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1.
Adv Dent Res ; 29(1): 35-41, 2018 02.
Article in English | MEDLINE | ID: mdl-29355419

ABSTRACT

Over 1 in 5 dental patients report moderate to severe dental fear. Although the efficacy of cognitive-behavioral treatment (CBT) for dental fear has been examined in over 20 randomized controlled trials-with 2 meta-analyses finding strong average effect sizes ( d > 1)-CBT has received almost no dissemination beyond the specialty clinics that tested it. The challenge, then, is not how to treat dental fear but how to disseminate and implement such an evidence-based treatment in a way that recognizes the rewards and barriers in the US health care system. This mixed-method study investigated the potential of disseminating CBT through care from a mental health provider from within the dental home, a practice known as evidence-based collaborative care (EBCC). Two preadoption studies were conducted with practicing dentists drawn from a self-organized Practice-Based Research Network in the New York City metropolitan area. The first comprised 3 focus groups ( N = 17), and the second involved the administration of a survey ( N = 46). Focus group participants agreed that CBT for dental fear is worthy of consideration but identified several concerns regarding its appeal, feasibility, and application in community dental practices. Survey participants indicated endorsement of factors promoting the use of EBCC as a mechanism for CBT dissemination, with no factors receiving less than 50% support. Taken together, these findings indicate that EBCC may be a useful framework through which an evidence-based treatment for dental fear treatment can be delivered.


Subject(s)
Attitude of Health Personnel , Cognitive Behavioral Therapy , Dental Anxiety/prevention & control , Dental Offices , Dentists , Aged , Diffusion of Innovation , Evidence-Based Dentistry , Female , Focus Groups , Humans , Male , Middle Aged , New York City , Surveys and Questionnaires , United States
2.
Caries Res ; 51(2): 149-159, 2017.
Article in English | MEDLINE | ID: mdl-28132053

ABSTRACT

Research has garnered support for a systemic view of factors affecting child dental caries that accounts for the influence of social factors such as the family environment. Our previous work has demonstrated the association between mother-to-father emotional aggression and child caries. The present study builds on these results by evaluating pathways that might explain this relation. Families (n = 135) completed a multimethod assessment of mother-to-father emotional aggression, child caries, and several hypothesized mediators (i.e., child cariogenic snack and drink intake, child internalizing behaviors, child salivary cortisol and α-amylase reactivity, parental laxness, child oral hygiene maintenance, and parental socialization of child oral hygiene maintenance). Mediation analyses partially supported the role of the child's diet as a mechanism linking mother-to-father emotional aggression and child caries. However, children's neglect of oral hygiene, parental laxness, and child emotional and biological disturbances failed to stand as conduits for this association. Future investigations should expand upon these results to better establish the causal links that could only be suggested by the present cross-sectional findings.


Subject(s)
Aggression , Dental Caries/epidemiology , Family Relations/psychology , Oral Hygiene , Parents/psychology , Adult , Child , Cross-Sectional Studies , Dental Caries/etiology , Female , Humans , Male
3.
Prog Urol ; 25(10): 565-75, 2015 Sep.
Article in French | MEDLINE | ID: mdl-26116407

ABSTRACT

GOAL: Describe lower urinary tract dysfunction and anorectal disorders to children with cerebral palsy (CP), indicating their impact on quality of life. MATERIALS: This was a prospective single-center study. A data collection was: type of PC, Gross Motor Function-Classification System (GMF-CS), mainstream education or not, Functional Independence Measure in children (MIF-kid), standardized vesicosphincteric symptoms and quality of life questionnaires (specific issue of impact sphincter dysfunction and generic scale Kidscreen-52). RESULTS: Between January and March 2013, 19 children aged 5-17 years were included, including 16 into mainstream schooling. Of the 19, 16 had bladder and sphincter disorders: 14 urinary incontinence, 3 nycturies, 6 dysuria, 12 urgenturies, no urinary infection. Of the 14 urinary incontinence, 13 were in school. Of the 16 children enrolled, 5 were daytime fecal incontinence and 2 nocturnal fecal incontinence. Functional scores (GMF-CS and MIF-kid) children urinary incontinence were lower than those of children urinary continents (P=0.04 and 0.0007). Ten children had an impact of these disorders on quality of life. All were enrolled, eight (80%) in the mainstream. CONCLUSION: The bladder and sphincter disorders were common in children with CP. They led to an impact on quality of life in more than half of the children studied, mostly educated in mainstream schools.


