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Biomedical subjects

I Clarke

Publications and source records attributed to I Clarke.

At least 19 recordsLinked to original sources
PubMed2001

Strategic decision-making among top executives in acute-care hospitals.

Recent changes within the dynamic healthcare industry have necessitated further assessment of the strategic thought processes associated with financial success. Therefore, this study explored hospital executive's use of a comprehensive strategy-making process and its impact on performance in acute care hospitals. Taken as a whole, the strategy-making process is found to be positively associated with financial performance. Supplementary analysis, investigating the unique effects of environmental planning, scanning and analysis, revealed that, when considered separately, scanning and analysis contribute significantly to performance, whereas strategic planning, as classically defined, does not. Implications for decision-making in hospital settings are discussed.

Chief Executive Officers, Hospital↗
PubMed2000

Human tumour and dendritic cell hybrids generated by electrofusion: potential for cancer vaccines.

Hybrid cells created by fusion of antigen presenting and tumour cells have been shown to induce potent protective and curative anti-tumour immunity in rodent cancer models. The application of hybrid cell vaccines for human tumour therapy and the timely intervention in disease control are limited by the requirement to derive sufficient autologous cells to preserve homologous tumour antigen presentation. In this study, the efficiency of various methods of electrofusion in generating hybrid human cells have been investigated with a variety of human haemopoietic, breast and prostate cell lines. Cell fusion using an electrical pulse is enhanced by a variety of stimuli to align cells electrically or bring cells into contact. Centrifugation of cells after an exponential pulse from a Gene Pulser electroporation apparatus provided the highest yield of mixed cell hybrids by FACS analysis. An extensive fusogenic condition generated in human cells after an electrical pulse contradicts the presumption that prior cell contact is necessary for cell fusion. Alignment of cells in a concurrent direct current charge and osmotic expansion of cells in polyethylene glycol also generated high levels of cell fusion. Waxing of one electrode of the electroporation cuvette served to polarize the fusion chamber and increase cell fusion 5-fold. Optimisation of a direct current charge in combination with a fusogenic pulse in which fusion of a range of human cells approached or exceeded 30% of the total pulsed cells. The yield of hybrid prostate and breast cancer cells with dendritic cells was similar to the homologous cell fusion efficiencies indicating that dendritic cells were highly amenable to fusion with human tumour cells under similar electrical parameters. Elimination of unfused cells by density gradient and culture is possible to further increase the quantity of hybrid cells. The generation and purification of quantities of hybrid cells sufficient for human vaccination raises the possibility of rapid, autologous tumour antigen presenting vaccines for trial with common human tumours.

Cancer Vaccines↗
PubMed2000

Management of hospital outbreaks of gastro-enteritis due to small roundstructured viruses.

Small round structured viruses (SRSVs, Norwalk-like viruses, NLVs) are the most common cause of outbreaks of gastro-enteritis in hospitals and also cause outbreaks in other settings such as schools, hotels, nursing homes and cruise ships. Hospital outbreaks often lead to ward closure and major disruption in hospital activity. Outbreaks usually affect both patients and staff, sometimes with attack rates in excess of 50%. For this reason, staff shortages can be severe, particularly if several wards are involved at the same time. SRSVs may be spread by several routes: faecal-oral; vomiting/aerosols; food and water. Viruses may be introduced into the ward environment by any of these routes and then propagated by person-to-person spread. In an outbreak setting, the diagnosis can usually be made rapidly and confidently on clinical and epidemiological grounds, particularly if vomiting is a prominent symptom. By the time an SRSV outbreak has been recognized at ward level, most susceptible individuals will have been exposed to the virus and infection control efforts must prioritize the prevention of spread of infection to other clinical areas bycontainment of infected/exposed individuals (especially the prevention of patient and staff movements to other areas), hand-hygiene and effective environmental decontamination. This report of the Public Health Laboratory Service Viral Gastro-enteritis Working Group reviews the epidemiology of outbreaks of infection due to SRSVs and makes recommendations for their management in the hospital setting. The basic principles which underpin these recommendations will also be applicable to the management of some community-based institutional outbreaks.

Caliciviridae Infections↗
PubMed2000

Prolactin levels in sudden unexpected death in epilepsy.

