PubMed Health⌕ Search

Biomedical subjects

Robert Wesley

Publications and source records attributed to Robert Wesley.

17 recordsLinked to original sources
PubMed2006

Effect of prefrontal cortex damage on resolving lexical ambiguity in text.

The function of suppression of context-inappropriate meanings during lexical ambiguity resolution was examined in 25 adults with prefrontal cortex damage (PFCD) localized to the left (N=8), right (N=6), or bilaterally (N=11); and 21 matched Controls. Results revealed unexpected inverse patterns of suppression between PFCD and Control groups, with measures suggesting decreased interference across time in the PFCD group and increased interference in the Control group. The PFCD group, however, had significantly lower accuracy rates for the context-inappropriate condition. Results suggest a loss of the control aspects of inhibitory processes in lexical ambiguity resolution following PFCD. An aging effect on suppression function is also suggested.

Adult↗
PubMed2006

Anti-N-methyl-D-aspartate receptor antibodies, cognitive dysfunction, and depression in systemic lupus erythematosus.

OBJECTIVE: To assess the association of cognitive dysfunction and depression with serum antibodies to N-methyl-D-aspartate (NMDA) receptor (anti-NR2) and analyze clinical and neuroimaging correlates in patients with systemic lupus erythematosus (SLE). METHODS: Sixty patients underwent neurocognitive assessment, evaluation for depression with the Beck Depression Inventory II (BDI-II) and psychiatric interview (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition [DSM-IV] criteria), brain magnetic resonance imaging, and proton magnetic resonance spectroscopy imaging (1H-MRSI). Cognition was assessed in 5 domains: memory, attention/executive, visuospatial, motor, and psychomotor, and adjusted to each individual's best level of prior cognitive functioning estimated from the reading subtest of the Wide Range Achievement Test-3 (WRAT-3). Serum anti-NR2 antibodies were measured by enzyme-linked immunosorbent assay using a pentapeptide from the human NMDA receptor. RESULTS: Cognitive dysfunction was found in 28 of 60 patients (mild in 8, moderate in 20) before adjustment for WRAT-3 and in 35 of 60 patients (mild in 15, moderate in 11, and severe in 9) after adjustment for WRAT-3. The changes were most pronounced in the memory and visuospatial domains. There was no significant association between anti-NR2 antibody levels and cognition. On 1H-MRSI, patients with moderate or severe cognitive dysfunction had significantly higher choline:creatine ratios in the dorsolateral prefrontal cortex and the white matter, compared with patients with mild or absent cognitive dysfunction. Anti-NR2 antibodies were significantly correlated with BDI scores; patients with BDI-II scores of > or =14 had higher serum levels of anti-NR2 antibodies (P = 0.005, 95% confidence interval 0.83, 4.31), and there was a trend toward higher anti-NR2 antibody levels among patients who fulfilled the DSM-IV criteria for major depression. CONCLUSION: Serum anti-NR2 antibodies are associated with depressive mood but not with cognitive dysfunction in SLE at a given time point. Larger longitudinal studies are needed to address the possible association between anti-NR2 antibodies and depression in SLE.

Adult↗
PubMed2006

Effects of aging on current vocalization threshold in mice measured by a novel nociception assay.

BACKGROUND: Age-related changes in nociception have been extensively studied in the past decades. However, it remains unclear whether in addition to the increased incidence of chronic illness, age-related changes in nociception contribute to increased prevalence of pain in the elderly. Although a great deal of evidence suggests that nociception thresholds increase with aging, other studies yield disparate results. The aim of this investigation was to longitudinally determine the effect of aging on nociception. METHODS: The authors developed a nociception assay for mice using electrical stimuli at 2,000, 250, and 5 Hz that reportedly stimulate Abeta, Adelta, and C sensory nerve fibers, respectively. A system was designed to automate a method that elicits and detects pain-avoiding behavior in mice. Using a Latin square design, the authors measured current vocalization thresholds serially over the course of mice's life span. RESULTS: For 2,000-Hz (Abeta), 250-Hz (Adelta), and 5-Hz (C) electrical stimuli, current vocalization thresholds first decreases and then increases with aging following a U-shaped pattern (P < 0.001). In addition, average current vocalization thresholds at youth and senescence are significantly higher than those at middle age for the 250-Hz (Adelta) and 5-Hz (C fiber) electrical stimulus (P < 0.05). CONCLUSIONS: Using a novel and noninjurious nociception assay, the authors showed that over the life span of mice, current vocalization threshold to electrical stimuli changes in a U-shaped pattern. The findings support the notion that age-related changes in nociception are curvilinear, and to properly study and treat pain, the age of subjects should be considered.

