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Biomedical subjects

C McDonald

Publications and source records attributed to C McDonald.

At least 19 recordsLinked to original sources
PubMed2000

The Variability of Seyfert 1.8 and 1.9 Galaxies at 1.6 Microns.

We present a study of Seyfert 1.5-2.0 galaxies observed at two epochs with the Hubble Space Telescope (HST) at 1.6 µm. We find that unresolved nuclear emission from nine of 14 nuclei varies at the level of 10%-40% on timescales of 0.7-14 months, depending upon the galaxy. A control sample of Seyfert galaxies lacking unresolved sources and galaxies lacking Seyfert nuclei show less than 3% instrumental variation in equivalent aperture measurements. This proves that the unresolved sources are nonstellar and associated with the central parsecs of active galactic nuclei. Unresolved sources in Seyfert 1.8 and 1.9 galaxies are not usually detected in HST optical surveys; however, high angular resolution infrared observations will provide a way to measure time delays in these galaxies.

Journal Article↗
PubMed2000

Early and late environmental risk factors for schizophrenia.

Although a high proportion of liability to schizophrenia is under genetic control, a number of environmental risk factors have been identified. The earliest of these are complications of pregnancy and birth, though whether these cause or reflect disturbed brain development is not absolutely clear. Neurodevelopmental deviance is also indicated by neurological dysfunction, social, behavioural and cognitive deficits during childhood. Immigrant status is a significant risk factor, especially prominent among the African Caribbean population in England, though the mechanism is unknown. Later environmental risk factors include adverse life events and substance abuse. An additive model of multiple genetic and environmental risk factors of small effect may be too simplistic and an interactive model where genetic predisposition is compounded by environmental effects is more in keeping with current evidence. The nature of such interactions can be explored more fully when susceptibility genes for schizophrenia are identified.

Brain↗
PubMed2000

Minimal-model estimates of insulin sensitivity are insensitive to errors in glucose effectiveness.

The minimal-model method allows for estimation of insulin sensitivity (S(I) = P(3)/P(2)) and glucose effectiveness (S(G) = P(1)) from the time course of glucose and insulin after a glucose bolus. We previously demonstrated that the minimal-model results in overestimates of S(G) in subjects with normal insulin secretory function. To determine whether overestimation of S(G) has an impact on estimation of S(I), we examined model estimation of S(I) when S(G) was constrained to levels below that found by the regular minimal-model fit. Fifty-six glucose tolerance tests from lean and obese women, with and without polycystic ovary syndrome, were used. S(I) ranged from 0.2-22.6 x 10(-4) min(-1)/(microU/mL), and S(G) ranged from 0.8-3.8 x 10(-2) min(-1) for the standard minimal-model fits. Constraining S(G) to as low as 40% of the unconstrained value resulted in a 4-fold increase in P2 and P3, but only a 3% reduction in S(I). We conclude that estimation of the insulin sensitivity index is independent of errors in minimal-model-derived estimates of glucose effectiveness.

Adult↗
PubMed1999

Risk of breast cancer in women with palpable breast cysts: a prospective study. Edinburgh Breast Group.

BACKGROUND: 7% of women in the western world develop palpable breast cysts. Studies of the relation between cysts and breast cancer have conflicting results. There are two clearly defined types of cyst. We investigated whether one cyst type is associated with a higher rate of breast-cancer development than the other. METHODS: We studied 1374 women with palpable breast cysts presenting between 1981 and 1987, who had cysts aspirated between 1981 and 1989. Cysts were classified as type I if the sodium/potassium (Na+/K+) ratio in the cyst fluid was less than 3, or type II if the Na+/K+ ratio was 3 or more. Data on incidence of breast cancer were available until January, 1995, and we compared them with the expected numbers of cancers calculated from age-specific breast-cancer incidence in Scotland in 1988. FINDINGS: 65 cancers developed during follow-up. The overall standardised incidence rate of breast cancer in patients with palpable cysts was 2.81 (95% CI 2.17-3.59). The relative incidence rate was increased for all cyst types. The standardised incidence rate of developing breast cancer among women younger than 45 years was highest at 5.94 (2.97-10.63), with a significant trend for decreasing relative incidence rate with age (p<0.05). Women older than 54 years had a standardised incidence rate of 1.73 (0.86-3.10). The standardised incidence rate of breast cancer was highest in the first year after aspiration (7.02 [3.73-12.00]) but the risk was still raised after 5 years (2.68 [1.84-3.76]). INTERPRETATION: Women with breast cysts are at an increased risk of breast cancer, especially at younger ages. The type of cyst did not alter the associated relative incidence rate of breast-cancer development.

