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Biomedical subjects

J Ferguson

Publications and source records attributed to J Ferguson.

At least 37 records · Page 2Linked to original sources
PubMed2000

Comparison of an in vitro cellular phototoxicity model against controlled clinical trials of fluoroquinolone skin phototoxicity.

Many therapeutic drugs induce phototoxic skin responses following exposure to solar or artificial ultraviolet radiation sources. Several in vitro model systems have been developed to predict drug phototoxicity but none have been conducted in parallel with controlled clinical phototoxicity studies on systemically administered pharmaceuticals. The in vitro phototoxicity of eight fluoroquinolone (FQ) antibiotics (ciprofloxacin, grepafloxacin, lomefloxacin, norfloxacin, ofloxacin, trovafloxacin, BAYy3118, moxifloxacin) was determined by exposing Chinese hamster fibroblasts to UVA radiation. Cell damage was quantified with standard MTT or neutral red assays and an in vitro phototoxic index calculated (PI(vit)=% cell viability with UVA alone /% cell viability with UVA+FQ) for each endpoint. Clinical photosensitizing ability of the eight systemically administered FQ was investigated using double-blind, placebo and positive controlled, clinical skin phototesting of normal subjects. Minimal erythema doses at 365+/-30nm were determined before and after 6-7 days of FQ ingestion and PI(clin) (minimal erythema dose without FQ/minimal erythema dose with FQ) calculated. Linear regression analysis of PI(vit) vs PI(clin) gave correlations of up to 0.893. Principal components analysis of PI(vit), daily dose, plasma levels and photophysical (absorption) properties of the eight FQ showed that phototoxic (arbitrarily defined as PI(clin)> or =2) and non-phototoxic (PI(clin)<2) FQ could be completely discriminated using these parameters, and that the in vitro models were able to rank the relative phototoxic potential of the eight FQ.

Animals↗
PubMed2000

Time course of skin photosensitivity following trimethylpsoralen bath PUVA.

One aspect of bath photochemotherapy (PUVA) that requires clarification is the duration of psoralen-induced cutaneous photosensitisation under conditions simulating clinical use. Using a half back comparison study technique, we investigated the persistence of trimethylpsoralen (TMP)-induced photosensitivity in skin irradiated to simulate a first PUVA exposure compared with un-irradiated skin. Baseline UVA minimal erythema dose and minimal phototoxic dose (MPD) were determined in 13 healthy volunteers. After readings at 72 h, subjects were bathed in TMP bath water for 15 min and one half of the back was immediately exposed to 40% of the MPD. Test sites (1.5 cm2) on both halves of the back were then irradiated with a UVA dose series at 15 min, 5, 10, 24, 34, 48 and 72 h after the bath. MPD readings were recorded visually at 72 h after each UVA exposure. The UVA MED was >25 J/cm2 in all the subjects. At each time point, a phototoxic index (PI) was calculated as UVA MED/MPD. In un-irradiated skin, photosensitivity returned to normal (PI=1) within 24 h after the TMP bath. In contrast, skin pre-irradiated to simulate the first PUVA treatment was still significantly photosensitive (PI=2.3; P=0.002) at 48 h. Contrary to previous recommendations, these data suggest that patients should be advised to avoid ambient or artificial sources of UVA throughout their course of TMP bath PUVA to reduce the risk of phototoxic erythema.

Back↗
PubMed2000

The effect of whole-body sunbed ultraviolet A exposure on the pharmacokinetics of the photolabile drug nifedipine.

The calcium antagonist nifedipine absorbs ultraviolet A (UVA) radiation and readily photodegrades in vitro to a toxic nitroso-pyridine photoproduct. We examined whether whole body exposure of normal subjects to sunbed UVA radiation would affect the pharmacokinetics of nifedipine. Eight healthy, male, Caucasian volunteers (phototypes I-III) participated in this ethically approved, randomised, cross-over study. Each subject attended on 2 occasions, one week apart, and on each occasion was given a single oral dose (10 mg) of nifedipine following which blood samples were collected at 0, 0.5, 1. 1.5, 2, 2.5, 3, 3.5, 4, 5, 6 and 7 h. During one of the visits, 15 min after nifedipine ingestion, a whole-body UVA (sunbed comprising Philips R-UVA lamps) dose of 70% of the individual's predetermined minimal phototoxic dose was delivered over a period of 17-36 min. Plasma nifedipine levels were measured using a standard reverse-phase high-performance liquid chromatography method. The area under the plasma concentration-time curve (AUC) of nifedipine during the UVA irradiation session (median 206 ng x ml(-1) x h(-1)) was significantly higher than during the non-irradiation control session (median 174.5 ng x ml(-1) x h(-1)) (P=0.03; 95% C.I. for difference in medians 9.9 to 55.9 ng x ml(-1) x h(-1)). UVA irradiation did not significantly affect any of the other measured pharmacokinetic parameters (Cmax, t 1/2, tmax). We demonstrate that sunbed UVA irradiation does not lead to in vivo photodegradation of nifedipine in healthy humans after a single dose. The apparent increase in AUC during UVA irradiation may be due to slightly slower metabolism of nifedipine in the presence of toxic photoproduct(s) or due to blood distribution changes affecting liver blood flow.

