criteria to that of the Hachinski Ischemic Score (HIS). The study was comprised of a retrospective chart review and clinicopathologic correlation, and took place in 304-bed acute-care geriatric hospital. The subjects were 113 autopsied elderly patients with dementia, who were assessed to determine sensitivity and specificity of the ADDTC and NINDS-AIREN criteria for possible VaD. Sensitivity and specificity were calculated using the neuropathologic diagnosis as a gold standard. Sensitivity was 0.63, and specificity was 0.64 for the ADDTC, 0.58 sensitivity and 0.80 specificity for the NINDS, and 0.43 sensitivity and 0.88 specificity for the HIS. Test combinations did not lead to substantial gains in sensitivity or specificity. The majority of patients with Alzheimer's disease were successfully excluded by the ADDTC (87%), the NINDS-AIREN (91%), and the HIS (97%). The proportion of mixed dementia cases clinically misclassified as VaD was 54% for the ADDTC, 29% for the NINDS-AIREN, and 18% for the HIS. Low sensitivity is the main weakness of the above clinical criteria for possible VaD. Mixed dementia is better excluded by the NINDS-AIREN than the ADDTC. Data from this validation study should provide valuable information to clinicians and researchers who wish to apply these criteria to the diagnosis of VaD.

Aged↗
PubMed1996

Mice lacking the gene encoding tissue-type plasminogen activator show a selective interference with late-phase long-term potentiation in both Schaffer collateral and mossy fiber pathways.

The gene encoding tissue-type plasminogen activator (t-PA) is an immediate response gene, downstream from CREB-1 and other constitutively expressed transcription factors, which is induced in the hippocampus during the late phase of long-term potentiation (L-LTP). Mice in which the t-PA gene has been ablated (t-PA-/-) showed no gross anatomical, electrophysiological, sensory, or motor abnormalities but manifest a selective reduction in L-LTP in hippocampal slices in both the Schaffer collateral-CA1 and mossy fiber-CA3 pathways. t-PA-/- mice also exhibit reduced potentiation by cAMP analogs and D1/D5 agonists. By contrast, hippocampal-dependent learning and memory were not affected in these mice, whereas performance was impaired on two-way active avoidance, a striatum-dependent task. These results provide genetic evidence that t-PA is a downstream effector gene important for L-LTP and show that modest impairment of L-LTP in CA1 and CA3 does not result in hippocampus-dependent behavioral phenotypes.

Animals↗