Adult↗
PubMed1999

CD34+-selected peripheral blood progenitor cell transplantation in patients with multiple myeloma: tumour cell contamination and outcome.

Thirty-six patients with multiple myeloma (23 PR1, nine PR2, four stable disease) were entered into a pilot study evaluating the use of CD34+-selected peripheral blood progenitor cell transplantation (PBPCT) following high-dose melphalan alone or high-dose melphalan and total body irradiation. Peripheral blood progenitor cells (PBPCs) were mobilized with cyclophosphamide and granulocyte colony stimulating factor (G-CSF). CD34+ selection using the Cellpro Ceprate-SC system was performed in 22 cases with an adequate yield in 20. 10 patients failed to mobilize sufficient cells to permit selection and in four cases selection was not performed for other reasons. 16 patients therefore received unselected PBPC. Tumour cell contamination was evaluated by IgH gene fingerprinting (fpPCR). Harvested PBPC were fpPCR positive in 13/20 CD34+-selected cases and remained positive after selection in seven. Harvested PBPC were studied in 9/16 patients receiving unselected cells; fpPCR was positive in five and negative in four. There was no difference in event-free survival (EFS) between the CD34+-selected group and the unselected group (median 21 and 26 months, respectively, P=ns). The CD34+-selection process therefore reduced contamination but did not eliminate it completely, and in this small non-randomized study there was no apparent clinical benefit of CD34+ selection.

Adult↗
PubMed1999

Lexical priming on Neely's (1977) paradigm in Parkinson's disease: where do we stand?

In two published studies, we used a variant of Neely's (1977) lexical decision paradigm to study shifts of attention and automatic lexical activation in nondemented individuals with Parkinson's disease (McDonald, Brown, & Gorell, 1996; Spicer, Brown, & Gorell, 1994). Arnott and Chenery (in press) noticed differences between Neely's results and the results we observed in our control group that raise questions about some of the conclusions presented in the McDonald et al. (1996) and Spicer et al. (1994) papers. Even when considering the important differences between Neely's (1977) results and those in our control groups, we argue that our results support the conclusions of normal automatic semantic activation and deficient set-shifting in Parkinson's disease. We also introduce the notion of generalized priming to account for some of the priming effects observed in our studies.

Adult↗
PubMed1999

Cooperation of the transcriptional coactivators CBP and p300 with Stat6.

Interleukin-4 (IL-4) functions as a critical regulatory cytokine of the immune response. A major effect of IL-4 is the induction of specific gene expression mediated by activation of a latent transcription factor, Stat6. To understand the mechanism by which Stat6 induces gene transcription, the effects of two histone acetylase coactivators, CREB binding protein (CBP) and p300, were evaluated. Both CBP and p300 were found to cooperate with Stat6 for induction of Stat6-dependent transcription. This cooperation does not appear to be due to acetylation of Stat6. The adenoviral E1A oncoprotein, known to bind CBP and p300, can inhibit the ability of CBP and p300 to function as coactivators of Stat6. The cooperative effect of CBP and p300 depends on the presence of a carboxyl-terminal region of Stat6. Stat6 molecules lacking this region behave as negative interfering molecules for Stat6-dependent transcription. Point mutations within this region also affect transcription by Stat6 in response to IL-4, identifying a motif that appears to be required for transcription, possibly through functional cooperation with CBP/p300.

Acetylation↗
PubMed1999

Double blind, randomised, placebo controlled, crossover, multicentre study to determine the efficacy of a 0.1% (w/v) sodium hyaluronate solution (Fermavisc) in the treatment of dry eye syndrome.

