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Biomedical subjects

D A Stewart

Publications and source records attributed to D A Stewart.

At least 19 recordsLinked to original sources
PubMed1992

Terodiline causes polymorphic ventricular tachycardia due to reduced heart rate and prolongation of QT interval.

Recent reports have suggested an association between terodiline hydrochloride and cardiac arrhythmias. We report 4 patients presenting over a six month period who developed polymorphic ventricular tachycardia (polymorphic VT) while receiving treatment with this agent. In each case there was prolongation of QT interval on electrocardiogram (ECG). Two patients had hypokalaemia associated with diuretic therapy. In the 3 cases in which follow-up ECG was available, QT interval returned to normal after discontinuation of terodiline. In order to define the effects of terodiline on corrected QT interval (QTc) and heart rate in the elderly, a prospective study was performed in 8 elderly in-patients treated with terodiline for urinary incontinence. After 7 days treatment with terodiline 12.5 mg twice daily, there was a significant increase in QT by a mean of 29 ms, QTc by 15 ms and a decrease in resting heart rate by a mean of 6.7 beats.min-1. Terodiline increases QTc and reduces resting heart rate in elderly patients. Both these effects may be associated with polymorphic VT, a potentially life threatening arrhythmia. This drug should be avoided in patients with other known risk factors for polymorphic VT, particularly hypokalaemia and cardiac disease.

Aged↗
PubMed1992

Psychosocial adjustment in siblings of children with chronic life-threatening illness: a research note.

The psychosocial functioning of 10 siblings of children with chronic life-threatening illness and their parents was compared with 10 healthy matched controls. The main differences found were in family relationships, with the index siblings expressing more negative emotion in relation to their fathers than controls, index mothers being less involved in social activities and index fathers being less involved with the extended family. No significant differences were found in any of the measures of depression, anxiety and self concept. Index siblings expressed a number of other concerns such as a fear of the break up of their family after the sick child died. The need for increased awareness of the welfare of healthy siblings as well as closer involvement of the fathers is discussed.

Adolescent↗
PubMed1992

Androgen blockade does not affect sleep-disordered breathing or chemosensitivity in men with obstructive sleep apnea.

As sleep apnea is more prevalent in men and testosterone has known effects on sleep apnea and chemosensitivity, reduction of androgen activity may influence sleep-disordered breathing and respiratory control. We studied the effect of 1 wk of treatment with flutamide, a nonsteroidal antiandrogen, on sleep, respiration, and ventilatory control in eight men with sleep apnea. Results on flutamide were compared with two baseline studies performed before and after the drug treatment period. Although effective androgen blockade was achieved as evidenced by increased hormone levels, flutamide had no effect on sleep architecture or chemoresponsiveness to hypoxia and hypercapnia. There was a trend towards a reduction in respiratory disturbance index in both NREM and REM sleep (41 +/- 4 baseline versus 34 +/- 3 flutamide, p = 0.09 NREM; 53 +/- 4 baseline versus 48 +/- 3 flutamide, p = 0.16 REM), but this was not significant. Our results indicate that androgen blockade had no clinically significant effect on sleep, sleep-disordered breathing, or chemosensitivity in patients with moderate to severe sleep apnea. More specific blockers such as gonadotrophin-releasing hormone analogs may have more clinical effect or, alternatively, androgen blockade may be more beneficial in patients with milder sleep apnea.

Adult↗
PubMed1992

Role of toxic ingredients in silicone oils in the induction of increased corneal endothelial permeability.

Silicone oils may induce pathological changes in corneas or retinas by unknown mechanisms but the effects are probably related to certain specific components. Low molecular weight compounds have been implicated in the induction of toxic tissue reactions. Several of these components, that occur as contaminants or by-products in crude silicone oils, were tested for their ability to alter corneal endothelial permeability. In vitro inulin/dextran permeability was measured after one week of in vivo exposure to a non-toxic oil to which various low molecular weight components were added. At least 75% of the anterior chamber volume was replaced with oil +/- additives. A long-chain silanol-terminated polydimethylsiloxane (1000 cps) at 2 mg/ml, tetramethyl-ammonium siloxanolate (a catalyst) at 1 mg/ml and a mixture of a series of linear compounds (MM through MD10M) each at 10 mg/ml all caused a large corneal endothelial permeability increase. A mixture of two short-chain silanol-terminated compounds was less damaging, as was a mixture of a cyclic series. Evidently certain compounds can induce toxic effects on the corneal endothelium whereas other compounds are much less toxic. The linear series and the catalyst, that induce corneal endothelial changes, have been shown to occur in silicone oils.

