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Biomedical subjects

J Ferguson

Publications and source records attributed to J Ferguson.

At least 91 records · Page 5Linked to original sources
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 This recombinant virus, in which the U(L)34 protein coding sequence has been replaced by green fluorescent protein, forms minute plaques and replicates in single-step growth experiments to titers 3 to 5 log orders of magnitude lower than wild-type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↗
PubMed1999

Management of biliary tract complications following liver transplantation.

BACKGROUND: A review of biliary tract complications was performed in 32 patients who underwent liver transplantation by the Western Australian Liver Transplantation Service during a 2-year period. METHODS: A review was made of patient data collected prospectively, and confirmed by retrospective casenote review. RESULTS: A total of 30 patients (31 grafts) survived more than 2 days after transplantation, and of these 28 had an end-to-end biliary anastomosis. Analysis of these 28 patients found that eight of 17 patients with T-tubes had complications: three leaks at T-tube removal; two strictures and leaks; and three strictures. Six of 11 patients without a T-tube had complications: one leak; three strictures and leaks; and two strictures. Predisposing factors were present in eight of the 14 patients with biliary tract complications: hepatic artery stenosis in three; and one each with hepatic artery thrombosis; biliary calculi; donor-recipient bile duct mismatch; severe cellular rejection: and prolonged postoperative hypotension. Acute rejection, steroid-resistant rejection and cytomegalovirus infection were all significantly more common in those patients with biliary tract complications compared with those without. There was no difference in cold ischaemic time or donor age. Twelve of the 14 patients with biliary complications required endoscopic stenting with or without balloon dilation, and eight patients required radiological percutaneous drainage of bile collections. Only one patient required biliary reconstruction and two patients required re-transplantation. One patient died of uncontrolled infection. Of three patients who underwent choledochojejunostomy, biliary leak developed in two patients, both of whom required operative biliary and hepatic repair. One of the three patients died from disseminated Aspergillus infection. The median total hospital stay of patients with biliary complications was 61 days (range: 30-180 days) compared with 33.5 days (range: 22-70 days) for patients without. Of patients with end-to-end biliary anastomosis, 50% had biliary tract complications and more than half of these had predisposing factors. The majority of biliary complications were managed without the need for surgery. CONCLUSION: A total of 50% of patients with end-to-end biliary anastomosis had biliary tract complications. Biliary strictures presented later than leaks, and the majority of these complications were managed without the need for surgery.

Adolescent↗
PubMed1999

Myelination and behaviour of tenascin-C null transgenic mice.

The extracellular matrix glycoprotein tenascin-C is widely expressed during development and repair, making it surprising that few abnormalities have been found in transgenic mice lacking this molecule. We have therefore re-examined the transgenic mice described by Saga et al. [Saga, Y., Yagi, T., Ikawa, Y., Sakakura, T. & Aizawa, S. (1992) Genes Dev., 6 1821-1831] in which tenascin-C was knocked-out by homologous recombination, focusing on two aspects of the nervous system likely to reveal any abnormalities that might follow the loss of tenascin-C. First, we have determined the pattern of myelin and distribution of oligodendrocyte precursor cells in those areas, such as the optic nerve and retina where local concentrations of tenascin-C have been proposed to act as barriers to oligodendrocyte precursor migration and so prevent inappropriate myelination. Secondly, we have examined the behaviour of the mice in a number of well-characterized tests, e.g. beam-walking, passive avoidance and the Morris water maze. We find no abnormalities of myelination or oligodendrocyte precursor distribution in adult mice, showing that local concentrations of tenascin-C are not the sole mechanism responsible for the pattern of myelination in these regions of CNS. However, we do find a number of behavioural abnormalities in these mice and show that hyperlocomotion and deficits in coordination during beam walking can be ascribed to tenascin-C deficiency. The effects on coordination are, however, not seen on a 129 genetic background. Taken together, these results significantly extend the phenotype associated with tenascin-C deficiency but argue against a role in myelination.

Animals↗
PubMed1999

A genomic screen of autism: evidence for a multilocus etiology.

We have conducted a genome screen of autism, by linkage analysis in an initial set of 90 multiplex sibships, with parents, containing 97 independent affected sib pairs (ASPs), with follow-up in 49 additional multiplex sibships, containing 50 ASPs. In total, 519 markers were genotyped, including 362 for the initial screen, and an additional 157 were genotyped in the follow-up. As a control, we also included in the analysis unaffected sibs, which provided 51 discordant sib pairs (DSPs) for the initial screen and 29 for the follow-up. In the initial phase of the work, we observed increased identity by descent (IBD) in the ASPs (sharing of 51.6%) compared with the DSPs (sharing of 50.8%). The excess sharing in the ASPs could not be attributed to the effect of a small number of loci but, rather, was due to the modest increase in the entire distribution of IBD. These results are most compatible with a model specifying a large number of loci (perhaps >/=15) and are less compatible with models specifying </=10 loci. The largest LOD score obtained in the initial scan was for a marker on chromosome 1p; this region also showed positive sharing in the replication family set, giving a maximum multipoint LOD score of 2.15 for both sets combined. Thus, there may exist a gene of moderate effect in this region. We had only modestly positive or negative linkage evidence in candidate regions identified in other studies. Our results suggest that positional cloning of susceptibility loci by linkage analysis may be a formidable task and that other approaches may be necessary.