BACKGROUND/AIMS: Hyaluronan (sodium hyaluronate) has been shown to confer objective and subjective improvement in patients with dry eye syndrome. This study compared the efficacy and safety of a 0.1% solution of hyaluronan with 0.9% saline, when administered topically to the eye, in the treatment of symptoms of severe dry eye syndrome. METHODS: A randomised, double blind, crossover clinical trial in which subjects were randomised to receive either hyaluronan or saline, applied as one or two drops to the eye, three or four times a day or as required. After 28 days' treatment, subjects crossed over to the other study medication for a further 28 days' treatment. RESULTS: 70 subjects were included in the analyses of efficacy and significant improvements in Schirmer's score (p=0.0006) and rose bengal staining score (p=0.0001) were observed during treatment with hyaluronan. In a subjective assessment of the effectiveness of two treatments, a majority of subjects felt that hyaluronan was more effective than saline in alleviating the symptoms of burning and grittiness (p<0.001). No adverse events attributable to hyaluronan treatment were reported. CONCLUSION: The study demonstrates a clear benefit of hyaluronan over saline, in both subjective and objective assessments of dry eye syndrome. Hyaluronan was shown to be well tolerated.

Adult↗
PubMed1999

Validity of the Dementia Rating Scale in assessing cognitive function in Parkinson's disease.

Two studies examined the validity of the Dementia Rating Scale (DRS) as a measure of cognitive functioning among patients with Parkinson's disease (PD). The DRS accounted for more variation in the level of cognitive functioning of PD patients than either the Mini-Mental Status Examination or a battery of tests selected to assess specific cognitive deficits associated with PD. Further, DRS subtests displayed strong convergent and discriminant validity with a comprehensive Criterion Neuropsychology Battery. The DRS subtests appear to be valid measures of attention, perseveration, conceptualization, and memory among PD patients. However, the DRS-Construction subtest should be supplemented with additional visuoconstructional items to provide a thorough screen of cognitive functioning in PD. Although about three-quarters of nondemented PD patients did not appear to have any specific cognitive deficits on the DRS, the remaining patients were impaired on the Construction or Initiation/Perseveration subtests of the DRS. In summary, the DRS is a valid mental status screening test of cognitive functioning for individuals with PD.

Aged↗
PubMed1999

Spinal sonography and magnetic resonance imaging in patients with repaired myelomeningocele: comparison of modalities.

The goals of this study were to evaluate the feasibility of using ultrasonography of the spine in the follow-up evaluation of patients with repaired myelomeningocele at birth and to compare sonography with the accepted modality of magnetic resonance imaging. Over a period of 4 years we performed 165 sonographic studies in 101 patients; 107 sonographic studies had MR imaging results for comparison. We collected our data prospectively. The quality of the sonograms was good in 110 of 129 studies, acceptable in 17 of 129, and poor in two of 129. The sonographic examinations failed in 33 of 165 studies (20%). Concordant information was obtained between ultrasonography and magnetic resonance imaging in the following percentage of studies: level of the distal end of the cord in 82%, position of the cord in the canal in 59%, presence of hydromyelia in 63%, cord duplication in 96%, adhesions in 16%, intradural mass in 37%, cord measurements in 85%, and dural sac measurements in 83%. At the lumbosacral level, we saw no cord pulsation in 57% of the studies in patients with cord adhesions and in 20% of those without adhesions. At the lower thoracic level, we saw no pulsation in 35% of the studies in patients with cord adhesions and in 7% of those without adhesions. Postoperative studies of cord release surgery in eight patients showed varied findings. We conclude that in those patients who have a spinal defect or interlaminar space allowing proper visualization of the lumbosacral spinal canal, ultrasound can provide fairly similar information to that obtained with magnetic resonance imaging of that area with no need for sedation and at a reduced cost. Ultrasonography seems more sensitive than magnetic resonance imaging in the detection of cord adhesions, which is particularly relevant in the diagnosis of tethering.

Adolescent↗
PubMed1999

Promoting the power of nursing identity.

As a group, nurses have traditionally expressed ambivalence toward feminists and have at times even distanced themselves from the feminist movement. The reason is obvious: Feminists have focused much of their energy on the non-traditional fields of work for women, with the result that women in traditionally female occupations such as nursing and teaching have felt ignored and even silently chastized by feminists.

Canada↗
PubMed1998

Re-evaluating the role of His-143 in the mechanism of type I dehydroquinase from Escherichia coli using two-dimensional 1H,13C NMR.