Animals↗
PubMed1992

Intraocular gas effects on corneal endothelial permeability.

We examined the effects of intraocular gases on the permeability of the rabbit corneal endothelium to inulin and dextran. Volumes of air (0.16 ml), sulfur hexafluoride (SF6) (0.08 ml), and octafluoropentane (C3F8) (0.04 ml) were infused into the anterior chamber at constant intraocular pressure so that all volumes were equal after expansion. The inulin/dextran permeability was statistically decreased by infusion with Ringer, while air caused an 8.4% increase in dextran permeability but no effect on inulin flux. These small effects were of no biological significance. SF6 caused a 16% and 13% increase in inulin and dextran permeability, respectively, while C3F8 caused an 18% increase in both inulin and dextran permeability. Longevity of gas in the anterior chamber appears important in delineating the deleterious effects. The gases per se do not appear toxic but rather disrupt normal physiologic function through physical process.

Air↗
PubMed1992

The roles of general and geriatric medicine in the provision of acute medical care for elderly patients.

To determine whether there are differences between elderly patients admitted acutely to general medicine and those admitted to geriatric medical wards, and whether the patients are appropriately referred, a prospective survey of 426 consecutive patients aged 65 years or over admitted acutely to general medical and geriatric wards over a three month period was performed. A total of 286 patients were admitted to general medicine (GM) and 140 to the geriatric unit (GER). GER patients were older (81.0 v. 75.8 years) and had greater pre-morbid functional impairment and incontinence. Fewer GER patients presented with readily apparent organ specific diagnoses (56% v. 94%). Median length of stay was longer in GER patients (23 days v. 9 days). Variables independently predictive of GER admission were increasing age, increasing duration of illness, poor pre-morbid functional status and prior reliance on a carer. Length of stay was not associated with unit of admission allowing for the variables described above. GER patients are a different population. They have more chronic illness and functional impairment, and are more likely to require multidisciplinary assessment and rehabilitation in addition to treatment of presenting illness. Elderly patients are appropriately referred by General Practitioners (GPs) without a formal admissions policy.

Aged↗
PubMed1991

Assignment of the human prohibitin gene (PHB) to chromosome 17 and identification of a DNA polymorphism.

Prohibition is a recently identified antiproliferative protein whose exact role in the cell is under investigation. To determine the human chromosomal location of the prohibition gene (PHB) and whether this site corresponds to that of any suspected tumor suppressor gene, we have analyzed DNA from three sources by hybridization analysis: mouse--human hybrid cell lines, hybrid cell lines containing portions of human chromosomes, and human metaphase chromosomes in situ. All three techniques confirm a location in the region 17q21-q22, a region genetically linked to early-onset human breast cancer. Further analysis will be required to establish the significance of this relationship; Southern hybridizations show a polymorphic EcoRI site that may be useful for this purpose.

Blotting, Southern↗
PubMed1991

Prohibitin, an evolutionarily conserved intracellular protein that blocks DNA synthesis in normal fibroblasts and HeLa cells.

Genes that act inside the cell to negatively regulate proliferation are of great interest because of their implications for such processes as development and cancer, but these genes have been difficult to clone. This report details the cloning and analysis of cDNA for prohibitin, a novel mammalian antiproliferative protein. Microinjection of synthetic prohibitin mRNA blocks entry into S phase in both normal fibroblasts and HeLa cells. Microinjection of an antisense oligonucleotide stimulates entry into S phase. By sequence comparison, the prohibitin gene appears to be the mammalian analog of Cc, a Drosophila gene that is vital for normal development.

Amino Acid Sequence↗
PubMed1991

Doppler echocardiography in elderly patients with ejection systolic murmurs.

Thirty-nine elderly patients, mean age 77 years (range 65 to 96), with ejection systolic murmurs were studied to evaluate the functional significance of these murmurs. Subjects were evaluated clinically, by 2-D echocardiography, and by a full Doppler echocardiography study. Good quality Doppler signals were obtained in 35 subjects. Mitral regurgitation was found to be the only significant valvular lesion in 6 patients (17%). Doppler gradients in systole across the aortic valve were less than 30 mmHg in 28 subjects (80%) and were considered not significant. Gradients of greater than 30 mmHg representing significant aortic stenosis were found in 7 subjects (20%). The clinical sensitivity in detecting significant aortic stenosis was 44% and specificity was 81%. Doppler evidence of significant aortic stenosis was found in a substantial proportion of these elderly subjects. Neither clinical assessment nor 2-D echocardiography can be relied on to exclude this condition.

