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Biomedical subjects

G Francis

Publications and source records attributed to G Francis.

At least 19 recordsLinked to original sources
PubMed2005

Prospective assessment of changing from placebo to IFN beta-1a in relapsing MS: the PRISMS study.

The efficacy of interferon (IFN) beta has been shown in several placebo-controlled, parallel-group studies in relapsing-remitting multiple sclerosis (RRMS). PRISMS, the largest such study to date, clearly demonstrated the efficacy of IFN beta-1a on all outcome measures over 2 years during the placebo-controlled, parallel-group phase. However, this study's placebo-crossover design also provided us with a unique opportunity to conduct a prospective within-group assessment, eliminating the impact of inter-patient variability. At the start of year 3, patients receiving placebo during years 1-2 were re-randomized in a dose-blinded fashion to receive IFN beta-1a, 22 or 44 mcg subcutaneously three times weekly, during years 3 and 4. Clinic visits occurred 3-6 monthly and T2 MRI scans were obtained after 1 and 2 years on therapy. Comparison of the mean relapse count per patient over 2 years (the primary outcome measure) during time on placebo (years 1 and 2) with that during active treatment (years 3 and 4) revealed a decrease from 2.6 to 1.2 in both dose groups (54% relative reduction; p<0.001). Disability progression, T2 MRI lesion activity and accumulation of T2 lesion burden were also significantly improved with therapy (p<0.01). No new safety issues were noted. These data provide further support for IFN beta-1a's efficacy in RRMS. The ability to detect significant treatment effects with reduced patient numbers in this type of before/after analysis, may be due to the reduction in inter-patient variability.

Adult↗
PubMed2005

Interferon-beta-1a induces increases in vascular cell adhesion molecule: implications for its mode of action in multiple sclerosis.

We investigated soluble vascular cell adhesion molecule-1 (sVCAM) levels and MRI lesions over 24 weeks in 15 Relapsing Remitting MS (RRMS) patients randomized prospectively to receive once-weekly (qw) IFN-beta-1a 30 mug intramuscularly (IM) (Group I, 8 patients) or three-times-weekly (tiw) IFN-beta-1a 44 mug subcutaneously (SC) (Group II, 7 patients). Both groups demonstrated a significant increase in sVCAM during treatment when compared to pre-treatment levels. Patients on IFN-beta-1a 44 mug SC tiw had a significant (p<0.0001) mean increase in sVCAM of 321.9 ng/ml which was significantly greater (p<0.0001) than with IFN-beta-1a 30 mug IM qw (68.6 ng/ml). There was a negative correlation between combined unique (CU) MRI lesions and sVCAM levels within the IFN-beta-1a 44 mug SC tiw group (slope=-0.00106, p=0.009). We postulate that the mode of action of IFN-beta therapy in MS may involve the induction of an increase in sVCAM. sVCAM could bind VLA-4 on T-cells and intercept their adhesion to the blood brain barrier (BBB). This mechanism is consistent with the observed clinical effect of IFN-beta in reducing MRI contrast enhancing lesions.

Analysis of Variance↗
PubMed2004

Clinical implementation of dynamic intensity-modulated radiotherapy: radiographers' perspectives.

The ability of intensity-modulated radiotherapy (IMRT) to sculpt the dose distribution closely around the tumour volume has the potential to have a major impact on radiotherapy clinical practice. However, dynamic IMRT treatment delivery differs from that of conventional treatment because of the constantly moving multileaf collimators (MLCs) and higher monitor units (MUs) required. The implementation of new technology can be affected by the users response. Radiographers' attitudes regarding technology and their perceptions of the clinical implementation of IMRT were explored using a qualitative study based on semi-structured interviews. 16 radiographers were interviewed and data was analysed using a framework analysis to identify themes and categories. The majority of radiographers (12/16) demonstrated positive attitudes regarding technology. The introduction of IMRT was seen to be stimulating and motivating. Negative aspects were associated with increased stress from learning new skills and the additional pressure of the increased workload. Although there were contradictory views regarding the effect of the increased use of technology on the patient-radiographer relationship, technological skills and patient care were not found to be mutually exclusive. Radiographers' perceptions regarding the clinical implementation of IMRT appeared to be influenced by their mainly positive attitudes regarding technology. With the current problems of recruitment and retention of radiographers, full exploitation of modern technology could be used to improve job satisfaction. However, careful integration is required to balance training needs with service demands.

Adult↗
PubMed2003

Clinical applications of B-type natriuretic peptide (BNP) testing.

