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S Fitzgerald

Publications and source records attributed to S Fitzgerald.

At least 19 recordsLinked to original sources
PubMed2006

Ensembl 2007.

The Ensembl (http://www.ensembl.org/) project provides a comprehensive and integrated source of annotation of chordate genome sequences. Over the past year the number of genomes available from Ensembl has increased from 15 to 33, with the addition of sites for the mammalian genomes of elephant, rabbit, armadillo, tenrec, platypus, pig, cat, bush baby, common shrew, microbat and european hedgehog; the fish genomes of stickleback and medaka and the second example of the genomes of the sea squirt (Ciona savignyi) and the mosquito (Aedes aegypti). Some of the major features added during the year include the first complete gene sets for genomes with low-sequence coverage, the introduction of new strain variation data and the introduction of new orthology/paralog annotations based on gene trees.

Animals↗
PubMed2006

Salicylate- and quinine-induced tinnitus and effects of memantine.

CONCLUSION: Memantine, an antiglutamatergic drug, has been proposed as a treatment for tinnitus. OBJECTIVES: The purpose of this study was to determine if memantine would prevent salicylate-induced tinnitus. Local field potentials were also recorded from auditory cortex to determine what effect salicylate, memantine, and the combination of both drugs would have on evoked potential amplitudes. MATERIALS AND METHODS: Schedule induced polydipsia-avoidance conditioning was used to identify the doses of salicylate or quinine that reliably induced tinnitus in rats. Rats were trained to lick for water during quiet intervals and avoid licking during sound intervals. RESULTS: Rats injected with saline or a low dose of sodium salicylate or quinine failed to develop tinnitus-like behaviors. However, high doses of salicylate (150-300 mg/kg/day) or quinine (100-150 mg/kg/day) greatly reduced licks-in-quiet, behavior consistent with the presence of tinnitus. Licks-in-quiet increased slightly when memantine (1.5 or 3 mg/kg/day) was co-administered with salicylate; however, the effect was not statistically significant or dose-dependent. These results indicate that memantine does not completely suppress salicylate-induced tinnitus. Cortical auditory evoked potential amplitude increased after salicylate treatment; co-administration of memantine failed to block this salicylate-induced increase.

Analgesics, Non-Narcotic↗
PubMed2002

Onset of symptom relief with rabeprazole: a community-based, open-label assessment of patients with erosive oesophagitis.

BACKGROUND: In numerous clinical trials, proton pump inhibitors have demonstrated potent acid suppression and healing of erosive oesophagitis, as well as successful symptom relief for the entire spectrum of gastro-oesophageal reflux disease. AIM: The 'Future of Acid Suppression Therapy' (FAST) trial evaluated, in actual clinical practice, the timing of symptom relief, changes in symptom severity, health-related quality of life and safety in endoscopically confirmed erosive gastro-oesophageal reflux disease treated with rabeprazole. METHODS: This open-label, multicentre study enrolled 2579 patients to receive rabeprazole treatment using 20 mg once daily for 8 weeks. Between two clinical visits (at enrollment and week 8), patients used an interactive voice response system to rate gastro-oesophageal reflux disease symptoms. Subgroup analyses of efficacy were conducted for gender, age, Hetzel-Dent grade, presence of Barrett's oesophagus and for patients reporting previously ineffective symptom relief with omeprazole or lansoprazole. RESULTS: On day 1, rabeprazole significantly decreased daytime and night-time heartburn severity, regurgitation and belching. Complete relief of daytime and night-time heartburn was achieved in 64.0% and 69.2% of symptomatic patients, respectively, on day 1, and in 81.1% and 85.7% of patients, respectively, on day 7. Patients with moderate or severe heartburn symptoms at baseline achieved an even greater degree of satisfactory symptom relief (none or mild) from day 1 onwards. The median time to satisfactory heartburn relief was 2 days. Subgroup analyses showed no consistent differences in efficacy compared to the overall population treated. Health-related quality of life in patients was significantly lower than that of the US general population and improved significantly after 8 weeks of rabeprazole therapy. Rabeprazole was well tolerated, with headache as the most common adverse event, reported by less than 2% of the study population. CONCLUSIONS: In this large, open-label trial, rabeprazole rapidly and effectively relieved gastro-oesophageal reflux disease symptoms in most patients with erosive oesophagitis. Substantial symptom relief was noted on day 1; improvement continued over the first week and at week 4. By week 8, the health-related quality of life had also improved vs. baseline.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2001

CD40 employs p38 MAP kinase in IgE isotype switching.