Aging↗
PubMed2006

Use of heparin versus lepirudin flushes to prevent withdrawal occlusion of central venous access devices.

STUDY OBJECTIVE: To determine whether lepirudin flushes are more effective than heparinized saline in preventing withdrawal occlusion of central venous access devices. DESIGN: Randomized, double-blind clinical trial. SETTING: Research institution-tertiary referral center. PATIENTS: Forty-nine adults undergoing bone marrow transplantation for hematologic malignancies or metastatic solid tumors. INTERVENTION: Twenty-four patients received heparin and 25 received lepirudin flushes. The heparin dose was 3 ml of porcine heparin 100 U/ml (300 U) per catheter lumen at least once/day; the lepirudin dose was 3 ml of lepirudin 100 microg/ml (300 microg) per catheter lumen at least once/day. After 3-4 weeks, all 49 patients received the heparin flushes. MEASUREMENTS AND MAIN RESULTS: Efficacy was assessed by the frequency with which the patients were treated with alteplase instillations for withdrawal occlusion of their central venous access devices during the first 4 months of catheterization. Three (12.5%) patients treated with heparin alone and five (20%) treated initially with lepirudin required alteplase instillations for an estimated relative risk with lepirudin versus heparin of 1.6 (95% confidence interval [CI] 0.40-13.86, p=0.70). CONCLUSION: Lepirudin was not more effective than heparin, which may have been related to the conservative dose of lepirudin administered. However, higher lepirudin doses are likely to incur an unacceptable risk of systemic anticoagulation.

Anticoagulants↗
PubMed2006

Intra-rater and inter-rater reliability of the 10-point Manual Muscle Test (MMT) of strength in children with juvenile idiopathic inflammatory myopathies (JIIM).

OBJECTIVE: Children with juvenile idiopathic inflammatory myopathies (JIIM) present with muscle inflammation and decreased strength that may affect their functional abilities. The purpose of this study was to determine the intra-rater and inter-rater reliability of the 0 to 10-point manual muscle testing method for children with JIIM. METHODS: For the intra-rater and inter-rater reliability studies, 10 and 9 children with JIIM participated, respectively. For intra-rater reliability, one pediatric therapist completed two assessments in one day with a one-hour break. For inter-rater reliability, four therapists assessed the same child within a single morning. RESULTS: Spearman correlations for intra-rater reliability ranged from 0.70 to 1.00. Kendall's W coefficient for inter-rater reliability of groups of muscles (total, proximal, distal, and peripheral) ranged from 0.51 to 0.76. CONCLUSIONS: The total, proximal, and peripheral Manual Muscle Test (MMT) score, using the 0-10 point scale, has acceptable reliability in JIIM patients.

Adolescent↗
PubMed2005

A suboptimal endometrial pattern is associated with a reduced likelihood of pregnancy after a day 5 embryo transfer.

This retrospective study examined the association of endometrial pattern and pregnancy after a day 5 ET. The pregnancy rate of women with a triple-line ultrasound endometrial pattern on the day of hCG administration was significantly higher than the pregnancy rate of women with the other ultrasound patterns. This observation suggests that, in a subset of patients, a suboptimal endometrial lining may interfere with assisted reproductive technology success.

Adult↗
PubMed2005

Meta-analysis of natural therapies for hyperlipidemia: plant sterols and stanols versus policosanol.

