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Biomedical subjects

M Fennell

Publications and source records attributed to M Fennell.

16 recordsLinked to original sources

Hospital diversification into long-term care.

In the 1990s, acute care hospitals in the United States encountered an unstable operating environment created by a series of transformations in the health care delivery system and long-term-care market. Confronted with an array of economic pressures and demographic changes, hospitals were motivated to engage in long-term-care diversification, such as establishing a long-term-care unit or providing home health services, as a means of entering new markets and ensuring financial stability. This article examines the organizational, market, and community factors associated with this strategic activity among a national sample of urban and rural hospitals.

Catchment Area, Health↗

Influenza outbreak in a correctional facility.

The outbreak of influenza in a corrections facility occurred during August 2000. The outbreak progressed following introduction of the disease by a member of the public to the facility. Rapid diagnosis and typing of the influenza isolates was available, although two prisoners required hospital admission due to the severity of complications at the time of diagnosis. The group demonstrated rapid transmission of the virus by the respiratory route and probably by fomites. The identified infecting virus was A/Moscow-like, an H3N2 subtype typically associated with large outbreaks. Prevention of such outbreaks will involve either achieving high rates of vaccination within the risk groups, or rapid (possibly point of care) diagnosis with the institution of antiviral therapy within 48 hours of symptoms. Influenza control within institutions is feasible using such strategies, although it requires considerable planning to have such approaches in place during winter--a time when institutional staff absenteeism is typically high.

Disease Outbreaks↗

Presumptive summer influenza A: an outbreak on a trans-Tasman cruise.

A number of recent reports from the Northern Hemisphere have drawn attention to the occurrence of summer outbreaks (May to August) of influenza A among cruise ship passengers and their contacts. In cases amongst passengers returning to Canada from Alaska, exposure appears to have occurred during the land-based Alaskan tour with illness developing during the subsequent cruise. A late summer outbreak of influenza A among passengers and crew on the return leg of a 14-day Sydney-New Zealand-Sydney cruise is reported in this article.

Australia↗

Enhanced neuronal differentiation of NTera-2 cells expressing neuronally restricted beta2 adrenergic receptor.

NTera-2/D1 (NT2) is a human teratocarcinoma cell line which can be cultured as a dividing population of precursor cells that can be manipulated with retinoic acid (RA) to yield post-mitotic neurons. Precursor cells were transfected with the human beta2 adrenergic receptor, controlled by the neuronal cell specific rat synapsin-1 promoter. Transfected precursor cells did not display elevated expression of the beta2 adrenergic receptor. Upon differentiation to a neuronal phenotype with RA, betaSyn2 and betaSyn4 (beta2Syn-NT2; ATCC CRL-12356) displayed elevated beta2 adrenergic receptor levels, and an elevated coupling to cAMP production. It was also observed that the elevated expression of the beta2 adrenergic receptor in the neuronal NT2 cells resulted in an enhanced level of neuronal differentiation compared to the wild type cells. These results demonstrate that the neuronally restricted expression of the human beta2 adrenergic receptor in NT2 neurons results in increased receptor levels and receptor stimulated generation of cAMP, this may result in the observed improvement in neuronal differentiation.

Animals↗

Rhodopsin-family receptors associate with small G proteins to activate phospholipase D.

G-protein-coupled receptors of the rhodopsin family transduce many important neural and endocrine signals. These receptors activate heterotrimeric G proteins and in many cases also cause activation of phospholipase D, an enzyme that can be controlled by the small G proteins ARF and RhoA. Here we show that the activation of phospholipase D that is induced by many, but not all, Ca2+-mobilizing G-protein-coupled receptors is sensitive to inhibitors of ARF and of RhoA. Receptors of this type were co-immunoprecipitated with ARF or RhoA on exposure to agonists, and the effects of GTP analogues on ligand binding to the receptor changed to a profile that is characteristic of small G proteins. These receptors contain the amino-acid sequence AsnProXXTyr in their seventh transmembrane domain, whereas receptors capable of activating phospholipase D without involving ARF contain the sequence AspProXXTyr. Mutation of this latter sequence to AsnProXXTyr in the gonadotropin-releasing hormone receptor conferred sensitivity to an inhibitor of ARF, and the reciprocal mutation in the 5-HT2A receptor for 5-hydroxy-tryptamine reduced its sensitivity to the inhibitor. Receptors carrying the AsnProXXTyr motif thus seem to form functional complexes with ARF and RhoA.