IgE switching requires the prior induction of C epsilon germline transcripts which is mediated by the concerted binding of STAT-6 and NF kappa B to the C epsilon promoter. These transcription factors are regulated by IL-4 and CD40, respectively. However the latter can effect other signaling pathways and the present study explores the role of p38 MAPK in induction of C epsilon germline transcripts. CD40 and IL-4, both alone and in synergy, were initially shown to activate the C epsilon promoter in a B cell lymphoma cell line. Under the same conditions CD40 caused activation of p38 MAPK, whereas IL-4 was ineffective. The p38 MAPK inhibitor, SB203580, and a dominant negative form of p38 MAPK decreased the CD40 activation of the C epsilon promoter by reducing the ability of CD40 to increase the transactivation potential of NF kappa B. This study suggests that p38 MAPK is crucially important in mediating CD40 activation of NF kappa B which acts to induce C epsilon germline transcripts, ultimately facilitating IgE switching.

CD40 Antigens↗
PubMed2001

Sonographic diagnosis and follow-up of idiopathic hepatic artery aneurysm, an unusual cause of obstructive jaundice.

Hepatic artery aneurysms are rare. We report an idiopathic hepatic artery aneurysm causing obstructive jaundice in a case in which the common hepatic artery arose from the superior mesenteric artery. The diagnosis of hepatic artery aneurysm was suggested by gray-scale sonography, which showed that the common bile duct and intrahepatic biliary radicles were dilated with no obvious intraluminal abnormality and showed no evidence of a mass in the head of the pancreas. A papillotomy of the papilla duodeni major was performed to relieve the cholestasis. Repeat sonography 2 weeks later showed dilatation of the common bile duct and a cyst-like lesion at the porta hepatis impressing the anterior part of the common bile duct. Doppler sonography confirmed pulsatile flow within the cyst-like lesion. Helical CT showed a well-circumscribed lesion with a density similar to that of the abdominal aorta, and mesenteric angiography showed a 3-cm, smooth aneurysm arising from the common hepatic artery, which originated from the superior mesenteric artery. The aneurysm was successfully treated with transcatheter embolization.

Aneurysm↗
PubMed2001

Methodological considerations when conducting direct observation in an outdoor environment: our experience in local parks.

OBJECTIVE: This paper discusses some of the inherent methodological limitations of gathering data via direct observation using local parks as a case study. METHODS: Direct observation was carried out in five parks on seven non-consecutive days in 1998 and on matched days in 1999. Information recorded for each person included the time of park entry and exit, gender, age group, and activity/ies undertaken while in the park. METHODOLOGICAL CONSIDERATIONS: The location of the observation point, observer reliability, recording and accuracy of data, and specific issues related to outdoor observation areas should all be considered when designing a study incorporating direct observation as a data collection method. CONCLUSIONS: Direct observation can provide valuable information. However, pilot testing is essential for minimising potential problems associated with this method and optimising data quality. IMPLICATIONS: The issues discussed in this paper provide a useful guide for other researchers undertaking direct observation in outdoor environments.

Data Collection↗
PubMed2001

Vascular stiffness in women with systemic lupus erythematosus.