STUDY OBJECTIVE: To compare the efficacy and safety of plant sterols and stanols as well as policosanol in the treatment of coronary heart disease, as measured by a reduction in low-density lipoprotein cholesterol (LDL) levels. DESIGN: Systematic review and meta-analysis of randomized controlled trials. PATIENTS: A total of 4596 patients from 52 eligible studies. MEASUREMENTS AND MAIN RESULTS: We searched MEDLINE, EMBASE, the Web of Science, and the Cochrane Library from January 1967-June 2003 to identify pertinent studies. Reduction of LDL levels was the primary end point; effects on other lipid parameters and withdrawal of study patients due to adverse effects were the secondary end points. Weighted estimates of percent change in LDL were -11.0% for plant sterol and stanol esters 3.4 g/day (range 2-9 g/day [893 patients]) versus -2.3% for placebo (769 patients) in 23 eligible studies, compared with -23.7% for policosanol 12 mg/day (range 5-40 mg/day [1528 patients]) versus -0.11% for placebo (1406 patients) in 29 eligible studies. Cumulative p values were significantly different from placebo for both (p<0.0001). The net LDL reduction in the treatment groups minus that in the placebo groups was greater with policosanol than plant sterols and stanols (-24% versus -10%, p<0.0001). Policosanol also affected total cholesterol, high-density lipoprotein cholesterol (HDL), and triglyceride levels more favorably than plant sterols and stanols. Policosanol caused a clinically significant decrease in the LDL:HDL ratio. Pooled withdrawal rate due to adverse effects and combined relative risk for patients who withdrew were 0% and 0.84, respectively (95% confidence interval [CI] 0.36-1.95, p=0.69), for plant sterols and stanols across 20 studies versus 0.86% and 0.31, respectively (95% CI 0.20-0.48, p<0.0001), for policosanol across 28 studies. CONCLUSION: Plant sterols and stanols and policosanol are well tolerated and safe; however, policosanol is more effective than plant sterols and stanols for LDL level reduction and more favorably alters the lipid profile, approaching antilipemic drug efficacy.

Anticholesteremic Agents↗
PubMed2004

Long-term interferon-gamma therapy for patients with chronic granulomatous disease.

BACKGROUND: Chronic granulomatous disease (CGD) is a rare disorder of phagocytes in which absent production of superoxide and hydrogen peroxide in phagocytes predisposes patients to bacterial and fungal infections. Infections are dramatically reduced by prophylaxis with antibiotics, antifungals, and interferon- gamma (IFN-gamma ). METHODS: Seventy-six patients with CGD were enrolled in an uncontrolled, open-label follow-up study to assess the long-term clinical safety and efficacy of IFN-gamma therapy. Patients received IFN-gamma subcutaneously 3 times per week. RESULTS: We observed patients for up to 9 years, for a total observation period of 328.4 patient-years. The incidence of serious infections was 0.30 infections per patient-year; for serious bacterial infections, the incidence was 0.18 cases per patient-year, and for serious fungal infections, it was 0.12 cases per patient-year. Thirty-seven percent of patients reported an adverse event, the most common of which was fever. Twenty-six patients withdrew from the study (3 because of adverse events, 15 because of patient preference, and 8 because of transfer to another trial). There were no life-threatening IFN-gamma-related adverse events and no discernible effects on growth. The overall mortality rate was 1.5% per patient-year. CONCLUSION: IFN-gamma prophylaxis for CGD appears to be effective and well tolerated over a prolonged period of time.

Adolescent↗
PubMed2004

Jugular venous sampling: an alternative to petrosal sinus sampling for the diagnostic evaluation of adrenocorticotropic hormone-dependent Cushing's syndrome.

Bilateral sampling of the inferior petrosal sinuses (IPSS) to distinguish Cushing's disease from the ectopic ACTH syndrome is accurate but risky and technically difficult. Bilateral sampling of the internal jugular vein (JVS) is simpler and presumably safer. To compare jugular and petrosal sinus venous sampling for distinguishing Cushing's disease from ectopic ACTH syndrome, we studied 74 patients with surgically proven Cushing's disease, 11 with surgically confirmed, and three with occult ectopic ACTH secretion. Patients underwent JVS and IPSS with administration of CRH on separate days. Ratios of central-to-peripheral ACTH in venous samples were calculated. At 100% specificity, IPSS correctly identified 61 of 65 patients with Cushing's disease [sensitivity, 94%; confidence interval (CI), 84-98%]. When patients with abnormal venous drainage were excluded, sensitivity was 98% (CI, 90-100%). JVS had a sensitivity of 83% (CI, 71-91%) at 100% specificity. Receiver operated characteristics plot areas under the curve were similar (0.968 +/- 0.020 and 0.974 +/- 0.016, area under the curve +/- se, JVS vs. IPSS). Although petrosal sampling had better diagnostic accuracy, CIs overlapped (95% CI, 90-100% vs. 86% CI, 78-94%). Centers with limited sampling experience may choose to use the simpler JVS and refer patients for IPSS when the results are negative.