Many claims have been made in recent years regarding the utility of plasma B-type natriuretic peptide (BNP) concentration measurements in the diagnosis, risk stratification and monitoring of patients with heart failure. This paper summarizes the current evidence and provides guidance for practising clinicians. Overall, plasma BNP testing appears to be of most value in the diagnostic arena, where it is likely to improve the performance of non-specialist physicians in diagnosing heart failure. In clinical practice, BNP testing is best used as a 'rule out' test for suspected cases of new heart failure in breathless patients presenting to either the outpatient or emergency care settings; it is not a replacement for echocardiography and full cardiological assessment, which will be required for patients with an elevated BNP concentration. Although work is ongoing in establishing the 'normal' values of BNP, heart failure appears to be highly unlikely below a plasma concentration of 100 pg/ml. However, as BNP levels rise with age and are affected by gender, comorbidity and drug therapy, the plasma BNP measurement should not be used in isolation from the clinical context.

Ambulatory Care↗
PubMed2002

Randomized, comparative study of interferon beta-1a treatment regimens in MS: The EVIDENCE Trial.

BACKGROUND: Interferon beta (IFNbeta) reduces relapses and MRI activity in relapsing-remitting MS (RRMS), with variable effects on disability. The most effective dose regimen remains controversial. METHODS: This randomized, controlled, multicenter trial compared the efficacy and safety of IFNbeta-1a (Rebif) 44 micro g subcutaneously three times weekly (tiw), and IFNbeta-1a (Avonex) 30 micro g IM once weekly (qw) in 677 patients with RRMS. Assessors blinded to treatment performed neurologic and MRI evaluations. The primary endpoint was the proportion of patients who were relapse free at 24 weeks; the principal MRI endpoint was the number of active lesions per patient per scan at 24 weeks. RESULTS: After 24 weeks, 74.9% (254/339) of patients receiving IFNbeta-1a 44 micro g tiw remained relapse free compared with 63.3% (214/338) of those given 30 micro g qw. The odds ratio for remaining relapse free was 1.9 (95% CI, 1.3 to 2.6; p = 0.0005) at 24 weeks and 1.5 (95% CI, 1.1 to 2.1; p = 0.009) at 48 weeks, favoring 44 micro g tiw. Patients receiving 44 micro g tiw had fewer active MRI lesions (p < 0.001 at 24 and 48 weeks) compared with those receiving 30 micro g qw. Injection-site reactions were more frequent with 44 micro g tiw (83% vs 28%, p < 0.001), as were asymptomatic abnormalities of liver enzymes (18% vs 9%, p = 0.002) and altered leukocyte counts (11% vs 5%, p = 0.003) compared with the 30 micro g qw dosage. Neutralizing antibodies developed in 25% of 44 micro g tiw patients and in 2% of patients receiving 30 micro g qw. CONCLUSIONS: IFNbeta-1a 44 micro g subcutaneously tiw was more effective than IFNbeta-1a 30 micro g IM qw on all primary and secondary outcomes investigated after 24 and 48 weeks of treatment.

Adolescent↗
PubMed2002

A new cell line-based neutralization assay for primary HIV type 1 isolates.

Simple and standardized assays for detection and quantification of neutralizing antibodies to primary HIV-1 isolates are needed in research on HIV-1 vaccines and pathogenesis. Here we describe a new HIV-1 neutralization assay that is based on plaque formation in U87.CD4-CCR5 and U87.CD4-CXCR4 cells, which is an attractive alternative to peripheral blood mononuclear cell-based assays. Infected cells form syncytia, that is, plaques, that can be stained with hematoxylin and enumerated by light microscopy. Neutralization is determined by the ability of a serum to reduce the number of plaque-forming units (PFU) relative to controls exposed to medium or negative serum. The intraassay variation of the plaque-forming unit determinations was tested with 15 serum-virus combinations and showed good reproducibility. The differences ranged from -19 to +27% and had a standard deviation of +/- 9.1%. On the basis of these data the cutoff for neutralization (i.e., plaque reduction) was set to 30% (3.3 standard deviations). Virus titration experiments showed that neutralization results were dependent on virus dose and therefore the neutralization assays should be performed with a virus dose of 10-100 PFU/well. The reproducibility of the new neutralization assay was tested with 4 primary viruses and 9 sera for a total of 20 virus-serum combinations. The mean difference in neutralization (i.e. plaque reduction) determinations performed on different days was as small as 11%. None of 10 Swedish sera and 1 Ugandan plasma pool from HIV-1-uninfected subjects were positive for neutralization, indicating that the assay has high specificity. In summary, the new U87.CD4 cell line-based neutralization assay for primary HIV-1 isolates is a highly reproducible, sensitive, and high-throughput assay that is well suited for large-scale HIV-1 neutralization studies.

CD4-Positive T-Lymphocytes↗
PubMed2002

The efficacy of lidocaine administered via the LITA tracheal tube in attenuating the extubation response in beta-blocked patients following craniotomy.