Large-vessel manifestations of systemic lupus erythematosus (SLE), a multisystem disease characterized by disturbances in the immune system, include higher than expected rates of hypertension and cardiovascular disease. Reductions in the elasticity of central arteries may act as a marker of early changes that predispose to the development of major vascular disease. This study evaluated risk factors associated with aortic stiffness measured by pulse wave velocity (PWV) in women with SLE. We expected SLE-specific factors, especially variables indicative of inflammation and active disease, to be associated with increasing PWV. The study population included 220 women currently enrolled in the Pittsburgh Lupus REGISTRY: All risk factor data were collected on the day of the ultrasound examinations. PWV waveforms were collected from the right carotid and femoral arteries by Doppler probes. The mean age of the women was 45.5+/-10.8 years, the median SLE disease duration approximated 9 years, and the mean PWV was 6.1+/-1.7 m/s. Multiple regression models were stratified by menopausal status. Among postmenopausal women, PWV risk factors were primarily traditional factors and included age, systolic blood pressure, family history of vascular disease, carotid plaque, creatinine, obesity, glucose, white cell count, and cumulative SLE organ damage. Among premenopausal women, PWV risk factors consisted of a mix of SLE-related and traditional variables and included higher C3 levels, presence of ds-DNA antibodies, nonuse of hydroxychloroquine, lower leukocyte count, higher mean arterial pressure, and carotid plaque. SLE-specific variables appeared to be associated with increases in aortic PWV, indicating central artery stiffening. This was seen most clearly among premenopausal women. This finding may partially explain the higher rates of cardiovascular disease and hypertension observed in young women with SLE.

Adult↗
PubMed2001

Bone densitometry in clinical practice: longitudinal measurements at three sites in postmenopausal women on five treatments.

We report sequential changes in bone mineral density (BMD) at the forearm, hip and spine in 340 consecutive postmenopausal women referred by 103 general practitioners and six specialists, and who were either untreated or being treated with calcium, estrogen, norethisterone or calcitriol for a median period of 25 months (range 11-52). The mean annual rate of change in BMD at the three sites was: 1.39% in 44 women on norethisterone; 0.94% in 107 women on estrogen (both p < 0.001); 0.24% (not significant) in 52 women on calcitriol; -0.53% in 92 women on calcium; and -1.06% in 45 women on no treatment (both p < 0.01). The mean annual rate of change at the three sites in the 295 treated women was 0.43%, which was significantly positive (p < 0.001) and was 1.49 percentage points more positive than in the untreated women (p < 0.001). The greatest mean difference between treated and untreated patients was seen at the forearm, where it was 2.16 percentage points (p < 0.001). This was significantly greater than the difference at the femoral neck (1.21 percentage points (p = 0.037)) and lumbar spine (1.10 percentage points (p = 0.044)). The data did not change significantly after correction for age, years since menopause or baseline BMD. Those who started the treatments at baseline gained bone faster than those who were continuing on existing therapies, but this difference was not significant at any site. In the hormone- and calcitriol-treated groups, there was no significant difference between those who had a calcium supplement and those who did not. We conclude that the effects of treatment on BMD in clinical practice are comparable to those predicted from clinical trials, that there are significant differences between the responses to treatment at different sites and that the forearm appears to be the most sensitive site, in this series at least.

Absorptiometry, Photon↗
PubMed2000

Tumour-necrosis-factor-receptor-associated factor 6, NF-kappaB-inducing kinase and IkappaB kinases mediate IgE isotype switching in response to CD40.

The process of IgE switching requires the prior transcription of the unrearranged Cepsilon gene, which leads to its recombination with the VDJ region. The activation of NF-kappaB by CD40 is a key process in facilitating this transcription by promoting the activation of the Cepsilon promoter. The present study explores the uncharacterized signalling pathways employed by CD40 in activating NF-kappaB by the overexpression of genes encoding wild-type and dominant-negative forms of the signalling components tumour-necrosis-factor-receptor-associated factor 6 (TRAF-6), NF-kappaB-inducing kinase (NIK), IkappaB kinase (IKK)-1 and IKK-2 in the BJAB B-cell line. The overexpression of TRAF-6 or NIK was sufficient to activate NF-kappaB and the Cepsilon promoter, whereas their dominant-negative counterparts decreased the ability of CD40 to activate NF-kappaB and the Cepsilon promoter. The overexpression of wild-type IKK-1 or IKK-2 seemed to cause toxic effects on the cells, whereas the dominant-negative forms were selective in their blockade of NF-kappaB and the Cepsilon promoter. These results suggest that CD40 employs TRAF-6, which presumably recruits NIK, which in turn employs IKK-1/IKK-2 to activate NF-kappaB and the Cepsilon promoter, the prologue to IgE switching. Thus the findings define a crucially important pathway in the generation of allergic states.