PURPOSE: To assess serum prolactin levels in sudden unexpected death in epilepsy (SUDEP) and control groups to test the hypothesis that if seizures occur routinely as a terminal event in SUDEP, then raised prolactin levels may be an indicator of terminal seizure. METHODS: Blood was taken for measurement of prolactin levels from subjects with SUDEP and three control groups. The control groups were those with epilepsy dying from causes other than epilepsy (e.g., ischemic heart disease or injuries), physiologically stressed individuals without epilepsy (they were admitted to the hospital after an acute illness and died after several hours to 3 days), and nonepileptic rapid deaths (these people collapsed suddenly and died at the scene). In the SUDEP group, evidence for terminal seizure was considered to be at least one of the following: body found half on, half off the bed, or urinary incontinence at the scene, or bitten lips or tongue at autopsy. RESULTS: There was evidence for terminal seizure at the scene or at autopsy in four of the 10 SUDEP cases. Serum prolactin levels were not significantly increased in the SUDEP group compared with the controls. None of the SUDEP subjects, including those with clinical evidence of a terminal seizure, had high prolactin levels characteristic of those observed after seizures in living subjects. CONCLUSIONS: Prolactin levels are not raised in SUDEP, even if there is evidence of terminal seizure. As prolactin takes 15-20 min to peak after a seizure in life, there may be insufficient time for a prolactin increase to occur in SUDEP. Thus prolactin levels cannot be used to determine if a deceased individual with epilepsy had a seizure or to answer the broad question whether SUDEP is always associated with a terminal seizure.

Adolescent↗
PubMed1998

Influence of maternal dexamethasone administration on thermoregulation in lambs delivered by caesarean section.

We have previously shown that lambs delivered by caesarean section 1 week prematurely become hypothermic due to reduced brown adipose tissue function in conjunction with low plasma concentrations of cortisol and thyroid hormones. The present study therefore aimed to determine whether maternal dexamethasone (a synthetic corticosteroid) administration could improve thermoregulation in premature lambs to the extent that they become similar to term lambs. Lambs were either delivered by caesarean section into a warm (30 degrees C; WD) or cool (15 degrees C; CD) ambient temperature at 140 days of gestation, 2 days after maternal dexamethasone treatment, or at 146 days for controls. During the first 30 min of life the decline in colonic temperature was greater in dexamethasone treated lambs compared with controls delivered into the same ambient temperature. All lambs then restored colonic temperature although this adaptation took longest in dexamethasone treated lambs CD but these subsequently attained highest plateau colonic temperatures. Oxygen consumption, breathing frequency and plasma free fatty acid concentrations were highest in dexamethasone treated lambs CD. There were no differences in plasma thyroid hormones between groups, but cortisol concentrations were lower in dexamethasone treated lambs irrespective of delivery temperature. Analysis of brown adipose tissue samples at 6 h of life demonstrated that dexamethasone treated lambs WD had more uncoupling protein and, in both dexamethasone treated and control lambs, uncoupling protein content was higher in lambs CD compared with those WD. An effect of ambient temperature on thermogenic activity was only observed in the dexamethasone treated group. It is concluded that maternal dexamethasone treatment can significantly improve thermoregulation after birth following premature delivery by caesarean section. As a consequence, dexamethasone treated lambs delivered 1 week prematurely do not remain hypothermic and have higher or similar colonic temperatures compared with untreated lambs born 1-2 days before term.

Adipose Tissue, Brown↗
PubMed1997

Localization of intravenously administered verocytotoxins (Shiga-like toxins) 1 and 2 in rabbits immunized with homologous and heterologous toxoids and toxin subunits.

Rabbits challenged intravenously with Shiga toxin or with Escherichia coli verocytotoxin 1 or 2 (VT1 or VT2) are known to develop diarrhea, paralysis, and death, which can be prevented by immunization with a toxoid. The pathological effects of VT1 in the central nervous system and the gastrointestinal tract of unimmunized rabbits correlate with the localization of 125I-VT1 in these tissues, whereas in immunized animals, localization of 125I-VT1 in target tissues is inhibited and labeled toxin is cleared by the liver and spleen. By using the approach described above in this study, rabbits immunized with VT1 toxoid, VT2 toxoid, or with the A or B subunit of each toxin were challenged with intravenous 125I-VT1 or 125I-VT2. After 2 h, the animals were sacrificed, and selected tissues were analyzed for uptake of labeled toxin. It was found that animals immunized with either VT1 toxoid or VT2 toxoid were protected from target tissue uptake of both 125I-VT1 and 125I-VT2. Rabbits immunized with either the VT1 A or VT2 A subunit were also protected from target tissue uptake of both the homologous and heterologous 125I-labeled holotoxins. In contrast, in animals immunized with the toxin B subunits, protection extended only against challenge by the homologous toxin. These results provide evidence of VT1 and VT2 cross-neutralization in vivo in the rabbit model and indicate that the in vivo cross-neutralization is a function, mainly, of antibodies directed to the VT A subunits. This suggests that the VT1 A or VT2 A subunit may be a suitable immunogen for immunizing humans against systemic VT-mediated disease.

