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Biomedical subjects

I C Taylor

Publications and source records attributed to I C Taylor.

At least 19 recordsLinked to original sources

A prospective study of the process of assessment and care management in the discharge of elderly patients from hospital.

Assessment and care management (ACM) of elderly patients prior to discharge from hospital has been in place since 1993. It involves a complex multi-disciplinary assessment of needs which may delay discharge from hospital. We prospectively studied the process of ACM in a group of patients discharged from hospital over a three month period. The times taken for completion of the necessary reports, and any delays in the process were recorded. The times of each individual step in the process were correlated to overall length of stay and to the length of the care management process. The effect of intercurrent illnesses or other delays was studied. Of the available sample (n = 83), 16 patients died and two required long term hospital care. The median length of stay of the remainder (n = 65) was 36 days (range 5-149 days). The median time from the start of the ACM process to discharge was 22 days (0-89 days). The strongest correlation with total length of stay was the time from admission until ACM commenced (rho = 0.661, p < 0.0001). The time spent in the ACM process was related strongly to the time taken for the Care Manager to process the applications (rho = 0.682, p < 0.0001). Delay was recorded in 17 (24%) cases, resulting in an increased length of stay (p < 0.001). While care management may help in appropriate placement after hospital discharge, these results suggest that it is prone to delays outside the hospital setting. Such delays result in patients waiting in hospital for care packages to be set up in the community. This has implications for acute hospital services.

Aged↗

Pharmacokinetics of flosequinan in patients with heart failure.

OBJECTIVE: The pharmacokinetics of flosequinan were studied in a group of 18 patients with chronic cardiac failure. RESULTS: After a single dose of 100 mg, Cmax of the parent compound (2.52 mg.l-1) was recorded at 1.4 h, and of the sulphone metabolite flosequinoxan at 21.7 h. The plasma elimination half lives of the parent compound (6.4 h) and of the metabolite (54.3 h) were prolonged compared to previous studies in normal volunteers. After repeated dose administration for 36 days, the kinetics of the parent compound and metabolite remained essentially unchanged with an expected significant accumulation of metabolite (Cmax 8.4 vs 3.21 mg.l-1). No adverse effects were observed. CONCLUSION: It is possible that altered drug kinetics in patients with heart failure, probably related to altered hepatic blood flow, could contribute to drug toxicity.

Aged↗

Overexpression of the Sky receptor tyrosine kinase at the cell surface or in the cytoplasm results in ligand-independent activation.

Most receptor tyrosine kinases are activated by dimerization induced by their cognate ligands. Protein S, an abundant serum protein previously shown to be a potent anticoagulation factor, has been proposed to be a ligand for the Sky tyrosine kinase (Stitt et al., 1995). Here we show that Sky, when expressed to high levels, is tyrosine phosphorylated even in the absence of a ligand. Furthermore, a version of Sky (termed Sky delta SS) engineered to be overexpressed in the cytoplasm and thus in a ligand-free environement, can function as a dimeric tyrosine kinase. Sky delta SS can transform RatB1a fibroblasts and thus retains all the properties of the full-length Sky kinase. These data suggest that Sky, when overexpressed either at the cell surface or in the cytoplasm, is competent to form dimers even in the absence of its ligand. We also demonstrate that an isoform of Sky, originally reported as Brt and here termed Sky Isoform I, resides in the cytoplasm. Therefore, the activities of Sky delta SS we describe may reflect those of the naturally occurring Isoform I.

Animals↗

Mouse mammary tumors express elevated levels of RNA encoding the murine homology of SKY, a putative receptor tyrosine kinase.

To gain insight into the signal transduction pathways utilized by the Wnt-1-responsive mammary epithelial cell line C57MG, we screened for non-src family member tyrosine kinases expressed in these cells using a polymerase chain reaction-based technique. We identified five cDNA clones encoding receptor tyrosine kinases for which the ligand is known (fibroblast growth factor receptor, platelet-derived growth factor receptor, epithelial growth factor receptor, insulin receptor, and insulin-like growth factor receptor), two putative receptor tyrosine kinases for which the ligand remains to be identified (the products of ryk and the mouse klg homolog), and a novel tyrosine kinase. We cloned cDNAs encoding both the murine and human homologs of this kinase, the sequences of which were subsequently published under the names sky (Ohashi, K., Mizuno, K., Kuma, K., Miyata, T., and Nakamura, T. (1994) Oncogene 9, 699-705) and rse (Mark, M. R., Scadden, D. T., Wang, Z., Gu, Q., Goddard, A., and Godowski, P. J. (1994) J. Biol. Chem. 269, 10720-10728). Mouse sky RNA levels are abundant in mammary tumors derived from transgenic mice that express wnt-1, fgf-3, or both oncogenes in their mammary glands. However, little or no expression of sky is detected in mammary glands from virgin animals or in preneoplastic mammary glands from wnt-1 transgenic mice. Moreover, we find that the human homolog of sky is expressed at elevated levels when normal human mammary epithelial cells are rendered tumorigenic by the introduction of two viral oncogenes. Transient transfection of the human SKY cDNA into the quail fibrosarcoma cell line QT6 reveals that SKY is an active tyrosine kinase that augments the level of cellular phosphotyrosine. Introduction of murine Sky into RatB1a fibroblasts by retrovirus-mediated gene transfer results in morphological transformation, growth in soft agar, and the formation of tumors in nude mice. These data raise the possibility that the Sky tyrosine kinase is involved in the development and/or progression of mammary tumors.