Adult↗
PubMed2000

Guidelines for topical PUVA: a report of a workshop of the British photodermatology group.

Psoralen photochemotherapy [psoralen ultraviolet A (PUVA)] plays an important part in dermatological therapeutics, being an effective and generally safe treatment for psoriasis and other dermatoses. In order to maintain optimal efficacy and safety, guidelines concerning best practice should be available to operators and supervisors. The British Photodermatology Group (BPG) have previously published recommendations on PUVA, including UVA dosimetry and calibration, patient pretreatment assessment, indications and contraindications, and the management of adverse reactions.1 While most current knowledge relates to oral PUVA, the use of topical PUVA regimens is also popular and presents a number of questions peculiar to this modality, including the choice of psoralen, formulation, method of application, optimal timing of treatment, UVA regimens and relative benefits or risks as compared with oral PUVA. Bath PUVA, i.e. generalized immersion, is the most frequently used modality of topical treatment, practised by about 100 centres in the U.K., while other topical preparations tend to be used for localized diseases such as those affecting the hands and feet. This paper is the product of a recent workshop of the BPG and includes guidelines for bath, local immersion and other topical PUVA. These recommendations are based, where possible, on the results of controlled studies, or otherwise on the consensus view on current practice.

Administration, Oral↗
PubMed2000

Design of the blockade of the glycoprotein IIb/IIIa receptor to avoid vascular occlusion (BRAVO) trial.

BACKGROUND: Platelets play a key role in the pathogenesis of atherosclerosis, thrombosis, and acute coronary and cerebrovascular syndromes. Inhibition of platelet function by acetylsalicylic acid (aspirin) has been shown to reduce the incidence atherothrombotic events in patients with coronary, cerebrovascular, or peripheral vascular disease. Thienopyridine agents, however, including ticlopidine and clopidogrel, inhibit the adenosine diphosphate receptor and have modestly superior effects compared with aspirin on reduction of death, myocardial infarction, and stroke among a broad group of patients with vascular disease. More effective antithrombotic agents are still required to treat patients at high risk for recurrent vascular events. METHODS: Lotrafiban, a selective, nonpeptide antagonist of the human platelet fibrinogen receptor (glycoprotein [GP] IIb/IIIa [alphaIIb/beta3 integrin]), blocks the binding of fibrinogen to the GP IIb/IIIa receptor, which is the final common pathway of platelet aggregation. Lotrafiban at doses of up to 50 mg twice daily was well-tolerated in a 12-week, double-blind, placebo-controlled, dose-ranging study in patients with recent myocardial infarction, unstable angina, transient ischemic attack, or stroke when added to aspirin therapy. On the basis of these results, a dosing regimen was selected for the phase III Blockage of the Glycoprotein IIb/IIIa Receptor to Avoid Vascular Occlusion (BRAVO) trial based on pharmacodynamics and drug tolerability. In the pivotal BRAVO study, lotrafiban therapy is being evaluated in patients who have had a recent myocardial infarction, unstable angina, transient ischemic attack, or ischemic stroke, or who present at any time after a diagnosis of peripheral vascular disease combined with either cardiovascular or cerebrovascular disease. RESULTS: The efficacy evaluation will be based on a composite end point of clinical events (death by any cause, myocardial infarction, stroke, recurrent ischemia requiring hospitalization, or urgent ischemia-driven revascularization). The target enrollment is 9200 patients worldwide. Approximately 700 centers will participate and will be distributed within 30 countries across North America, Europe, Australia, and Asia.

Administration, Oral↗
PubMed2000

A comparison of the photosensitizing potential of trovafloxacin with that of other quinolones in healthy subjects.