ACTH Syndrome, Ectopic↗
PubMed2004

Is thyroid hormone suppression therapy prothrombotic?

The purpose of this study was to determine whether chronic thyroid hormone suppression therapy (THST) is prothrombotic. We obtained blood samples from 14 thyroid cancer patients while on THST and after they had become hypothyroid for radioiodine whole-body scanning and therapy. Prothrombin fragment 1 + 2, fibrinogen, factor VIII, antithrombin, tissue plasminogen activator antigen (tPA), plasminogen activator inhibitor 1 (PAI-1), PAI-1/tPA, and C-reactive protein were significantly (P < 0.05) higher in the hyper- than in the hypothyroid state, whereas protein C and plasmin-antiplasmin complexes were significantly lower during the hyperthyroid period. When the 10 female patients were hyperthyroid, their levels of prothrombin fragment 1 + 2, fibrinogen, protein S, antithrombin, tPA, PAI-1, and PAI-1/tPA were significantly higher (P </= 0.05) than in healthy female controls, whereas when the female patients were hypothyroid, their antithrombin and plasmin-antiplasmin were lower and their protein S was higher than in controls. Factor II, plasminogen, and D-dimer were not significantly affected by the thyroid status in either assessment. In conclusion, we found evidence that the majority of patients treated with THST have a prothrombotic profile.

Adult↗
PubMed2003

A simple method to predict response to immunosuppressive therapy in patients with myelodysplastic syndrome.

Immunosuppression with antithymocyte globulin (ATG) or cyclosporine (CSA) can be used to treat the cytopenia associated with myelodysplastic syndrome (MDS). Previously, we identified HLA-DR15, younger age, and shorter duration of red cell transfusion dependence as pretreatment variables that correlate significantly with a response. Using these pretreatment variables we have devised a simple method to prospectively identify patients with low or high probabilities of response to immunosuppression. The ability of this system to predict response was confirmed in a separate cohort of 23 patients with MDS treated with immunosuppression.

Adult↗
PubMed2003

Itraconazole to prevent fungal infections in chronic granulomatous disease.

BACKGROUND: Chronic granulomatous disease is a rare disorder in which the phagocytes fail to produce hydrogen peroxide. The patients are predisposed to bacterial and fungal infections. Prophylactic antibiotics and interferon gamma have reduced bacterial infections, but there is also the danger of life-threatening fungal infections. We assessed the efficacy of itraconazole as prophylaxis against serious fungal infections in chronic granulomatous disease. METHODS: Thirty-nine patients at least 5 years old (6 female and 33 male; mean age, 14.9 years) were enrolled in a randomized, double-blind, placebo-controlled study. After the initially assigned treatment, each patient alternated between itraconazole and placebo annually. Patients 13 years of age or older and all patients weighing at least 50 kg received a single dose of 200 mg of itraconazole per day; those less than 13 years old or weighing less than 50 kg received a single dose of 100 mg per day. The primary end point was severe fungal infection, as determined by histologic results or culture. RESULTS: One patient (who had not been compliant with the treatment) had a serious fungal infection while receiving itraconazole, as compared with seven who had a serious fungal infection while receiving placebo (P=0.10). No patient receiving itraconazole but five patients receiving placebo had a superficial fungal infection. No serious toxic effects were noted, although one patient had a rash and another had elevated results on liver-function tests; both of these effects resolved with the discontinuation of itraconazole. CONCLUSIONS: Itraconazole prophylaxis appears to be an effective and well-tolerated treatment that reduces the frequency of fungal infections in chronic granulomatous disease, but monitoring for long-term toxic effects is warranted.

Adolescent↗
PubMed2003

Global surface ultraviolet radiation intensity may modulate the clinical and immunologic expression of autoimmune muscle disease.