Aged↗
PubMed1990

Discordant effects of aging on prolactin and luteinizing hormone-beta messenger ribonucleic acid levels in the female rat.

To examine the molecular genetic basis for the age-related increase in PRL secretion and decrease in LH production in the rat, we measured steady state levels of PRL and LH beta mRNA in pituitary homogenates and cell lysates from monolayer adenohypophyseal cultures. These mRNA levels were compared with the corresponding levels of immunoreactive PRL and LH in sera and culture media. Paired groups (n = 4-10/group) of intact and 4-week ovariectomized mature (6-7 months old) and old (23-25 months old) female Wistar rats were studied. Serum PRL levels were 550% higher in intact old vs. mature rats (P less than 0.001), whereas the corresponding pituitary homogenate levels of PRL mRNA were similar (P greater than 0.4). Medium PRL concentrations were 230% greater (P less than 0.006) whereas cell lysate concentrations of PRL mRNA were unaltered (P greater than 0.2) in monolayer cultures from intact old vs. mature rats. Serum PRL levels were 650% higher (P less than 0.003) and pituitary homogenate PRL mRNA levels were slightly increased (P less than 0.04) in ovariectomized old vs. mature rats. Neither serum LH values (P greater than 0.07) nor pituitary homogenate LH beta mRNA levels (P greater than 0.1) differed in intact old and mature rats, whereas the corresponding medium concentrations of LH were reduced (P less than 0.001). Ovariectomized old vs. mature rats exhibited reductions in serum (P less than 0.02) and medium (P less than 0.001) LH concentrations, as well as in pituitary homogenate (P less than 0.002) and cell lysate (P less than 0.006) LH beta mRNA levels. Thus, these data revealed coordinate decreases with age in LH beta mRNA and LH secretion, particularly in ovariectomized rats, suggesting an age-related alteration at or before LH beta gene transcription. These findings parallel observations on other genes whose products change with age. In contrast, the observation that the increased secretion of PRL in old rats is accompanied by little or no increase in PRL mRNA is novel and suggests that age-related alterations in PRL gene expression proceed through a posttranscriptional mechanism.

Aging↗
PubMed1990

Rationale and strategies for American Sign Language intervention.

A Midwest school district established a demonstration Total Communication Project. Its goal was for teachers to become consistent in their role modeling of English and American Sign Language (ASL). English was the primary language of the classroom and ASL was used as an intervention tool. There has been little research on the effectiveness of ASL in the classroom. By implementing an ASL intervention program this project is a first step in establishing an environment conducive to investigating the effectiveness of ASL intervention for teaching deaf students. This paper describes: (a) techniques used for identifying classroom situations that call for the use of ASL; (b) discourse situations that influence the use of different language codes in total communication classrooms; and (c) guidelines for code-switching between English and ASL.

Communication Methods, Total↗
PubMed1989

Isolation of a cDNA that hybrid selects antiproliferative mRNA from rat liver.

Studies of chromosome loss in inherited cancers, of fusions between proliferating and quiescent cells, and of microinjection of RNA from quiescent cells into proliferation competent cells have all provided evidence for antiproliferative genes in mammalian cells. In this report, we describe a partial cDNA clone isolated on the basis of its preferential hybridization to RNA from normal versus regenerating rat liver. The corresponding mRNA, enriched by hybrid selection, was microinjected into normal human diploid fibroblasts in cell culture, resulting in a 53% decrease in the fraction of nuclei incorporating tritiated thymidine. This mRNA is 2 kb in size and is expressed in eight tissues examined.

Animals↗
PubMed1989

Rain and windchill as factors in the occurrence of pneumonia in sheep.

A computerised information retrieval system of abattoir pathology and meteorological data has been used to investigate the effect of prevailing weather conditions on the occurrence of pleurisy and pneumonia in the sheep population of Northern Ireland. Significant correlation coefficients were found between the percentage condemnations due to pleurisy and pneumonia in sheep and rainfall, windspeed, temperature and humidity. The most significant correlation was found with windspeed. The paper describes the calculation of a new meteorological variable, the rain/windchill factor. Very highly significant correlation coefficients were found between the percentage lung condemnations in sheep and the rain/windchill factor prevailing during the same month and both one and two months previously. The paper discusses the practical implications of these findings for sheep production and highlights the desirability of protecting sheep from adverse climatic conditions during the winter months.

Abattoirs↗