PubMed Health⌕ Search

Biomedical subjects

Richard Jones

Publications and source records attributed to Richard Jones.

32 records · Page 2Linked to original sources
PubMed2004

Anticonvulsant hypersensitivity syndrome: treatment with corticosteroids and intravenous immunoglobulin.

We describe the case of a patient in whom anticonvulsant hypersensitivity syndrome developed during treatment with phenytoin and progressed when therapy was changed to phenobarbital. Although therapeutic options remain controversial, corticosteroids and IV immunoglobulin were used in our patient. The patient had a complete recovery, suggesting the potential benefit of corticosteroids and IV immunoglobulin for anticonvulsant hypersensitivity syndrome.

Adult↗
PubMed2004

Opposing influences of prenatal and postnatal weight gain on adrenarche in normal boys and girls.

Associations between low birth weight and higher adrenal androgen secretion before puberty have yet only been reported in case-control studies in girls. We examined the influence of birth weight and early postnatal weight gain on overnight-fasting adrenal androgen and cortisol levels in 770 children from a large normal United Kingdom birth cohort at age 8 yr. In univariate analyses, adrenal androgen levels were inversely related to birth weight sd score in each sex [dehydroepiandrosterone sulfate in boys: regression coefficient (B) = -2.5 microg/dl/SD; 95% confidence interval (CI), -4.7 to -0.2; in girls: B = -3.8 microg/dl/SD; 95% CI, -6.2 to -1.4; androstenedione in boys: B = -0.15 nmol/liter/sd, 95% CI, -0.25 to -0.6; in girls: B = -0.13 nmol/liter/SD; 95% CI, -0.24 to -0.02). In multivariate analyses, both lower birth weight and larger current body weight predicted higher adrenal androgen levels (P < 0.005 for all comparisons). Allowing for current weight, children who showed rapid postnatal weight gain between 0 and 3 yr had higher dehydroepiandrosterone sulfate (P = 0.002) and androstenedione (P = 0.004) levels at 8 yr. In contrast, cortisol levels were unrelated to birth weight or current body size. In summary, the relationship between lower birth weight and higher childhood adrenal androgen levels was continuous throughout the range of normal birth weights, and was similar in boys and girls. Adrenal androgen levels were highest in small infants who gained weight rapidly during early childhood. We suggest that higher adrenal androgen secretion could contribute to links between early growth and adult disease risks, possibly by enhancing insulin resistance and central fat deposition.

Adrenal Cortex↗
PubMed2003

Inter-rater reliability of nursing home quality indicators in the U.S.

BACKGROUND: In the US, Quality Indicators (QI's) profiling and comparing the performance of hospitals, health plans, nursing homes and physicians are routinely published for consumer review. We report the results of the largest study of inter-rater reliability done on nursing home assessments which generate the data used to derive publicly reported nursing home quality indicators. METHODS: We sampled nursing homes in 6 states, selecting up to 30 residents per facility who were observed and assessed by research nurses on 100 clinical assessment elements contained in the Minimum Data Set (MDS) and compared these with the most recent assessment in the record done by facility nurses. Kappa statistics were generated for all data items and derived for 22 QI's over the entire sample and for each facility. Finally, facilities with many QI's with poor Kappa levels were compared to those with many QI's with excellent Kappa levels on selected characteristics. RESULTS: A total of 462 facilities in 6 states were approached and 219 agreed to participate, yielding a response rate of 47.4%. A total of 5758 residents were included in the inter-rater reliability analyses, around 27.5 per facility. Patients resembled the traditional nursing home resident, only 43.9% were continent of urine and only 25.2% were rated as likely to be discharged within the next 30 days. Results of resident level comparative analyses reveal high inter-rater reliability levels (most items >.75). Using the research nurses as the "gold standard", we compared composite quality indicators based on their ratings with those based on facility nurses. All but two QI's have adequate Kappa levels and 4 QI's have average Kappa values in excess of.80. We found that 16% of participating facilities performed poorly (Kappa <.4) on more than 6 of the 22 QI's while 18% of facilities performed well (Kappa >.75) on 12 or more QI's. No facility characteristics were related to reliability of the data on which Qis are based. CONCLUSION: While a few QI's being used for public reporting have limited reliability as measured in US nursing homes today, the vast majority of QI's are measured reliably across the majority of nursing facilities. Although information about the average facility is reliable, how the public can identify those facilities whose data can be trusted and whose cannot remains a challenge.