Subject(s)
Cerebral Palsy/complications , Fecal Incontinence/etiology , Lower Urinary Tract Symptoms/etiology , Adolescent , Child , Child, Preschool , Female , Humans , Male , Prospective Studies , Quality of Life
4.
J Eur Acad Dermatol Venereol ; 24(1): 43-9, 2010 Jan.
Article in English | MEDLINE | ID: mdl-19552716

ABSTRACT

BACKGROUND: Atopic dermatitis (AD) is a common inflammatory skin disease. Methotrexate (MTX) was suggested as an effective treatment option in cases of moderate-to-severe atopic dermatitis. This study assessed the efficacy and safety of treatment with low weekly doses of methotrexate for moderate-to-severe AD in adults. METHODS: Twenty adult patients with moderate-to-severe AD were included in this retrospective study. Those patients were unresponsive to topical treatments, antihistamines and at least one of the second-line treatments. MTX in low weekly doses of 10-25 mg was administered orally or intramuscularly with folic acid supplementation 5 mg per week for at least 8-12 weeks. The response to treatment was evaluated by change in SCORAD (SCORing Atopic Dermatitis), DLQI (Dermatology Quality of Life Index) and the global assessment of the clinical response score. RESULTS: After 8-12 weeks of treatment, we observed an objective response in most patients. There were 16 responders and 4 non-responders. The mean SCORAD and DLQI decreased by 28.65 units (44.3%) and 10.15 units (43.5%), respectively. The first improvement was observed after a period ranging from 2 weeks to 3 months (mean 9.95 w +/- 3.17). Treatment was more effective in adult onset AD than in childhood onset. Tolerance of treatment was good. However, nausea and an increase of liver enzymes were observed in 5 patients and 3 of them required a transient discontinuation of MTX. One patient developed peripheral neuropathy, which was resolved several weeks after the discontinuation of MTX. CONCLUSION: MTX seems to be an effective and safe second-line treatment for patients with moderate-to-severe atopic dermatitis. A randomized, controlled study is warranted.


Subject(s)
Dermatitis, Atopic/drug therapy , Immunosuppressive Agents/therapeutic use , Methotrexate/therapeutic use , Adult , Aged , Aged, 80 and over , Dose-Response Relationship, Drug , Female , Folic Acid/administration & dosage , Follow-Up Studies , Humans , Immunosuppressive Agents/administration & dosage , Male , Methotrexate/administration & dosage , Middle Aged , Retrospective Studies , Severity of Illness Index
5.
Gastroenterol Clin Biol ; 33(2): 109-14, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19201117

ABSTRACT

AIM: The aim of the study was to assess the evolution of bone mineral density (BMD) in children with celiac disease and to evaluate the effect of a gluten-free diet (GFD). METHODS: Altogether, 44 children (31 girls and 13 boys) were followed-up. BMD was measured by dual-energy X-ray absorptiometry of the lumbar spine (Hologic QDR 4500). Results are expressed as absolute values for BMD, and as Z scores for chronological age (BMD/CA) and bone age (BMD/BA). Patients were divided into two groups according to whether they followed a diet without (n=34) or with (n=10) gluten for at least 1 year. All patients were clinically free of symptoms at the end of the follow-up. RESULTS: At inclusion, 26 patients (59%) were delayed in bone age, 17 children (38%) had a BMD/CA< or =1 S.D. and six (13.6%) had a BMD/CA< or =2 S.D., whereas nine children (20%) had a BMD/BA< or =1 S.D. and three (6.8%) had a BMD/BA< or =2 S.D. During the follow-up, the BMD increase was greater in the GFD group, as determined by the BMD/CA/year (+0.05+/-0.3 vs -0.34+/-0.4 S.D.; P<0.01) and BMD/BA/year (-0.02+/-0.4 vs -0.4+/-0.6 S.D.; P<0.05). The gain in BMD/BA was smaller in the GFD group because of their need to catch up in bone maturation. CONCLUSION: Celiac children not following a GFD show delays in both bone maturation and mineralization. This prospective study confirms the importance of maintaining a GFD in children with celiac disease until the end of skeletal mineralization even in asymptomatic patients following a non-restricted diet.