ADP-Ribosylation Factors↗

Two psychological treatments for hypochondriasis. A randomised controlled trial.

BACKGROUND: Hypochondriasis is generally considered difficult to manage. This study aimed to assess the effectiveness of cognitive therapy and to compare it with an equally credible, alternative treatment. METHOD: Forty-eight patients with hypochondriasis were initially randomly assigned to either cognitive therapy, behavioural stress management or a no treatment waiting list control group. At the end of the waiting period, patients in the control group were randomly assigned to one of the two treatments. Assessments were at pre-, mid- and post-treatment or waiting list and at three-, six- and 12-month post-treatment follow-up. RESULTS: Comparisons with the waiting list group showed both treatments were effective. Comparisons between the treatments showed that cognitive therapy was more effective than behavioural stress management on measures of hypochondriasis, but not general mood disturbance at mid-treatment and at post-treatment. One year after treatment patients who had received either treatment remained significantly better than before treatment, and on almost all measures the two therapies did not differ from each other. CONCLUSIONS: Cognitive therapy is a specific treatment for hypochondriasis. Behavioural stress management is also effective but its specificity remains to be demonstrated.

Adult↗

Effect of tyrosine kinase inhibitors on luteinizing hormone-releasing hormone (LHRH)-induced gonadotropin release from the anterior pituitary.

A range of selective tyrosine kinase inhibitors, piceatannol, methyl-2,5-dihydroxycinnamate (MDC), genistein, psi-tectorigenin and lavendustin A, all reduced luteinizing hormone-releasing hormone (LHRH)-induced luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release from pro-oestrous rat hemipituitaries incubated in vitro. In general, both 'initial' release and the augmented release resulting from LHRH self-priming, were reduced in parallel in a concentration-dependent fashion. The effects of piceatannol were independent of the steroidal status of the pituitary tissue. Both piceatannol and MDC greatly reduced LH release by ionomycin and a protein kinase C (PKC) activator, phorbol 12,13-dibutyrate (PDBu), suggesting that the tyrosine kinase(s)-dependent step is in the later stages of the stimulus-secretion pathway activated by the LHRH receptor. These data were supported by immunoblots for phosphotyrosine showing that in the gonadotrope-derived alpha T3-1 cell line, treatment with LHRH caused piceatannol-sensitive increases in specific tyrosine phosphorylation of several proteins (major bands at 65-75 and 120-130 kDa). Treatment of cells with PDBu mimicked the tyrosine phosphorylations evoked by LHRH whereas the PKC inhibitor, GF109203X, partially reduced both LHRH- and PDBu-induced tyrosine phosphorylations. Direct effects of MDC and piceatannol on PKC were assessed in an in vitro PKC assay; piceatannol, but not MDC, inhibited PKC activity but at considerably higher concentrations than required for inhibition of LHRH-induced gonadotropin secretion. These data support a role for tyrosine kinase activation in LHRH-induced secretion.

Animals↗

Modification of tumour glucose metabolism for therapeutic benefit.

Tumours have a much greater dependence than normal tissues on anaerobic glycolysis for energy generation. We have studied the effects of glycolysis inhibition on tumour cells in vitro. Cellular ATP fell during exposure of cells in air to 2-deoxy glucose or to the lactate dehydrogenase inhibitor oxamate. Glycolysis inhibition alone did not alter clonogenic cell survival over 6 h, but a 6-h exposure to oxamate combined with doxorubicin (Dox) gave greater than additive cell killing. This effect was greatest when oxamate was dosed after Dox, suggesting that oxamate inhibited repair of Dox-induced damage. Oxamate also gave greater than additive cell killing in multicellular spheroids when combined with Dox and there was a greater than additive growth delay in spheroids dosed with Dox plus oxamate. These data demonstrate that inhibition of anaerobic glycolysis might be used to obtain a significant therapeutic gain in combination treatments with cytotoxic drugs or radiotherapy.