Base Sequence↗
PubMed2000

Sexually transmitted disease clinic clients at risk for subsequent gonorrhea and chlamydia infections: possible 'core' transmitters.

BACKGROUND: From an sexually transmitted disease (STD) intervention perspective, developing a practical way to identify persons in core transmitter groups has been difficult. However, persons who have repeated STD infections may be in such groups. GOAL: To evaluate a self-administered risk assessment approach that would identify STD clinic clients who were at an increased risk of being involved in gonorrhea (GC) or chlamydia (CT) transmission in the subsequent year. STUDY DESIGN: Prospective cohort of consecutive STD clinic clients with a 1-year follow-up period. RESULTS: During a 6-month period in 1995, 2576 STD clinic clients in San Diego completed a risk assessment. Of those clients, 204 (7.9%) had a subsequent STD and 79 (3.1%) had a subsequent GC or CT infection during the 1-year follow-up period. The strongest predictor of a subsequent GC/CT was having a recent history or current clinic visit diagnosis of GC or CT (6.1% subsequent GC/CT rate). The more past episodes of GC or CT, the higher the subsequent GC/CT rate. Unsafe sexual behavior had little effect on further increasing subsequent GC/CT risk. CONCLUSION: STD clinic clients with a recent history of GC or CT and a high risk of subsequent GC/CT may be core transmitters who could likely benefit from risk reduction, periodic screening for GC/CT, symptom recognition counseling, and preventive treatment-the essential elements of STD-prevention case management.

California↗
PubMed2000

Analysis of position and isometric joysticks for powered wheelchair driving.

The control interface is one of the most critical components of the electric-powered wheelchair (EPW). The control interface must accommodate the user's limitations and maximize the user's abilities. This study extended Fitts' Law for target-acquisition to a continuously updated target. The extended Fitts' Law was used to examine EPW driving with a standard position sensing joystick and a prototype isometric joystick (IJ). The extended Fitts' Law provides insight into the difficulty of performing target-acquisition tasks with an EPW. The test results showed significant differences (p < 0.05) among the two types of joysticks for selected measures of information processing capacity, movement time, root-mean-square-error, and average velocity while performing turning maneuvers. The mean values indicate that the IJ may provide superior turning performance.

Algorithms↗
PubMed2000

Rural parents' communication with their teen-agers about sexual issues.

This survey assessed rural parents' (n = 374) perceptions of the characteristics, content, and comfort level of discussions about sexual issues with their teens. Almost all parents (94%) reported they had talked with their teens about sex. Two-thirds (65%) reported being comfortable talking with their teens about sexual issues. From a list of 17 potential topical areas in sexual communication, parents were most likely to discuss with their teens the responsibilities of being a parent (46%), sexually transmitted diseases (40%), dating behavior (37%), and not having sex until marriage (36%). Most parents (80%) believed that the majority of sexuality education should be provided by the family and supplemented by outside organizations, preferably schools. Almost all parents (92%) believed sexuality education should include information on birth control methods including condoms. Almost two of three parents (64%) believed schools should begin teaching sexuality education before students reach seventh grade. Parents (52%) claimed they could best be helped in communicating with their teens by receiving a regular newsletter regarding teen sexual issues.

Adolescent↗
PubMed2000

Role of sympathetic nervous system and neuropeptides in obesity hypertension.