OBJECTIVE: To determine if geoclimatic factors may influence the nature and frequency of dermatomyositis (DM), polymyositis, and associated autoantibodies around the world. METHODS: We assessed, in the first global evaluation of these conditions, the relationship between 13 geoclimatic variables that may modulate disease and the relative proportion of DM and its associated autoantibody anti-Mi-2, directed against an SNF2-superfamily helicase associated with the nucleosome remodeling and histone acetylation and deacetylation complex, in a global myositis population. Altogether, 919 consecutive patients from populations at 15 locations were studied. RESULTS: Univariate and multivariate analyses demonstrated that of the variables evaluated, surface ultraviolet (UV) radiation intensity (irradiance) most strongly contributed to the relative proportion of DM and was strongly related to the proportion of anti-Mi-2 autoantibodies (weighted r = 0.939, P < 4 x 10(-7) and weighted r = 0.69, P = 0.02, respectively). Published ethnogeographic immunogenetic allele frequencies imply that the striking differences in the proportion of DM- and DM-specific autoantibodies observed around the world are not the result of inherent global variations in known genetic risk factors. CONCLUSION: These data suggest that UV radiation exposure may modulate the clinical and immunologic expression of an autoimmune disease in different populations around the world.

Autoantibodies↗
PubMed2003

Effect of ethanol on the central oscillator in essential tremor.

We investigated the effects of ethanol and diazepam on the central, mechanical, and mechanical reflex components of tremor in patients with essential tremor (ET). A double-blind crossover study (ethanol or diazepam) was conducted on 2 separate days. Dose of ethanol or diazepam was calculated in each individual according to height, weight, and age in 10 patients with ET. The postural tremor amplitude at the wrist was recorded using a three-dimensional accelerometer placed on the dorsum of the hand. Electromyogram (EMG) was recorded with surface electrodes placed on the forearm extensors and flexors. To separate central and mechanical (reflex) components, a 500-g weight was placed on the dorsum of the hand during a second tremor measurement. Tremor recordings were done at baseline and 30, 60, 90, and 120 minutes after drug ingestion. Ethanol and diazepam blood levels were measured at baseline and after 20, 40, 80, and 120 minutes. Blood ethanol and diazepam levels were highest after 40 and 80 minutes. The amplitude of the central component 60 minutes after ingestion of ethanol was decreased significantly (P = 0.029) compared with diazepam. Our findings suggest that the improvement in tremor after ethanol ingestion was due, at least in part, to an effect on a central oscillator.

Biological Clocks↗
PubMed2002

Adrenomedullary function may predict phenotype and genotype in classic 21-hydroxylase deficiency.

Classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is characterized by decreased synthesis of glucocorticoids and mineralocorticoids, adrenal hyperandrogenism, and impaired development and function of the adrenal medulla. Although genotype can usually predict phenotype, genotype-phenotype discordance has been described. We investigated the association between adrenomedullary function, disease severity, and genotype in 37 children [22 males and 15 females; age range, 4.7-14.9 yr; 28 salt-wasting (SW) and 9 simple virilizing (SV) CAH] with classic 21-hydroxylase deficiency. Plasma and 24-h urinary catecholamines and their metabolites, and the 21-hydroxylase genotype were determined in all patients. The disease-causing mutations were divided into 4 groups (Null, A, B, and C) according to in vitro 21-hydroxylase activity as previously described. Genotype groups Null (n = 9) and A (n = 15) were predicted to result in SW CAH, group B (n = 8) was predicted to have the SV phenotype, and group C (n = 1) was predicted to have nonclassic CAH. A fifth group, D (n = 4), included patients in whom mutations were detected in only 1 allele. Plasma total metanephrine (420.1 +/- 60.0 vs. 657.7 +/- 67.8 pg/ml; P = 0.04) and free metanephrine (13.4 +/- 1.7 vs. 24.0 +/- 4.1 pg/ml; P = 0.008) concentrations were significantly lower in children with SW CAH than in those with the SV form of the disease. Plasma free metanephrine concentrations best predicted phenotype, with accuracy similar to that of genotype. Concordance rates between genotype and phenotype were higher in the most severely affected patients (Null, 88.9%; A, 93.3%; B, 75%; plasma free metanephrine, <18.5 pg/ml: SW, 92%). The plasma free metanephrine concentration correlated with the expected 21-hydroxylase activity based on genotype, and there was a significant trend for free metanephrine concentrations across the three genotype groups (P < 0.0001). Our findings indicate that measurement of adrenomedullary function, best assessed by the free metanephrine concentration, is a useful biomarker of disease severity in 21-hydroxylase deficiency. Molecular genotype and plasma free metanephrine concentration predict phenotype with similar accuracy. Both methods are more accurate in the most severe forms of the disease.

Adolescent↗