Subject(s)
Bone Density , Celiac Disease/diet therapy , Diet, Gluten-Free , Absorptiometry, Photon , Adolescent , Age Determination by Skeleton , Bone Development , Bone Diseases, Metabolic/diet therapy , Bone Diseases, Metabolic/etiology , Celiac Disease/complications , Celiac Disease/diagnosis , Child , Child, Preschool , Female , Humans , Infant , Longitudinal Studies , Lumbar Vertebrae , Male , Prospective Studies
6.
J Med Chem ; 46(13): 2683-96, 2003 Jun 19.
Article in English | MEDLINE | ID: mdl-12801232

ABSTRACT

Previous data have shown that RXR-selective agonists (e.g., 3 and 4) are insulin sensitizers in rodent models of non-insulin-dependent diabetes mellitus (NIDDM). Unfortunately, they also produce dramatic increases in triglycerides and profound suppression of the thyroid hormone axis. Here we describe the design and synthesis of new RXR modulators that retain the insulin-sensitizing activity of RXR agonists but produce substantially reduced side effects. These molecules bind selectively and with high affinity to RXR and, unlike RXR agonists, do not activate RXR homodimers. To further evaluate the antidiabetic activity of these RXR modulators, we have designed a concise and systematic structure-activity relationship around the 2E,4E,6Z-7-aryl-3-methylocta-2,4,6-trienoic acid scaffold. Selected compounds have been evaluated using insulin-resistant rodents (db/db mice) to characterize effects on glucose homeostasis. Our studies demonstrate the effectiveness of RXR modulators in lowering plasma glucose in the db/db mouse model.


Subject(s)
Caprylates/chemical synthesis , Diabetes Mellitus, Type 2/blood , Hypoglycemic Agents/chemical synthesis , Receptors, Retinoic Acid/drug effects , Transcription Factors/drug effects , Animals , Blood Glucose/analysis , Caprylates/chemistry , Caprylates/pharmacology , Hypoglycemic Agents/chemistry , Hypoglycemic Agents/pharmacology , Insulin Resistance , Male , Mice , Radioligand Assay , Rats , Rats, Sprague-Dawley , Receptors, Retinoic Acid/metabolism , Retinoid X Receptors , Structure-Activity Relationship , Transcription Factors/metabolism
7.
Eur J Neurol ; 10(1): 83-6, 2003 Jan.
Article in English | MEDLINE | ID: mdl-12535000

ABSTRACT

A 53-year-old man presented with optic neuritis, followed within 10 weeks by a subacute progression of weakness, ataxia, and multiple cranial nerve palsies. Cranial magnetic resonance imaging demonstrated multiple T2-hyperintense lesions extending from the ponto-medullary junction to the thalamus and internal capsule. Cerebrospinal fluid analysis showed lymphocytic pleocytosis with elevated protein content. A brain biopsy revealed inflammatory changes. After a month long period of inexorable worsening, the patient was treated with intravenous immunoglobulins (2 g/kg). He responded to treatment, and recovered over the subsequent 3 months. The patient's response to treatment suggests that intravenous immunoglobulins should be considered in patients with inflammatory brain disorders.


Subject(s)
Encephalitis/drug therapy , Immunoglobulins, Intravenous/therapeutic use , Rhombencephalon/pathology , Encephalitis/diagnosis , Encephalitis/immunology , Gliosis/immunology , Gliosis/pathology , Humans , Male , Middle Aged , Rhombencephalon/immunology
8.
J Consult Clin Psychol ; 69(3): 567-72, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11495186

ABSTRACT

A system for categorizing partner-violent men as either reactive or proactive aggressors was developed and evaluated in the present study. Sixty partner-violent men were reliably categorized, and the distribution (62% reactive, 38% proactive) fell within the expected range. Some construct validity was demonstrated, as several significant predicted group differences were found on factors of theoretical relevance to the typology model (affectivity, personality, and violence in the family-of-origin). Proactively versus reactively categorized participants were (a) more dominant and less angry during a 10-min interpartner interaction, (b) more antisocial and aggressive-sadistic and less dependent, and (c) more frequently classified as psychopathic (17% vs. 0%). Research and clinical implications of the system are discussed, as is the potential overlap between the reactively and proactively categorized partner-violent men in this study with previously identified types.