Animals↗
PubMed1997

Comparison of the western blot assay with the neutralizing-antibody and enzyme-linked immunosorbent assays for measuring antibody to verocytotoxin 1.

A Western blot (immunoblot) assay (WBA) was developed to detect immunoglobulin G (IgG) antibodies against Escherichia coli Verocytotoxin 1 (VT1) by using a chemiluminescence detection system. The assay was compared with a VT1-neutralizing-antibody (VT1-NAb) assay and an anti-VT1 IgG enzyme-linked immunosorbent assay (ELISA). When four human serum samples that were known to be positive by VT1-NAb assay and ELISA were titrated to the endpoint by the three assays, the WBA gave endpoint titers that were up to 8-fold higher than those by ELISA and up to 256-fold higher than those by the VT1-NAb assay. Of 32 serum samples that were known to be positive by VT1-NAb assay and ELISA, 31 (97%) were positive by WBA; the one sample with a discrepant result gave borderline results by the VT1-NAb assay and ELISA. Of 52 serum samples that were known to be negative by the VT1-NAb assay and ELISA, 50 (96%) were negative and 2 (4%) were positive by WBA. Of 44 serum samples that gave discrepant results by the VT1-NAb assay and ELISA, neither of the latter correlated with the results of WBA. In an investigation of 19 pairs of acute- and convalescent-phase serum samples from patients with hemolytic-uremic syndrome, 10 pairs that were positive by the VT1-NAb assay were also WBA positive, while 9 pairs that were NAb negative were also WBA negative. The WBA is inherently more specific and sensitive than either the NAb assay or the ELISA and may be used as a "gold standard" to detect IgG antibodies to VT1. Like the NAb assay and the ELISA for detecting antibodies to VT1, the WBA has little to offer in the diagnostic setting but is expected to play an important role in seroepidemiological studies.

Animals↗
PubMed1994

Effects in vitro of new growth hormone releasing peptide (GHRP-1) on growth hormone secretion from ovine pituitary cells in primary culture.

Continuous perifusion of pituitary cells was used to study the effects of a newly synthesized GHRP (GHRP-1 or KP 101) on growth hormone (GH) secretion from ovine pituitary cells and these have been compared to effects of growth hormone-releasing factor (GRF) and the original growth hormone-releasing peptide (GHRP-6). GH was continuously released at a constant rate during perifusion and secretion was increased by KP 101, GHRP-6 and GRF in a dose-dependent manner. The half-maximal effective dose of KP 101 and GHRP-6 was 10(-7) M, an order of magnitude higher than that for GRF. The maximal effects of KP 101 and GHRP-6 were similar but significantly less than the maximal effect of GRF. Blockade of calcium channels with Cd2+ (2 mM) totally and reversibly abolished the releasing effects of all three peptides. Like GHRP-6, the GH release induced by KP 101 was not affected by a GRF antagonist ([Ac-Tyr1, D-Arg2]-GRF 1-29, 1 microM) which significantly reduced the effect of GRF on GH release. For each peptide, the response to a second application (1 h after the first application) was lower than the first response. When GRF (or KP 101, GHRP-6) was applied first and then KP 101 or GHRP-6 (or GRF) given 1 h later, the second response was not attenuated. Only a small additive effect on the release of GH by GRF was obtained by the co-administration of either KP 101 or GHRP-6. This result was achieved with maximal doses of the peptides, but not with half-maximal doses.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1993

Many peptides that are present in the external zone of the median eminence are not secreted into the hypophysial portal blood of sheep.

Apart from the well recognized factors that are produced by the hypothalamus and secreted into hypophysial portal blood to regulate pituitary function, there is a range of neuropeptides that are present in the median eminence and could be secreted to serve a modulatory function. In this study we have collected hypophysial portal blood and jugular venous blood from sheep in an attempt to identify which of these putative modulatory peptides might be secreted from the median eminence. We have measured neuropeptide Y (NPY), substance P (SP), galanin (GAL), neurokinin A (NKA), peptide histidine isoleucine (PHI), vasoactive intestinal peptide (VIP), neurotensin (NT) and cholecystokinin (CCK). We also examined the sheep median eminence using immunohistochemistry for NPY, SP and GAL and determined degradation profiles of NPY, SP, GAL and NKA in portal and jugular plasma. In no instance did we find that levels of the above peptides were consistently higher in portal blood than in peripheral blood. In some cases levels of peptide were lower in portal plasma e.g. for NPY (6/10 sheep). In one experimental series SP levels in portal plasma were significantly (p < 0.05) lower than levels in jugular plasma but this was not found in another experimental series. Galanin levels were significantly (p < 0.01) lower in portal plasma compared to levels in jugular plasma. We conducted in vitro studies to determine whether or not the above peptides are selectively degraded in portal blood but were unable to show any differences between the rates of degradation in portal and jugular plasma. Immunohistochemistry revealed projections into the external zone of the median eminence for NPY, GAL and SP. This study shows that none of the above peptides are secreted into the hypophysial portal blood of sheep. For some peptides e.g. GAL, enzymes from the endothelial cells of the portal vessels may enhance degradation. Projections into the external zone of the median eminence of neuronal systems containing these peptides may serve to modulate the secretion of the well recognized release and inhibiting factors by acting on the neurosecretory terminals.