Obesity is the most common cause of human essential hypertension in most industrialized countries. Although the precise mechanisms of obesity hypertension are not fully understood, considerable evidence suggests that excess renal sodium reabsorption and a hypertensive shift of pressure natriuresis play a major role. Sympathetic activation appears to mediate at least part of the obesity-induced sodium retention and hypertension since adrenergic blockade or renal denervation markedly attenuates these changes. Recent observations suggest that leptin and its multiple interactions with neuropeptides in the hypothalamus may link excess weight gain with increased sympathetic activity. Leptin is produced mainly in adipocytes and is believed to regulate energy balance by acting on the hypothalamus to reduce food intake and to increase energy expenditure via sympathetic activation. Short-term administration of leptin into the cerebral ventricles increases renal sympathetic activity, and long-term leptin infusion at rates that mimic plasma concentrations found in obesity raises arterial pressure and heart rate via adrenergic activation in non-obese rodents. Transgenic mice overexpressing leptin also develop hypertension. Acute studies suggest that the renal sympathetic effects of leptin may depend on interactions with other neurochemical pathways in the hypothalamus, including the melanocortin-4 receptor (MC4-R). However, the role of this pathway in mediating the long-term effects of leptin on blood pressure is unclear. Also, it is uncertain whether there is resistance to the chronic renal sympathetic and blood pressure effects of leptin in obese subjects. In addition, leptin also has other cardiovascular and renal actions, such as stimulation of nitric oxide formation and improvement of insulin sensitivity, which may tend to reduce blood pressure in some conditions. Although the role of these mechanisms in human obesity has not been elucidated, this remains a fruitful area for further investigation, especially in view of the current "epidemic" of obesity in most industrialized countries.

Animals↗
PubMed1999

Frequency of fractures in women with systemic lupus erythematosus: comparison with United States population data.

OBJECTIVE: To describe the frequency of self-reported fractures in a large population-based cohort of women with lupus, to compare the frequency of self-reported fractures between lupus patients and women of similar age in the general population by use of data from the 1994 National Health Interview Survey (NHIS), and to describe the associated risk factors for fracture in women with lupus. This study is a secondary analysis of data collected to assess cardiovascular risk in women with lupus. METHODS: Fractures and associated risk factors were ascertained by self report in this retrospective cohort study of 702 living women with lupus who were followed up for 5,951 person-years. Self-reported fractures were verified in a subset of patients. A Weibull regression model was used to assess risk factors associated with time from lupus diagnosis to fracture in the univariate and multivariate analyses. Age-specific standard morbidity ratios (SMRs) were calculated to determine whether fracture occurrence was greater than expected in women with lupus. RESULTS: Eighty-six (12.3%) of 702 women reported at least 1 fracture following the diagnosis of lupus. The sites of the first fracture were the leg (n = 32), foot (n = 16), arm (n = 15), spine (n = 9), rib (n = 7), hip (n = 2), pelvis (n = 2), hand (n = 1), shoulder (n = 1), and finger (n = 1). Fracture risk was increased in the lupus cohort compared with women of similar age from the United States population, using weighted data from the 1994 NHIS (SMR 4.7; 95% confidence interval 3.8, 5.8). Variables in the univariate analysis that were significantly associated (P < 0.05) with time from lupus diagnosis to fracture were older age at lupus diagnosis, longer disease duration, longer duration of corticosteroid use, less use of oral contraceptives, and menopause status. In the multivariate analysis, independent determinants of time from lupus diagnosis to fracture were older age at lupus diagnosis and longer duration of corticosteroid use. CONCLUSION: Fractures occurred in 12.3% of lupus patients who were followed up for 5,951 person-years. There was nearly a 5-fold increase in fracture occurrence in the women with lupus compared with women from the US population. Older age at lupus diagnosis and longer use of corticosteroids were associated with time from lupus diagnosis to fracture. With increased life expectancy of lupus patients, fracture occurrence is a major threat to the health of these women. Prevention strategies must be directed toward minimizing the occurrence of fractures in these patients.

Adrenal Cortex Hormones↗