Subject(s)
Antisocial Personality Disorder/diagnosis , Internal-External Control , Spouse Abuse/psychology , Violence/psychology , Adult , Aggression/psychology , Antisocial Personality Disorder/psychology , Humans , Male , Middle Aged , Personality Assessment
9.
Mol Endocrinol ; 15(8): 1360-9, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11463859

ABSTRACT

The RXR serves as a heterodimer partner for the PPARgamma and the dimer is a molecular target for insulin sensitizers such as the thiazolidinediones. Ligands for either receptor can activate PPAR-dependent pathways via PPAR response elements. Unlike PPARgamma agonists, however, RXR agonists like LG100268 are promiscuous and activate multiple RXR heterodimers. Here, we demonstrate that LG100754, a RXR:RXR antagonist and RXR:PPARalpha agonist, also functions as a RXR:PPARgamma agonist. It does not activate other LG100268 responsive heterodimers like RXR:liver X receptoralpha, RXR:liver X receptorbeta, RXR:bile acid receptor/farnesoid X receptor and RXR:nerve growth factor induced gene B. This unique RXR ligand triggers cellular RXR:PPARgamma-dependent pathways including adipocyte differentiation and inhibition of TNFalpha-mediated hypophosphorylation of the insulin receptor, but does not activate key farnesoid X receptor and liver X receptor target genes. Also, LG100754 treatment of db/db animals leads to an improvement in insulin resistance in vivo. Interestingly, activation of RXR:PPARgamma by LG100268 and LG100754 occurs through different mechanisms. Therefore, LG100754 represents a novel class of insulin sensitizers that functions through RXR but exhibits greater heterodimer selectivity compared with LG100268. These results establish an approach to the design of novel RXR-based insulin sensitizers with greater specificity.


Subject(s)
Blood Glucose/metabolism , Receptors, Cytoplasmic and Nuclear/agonists , Receptors, Retinoic Acid/agonists , Retinoids/pharmacology , Tetrahydronaphthalenes/pharmacology , Transcription Factors/agonists , 3T3 Cells , Adipocytes/drug effects , Adipocytes/metabolism , Animals , Cell Differentiation/drug effects , Diabetes Mellitus/blood , Diabetes Mellitus/drug therapy , Dimerization , Insulin Resistance , Mice , Nicotinic Acids/pharmacology , Phosphorylation , Receptor, Insulin/metabolism , Receptors, Cytoplasmic and Nuclear/drug effects , Receptors, Cytoplasmic and Nuclear/physiology , Receptors, Retinoic Acid/drug effects , Receptors, Retinoic Acid/physiology , Retinoid X Receptors , Retinoids/therapeutic use , Tetrahydronaphthalenes/therapeutic use , Transcription Factors/drug effects , Transcription Factors/physiology , Tumor Necrosis Factor-alpha/pharmacology
10.
J Fam Psychol ; 15(2): 334-46, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11458637

ABSTRACT

Relationship adjustment (e.g., Dyadic Adjustment Scale; DAS) and physical aggression (e.g., Conflict Tactics Scale) measures are used both as screening tools and as the sole criterion for classification. This study created face valid diagnostic interviews for relationship distress and physical abuse, through which one could compare preliminarily the classification properties of questionnaire reports. The DAS (and a global measure of relationship satisfaction) had modest agreement with a structured diagnostic interview; both questionnaires tended to overdiagnose distress compared with the interview. Results for partner abuse reiterated the need to go beyond occurrence of aggression as the sole diagnostic criterion, because men's aggression was more likely than women's to rise to the level of "abuse" when diagnostic criteria (injury or substantial fear) were applied.


Subject(s)
Conflict, Psychological , Interpersonal Relations , Spouse Abuse/psychology , Surveys and Questionnaires , Adult , Female , Humans , Male , Predictive Value of Tests
11.
Psychol Assess ; 13(1): 5-35, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11281039

ABSTRACT

The purpose of this review is to provide a balanced examination of the published research involving the observation of couples, with special attention toward the use of observation for clinical assessment. All published articles that (a) used an observational coding system and (b) relate to the validity of the coding system are summarized in a table. The psychometric properties of observational systems and the use of observation in clinical practice are discussed. Although advances have been made in understanding couple conflict through the use of observation, the review concludes with an appeal to the field to develop constructs in a psychometrically and theoretically sound manner.