Amino Acid Sequence↗

Severe hyponatraemia associated with selective serotonin reuptake inhibitors.

Depression in the elderly is a common problem, cited as occurring in up to 10% of elderly people living at home, half of whom may need specialist referral. The introduction of selective serotonin reuptake inhibitors has been reported as a major advance in the treatment of depression in that they are less sedating, have fewer anticholinergic effects and are less toxic in overdose. We report three cases of severe hyponatraemia, seen in the past 12 months, associated with the selective serotonin reuptake inhibitors fluoxetine and sertraline. Hyponatraemia has been reported as a rare adverse effect of selective serotonin reuptake inhibitors.

1-Naphthylamine↗

Patterns of admission and discharge in an acute geriatric medical ward.

Patients admitted to a 30 bedded acute geriatric medical ward in 1993 were followed up to discharge. The admission rate on weekend days was half that for weekdays. Six percent of ward discharges occurred at weekends, over half being due to death. Respiratory, cardiovascular and central nervous systems disorders were the commonest reasons for admission (56%) and death (73%). Greater emphasis should be placed on discharging patients at weekends.

Acute Disease↗

Geriatric medicine: the anatomy of change.

We have studied workloads and patterns of care in geriatric medicine from 1982 to 1993 in the Ulster Hospital. There was a 137% rise in admissions, a 16% reduction in domiciliary visits and a 31% increase in ward assessments. The continuing care waiting list fell to zero in 1993. The number of new outpatients rose by a factor of 8.6 between 1987 and 1993. Between 1990 and 1993 there was an increased admission rate from nursing homes and of patients suffering from respiratory system diseases. Mortality rates fell from 27.8% in 1982 to 19.3% in 1990 and to 12.1% in 1993. Mean age and sex ratios remained unchanged over the years while the average length of stay halved from 43.3 to 22.6 days between 1990 and 1993. 81% of admissions in 1993 were emergencies. Care of the elderly in hospital and the interface with general medicine are changing.

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Admission of nursing home patients to geriatric medical wards.

Comparison was made between patients admitted from a nursing home and all other patients admitted to a geriatric medical unit in 1990 and 1993. The number of nursing home patient admissions rose from 26 in 1990 to 106 in 1993. Nursing home patients were frailer both physically and mentally with a dementia rate of 78% (in those who survived, 1993) and a mortality rate of 19.8% (1993), compared with a dementia rate of 19% and a mortality rate of 11.3% in all other admissions in 1993. Male patients admitted from a nursing home were more likely to die than females (33% versus 14.5%, 1993). Lengths of stay of nursing home patients were shorter, largely due to the availability of a 'safe environment' when discharged, but also related to shorter survival times. 61% of patient admissions from nursing homes in 1993 were considered 'unnecessary' and could have been avoided if specialist advice had been available before admission.

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'Assessment and care management'--a hospital perspective.

Patients placed from hospital to nursing or residential homes or to home under the intensive domiciliary care scheme were compared before and after the introduction of 'assessment and care management' on the 1st April 1993. In geriatric medical wards there was a 69% increase in the average length of stay for patients assessed and care managed and a 52% increase in the length of stay for self-funding patients compared with patients placed before the introduction of assessment and care management. Care managed patients discharged on the intensive domiciliary care scheme had a 66% increase in their length of hospital stay compared with care managed patients placed in private nursing homes. In contrast, the length of stay for care managed patients in other hospital wards was half that for geriatric medical wards.

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Pancreatic polypeptide and exocrine pancreatic function in the elderly.

The relationship between exocrine pancreatic function and plasma pancreatic polypeptide levels was studied in 14 normal elderly subjects and in ten elderly patients with exocrine pancreatic insufficiency determined by the para-amino-benzoic acid test. There was a decrease in the total pancreatic polypeptide response after a standard mixed meal in the group with pancreatic insufficiency (t = 2.753, p = 0.01). An increase above basal of less than 100% in plasma pancreatic polypeptide levels 30 min after a standard mixed meal is strongly associated with exocrine pancreatic insufficiency (Fisher's exact test, p = 0.005).

4-Aminobenzoic Acid↗

Steady state pharmacokinetic profile of indomethacin in elderly patients and young volunteers.