Aged↗
PubMed2003

Recombinant TCR ligand induces tolerance to myelin oligodendrocyte glycoprotein 35-55 peptide and reverses clinical and histological signs of chronic experimental autoimmune encephalomyelitis in HLA-DR2 transgenic mice.

In a previous study, we demonstrated that myelin oligodendrocyte glycoprotein (MOG)-35-55 peptide could induce severe chronic experimental autoimmune encephalomyelitis (EAE) in HLA-DR2(+) transgenic mice lacking all mouse MHC class II genes. We used this model to evaluate clinical efficacy and mechanism of action of a novel recombinant TCR ligand (RTL) comprised of the alpha(1) and beta(1) domains of DR2 (DRB1*1501) covalently linked to the encephalitogenic MOG-35-55 peptide (VG312). We found that the MOG/DR2 VG312 RTL could induce long-term tolerance to MOG-35-55 peptide and reverse clinical and histological signs of EAE in a dose- and peptide-dependent manner. Some mice treated with lower doses of VG312 relapsed after cessation of daily treatment, but the mice could be successfully re-treated with a higher dose of VG312. Treatment with VG312 strongly reduced secretion of Th1 cytokines (TNF-alpha and IFN-gamma) produced in response to MOG-35-55 peptide, and to a lesser degree purified protein derivative and Con A, but had no inhibitory effect on serum Ab levels to MOG-35-55 peptide. Abs specific for both the peptide and MHC moieties of the RTLs were also present after treatment with EAE, but these Abs had only a minor enhancing effect on T cell activation in vitro. These data demonstrate the powerful tolerance-inducing therapeutic effects of VG312 on MOG peptide-induced EAE in transgenic DR2 mice and support the potential of this approach to inhibit myelin Ag-specific responses in multiple sclerosis patients.

Amino Acid Sequence↗
PubMed2003

Cross-linking of cellular proteins by tissue transglutaminase during necrotic cell death: a mechanism for maintaining tissue integrity.

Tissue transglutaminase (tTG) is a Ca(2+)-dependent enzyme which cross-links proteins via epsilon(gamma-glutamyl)lysine bridges. There is increasing evidence that tTG is involved in wound repair and tissue stabilization, as well as in physiological mechanisms leading to cell death. To investigate the role of this enzyme in tissue wounding leading to loss of Ca(2+) homoeostasis, we initially used a model involving electroporation to reproduce cell wounding under controlled conditions. Two cell models were used whereby tTG expression is regulated either by antisense silencing in ECV 304 cells or by using transfected Swiss 3T3 cells in which tTG expression is under the control of the tet regulatory system. Using these cells, loss of Ca(2+) homoeostasis following electroporation led to a tTG-dependent formation of highly cross-linked proteinaceous shells from intracellular proteins. Formation of these structures is dependent on elevated intracellular Ca(2+), but it is independent of intracellular proteases and is near maximal after only 20 min post-wounding. Using labelled primary amines as an indicator of tTG activity within these 'wounded cells', we demonstrate that tTG modifies a wide range of proteins that are present in both the perinuclear and intranuclear spaces. The demonstration of entrapped DNA within these shell structures, which showed limited fragmentation, provides evidence that the high degree of transglutaminase cross-linking results in the prevention of DNA release, which may serve to dampen any subsequent inflammatory response. Comparable observations were shown when monolayers of cells were mechanically wounded by scratching. In this second model of cell wounding, redistribution of tTG activity to the extracellular matrix was also demonstrated, an effect which may serve to stabilize tissues post-trauma, and thus contribute to the maintenance of tissue integrity.

3T3 Cells↗
PubMed2003

Motilin effects on the proximal stomach in patients with functional dyspepsia and healthy volunteers.

This study investigates motilin effects on the proximal stomach in patients with functional dyspepsia (FD) and healthy volunteers. Eight healthy volunteers and 12 patients with FD were infused with synthetic motilin or placebo. Proximal gastric volume was measured with a barostat at constant pressure and during isobaric distensions. Abdominal symptoms were scored by visual analog scales. Plasma motilin concentrations were measured by radioimmunoassay. Motilin concentrations and baseline gastric volumes were similar for patients and healthy volunteers. Motilin, compared with placebo, reduced gastric volume by 112 ml [F(29,195); confidence interval (CI) 95%] in patients and by 96 ml [F(-7,200); CI 95%] in healthy volunteers. In patients, motilin decreased compliance by 76 ml/mmHg [F(9,143); CI 95%] compared with placebo, which was similar in volunteers [66 ml/mmHg; F(11,120); CI 95%]. Patients were more nauseous during motilin compared with placebo (P = 0.04), whereas healthy volunteers did not experience nausea. We conclude that in a fasted condition, FD patients have a similar proximal gastric motor response to motilin as healthy volunteers, but experience an exaggerated sensation of nausea.