Subject(s)
Conflict, Psychological , Interpersonal Relations , Observation/methods , Communication , Humans , Psychometrics/statistics & numerical data , Reproducibility of Results
12.
Mol Pharmacol ; 59(4): 765-73, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11259621

ABSTRACT

Both retinoid X receptor (RXR)-selective agonists (rexinoids) and thiazolidinediones (TZDs), PPAR (peroxisome proliferator-activated receptor)-gamma-specific ligands, produce insulin sensitization in diabetic rodents. In vitro studies have demonstrated that TZDs mediate their effects via the RXR/PPAR-gamma complex. To determine whether rexinoids lower hyperglycemia by activating the RXR/PPAR-gamma heterodimer in vivo, we compared the effects of a rexinoid (LG100268) and a TZD (rosiglitazone) on gene expression in white adipose tissue, skeletal muscle, and liver of Zucker diabetic fatty rats (ZDFs). In adipose tissue, rosiglitazone decreased tumor necrosis factor-alpha (TNF-alpha) mRNA and induced glucose transporter 4 (GLUT4), muscle carnitine palmitoyl-transferase (MCPT), stearoyl CoA desaturase (SCD1), and fatty acid translocase (CD36). In contrast, LG100268 increased TNF-alpha and had no effect or suppressed the expression of GLUT4, MCPT, SCD1, and CD36. In liver, the rexinoid increased MCPT, SCD1, and CD36 mRNAs, whereas rosiglitazone induced only a small increase in CD36. In skeletal muscle, rosiglitazone and LG100268 have similar effects; both increased SCD1 and CD36 mRNAs. The differences in the pattern of genes induced by the rexinoids and the TZDs in diabetic animals found in these studies suggests that these compounds may have independent and tissue-specific effects on metabolic control in vivo.


Subject(s)
Diabetes Mellitus, Experimental/metabolism , Hypoglycemic Agents/pharmacology , Nicotinic Acids/pharmacology , Tetrahydronaphthalenes/pharmacology , Thiazoles/pharmacology , Thiazolidinediones , Adipose Tissue/drug effects , Adipose Tissue/metabolism , Animals , Blood Glucose/drug effects , Diabetes Mellitus/drug therapy , Diabetes Mellitus/metabolism , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Experimental/drug therapy , Disease Models, Animal , Gene Expression/drug effects , Glucose Tolerance Test , Hyperglycemia/blood , Hyperglycemia/drug therapy , Hyperglycemia/etiology , Hyperinsulinism/blood , Hyperinsulinism/drug therapy , Hyperinsulinism/etiology , Liver/drug effects , Liver/metabolism , Male , Muscle, Skeletal/drug effects , Muscle, Skeletal/metabolism , Obesity , RNA, Messenger/analysis , Rats , Rats, Zucker , Receptors, Cytoplasmic and Nuclear/metabolism , Receptors, Retinoic Acid/agonists , Receptors, Retinoic Acid/genetics , Receptors, Retinoic Acid/metabolism , Retinoid X Receptors , Rosiglitazone , Transcription Factors/agonists , Transcription Factors/genetics , Transcription Factors/metabolism
13.
Mol Pharmacol ; 59(2): 170-6, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11160850

ABSTRACT

Hypertriglyceridemia is a frequent complication accompanying the treatment of patients with either retinoids or rexinoids, [retinoid X receptor (RXR)-selective retinoids]. To investigate the cellular and molecular basis for this observation, we have studied the effects of rexinoids on triglyceride metabolism in both normal and diabetic rodents. Administration of a rexinoid such as LG100268 (LG268) to normal or diabetic rats results in a rapid increase in serum triglyceride levels. LG268 has no effect on hepatic triglyceride production but suppresses post-heparin plasma lipoprotein lipase (LPL) activity suggesting that the hypertriglyceridemia results from diminished peripheral processing of plasma very low density lipoproteins particles. Treatment of diabetic rats with rexinoids suppresses skeletal and cardiac muscle but not adipose tissue LPL activity. This effect is independent of changes in LPL mRNA. In C2C12 myocytes, LG268 suppresses the level of cell surface (i.e., heparin-releasable) LPL activity without altering LPL mRNA. This effect is very rapid (t(1/2) = 2 h) and is blocked by the transcriptional inhibitor actinomycin D. These studies demonstrate that RXR ligands can have dramatic effects on the post-translational processing of LPL and suggest that skeletal muscle may be an important target of rexinoid action. In addition, these data underscore that the metabolic consequences of RXR activation are distinct from either retinoic acid receptor or peroxisome proliferator-activated receptor activation.