The steady-state pharmacokinetic profile of indomethacin was examined in twelve healthy volunteers (4 m, 8 f; 20-34 y) and in 12 elderly subjects (7 m, 5 f; 70-88 y). Two formulations of indomethacin were examined, providing duplicate data for each subject group. The subjects received each formulation of indomethacin (25 mg tid) for 6 days in a single blind crossover fashion. On day 7, after an overnight fast, a final 25 mg dose of indomethacin was given and plasma concentrations measured over the following 12 h. Kinetic parameters Cpmin, Tmax and AUC (0-12 h) were determined. There were no differences in the pharmacokinetic parameters between young and elderly subjects or between data for the two formulations of indomethacin. AUC values (micrograms.ml-1.h), for example, for the two formulations in the young subjects were 5.85 and 6.85 while the values for the elderly subjects were 6.55 and 6.50 respectively. When each treatment period was considered independently there was a significant difference between young and elderly subjects with regard to compliance. The rates of non compliance (over and under compliance) using a capsule count technique were, however, low with a mean maximum value of 5.8% being recorded for the elderly subjects.

Adult↗

Exocrine pancreatic insufficiency in presumed healthy elderly subjects.

A pilot study on exocrine pancreatic function, using the 2-day para-aminobenzoic acid (PABA) test, was performed on 21 healthy elderly and 26 healthy young subjects. A PABA excretion index (PEI) less than 55%, indicating moderate to severe exocrine pancreatic insufficiency (EPI), was found in 19% of the elderly group (95% confidence limits 5-42%). While the mean value of the PEI was significantly lower in the elderly compared with the young group (Mann-Whitney Z = 2.8, p less than 0.01), there was no significant difference when the elderly subgroup with PEI less than 55% was excluded. There was no evidence of a generalized moderate to severe decline in pancreatic exocrine function with increasing age; a mild to moderate decline cannot be excluded.

4-Aminobenzoic Acid↗

Activation domains of stably bound GAL4 derivatives alleviate repression of promoters by nucleosomes.

GAL4 derivatives containing an activation domain alleviated repression of a promoter during nucleosome assembly. A GAL4 derivative lacking an activation domain stably bound the promoter during nucleosome assembly but was not sufficient to preserve promoter function. The activation domain of GAL4 derivatives was essential for preserving promoter function, and thus the transcriptional stimulatory activity attributable to these activation domains increased dramatically during nucleosome assembly. Furthermore, promoter-bound activation domains allowed the formation of preinitiation complexes after nucleosome assembly. Finally, GAL4 derivatives containing activation domains significantly stimulated transcription through bacterially produced yeast TFIID only from nucleosome-assembled templates. These data indicate that acidic activation domains stimulate transcription by enhancing the ability of basal transcription factors to compete with nucleosomes for occupancy of the promoter.

Animals↗

RNA polymerase II carboxy-terminal domain contributes to the response to multiple acidic activators in vitro.

The largest subunit of RNA polymerase II contains a unique carboxy-terminal domain (CTD) that consists of repeats of the heptapeptide YSPTSPS. RNA polymerase II CTD truncation mutations affect the ability to induce transcription of a subset of yeast genes in vivo, and the lack of response to induction maps to the upstream activating sequences of these genes. Here, we report that progressive truncation of the yeast RNA polymerase II CTD causes progressive loss of trans-activator-dependent transcription in nuclear extracts but has little effect on elongation or termination. Specific transcription, which is reduced by up to 50-fold in these assays, can be restored in the defective nuclear extracts by adding purified wild-type RNA polymerase II. The defects in factor-dependent transcription are observed with templates that are assembled into nucleosomes as well as with templates that are not so assembled. Defects in factor-independent transcription are also observed, but these are not as profound as those observed in the presence of trans-activators. These results indicate that the RNA polymerase II CTD functions during transcription initiation and is required for normal levels of activated transcription in vitro.

Amino Acid Sequence↗

Facilitated binding of GAL4 and heat shock factor to nucleosomal templates: differential function of DNA-binding domains.

Regulatory factors must contend with chromatin structure to function. Although nucleosome structure and position on promoters can be important in determining factor access, the intrinsic ability of factors to bind to nucleosomal DNA might also play an essential regulatory role. We have used templates where nucleosomes were either randomly positioned or rotationally phased to demonstrate that two transcription factors, heat shock factor (HSF) and GAL4, differ significantly in their ability to bind to nucleosomes. GAL4 was able to bind to nucleosomal templates. Surprisingly, in contrast to its behavior on naked DNA, GAL4 bound better to multiple GAL4 sites than to a single GAL4 site on these templates. HSF alone was not able to bind to nucleosomal templates. HSF was able to bind to nucleosomal templates, however, when the TATA-binding factor TFIID was present. Consequently, binding to nucleosomal templates could be facilitated by adjacent binding of the same protein in the case of GAL4 but required binding of a second protein in the case of HSF. Taken together, these data demonstrate that regulatory factors differ in their inherent ability to bind to nucleosomal templates. These differences are likely to be important to the function of these factors in vivo.

Animals↗