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D O'Neill

Publications and source records attributed to D O'Neill.

At least 55 records · Page 3Linked to original sources
PubMed1999

Tissue-specific and developmental stage-specific DNA binding by a mammalian SWI/SNF complex associated with human fetal-to-adult globin gene switching.

SWI/SNF complexes in yeast and higher eukaryotes are thought to facilitate gene activation and transcription factor binding by disrupting repressive chromatin structures. Little is known, however, about how these complexes target specific genes for activation. We now have purified a specialized SWI/SNF-related complex (PYR complex) from murine erythroleukemia (MEL) cell nuclear extract that binds pyrimidine-rich elements at the human and murine beta-globin loci. PYR complex DNA-binding activity is restricted to definitive hematopoietic cells and is both DNA sequence- and length-dependent. Mass spectrometric identification of purified peptides and antibody supershift assays indicate that PYR complex contains at least four known mammalian SWI/SNF subunits: BAF57, INI1, BAF60a, and BAF170. PYR complex broadly footprints a 250-bp pyrimidine-rich element between the human fetal and adult beta-globin genes. A short intergenic deletion that removes this element from a human globin locus cosmid construct results in delayed human fetal-to-adult globin gene switching in transgenic mice. Taken together, the data suggest that PYR complex may act through this intergenic element to facilitate human fetal-to-adult globin gene switching, presumably by opening the locus in the region of the adult genes to permit the binding of beta-globin transcriptional activators.

Animals↗
PubMed1999

The allopurinol load test lacks specificity for primary urea cycle defects but may indicate unrecognized mitochondrial disease.

Thirty-three children ranging from 2 weeks to 12 years of age were selected for allopurinol loading, 16 on the basis of an increased urinary ourotate excretion detected by routine organic acid analysis (group A), and 17 for clinical reasons suggesting a urea cycle defect (group B). The allopurinol load test proved positive in 13 of 16 patients from group A, mean peak orotate 64.0 mumol/mmol creatinine (upper limit of reference range, 13.2) and 11 of 17 patients from group B, mean peak orotate 41.0 mumol/mmol creatinine (upper limit of reference range, 13.2). Thorough investigation of these patients including urinary and plasma amino acid analysis and, in 17 cases, liver biopsy for histology and measurement of ornithine carbamyltransferase (OCT) and carbamyl-phosphate synthetase (CPS) activity failed to identify any evidence of a urea cycle disorder. However, muscle biopsies performed in 11 patients showed some evidence of mitochondrial disease in four cases, two defined on the basis of reduced respiratory chain enzyme activity and two on the basis of mtDNA abnormalities. These findings indicate that an increased excretion of orotate in sick children may not be uncommon and that a positive allopurinol load test result may not indicate a specific inherited urea cycle defect. In addition, these results raise the interesting possibility that defective ureagenesis may be a feature of mitochondrial disease in some individuals.

Allopurinol↗
PubMed1999

Factors associated with prolonged symptoms and severe disease due to Clostridium difficile.

OBJECTIVE: toxigenic Clostridium difficile is responsible for a spectrum of disease severity ranging from mild diarrhoea to fulminant colitis. This study attempts to determine the proportion of patients in each category of severity and evaluate the risk factors for a more prolonged and complicated course. DESIGN: prospective cohort study. SETTING: university teaching hospital. SUBJECTS: all patients with symptomatic C. difficile infection during 4 months of an outbreak (January-April 1995); n=73; median age 74 years (range 17-91). MEASUREMENTS: incidence of C. difficile-associated disease (CDAD); severity of disease; percentage of patients in each category of severity; risk factors for severe disease/prolonged symptoms (univariate and multivariable analyses). RESULTS: the incidence of CDAD was 0.93%. Of the cases identified, 18 (24.7%) had mild, self-limiting disease; 26 (35.6%) had moderately severe disease; 23 (31.5%) had prolonged symptoms and six (8.2%) had a complicated course. Although CDAD was more common in older patients (P < 0.001), increasing age was not a risk factor for severity. Significant risk factors for severe CDAD included low Barthel and abbreviated mental test scores (P < 0.01, P < 0.001 respectively) and recent endoscopy (P=0.03). Logistic regression analysis revealed the following independent predictors of severe CDAD: endoscopy [odds ratios (OR) 4.0, P=0.03] and cognitive impairment (OR 11.0, P < 0.01). A trend towards significance was noted for nasogastric tube insertion (OR 3.1, P=0.08). Complications of infection included dehydration, malnutrition and faecal incontinence (which was statistically significantly associated with more severe disease; P < 0.01). CONCLUSION: risk factors for severity of CDAD include functional disability, cognitive impairment, and recent endoscopy. Anticipation of severe CDAD may limit morbidity and mortality.