Adenosine Triphosphate↗

Characterization of bromhexine and ambroxol in equine urine: effect of furosemide on identification and confirmation.

The purpose of this study was two-fold: (1) to develop a simple and sensitive screening procedure for identifying and confirming bromhexine and ambroxol and, (2) to determine the effect of furosemide on the detection of bromhexine, ambroxol, or their metabolites in urine. Female horses (450-550 kg) treated with bromhexine or ambroxol (1 g, p.o.) were used. Urine samples were collected up to 48 h post-drug administration and analysed. Blind samples were used in evaluating the sensitivity of these methods and reproducibility of the results. Bromhexine and ambroxol were extensively metabolized in the horse. These agents and their respective metabolites were identified and confirmed using thin-layer chromatography (TLC) and gas chromatography-mass spectrometry (GC-MS), respectively. Hydroxy-bromhexine and desmethyl-bromhexine were major metabolites found to be unique to bromhexine-treated horses. These metabolites selectively absent from ambroxol-treated horse urine provide a chemical means to distinguish bromhexine from ambroxol administration in horses. These specific metabolites were similarly identified and confirmed in "blind" horse urine samples. The concomitant presence of furosemide (300 mg, i.v.) with bromhexine or ambroxol did not mask the presence of these agents or alter their metabolite profile. By application of the methods described in this study, bromhexine and ambroxol metabolites in horse urine can be easily identified and confirmed.

Ambroxol↗

Comparison of behavior therapy and cognitive behavior therapy in the treatment of generalized anxiety disorder.

In a controlled clinical trial, 57 Ss meeting DSM-III-R criteria for generalized anxiety disorder, and fulfilling an additional severity criterion, were randomly allocated to cognitive behavior therapy (CBT), behavior therapy (BT), or a waiting-list control group. Individual treatment lasted 4-12 sessions; independent assessments were made before treatment, after treatment, and 6 months later, and additional follow-up data were collected after an interval of approximately 18 months. Results show a clear advantage for CBT over BT. A consistent pattern of change favoring CBT was evident in measures of anxiety, depression, and cognition. Ss were lost from the BT group, but there was no attrition from the CBT group. Treatment integrity was double-checked in England and in Holland, and special efforts were made to reduce error variance. Possible explanations for the superiority of CBT are discussed.

Analysis of Variance↗

Polymorphonuclear leucocyte motility in men with ankylosing spondylitis.

The polymorphonuclear leucocyte (PMN) response to a chemotactic or chemokinetic stimulus is enhanced in men with ankylosing spondylitis (AS). This effect does not parallel the severity of disease activity or the size of the acute phase response, and it is independent of non-steroidal anti-inflammatory drug treatment. Polymorph function is normal in HLA-B27 positive brothers of probands with AS and in other HLA-B27 positive individuals in the absence of disease. Polymorph motility is also normal in patients with psoriasis vulgaris or Crohn's disease, indicating that enhanced PMN motility is not a non-specific consequence of all inflammatory disorders.

Adult↗

Polymorphonuclear leukocyte function in psoriasis vulgaris.

Polymorphonuclear leukocyte (PMN) migration was assessed in vitro using the agarose plate method in patients with psoriasis vulgaris, and compared with an age- and sex-matched control group. No significant difference was found between the two groups in the PMN response to the chemotactic substances F-Met-Leu-Phe (FMLP) or zymosan activated serum (ZAS). Equally, the chemokinetic or chemotactic potential of psoriatic serum did not differ from control serum. Our results do not support a primary abnormality of PMN function in psoriasis.

Arthritis↗