Type I dehydroquinase from the shikimate pathway of Escherichia coli dehydrates dehydroquinate to dehydroshikimate. pH/log Vmax profiles of the enzyme indicate the presence of a single ionizing group with a pKa of 6.2. Chemical modification experiments with diethyl pyrocarbonate have identified the conserved residue His-143 as essential for catalysis in this enzyme and the pKa for this modification is also 6.2, implying that this is the single ionizing residue in dehydroquinase that may be acting as a general base in the catalytic mechanism. Subsequent mutagenesis of this residue (Leech, A. P., James, R., Coggins, J. R., and Kleanthous, C. (1995) J. Biol. Chem. 270, 25827-25836) further suggested that His-143 may be involved in Schiff base formation/breakdown as well as being the proton abstracting general base. The importance of this residue was confirmed by recent x-ray crystallographic data showing His-143 to be at the center of a hydrogen-bonded triad, flanked by the essential Schiff base forming residue Lys-170 and Glu-86. In the present study, we have used mutagenesis and 1H and 13C NMR to assign the resonance of His-143 and probe its ionization state to define more precisely its role in the mechanism of type I dehydroquinase. Following isotopic enrichment of wild-type and H143A dehydroquinase enzymes with [2-13C]histidine, the resonance for His-143 was assigned by comparing their 1H,13C heteronuclear single quantum correlation NMR spectra. pH titrations revealed that whether in the liganded or unliganded state, His-143 does not ionize over the pH range 6-9.5 and so cannot possess a pKa of 6.2. The NMR data are consistent with this residue remaining unprotonated at pH values optimal for the activity of this enzyme (pH > 7). The role of His-143 is re-evaluated in light of these and the recent structural data, and an alternative candidate for the pKa of 6.2 is discussed.

Carbon Isotopes↗
PubMed1998

A high-performance liquid-chromatographic assay for amphotericin B in a hydrophilic colloidal paste base.

A stability-indicating high-performance liquid-chromatographic (HPLC) assay has been developed for amphotericin B (AmB) in a paste, containing AmB, tobramycin (or gentamicin) sulphate, colistin sulphate, liquid paraffin and Orabase. Extraction of AmB was performed by partitioning the antibiotic between N,N-dimethylformamide (DMF) and cyclohexane, which led to precipitation of the polymeric materials and extraction of the liquid paraffin into the cyclohexane and AmB into the DMF. Analysis by HPLC of the latter layer gave a linear relationship between concentration and peak area response for the AmB over the range 5.0 x 10(-4) to 7.5 x 10(-3)% (w/v) (r = 0.9995) with a relative standard deviation of +/- 1.46% (n = 8). The efficiency of extraction was 1006 +/- 2.4% (n = 5).

Amphotericin B↗
PubMed1998

Prevention of precipitation of phenytoin in an infusion fluid by hydroxypropyl beta-cyclodextrin.

Injection of phenytoin is often diluted with infusion fluids before administration, which may lead to precipitation of the drug due to changes in pH and/or vehicle. It is not possible to add cyclodextrins to the original injections to prevent precipitation of the drug, because the quantities required would be impractical (>100% w/v). However, from a knowledge of the solubility of phenytoin in cyclodextrin solutions, it is possible to add sufficient amounts of a soluble cyclodextrin to infusion fluids to maintain the solubility of phenytoin after the original injection is diluted to clinical concentrations in the fluid. From solubility measurements, theoretical amounts of hydroxypropyl beta-cyclodextrin (HPCD), sufficient to prevent precipitation of phenytoin, were added to 0.9% w/v sodium chloride solution, adjusted to pH 7.0. Phenytoin injection was diluted to clinical concentrations in the cyclodextrin/NaCl solutions. The mixtures, together with analogous mixtures containing phenytoin, but no HPCD, were stored at 25 degrees C for 3 days. In the presence of the cyclodextrin no precipitates of phenytoin were observed, but in its absence an immediate massive precipitation of phenytoin occurred. This is a flexible method for using soluble cyclodextrins to prevent precipitates of drugs in infusion fluids, provided the cyclodextrin used is not toxic.

2-Hydroxypropyl-beta-cyclodextrin↗