Adolescent↗
PubMed1999

The association between demographic factors, disease severity and the duration of symptoms at clinical presentation in elderly people with dementia.

OBJECTIVE: To determine the association between factors unrelated to the disease process, the duration of symptoms and the degree of cognitive or functional impairment in elderly patients presenting with dementia. METHOD: The living situation, educational level, age, gender and diagnosis based on standardized criteria were recorded for 209 elderly patients presenting to a memory clinic with dementia. Cognitive and functional deficits were measured with the cognitive section of the Cambridge Mental Disorders of the Elderly Examination combined with the Mini-Mental State Examination and the abbreviated version of the Blessed dementia scale, respectively. RESULTS: 129 patients had a diagnosis of probable Alzheimer's disease, 19 had probable ischaemic vascular dementia and 61 had mixed dementia. There was no effect of diagnosis on duration of symptoms or dementia severity at the time of presentation. Patients living with a son or daughter were more functionally impaired than those living alone or with a spouse. Males had higher cognitive scores but did not have milder functional deficits. Patients with only a primary-school education had a trend towards lower cognitive scores at presentation but did not have more functional deficits. CONCLUSIONS: The gender of the patient and the relationship to the carer are associated with cognitive and functional scores at the time of presentation in patients with dementia.

Age Factors↗
PubMed1998

Community-acquired Clostridium difficile infection.

Clostridium difficile-associated disease (CDAD) is primarily a nosocomial condition. Community-acquired disease has been reported but the incidence is felt to be low and the rate of disease resulting in hospitalization is reported as negligible. We recently experienced a 6-month outbreak of CDAD (January to June 1995): 139 patients were involved and four deaths were attributable to pseudomembranous colitis. Early in the outbreak period we were aware that many new admissions presented with C. difficile cytotoxin B positive diarrhoea: in some cases this was the sole reason for hospitalization. This observation forms the basis of this report.

Adult↗
PubMed1998

Simultaneous outbreaks of two strains of toxigenic Clostridium difficile in a general hospital.

We report an outbreak of Clostridium difficile-associated disease (CDAD) in a large Dublin hospital. From January to June 1995, inclusive, 139 patients were affected; the mean age of cases was 68.8 +/- 19 years. Clinical information is available for 73 cases identified during the first four months of the outbreak. The majority of patients presented with abrupt onset of watery diarrhoea; however, 19.2% presented with an unexplained pyrexia following a course of antimicrobial therapy and 5.5% presented with a surgical acute abdomen. Twenty patients (27.4%) experienced relapsing disease and seven (9.6%) patients died. Seventy-six percent of cases received a cephalosporin prior to the onset of disease, the highest relative risks occurring with third-generation agents; however, 9.6% of patients affected had not been exposed to antimicrobial therapy in the preceding eight weeks. Pyrolysis mass spectrometry identified two clusters of isolates, representing two strains of C. difficile. There was marked spatial clustering of these strains, with each confined to a separate area of the hospital. Infection control measures and an antibiotic policy were introduced. Throughout the outbreak period the use of the most frequently used cephalosporin in the hospital increased; this was accompanied paradoxically by a reduction in the number of new cases of CDAD.

Aged↗
PubMed1998

Sensitization to human leukocyte antigen before and after the introduction of erythropoietin.

INTRODUCTION: Antibodies directed against human leukocyte antigens (HLAs) impact adversely on renal transplantation. Measures aimed at preventing such antibody formation are thus important. The introduction of recombinant human erythropoietin (rHuEpo) has permitted the reduction of blood transfusion in patients with chronic renal failure. The impact of rHuEpo on the incidence of sensitization in patients awaiting transplantation was therefore studied. METHODS: A retrospective analysis of the patients awaiting transplantation before (group A) and 4 years after (group B) the introduction of rHuEpo was performed in order to ascertain changing patterns in the use of blood transfusion and causes of sensitization. RESULTS: The total number of transfusions administered to haemodialysis patients decreased by 34% during the study period. This was accompanied by a significant reduction in the ratio of blood transfusion to haemodialysis treatment episodes (0.095 in group A to 0.06 in group B, P = 0.001). The number of patients sensitized as a consequence of blood transfusion decreased from 63% in group A to 28% in group B (P = 0.0004). The overall incidence of sensitization decreased from 50% in group A to 36.5% in group B (P = 0.008). This decrement was associated with a significant reduction in the mean waiting time for transplantation (42.1 +/- 1.1 vs 15.4 +/- 2.4 months, P < 0.0001). The incidence of sensitization due to previous transplantation increased during the study period from 41% in group A to 77% in group B, (P = 0.0004). There was no change in the number of patients sensitized due to pregnancy. CONCLUSION: The introduction of rHuEpo has resulted in a significant decrease in the requirements for blood transfusion among patients awaiting transplantation and is associated with a significant reduction in transfusion-related sensitization and mean waiting time for transplantation.

