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Biomedical subjects

D O'Neill

Publications and source records attributed to D O'Neill.

At least 91 records · Page 5Linked to original sources
PubMed1995

Management knowledge and skills required by U.K. and U.S. medical directors.

A survey was undertaken of the medical directors of National Health Service trusts in the South Thames Regional Health Authority of the United Kingdom. The purpose of the survey was to ascertain medical directors' views regarding the importance of various areas of administrative practice, their preparedness in these areas of administrative knowledge prior to taking up their roles as medical directors, and their views as to the body of knowledge required for future medical directors. The study was compared with a similar study undertaken in the United States. While there were many areas of agreement between the English and the American medical administrators, there were also areas of significant differences of opinion. The need to develop a recognized training program in medical administration is acknowledged.

Data Collection↗
PubMed1994

Evidence for a globin promoter-specific silencer element located upstream of the human delta-globin gene.

We describe the negative regulatory activity of a 1.7 kilobase (kb) region (R) in the human beta-globin locus located between 4.0 and 2.3 kb upstream of the delta-globin gene capsite, using a transient assay with the chloramphenicol acetyltransferase (CAT) reporter gene in mouse erythroleukemia (MEL) cells. The R region is deleted in most cases of deletion hereditary persistence of fetal hemoglobin (HPFH), but is unaffected in most delta beta zero-thalassemias. However, no experiments addressing its function in globin gene expression have been reported to date. We show that R inhibits CAT expression of constructs containing a fetal (gamma) or adult (beta) globin gene promoter, but does not affect expression of similar constructs using a non-globin (SV40) promoter. The inhibitory effect on the beta-globin promoter can be localized to a 651 bp sub-region of R. For the gamma-globin promoter, no sub-region of R can reproduce the level of inhibition associated with the entire region.

Animals↗
PubMed1994

Evidence for a lactate-anion exchanger in the rat jejunal basolateral membrane.

BACKGROUND/AIMS: The mechanism by which lactate, absorbed from the intestinal lumen or generated within the epithelium, crosses the basolateral membrane of the enterocyte and enters the bloodstream has not previously been characterized in detail. METHODS: L-lactate uptake into and efflux from isolated jejunal basolateral membrane vesicles was investigated at room temperature using rapid filtration techniques. RESULTS: Furosemide sensitive uptake of L-lactate was unaffected by cis sodium or proton gradients but could be stimulated by a trans gradient of bicarbonate and chloride. Kinetic analysis showed uptake to consist of a saturable component with a Michaelis constant (Km) of 3.2 mmol/L and a maximum velocity (Vmax) of 67 pmol.mg protein-1 x s-1 and a nonsaturable alpha-4-hydroxy-cinnamic acid insensitive component. Pyruvate, butyrate, acetate, valerate, and propionate competitively inhibited lactate uptake into the vesicles. Efflux of lactate from preloaded vesicles was furosemide sensitive and accelerated by a trans bicarbonate gradient as well as by 10 mmol/L acetate, butyrate, and pyruvate. CONCLUSIONS: It is concluded that there is a short chain-fatty acid carrier system in the intestinal basolateral membrane, which operates as an anion exchanger.

Animals↗
PubMed1994

Synergistic liver toxicity of copper and retrorsine in the rat.

To investigate the possible synergy between copper and retrorsine (a pyrrolizidine alkaloid) as a cause of Indian Childhood Cirrhosis, four groups of male Wistar rats were fed the following diets from weaning: A. Normal diet; B. Copper loaded (2 g CuSO4/kg diet); C. Retrorsine supplemented (Expt 1:25 mg/kg body weight/week by gavage, Expt 2:25 mg/kg food initially then 15 mg/kg food after 4 weeks); and D. Copper and retrorsine as above. Serial plasma samples were assayed for aminotransferases, albumin and bilirubin. Liver samples at biopsy and sacrifice provided samples for copper analysis and histology. Results showed that copper and retrorsine together significantly increased liver damage compared with feeding either alone as assessed by: 1. Increased mortality rate; 2. Decreased plasma albumin and increased plasma bilirubin (mainly conjugated) indicative of hepatocyte dysfunction; 3. Massive liver copper accumulation, and 4. Increased liver damage histologically. Thus retrorsine caused liver copper accumulation, and together copper and retrorsine led to severe hepatic dysfunction, characterised by hypoalbuminaemia and conjugated hyperbilirubinaemia. Plant alkaloids secreted in milk by grazing animals and copper from brass vessels may together produce Indian Childhood Cirrhosis.