Treatment with some quinolones is associated with an abnormal skin reaction following exposure to sunlight (photosensitivity). The objective of the current study was to compare the photosensitizing potential of a new quinolone, trovafloxacin, with that of ciprofloxacin, lomefloxacin and placebo. Forty-eight healthy males (age range 19-45 years) were randomized to receive a 7 day course of treatment with: (i) trovafloxacin 200 mg od; (ii) ciprofloxacin 500 mg bd; (iii) lomefloxacin 400 mg od; or (iv) placebo bd. Minimal erythema doses (MEDs) were assessed using a monochromator at baseline and on day 5 of treatment, for wavelengths of 305 +/- 5, 335 +/- 30, 365 +/- 30, 400 +/- 30 and 430 +/- 30 nm; 335 +/- 30 and 365 +/- 30 nm are within the UVA range. Immediate reaction MEDs were similar in all treatment groups. However, between baseline and day 5, the mean decreases in delayed-reaction MED (24 h) at 335 +/- 30 nm were only 18.99% for trovafloxacin versus placebo (P = 0.1267), compared with 53.77% (P 0.0001) and 64.13% (P 0.0001) for ciprofloxacin and lomefloxacin, respectively. Similarly, at 365 +/- 30 nm, trovafloxacin produced the smallest reduction in delayed MED versus placebo (43.66%), compared with ciprofloxacin (61.53%) and lomefloxacin (75.81%). These differences between trovafloxacin and ciprofloxacin and lomefloxacin were significant at both 335 +/- 30 and 365 +/- 30 nm (P 0.029). All MED values returned to baseline levels within 2 days of drug cessation. These results show that trovafloxacin has significantly less photosensitizing potential than either ciprofloxacin or lomefloxacin. This photosensitivity appears to be induced only by wavelengths in the UVA region, is maximal at 24 h and is a short-term effect.

Adult↗
PubMed2000

An outbreak of skin sepsis in abattoir workers caused by an 'unusual' strain of Streptococcus pyogenes.

An outbreak of indolent skin infections due to an 'unusual' serological type of Streptococcus pyogenes that lasted for 3 months and affected eight workers in an abattoir is described. The group A streptococcal (GAS) isolates were serotyped as M-type 59; however, they possessed a T-protein pattern (T5/27/44) that is not commonly associated with M-type 59. Further genotypic characterisation studies revealed that all eight isolates were indistinguishable by pulsed-field gel electrophoresis (PFGE) and possessed the emm gene encoding for the M-type 59. Once identified, and after a combination of penicillin treatment, exclusion of workers with lesions and reinforcement of standard hygiene precautions, no further cases developed. Although common in the 1970s and 1980s, streptococcal infections in this situation are now reported infrequently. This report serves to highlight the issues surrounding working practices in abattoirs.

Abattoirs↗
PubMed2000

Herpes simplex virus type 1 U(L)34 gene product is required for viral envelopment.

The herpes simplex virus type 1 U(L)34 gene encodes a protein that is conserved in all human herpesviruses. The association of the U(L)34 protein with membranes in the infected cell and its expression as a gamma-1 gene suggest a role in maturation or egress of the virus particle from the cell. To determine the function of this gene product, we have constructed a recombinant virus that fails to express the U(L)34 protein. This recombinant virus, in which the U(L)34 protein coding sequence has been replaced by green fluorescent protein, forms minute plaques and replicates in single-step growth experiments to titers 3 to 5 log orders of magnitude lower than wild-type or repair viruses. On Vero cells, the deletion virus synthesizes proteins of all kinetic classes in normal amounts. Electron microscopic and biochemical analyses show that morphogenesis of the deletion virus proceeds normally to the point of formation of DNA-containing nuclear capsids, but electron micrographs show no enveloped virus particles in the cytoplasm or at the surface of infected cells, suggesting that the U(L)34 protein is essential for efficient envelopment of capsids.

Animals↗
PubMed2000

Integration tutorials and seminars: a creative learning approach for occupational therapy curricula.

This paper, the first of two companion papers, describes a creative learning approach. Integration Tutorials and Seminars were developed to address concerns of regional fieldwork-education coordinators and preceptors about the ability of third-year student occupational therapists to integrate and apply academic and theoretical knowledge during fieldwork. This ability can be gained through experiential learning in the academic setting and is essential for the effective transfer of academic learning into the students' fieldwork-education experiences (Dale, 1994; Fidler, 1996; McCaugherty, 1991; Neistadt, 1996). The Modified Learning Model of Svinicki and Dixon (1987) was used as a template for an academic course fostering experiential learning. An important secondary goal was to nurture student self-directedness in learning using the philosophy of the Staged Self-Directed Learning Model (Grow, 1991). Case studies were used as a vehicle for engaging and challenging the students. The philosophy, guidelines and process of the Integration Tutorials and Seminars are presented and have the potential to be adapted for occupational therapy curricula around the globe.