Subject(s)
Lipoprotein Lipase/metabolism , Nicotinic Acids/pharmacology , Receptors, Retinoic Acid/metabolism , Tetrahydronaphthalenes/pharmacology , Transcription Factors/metabolism , Animals , Cells, Cultured , Heart/drug effects , Hypertriglyceridemia/blood , Hypertriglyceridemia/chemically induced , Lipoprotein Lipase/drug effects , Lipoproteins, VLDL/drug effects , Lipoproteins, VLDL/metabolism , Muscle, Skeletal/drug effects , Muscle, Skeletal/enzymology , Myocardium/enzymology , Myocardium/metabolism , Nicotinic Acids/adverse effects , Rats , Rats, Sprague-Dawley , Rats, Zucker , Receptors, Retinoic Acid/drug effects , Retinoid X Receptors , Retinoids , Tetrahydronaphthalenes/adverse effects , Transcription Factors/drug effects , Triglycerides/blood
14.
Proc Natl Acad Sci U S A ; 98(5): 2610-5, 2001 Feb 27.
Article in English | MEDLINE | ID: mdl-11226287

ABSTRACT

A common feature of many metabolic pathways is their control by retinoid X receptor (RXR) heterodimers. Dysregulation of such metabolic pathways can lead to the development of atherosclerosis, a disease influenced by both systemic and local factors. Here we analyzed the effects of activation of RXR and some of its heterodimers in apolipoprotein E -/- mice, a well established animal model of atherosclerosis. An RXR agonist drastically reduced the development of atherosclerosis. In addition, a ligand for the peroxisome proliferator-activated receptor (PPAR)gamma and a dual agonist of both PPARalpha and PPARgamma had moderate inhibitory effects. Both RXR and liver X receptor (LXR) agonists induced ATP-binding cassette protein 1 (ABC-1) expression and stimulated ABC-1-mediated cholesterol efflux from macrophages from wild-type, but not from LXRalpha and beta double -/-, mice. Hence, activation of ABC-1-mediated cholesterol efflux by the RXR/LXR heterodimer might contribute to the beneficial effects of rexinoids on atherosclerosis and warrant further evaluation of RXR/LXR agonists in prevention and treatment of atherosclerosis.


Subject(s)
Apolipoproteins E/physiology , Arteriosclerosis/prevention & control , Receptors, Retinoic Acid/metabolism , Transcription Factors/metabolism , ATP-Binding Cassette Transporters/physiology , Animals , Apolipoproteins E/genetics , Arteriosclerosis/genetics , Biological Transport , Cholesterol/metabolism , Mice , Mice, Inbred C57BL , Mice, Knockout , Retinoid X Receptors
15.
Behav Ther ; 32(1): 107-22, 2001.
Article in English | MEDLINE | ID: mdl-16733528

ABSTRACT

Using three different samples of couples (clinic, nondistressed community, and engaged), we found that 15 minutes was sufficient to witness enough behavior to make reliable (i.e., internally consistent) estimations of most Rapid Marital Interaction Coding System (Heyman & Vivian, 1993) code frequencies. Ten minutes is sufficient for many codes of interest. The ease in which "how much time is necessary" calculations can be made should entice behavioral investigators from a variety of content areas to publish such figures. By empirically investigating a factor that in most fields becomes reified through convention, investigators can conduct observational research that is both maximally efficient and maximally scientifically defensible.

16.
J Adv Nurs ; 32(4): 913-21, 2000 Oct.
Article in English | MEDLINE | ID: mdl-11095230

ABSTRACT

This qualitative study has aimed to explore children's, parents' and health professionals' experience of childhood chronic illness. Seven families and their professional carers participated in semistrucured interviews. The children's interviews were augmented with a 'drawing' technique. A grounded theory approach facilitated data collection and analysis. This paper debates the perceived passivity of the voice of children in health care and research and illustrates data collection methods that seek to give children and other disadvantaged groups a voice. The children who participated in this study are described as competent interpreters of their world.