Animals↗
PubMed1994

Sources of variance in ocular microtremor.

This study presents a preliminary investigation of the sources of variance in the measurement of ocular microtremor frequency in a normal population. When the results from both experienced and relatively inexperienced operators are pooled, factors that contribute significantly to the total variance include the measurement procedure (p < 0.001), day-to-day variations within subjects (p < 0.001), and inter-subject differences (p < 0.01). Operator experience plays a role in determining the measurement precision: the intra-subject coefficient of variation is about 5% for a very experienced operator, and about 14% for a relatively inexperienced operator.

Adult↗
PubMed1994

Iatrogenic lateral rectus palsies. A series of five postmyelographic cases.

The objective of this study was to assess the etiology of lateral rectus palsies in patients undergoing lumbar myelograms with Iopamidol (Isovue; ER Squibb and Sons, Princeton, NJ, USA; Niopam, E Merc, UK.). An audit of the departmental orthoptic record revealed two patients who had suffered abducens palsies after myelograms. A further search revealed three additional patients who had suffered similar complications. The incidence of abducens palsy in patients undergoing myelography with the contrast agent Iopamidol was found to be 1 in 500 in around 2,500 myelograms performed under standard conditions. It would appear that lateral rectus palsy in myelography is the result of the lumbar puncture, the neurotoxic effect of the contrast agent, or a combination of the two in patients with an already compromised neurophysiologic state. This is the first series to associate this problem with Iopamidol. Although usually a serious neurologic symptom, when associated with contrast myelography using Iopamidol it is important to appreciate that such symptoms usually resolve of their own accord.

Abducens Nerve↗
PubMed1993

In vitro transcription from the human A gamma-globin gene promoter.

We report enhanced transcription from the human A gamma-globin gene promoter in nuclear extracts (NE) of erythroleukemia (K562) cells compared with that in HeLa NE. We do not observe differences in transcription levels in the two extracts with nonglobin promoter templates. Our findings, indicating preferential recognition of the globin gene promoter by nuclear factors in K562 cells, are consistent with results of studies previously reported by ourselves and others. A novel finding described here is that the addition of a double-stranded octamer motif oligonucleotide to K562 NE increases the level of transcription from the A gamma-globin gene promoter, suggesting a potential role for an octamer motif-binding factor in the repression of A gamma-globin gene transcription. A cosmid construct containing extensive human gamma- and beta-globin gene promoter and structural sequences as well as upstream control sequences also exhibits higher levels of globin gene transcription in K562 NE than in HeLa NE. Our demonstration of the feasibility of efficient, globin promoter-specific in vitro transcription of this complex template offers a novel approach for the systematic analysis of the effects of putative regulatory factors on globin gene expression in vitro in the context of a genetic environment approximating that found in vivo.

Base Sequence↗
PubMed1993

Lack of clinical utility of cytomegalovirus blood and urine cultures in patients with HIV infection.

OBJECTIVE: To determine the clinical significance of cytomegalovirus (CMV) blood and urine cultures in patients with human immunodeficiency virus (HIV) infection. DESIGN: Inception cohort of patients with HIV infection and CMV culture data. SETTING: Government referral-based research hospital. PATIENTS: A total of 322 HIV-infected patients who had a CMV blood culture and 293 HIV-infected patients who had a CMV urine culture within 7 days of a CD4 determination. MEASUREMENTS: Cytomegalovirus blood and urine culture results; circulating CD4 lymphocyte counts; pathologic or retinopathic findings of CMV disease. RESULTS: Nine of 26 patients (34.6%) with CMV viremia subsequently developed CMV end-organ disease compared with 11 of 74 (14.9%) patients without viremia, (difference, 19.7%; 95% CI, -0.3% to 39.7%). Fifteen of 47 patients (31.9%) with CMV viruria developed end-organ disease compared with 4 of 43 (9.3%) patients without viruria, (difference, 22.6%; CI, 6.7% to 38.5%). Cytomegalovirus culture positivity had poor predictive value for the subsequent development of end-organ disease (35% for viremia and 28% for viruria). Further, patients with proven end-organ disease were often not viremic (45%), but most were viruric (88%). Cytomegalovirus viremia did not correlate with the presence of either fever or weight loss in this patient group. Both blood culture positivity and urine culture positivity varied inversely with the CD4 count (P = 0.0001 for both associations). CONCLUSIONS: The likelihood that a blood or urine culture will be positive in a patient with HIV infection correlates better with immunologic status than with current or future clinical status. Although the absence of CMV viruria may suggest that CMV disease is not present, CMV blood and urine cultures have poor diagnostic and predictive value and therefore should be used primarily for research purposes or drug susceptibility testing and not for making clinical decisions.