Animals↗
PubMed1991

Circulating half-lives of follicle-stimulating hormone and luteinizing hormone in pituitary extracts and isoform fractions of ovariectomized and intact ewes.

Previous studies have shown that the circulating half-life (t 1/2) of serum FSH in ewes after hypophysectomy (HPX) increased 10-fold after ovariectomy (OVEX). The basis for this difference was examined in this study by determining the circulating half-life of serum FSH and LH in HPX ewes after administration of pituitary extracts and gonadotropin isoform fractions. High-speed supernatants of pituitaries from gonadal-intact and OVEX ewes were fractionated by electrofocusing in sucrose gradients and based on the pI distribution of FSH and LH divided into four pools, pH 4.3-4.8, 4.8-5.55, 5.8-6.7, and 6.7-10. These extracts were administered by iv bolus injection to HPX gonadal-intact ewes and blood samples collected between 15-1000 min later. The clearance pattern for both serum FSH and LH was heterogenous, indicative of a major rapid and a minor slow dissociating component. A significant (P less than 0.05) difference in circulating half-lives (rapid component) was observed between pituitary extracts from intact and OVEX ewes for FSH (t 1/2 = 32.8 +/- 8.6 min vs. 89.9 +/- 32.3 min) but not LH (31.3 +/- 9.2 min vs. 39.3 +/- 6.1 min, respectively), whereas no significant difference was observed between the corresponding FSH or LH isoform preparations. To establish if the difference in circulating half-lives obtained after HPX and bolus iv injection was due to mode of delivery, an extract of pituitaries from OVEX ewes was infused for 12 h into HPX sheep and the t 1/2 values determined after cessation of treatment and compared to those after a bolus injection. The clearance of both FSH and LH from plasma after infusion was significantly prolonged than after a bolus injection. It is concluded that the difference in circulating half-lives of FSH between pituitary extracts from intact and OVEX ewes after bolus administration is due to a difference in pituitary FSH composition. However, the prolonged clearance with infusion compared to bolus administration suggests that extrapituitary factors are also responsible.

Animals↗
PubMed1990

Pharmacokinetic study of controlled-release choline theophyllinate in elderly patients.

Controlled-released choline theophyllinate tablets (Sabidal SR 270, Zyma) were administered to 17 elderly patients aged between 68 and 86 years (mean 76 +/- 7 years) until steady state was obtained. The dosage form was one tablet every 12 hours for four days. Plasma theophylline concentrations were measured by high-performance liquid chromatography after the first dose and during the fourth day for a 12-hour period. The tablets showed evidence of controlled-release properties: the maximum plasma concentration (10.8 +/- 2.5 mg/l) was obtained after 3.4 +/- 1.6 hours. The mean trough level was 6.6 +/- 1.5 mg/l and the difference between the peak and trough levels was 4.1 +/- 1.2 mg/l. The mean steady-state plasma theophylline concentration was 8.5 +/- 2.2 mg/l. The mean elimination half-life was 14 +/- 7 hours. The mean volume of distribution was 0.8 +/- 0.4 l/kg. The mean total body clearance was 0.05 +/- 1/h/kg. All values, the half-life excepted, were found to be within the ranges for the patients reported in the literature. The values show the usual interindividual variation.

Aged↗
PubMed1986

Cellular basis of host defence in pyelonephritis. II. Acute infection.

We have investigated the cellular basis of host defence mechanisms in experimental pyelonephritis. Cellular components of the host defence system were depleted using cyclophosphamide, methylprednisolone or radiation. Depletion of cellular competence did not affect the course of infection during the first 16 h after challenge with Escherichia coli, but after 96 h up to a 1000-fold increase in bacterial numbers in the kidneys of cytodepleted animals was demonstrable. When quantitative aspects of the relationship between cellular competence and host defence were studied, it was found that severe depletion of cellular components was necessary before host defence mechanisms were adversely affected. Thus while cellular mechanisms are quantitatively adequate and contribute to host defence in pyelonephritis they have little impact on the immediate post-infection phase. Non-cellular factors however, do limit bacterial proliferation in the acute phase and may be important determinants in the biology of pyelonephritis.

Acute Disease↗