Adult↗
PubMed2003

Renal diffusion and BOLD MRI in experimental diabetic nephropathy. Blood oxygen level-dependent.

PURPOSE: To investigate the possibility of using combined blood oxygen level-dependent (BOLD) imaging and diffusion-weighted imaging (DWI) to detect pathological and physiological changes in renal tissue damage of the kidney induced by chronic renal hyperfiltration. MATERIALS AND METHODS: The apparent diffusion coefficient (ADC) and the T(2)* value within the inner compartments of the kidneys of 17 rats with diabetes mellitus were compared with the results obtained from a control group (N = 16). The influence of dynamic changes of the renal function on the blood-oxygen saturation was evaluated by comparing the T(2)* values before and after the active reduction of tubular transport by furosemide injection. RESULTS: All compartments of the diabetic kidney showed significantly (P < 0.05) lower T(2)*-values compared to the control group. In particular, the very low values in the outer stripe (OS) of the outer medulla (OM) (T(2)*-normal: 69.4 +/- 10.9 msec; T(2)*-diabetic: 51.4 +/- 13.9 msec) indicated either hypoxia due to hyperfiltration, or renal blood volume changes. Diffusion imaging of the same area showed significantly lower ADC values (ADC-normal: 1.45 +/- 0.26; ADC-edema: 1.19 +/- 0.25 [10(-9)m(2)/s]) that correlated with pathological findings on histopathology. The injection of furosemide significantly (P < 0.05) increased T(2)* in all compartments of both populations while the ADC remained unchanged. CONCLUSION: BOLD-contrast imaging appears to be able to depict tissue at risk from ischemia by revealing information about the balance between tubular workload and delivery of oxygen, and thus may reflect a measure of the reserve capacity. The diffusion measurements apparently reveal complementary information. Although ADC imaging is not sensitive to the current energy metabolism, it appears toreflect the pathological changes within the issue. Therefore, ADC measurements may be a sensitive indicator of the severity of ischemic lesions.

Animals↗
PubMed2003

Structure and function of the vacuolar H+-ATPase: moving from low-resolution models to high-resolution structures.

In the absence of a high-resolution structure for the vacuolar H+-ATPase, a number of approaches can yield valuable information about structure/function relationships in the enzyme. Electron microscopy can provide not only a representation of the overall architecture of the complex, but also a low-resolution map onto which structures solved for individually expressed subunits can be fitted. Here we review the possibilities for electron microscopy of the Saccharomyces V-ATPase and examine the suitability of V-ATPase subunits for expression in high yield prokaryotic systems, a key step towards high-resolution structural studies. We also review the role of experimentally-derived structural models in understanding structure/function relationships in the V-ATPase, with particular reference to the complex of proton-translocating 16 kDa proteolipids in the membrane domain of the V-ATPase. This model in turn makes testable predictions about the sites of binding of bafilomycins and the functional interactions between the proteolipid and the single-copy membrane subunit Vph1p, with implications for the constitution of the proton translocation pathway.

Cell Membrane↗
PubMed2003

Using a new taxonomy to combine the uncombinable: integrating results across diverse interventions.

Researchers have examined numerous psychosocial and behavioral interventions intended to alleviate distress among family caregivers of persons with dementia. Many of these interventions are complex, combining numerous treatment components. Although some multicomponent interventions have been successful in reducing caregiver distress, the impact of specific elements of these interventions on outcomes is not known. The article presents results of an analytic approach that allows researchers to describe the individual elements of multicomponent interventions and to examine the relationships between those components and outcomes. This approach is successfully applied to interventions being evaluated in the Resources for Enhancing Alzheimer's Caregiver Health (REACH) program. The results indicate that actively targeting caregiver behavior is effective in achieving positive outcomes with respect to caregiver depression.

Aged↗
PubMedDate not supplied

Risk adjusting outcome measures for post-acute care.

This article examines whether different risk adjusters are needed for home care outcome measures for post-acute care clients. Multiple risk adjusters that met clinical and policy criteria were tested using multiple logistic regression on a sample of 4403 post-acute home care clients from Michigan. Two of the 6 outcome measures had substantially different risk adjusters for the post-acute care population versus the general population. Care should be taken to select outcome measures and risk adjusters for special home care populations.

Activities of Daily Living↗