Curriculum↗
PubMed2000

Transfer of telemedical support to Cornwall from a national telemedicine network during a solar eclipse.

During late 1998 and early 1999, planning officers in Cornwall predicted a huge increase in summer visitors to the county to observe the August solar eclipse. There was the possibility that a mass gathering in Cornwall could overload existing arrangements for handling accident and emergency patients. We therefore set up a telemedicine system to support the county's minor injury units (MIUs) from hospitals throughout the UK. Six main hospital accident and emergency departments outside Cornwall with existing links to their own MIUs were twinned with 10 of the 11 MIUs in Cornwall before the expected date of the gathering. The network was live for nine days, starting four days before the eclipse, and 2045 patients were seen in the 10 MIUs. There were 93 telemedicine calls from the 10 MIUs, involving 91 patients. Overall, 4.6% of the patients required a telemedicine consultation. Fifty-seven calls were made during working hours. Thirty-four patients were referred for further management, of whom 18 were referred on the same day. The transfer of telemedical support to a national network was successful.

Emergency Medical Services↗
PubMed1999

Tissue-specific expression of functional isoforms of mouse folypoly-gamma-glutamae synthetase: a basis for targeting folate antimetabolites.

Folates and folate antimetabolites are metabolically trapped in mammalian cells as polyglutamates, a process catalyzed by folylpoly-gamma-glutamate synthetase (FPGS). Using 5'-rapid amplification of cDNA ends, RNase protection assays, transfection of cDNAs into FPGS-deficient cells, and kinetic analysis of recombinant enzymes expressed in insect cells, it was determined that the species of active FPGS in mouse liver and kidney was different from that in mouse tumor cells, bone marrow, and intestine. The NH2-terminal peptide of hepatic enzyme contained 18 amino acids not found in enzyme from dividing tissues, and the specificity of the two isoforms for antifolates also differed, suggesting different architecture of the active sites. In most tissues, the expression of one isozyme or the other was an all-or-nothing event. The exclusive use of one of two alternative sets of initial coding exons in different tissues underlies this phenomenon, suggesting the design of antifolates specific for activation by individual FPGS isoforms and hence tissue-selective targeting of antifolate therapy for cancer, arthritis, or psoriasis.

Amino Acid Sequence↗
PubMed1999

The idiopathic photodermatoses.

The idiopathic photodermatoses present a challenge for dermatologists. Although, as in other specialty areas, the classical clinical presentation produces few problems, it is the severe forms and overlap cases that cause the most difficulty. It is fortunate that the semi-objective investigation of phototesting is available, which, when conducted carefully, reveals so much about the nature of this group of conditions. This essential investigation not only helps achieve a diagnosis, but also affords material for study and a means of monitoring therapy response or progress towards spontaneous resolution. Although these conditions are grouped together, throughout this century we have seen a continuing process of distinct diseases emerging as a consequence of careful clinical observation and investigation.

Age Factors↗
PubMed1999

Experience, knowledge and attitudes of mental health staff regarding patients' problematic drug and alcohol use.

OBJECTIVE: The aim of this study was to assess the experience, knowledge and attitudes of mental health staff regarding patients' problematic drug and alcohol use in order to provide direction for planned drug and alcohol education. METHOD: A 47-item questionnaire was developed and individually posted to all mental health staff employed by Central Sydney Area Health Service (n = 536). RESULTS: Three hundred and thirty-eight (63%) staff members completed the questionnaire. Thirty-six percent of respondents had received drug and alcohol training and 41% had drug and alcohol work experience. Drug and alcohol training and work experience were associated with increased drug and alcohol knowledge. Respondents' perception of their knowledge and competence was positively correlated with their actual knowledge. Most staff reported having regular contact with patients with psychotic illnesses and drug and alcohol problems. The majority considered the management of this patient group difficult and currently inadequate. Seventy percent believed that as mental health professionals they had a role to play in the management of their patients' drug and alcohol problems. Almost all (95%) were willing to participate in further education and training in this area. CONCLUSIONS: Mental health staff are often confronted with drug and alcohol problems in patients with psychotic illnesses. They perceive a need for drug and alcohol education and training specific to the management of these patients. Future research will need to evaluate outcomes of education and training programs for both staff and patients.

Adult↗