Adult↗
PubMed1993

Ergonomics aspects of crop production in tropical developing countries: a literature review.

Little is known about the extent to which ergonomics factors limit manual crop production operations in developing countries. This paper presents the findings of a review of the ergonomics literature, performed to identify and quantify such constraints in the tropics. Most of the literature reviewed reported studies of land preparation and weeding tasks. The practical application of the data from many of the studies was found to be limited. However, there was sufficient evidence to show that the use of different handtools to carry out a given task could influence the physiological cost incurred by the user, and that some tools performed more effectively than others in the completion of that task. This indicates that the application of ergonomics principles has the potential to relieve at least some of the drudgery associated with agricultural tasks carried out by resource-poor farmers in the tropics. The review highlights the need for a more comprehensive methodological and participative approach, and outlines a number of issues to be addressed in future research.

Journal Article↗
PubMed1993

Immunogenicity and adverse reactions of influenza vaccination in elderly patients given acetaminophen or placebo.

The objective was to examine the antibody responses to influenza immunization in an elderly population and the effect of prophylactic acetaminophen on adverse responses due to inactivated whole virus vaccine containing influenza A (H3N2 and H1N1) and B antigens. During the autumn of 1990, 100 patients 65 years or older were immunized and randomly allocated to receive placebo or 1,950 mg (2 x 975 mg) of acetaminophen. They recorded any local and systemic side effects over a 3-day period. Serology was performed on pre- and post (4-6 weeks) -vaccination sera. Age and gender distribution in the study were: 47% who were 75 years or older, and 61% of the patients were female. Most of the patients (97%) had pre-existing antibodies to Influenza A or B. Average peak preimmunization antibody titers were 40 to B Yamagata and A Taiwan (H1N1) and 80 for A Shanghai (H3N2). Half of each treatment group had a 4-fold or greater rise in antibody titer in response to the vaccine. Only 30% of patients immunized the previous year but 80% of those never vaccinated previously demonstrated a 4-fold or greater serological response to the vaccine. However, measurement of protection rates (HI >/= 40) before and after vaccination indicated 81.1-100% protection for the 3 viruses not influenced by treatment, gender or a history of previous vaccination. Both treatment groups had equally small numbers of patients who recorded systemic symptoms of drowsiness, myalgia, fever and chills and about 50% had arm soreness. Although about 80% of previously unimmunized adults mounted a 4-fold antibody rise to influenza vaccine antigens whereas booster effects were seen in only 30% of those immunized the previous year, protection rates were high (81-100%) after immunization and were not affected by acetaminophen treatment. Adverse effects (15% systemic and 50% local) were not ameliorated by 1950 mg of acetaminophen in these elderly patients.

Journal Article↗
PubMed1993

An evaluation of the efficacy and safety of tetrahydroaminoacridine (THA) without lecithin in the treatment of Alzheimer's disease.

Seventy-nine patients with probable Alzheimer's disease were enrolled into a double-blind, placebo-controlled cross-over study to assess the therapeutic effect and safety of THA (tetrahydroaminoacridine; tacrine) without concomitant lecithin administration. Forty-one patients completed the trial which consisted of two 12-week treatment phases separated by a 4-week wash-out period. Twenty-six subjects were withdrawn during the active treatment phase, mostly because of elevated transaminases or cholinergic side-effects, and ten during treatment with placebo. Statistical analyses were conducted on two groups of patients; those completing the cross-over and those with at least one evaluation in the first treatment period. This latter analysis, using the last observation carried forward was used to approximate an intention-to-treat analysis. THA was favoured over placebo in all three primary outcome measures (MMSE, ADAS Non-cognitive Scale, and the Functional Life Scale), but the results did not reach statistical significance. THA was favoured over placebo in five of the seven secondary outcome measures, but for only two of these was statistical significance attained. In terms of a three-point or greater increase in MMSE score, three to four times as many subjects improved on THA as on placebo.

Activities of Daily Living↗