Adolescent↗
PubMed1999

Fluoroquinolone phototoxicity: a comparison of moxifloxacin and lomefloxacin in normal volunteers.

Moxifloxacin, a broad-spectrum fluoroquinolone with the methoxy group at position 8 of the quinolone structure that is believed to confer reduced phototoxicity, was investigated in 32 healthy human male volunteers by a randomized double-blind placebo and positive control (lomefloxacin) phototest technique. A comparison of pre- and on-drug photosensitivity levels tested with an irradiation monochromator using relevant sunlight wavelengths, failed to demonstrate phototoxicity after administration of either placebo or moxifloxacin (200 mg or 400 mg/day) for 7 days. As expected, lomefloxacin (400 mg/day) phototoxicity was revealed at the UVA wavebands 335 +/- 30 nm and 365 +/- 30 nm (maximal at 24 h), with a phototoxic index of 3-4. The susceptibility to this effect rapidly normalized within 48 h of stopping the drug. No special protection from UVA wavelengths is necessary for those taking moxifloxacin.

Adult↗
PubMed1999

Prescribing of beta-2 agonists and inhaled steroids in England: trends between 1992 and 1998, and association with material deprivation, chronic illness and asthma mortality rates.

BACKGROUND: British Thoracic Society guidelines published in 1990, revised in 1993 and 1997, recommended that general practitioners should make greater use of inhaled steroids in the management of asthma. British Thoracic Society guidelines have also been published on the management of chronic obstructive pulmonary disease. The objective of this study was to examine trends in the prescribing of beta-2 agonists and inhaled steroids in England between 1992 and 1998, and to investigate the variation at health authority level in the use of these drugs. METHODS: This was an observational study using prescribing analysis and cost (PACT) data, mortality data and data from the 1991 Census for all 100 health authorities in England. RESULTS: The number of defined daily doses of beta-2 agonists prescribed per quarter increased by 20 per cent, from 142 million to 170 million between June 1992 and March 1998. The number of defined daily doses of inhaled steroids prescribed per quarter increased by 78 per cent during the same period, from 69.9 million to 124.7 million. The ratio of inhaled steroids to beta-2 agonists increased from 0.49 to 0.73. The number of items per 1000 specific therapeutic group age-sex related prescribing units (STAR-PUs) in 1997 in health authorities in England varied from 41 to 115 for beta-2 agonists and from 24 to 68 for inhaled steroids. The ratio of the number of items of inhaled steroids to beta-2 agonists varied from 0.50 to 0.70. At health authority level, prescribing rates were most strongly associated with the percentage of patients reporting chronic illness (correlation coefficient 0.82 for beta-2 agonists and 0.72 for inhaled steroids). There were significant negative correlations between the ratio of inhaled steroids to beta-2 agonists and both Jarman deprivation scores (r = -0.51) and chronic illness (r = -0.38). There were no significant associations between health authority prescribing rates and death rates from asthma in people aged 5-44 years. CONCLUSIONS: Prescribing of inhaled steroids has risen more quickly than that of beta-2 agonists between 1992 and 1998, resulting in a marked increase in the ratio of inhaled steroids to beta-2 agonists. At health authority level, there remains a wide variation in the use of beta-2 agonists and inhaled steroids.

Administration, Inhalation↗
PubMed1999

Placebo-controlled, multicenter study of sertraline treatment for obsessive-compulsive disorder.

The safety and efficacy of sertraline versus placebo were examined in a group of nondepressed outpatients with obsessive-compulsive disorder (OCD). Patients with moderate-to-severe OCD were recruited at 10 sites. After a 1-week placebo lead-in, patients were treated in a double-blind fashion for 12 weeks with sertraline or placebo. Sertraline was administered at a starting dose of 50 mg/day, with flexible titration up to 200 mg/day. The efficacy measures were the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), the National Institute of Mental Health Global Obsessive Compulsive Scale (NIMH), and the Clinical Global Impression Scale (CGI) Severity of Illness and Improvement subscales. One hundred sixty-seven patients were randomly assigned and received at least one dose of double-blind medication: 86 received sertraline and 81 received placebo. All efficacy measures showed significantly greater improvement in the sertraline group from the end of week 8 until the end of week 12. Significantly greater improvement (p < 0.05) in the sertraline group first became apparent by the end of week 3 on the Y-BOCS and the CGI Improvement scale, and by the end of weeks 6 and 8, respectively, on the NIMH and CGI Severity scale. Sertraline was well tolerated, without serious adverse effects. In conclusion, sertraline was safe and effective in the treatment of patients with OCD.

Adult↗