Subject(s)
Adaptation, Psychological , Adolescent, Hospitalized/psychology , Attitude to Health , Child, Hospitalized/psychology , Chronic Disease/psychology , Psychology, Adolescent , Psychology, Child , Adolescent , Attitude of Health Personnel , Child , England , Female , Humans , Internal-External Control , Male , Nursing Methodology Research , Nursing Staff, Hospital/psychology , Parents/psychology , Surveys and Questionnaires
17.
Science ; 289(5484): 1524-9, 2000 Sep 01.
Article in English | MEDLINE | ID: mdl-10968783

ABSTRACT

Several nuclear hormone receptors involved in lipid metabolism form obligate heterodimers with retinoid X receptors (RXRs) and are activated by RXR agonists such as rexinoids. Animals treated with rexinoids exhibited marked changes in cholesterol balance, including inhibition of cholesterol absorption and repressed bile acid synthesis. Studies with receptor-selective agonists revealed that oxysterol receptors (LXRs) and the bile acid receptor (FXR) are the RXR heterodimeric partners that mediate these effects by regulating expression of the reverse cholesterol transporter, ABC1, and the rate-limiting enzyme of bile acid synthesis, CYP7A1, respectively. Thus, these RXR heterodimers serve as key regulators of cholesterol homeostasis by governing reverse cholesterol transport from peripheral tissues, bile acid synthesis in liver, and cholesterol absorption in intestine.


Subject(s)
ATP-Binding Cassette Transporters/metabolism , Cholesterol/metabolism , Glycoproteins/metabolism , Intestinal Absorption/drug effects , Intestine, Small/metabolism , Liver/metabolism , Receptors, Cytoplasmic and Nuclear , Receptors, Retinoic Acid/metabolism , Transcription Factors/metabolism , ATP Binding Cassette Transporter 1 , ATP-Binding Cassette Transporters/genetics , Animals , Bile Acids and Salts/biosynthesis , Biological Transport/drug effects , Cholesterol 7-alpha-Hydroxylase/metabolism , Cholesterol, Dietary/administration & dosage , Cricetinae , DNA-Binding Proteins/metabolism , Dimerization , Gene Expression Regulation/drug effects , Glycoproteins/genetics , Homeostasis/drug effects , Ligands , Liver X Receptors , Macrophages, Peritoneal/metabolism , Male , Mesocricetus , Mice , Mice, Inbred C57BL , Mice, Knockout , Orphan Nuclear Receptors , Receptors, Retinoic Acid/agonists , Receptors, Retinoic Acid/genetics , Receptors, Thyroid Hormone/agonists , Receptors, Thyroid Hormone/genetics , Receptors, Thyroid Hormone/metabolism , Retinoid X Receptors , Transcription Factors/agonists
18.
Neurology ; 55(3): 443-6, 2000 Aug 08.
Article in English | MEDLINE | ID: mdl-10932286

ABSTRACT

Twelve patients with a median age of 75 years underwent gamma knife thalamotomy for essential tremor (ET) (n = 9) or MS-related tremor (n = 3). All 11 evaluable patients noted improvement in action tremor. Six of eight ET patients had complete tremor arrest, and the violent action tremor in all three patients with MS was improved. One patient developed transient arm weakness. Stereotactic radiosurgery for ET and MS-related tremor is safe and effective for patients who may be poor candidates for other procedures.


Subject(s)
Essential Tremor/etiology , Essential Tremor/surgery , Multiple Sclerosis/complications , Radiosurgery , Thalamus/surgery , Activities of Daily Living , Adult , Aged , Aged, 80 and over , Essential Tremor/rehabilitation , Female , Handwriting , Humans , Male , Middle Aged , Recovery of Function , Retrospective Studies , Treatment Outcome
19.
Mol Endocrinol ; 14(8): 1198-209, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10935544

ABSTRACT

Binding of agonists to nuclear receptors results in a conformational change in receptor structure that promotes interaction between activated receptors and coactivators. Receptor-coactivator interactions are mediated by the agonist-dependent formation of a hydrophobic pocket on the part of receptors, and short leucine-rich sequences termed LxxLL motifs or nuclear receptor boxes present in coactivators. RXR-PPARgamma (retinoid X receptor-peroxisome proliferator-activated receptor-gamma) heterodimers play important roles in adipocyte and macrophage differentiation and have been implicated as therapeutic targets in diabetes, atherosclerosis, and cancer. Analysis of interactions between RXR-PPARgamma heterodimers and coactivator nuclear receptor boxes suggests that RXR and PPARgamma can distinguish among coactivators by recognizing distinct structural features of nuclear receptor boxes. The results also indicate that coactivator choice by RXR is mediated by three nonconserved amino acids of the nuclear receptor box. The ability of an optimized seven-amino acid nuclear receptor box to specifically interact with RXR and function as a selective inhibitor suggests the coactivator-binding pocket may serve as a new target for drug discovery.