Blood Transfusion↗
PubMed1998

Basolateral D-glucose transport activity along the crypt-villus axis in rat jejunum and upregulation induced by gastric inhibitory peptide and glucagon-like peptide-2.

Phloridzin-insensitive D-glucose uptake into enterocytes isolated sequentially from along the crypt-villus axis showed the majority of transport activity to reside in cells from the upper third of the villus. In contrast, total postnuclear glucose transporter 2 (GLUT2) protein content of the cells was high even close to the crypt and was almost constant for the upper 80% of the villi. A 4 h lumenal perfusion in vivo with 100 mM D-glucose prior to harvesting the enterocytes produced a 2- to 3-fold increase in phloridzin-insensitive D-glucose uptake which extended down 70% of the villus. Vascular infusion in vivo with either 800 pM gastric inhibitory polypeptide (GIP) or glucagon-like peptide-2 (GLP-2) prior to harvesting enterocytes produced the same response as lumenal glucose, while glucagon like peptide-1 (GLP-1) had no effect. Inclusion of 30 microM brefeldin A (BFA), an inhibitor of protein trafficking, in the lumenal perfusate produced a small, but not significant, increase in the control uptake profile along the villus in isolated enterocytes. However, BFA significantly reduced the upregulation induced by lumenal glucose and vascular GIP and blocked the stimulation produced by vascular GLP-2. Biotinylation of surface proteins and isolation with protein A indicated that there was no change in the membrane abundance of GLUT2 after GLP-2 treatment. These results are discussed in relation to the role of gastrointestinal peptide hormones in controlling intestinal hexose transport and the possibility of protein trafficking being involved in mediating the upregulation of GLUT2 activity in the enterocyte basolateral membrane.

Animals↗
PubMed1997

Dementia and driving: an attempt at consensus.

The number of older drivers in Sweden will be rapidly increasing during the next decades. A possible relationship exists between the increased relative crash risk of older drivers and the prevalence of age-related diseases such as dementia. However, a clear-cut policy for evaluating driving competence in demented persons is still lacking. In recognition of this fact, the Swedish National Road Administration invited a group of researchers to formulate a consensus on the issue of driving and dementia. This consensus document is aimed at providing primary care physicians with practical advice concerning the assessment of cognitive status in relation to driving. Suggestions are based on a review of existing research and discuss the use of general and driving-specific sources of information available to the physician. Consensus was reached on the statement that a diagnosis of moderate to severe dementia precludes driving and that certain individuals with mild dementia should be considered for a specialized assessment of their driving competence.

Aged↗
PubMed1997

Botulinum toxin in fourth nerve palsies.

BACKGROUND: Botulinum toxin A (BTXA) has not been used routinely in the management of fourth nerve (IV N) palsy. However, it is known that the results of surgery can be unpredictable with a risk of over- or under-correction. METHODS: The results were reviewed of 20 patients, aged 19-70 years, with unilateral and bilateral IV N palsies who received BTXA injections to the inferior oblique or inferior rectus muscles. The aetiology was congenital in 12 (60%), traumatic in six (30%), due to myasthenia in one (5%), and unclear in one (5%). Fifty per cent of patients had had previous strabismus surgery to a maximum of four procedures. The mean pre-injection vertical deviation was 11 prism dioptres. All but two patients had a single injection. Average follow-up was 19 months. RESULTS: Ten patients (group I) received BTXA as a primary therapy. Following inferior oblique injection, six patients received little benefit and went on to surgery (83%) or continued with prisms (17%). Five patients from group I who had inferior rectus toxin were discharged symptom-free. Group 2 (10 patients) received BTXA for residual deviations postoperatively; in this group all except one patient with no fusion achieved long-term benefit following inferior rectus BTXA. In those who had inferior oblique injections, BTXA was useful in one patient (25%). Inferior rectus injection produced a greater chance of temporary reversal of the deviation. CONCLUSIONS: BTXA is of greatest benefit in patients with residual deviations particularly when the inferior rectus is injected, but is of limited value as a primary therapy in chronic IV N palsy.

Adult↗
PubMed1997

Logistics of performing an ophthalmic assessment in elderly inpatients.

To assess the feasibility of performing an ophthalmic assessment on elderly inpatients, we examined 48 patients over 75 years of age who were consecutively admitted to an acute elderly-care ward. Difficulties were encountered in 35 patients (73%). By employing simple methods to overcome these problems, useful information was obtained in all cases and the time taken to complete the examination ranged from six to 20 minutes (mean 7.5 minutes). Doctors looking after elderly patients should be encouraged to assess visual function and must not be deterred by anticipated logistical difficulties.

Aged↗