Subject(s)
Receptors, Retinoic Acid/genetics , Receptors, Retinoic Acid/metabolism , Trans-Activators/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism , Amino Acid Motifs , Amino Acid Sequence , Amino Acid Substitution , Animals , Binding Sites , CREB-Binding Protein , Carrier Proteins/genetics , Carrier Proteins/metabolism , Cell Line , Histone Acetyltransferases , Mediator Complex Subunit 1 , Molecular Sequence Data , Mutation , Nuclear Proteins/genetics , Nuclear Proteins/metabolism , Nuclear Receptor Coactivator 1 , Receptors, Cytoplasmic and Nuclear/genetics , Receptors, Cytoplasmic and Nuclear/metabolism , Recombinant Proteins/genetics , Recombinant Proteins/metabolism , Retinoid X Receptors , Trans-Activators/genetics
20.
Int J Obes Relat Metab Disord ; 24(8): 997-1004, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10951538

ABSTRACT

OBJECTIVE: To investigate whether retinoid X receptor agonists act as insulin sensitizers and compare their effects with that of thiazolidinedione BRL 49653 in obese Zucker rats. DESIGN: In two independent studies, obese Zucker rats were dosed orally once daily for 14 days with one of the following treatments: LG 100268 (20 mg/kg), LG 100324 (20 mg/kg), BRL 49653 (3 mg/kg) or vehicle. MEASUREMENTS: Daily food intake and body weight gain, blood glucose, plasma and pancreatic insulin, whole body glucose disposal (by euglycaemic-hyperinsulinaemic clamp) and tissue glucose utilization. RESULTS: The retinoid X receptor agonists (rexinoids) LG 100268 and LG 100324 caused a reduction in the food intake of obese Zucker rats relative to controls and to rats receiving BRL 49653. The two rexinoids also produced a marked decrease in the body weight gain, whereas the growth rate of rats treated with BRL 49653 tended to increase. Both rexinoids and BRL 49653 reduced the plasma insulin concentration of fed rats. LG 100268 and LG 100324 also significantly lowered blood glucose concentrations after 1 week of treatment. The 5 h fasted plasma insulin concentration was significantly lower in the rexinoid-treated groups and the terminal insulin level (at the end of the clamp) tended to be lower in all treated groups compared with animals given the dosing vehicle. However, pancreatic insulin content was not affected by any of the treatments. Under euglycaemic-hyperinsulinaemic clamp conditions, there were no significant differences in the rate of hepatic glucose output and whole body glucose disposal, except that, in experiment 1, BRL 49653 caused significant increase in the glucose infusion rate and muscle glucose utilization. In experiment 2, a similar glucose infusion rate to the controls was achieved in all treatment groups but the steady-state insulin concentration in the treated animals was only about 50% of that in the control animals, despite the fact that all rats received a similar insulin infusion concentration. This suggests that both the rexinoids and BRL 49653 increased insulin clearance. CONCLUSIONS: Chronic administration of retinoid X receptor agonists LG 100268 and LG 100324 to Zucker fa/fa rats reduces food intake and body weight gain, lowers plasma insulin concentrations while maintaining normoglycaemia, indicating an improvement of insulin sensitivity.


Subject(s)
Hypoglycemic Agents/pharmacology , Insulin Resistance , Nicotinic Acids/pharmacology , Obesity/metabolism , Receptors, Retinoic Acid/agonists , Tetrahydronaphthalenes/pharmacology , Thiazoles/pharmacology , Thiazolidinediones , Transcription Factors/agonists , Analysis of Variance , Animals , Blood Glucose/drug effects , Body Weight/drug effects , Eating/drug effects , Insulin/blood , Male , Rats , Rats, Zucker , Retinoid X Receptors , Rosiglitazone
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