The Laryngotracheal Instillation of Topical Anaesthetic (LITA) tracheal tube has an additional pilot tube through which local anaesthetic can be instilled into the larynx via 10 small holes above and below the cuff We studied 40 patients undergoing supratentorial craniotomy. They were premedicated with two oral doses of propranolol 1 mg.kg(-1). The anaesthetic consisted of infusions of remifentanil, propofol and vecuronium. On insertion of the first skin clip at the end of surgery, 5 ml of either saline or 2% lidocaine was injected into the appropriate lumen of the tracheal tube. There was no difference between the groups in the degree of coughing or the haemodynamic response to tracheal extubation.

Adolescent↗
PubMed2001

Perceived motion in orientational afterimages: direction and speed.

Two sets of experiments demonstrate new properties of motion in orientational after-effects. In a previous report, we showed that when observers adapted to a static bar grating whose elements varied in size or intensity from one side to the other, offset of the grating resulted in a motion after-effect, with the perceived motion in the direction of the largest or most intense bar. In the first new experiment, we show that similar results can be produced by varying the duration of the bar elements, with the direction of the motion after-effect toward the bar with the longest duration. In the second new experiment we demonstrate that the perceived speed of the motion after-effect is influenced by the spatial extent of the after-effect, with larger extents corresponding to faster speeds. The experimental findings are discussed in the context of a neural network theory of visual perception. In this theory, a moving oriented contour leaves a trail of activity among cortical cells tuned to orthogonal orientations. We hypothesize that the grating stimuli produce after-effects that mimic the pattern of oriented responses produced by a true moving contour, and the visual system interprets this pattern as a cue for motion. We also show how the model connects the properties of these motion after-effects to properties of visual persistence.

Figural Aftereffect↗
PubMed2001

Genetic susceptibility to MS: a second stage analysis in Canadian MS families.

Four published genome screens have identified a number of markers with increased sharing in multiple sclerosis (MS) families, although none has reached statistical significance. One hundred and five markers previously identified as showing increased sharing in Canadian, British, Finnish, and American genome screens were genotyped in 219 sibling pairs ascertained from the database of the Canadian Collaborative Project on Genetic Susceptibility to MS (CCPGSMS). No markers examined met criteria for significant linkage. Markers located at 5p14 and 17q22 were analyzed in a total of 333 sibling pairs and attained mlod scores of 2.27 and 1.14, respectively. The known HLA Class II DRB1 association with MS was confirmed (P<0.0001). Significant transmission disequilibrium was also observed for D17S789 at 17q22 (P=0.0015). This study highlights the difficulty of searching for genes with only mild-to-moderate effects on susceptibility, although large effects of specific loci may still be present in individual families. Future progress in the genetics of this complex trait may be helped by (1) focussing on more ethnically homogeneous samples, (2) using an increased number of MS families, and (3) using transmission disequilibrium analysis in candidate regions rather than the affected relative pair linkage analysis.

Canada↗
PubMed2001

Effects of Quillaja saponins on growth, metabolism, egg production and muscle cholesterol in individually reared Nile tilapia (Oreochromis niloticus).

The effects of supplementation of a Quillaja saponin (QS) mixture in the diets of tilapia have been studied using a respirometer system that allowed feeding and continuous measurement of oxygen consumption of individual fish. Five fish each were given control diet (C group) and control diet supplemented with 150 mg kg(-1) (S150 group) or 300 mg kg(-1) (S300 group) QS. At the end of 14 weeks the weight gain of the S300 group was significantly higher than control (P<0.05) whereas that of the S150 group had an intermediate value. The S150 group had a higher growth rate (P=0.05) after the first 3 weeks of feeding with the experimental diets, compared to the other two groups. At the end of the experiment the S300 group had significantly higher (P<0.05) average values for energy retention, apparent lipid conversion, carcass fat, energy and significantly lower (P<0.05) average values for apparently unutilised energy and carcass ash content compared to the C group. The corresponding values of the S150 group were intermediate between the C and S300 groups. One out of two female fish in the S150 group and both female fish in the S300 group never produced eggs during the entire 14-week experimental period. Contrarily, all three female fish in the control group and one out of the two female fish in the S150 group regularly produced eggs, at a rate of approximately once in every 14 days. The muscle cholesterol level in the S300 group was significantly higher than that of the C group. Possible mechanisms of action of the dietary saponins are discussed.

Animals↗
PubMed2001

Working patterns of trainee anaesthetists in the UK: results of a national postal survey.

The 'New Deal' restrictions on junior doctors' hours have major implications for the staffing of anaesthetic departments and the provision of adequate training. The results of a national postal survey demonstrate a decline in traditional on-call arrangements, especially in hard-pressed work sectors such as intensive care. A substantial number of anaesthetic departments have still completely to satisfy the hours restrictions in many work sectors. Many departments experience recruitment difficulties and express concern about both service and training issues.

Accreditation↗
PubMed2000

Treatment of acute disseminated encephalomyelitis with intravenous immunoglobulin.

Acute disseminated encephalomyelitis (ADEM) is a presumed immune-mediated, demyelinating disease of the CNS for which the standard treatment is high-dose steroids. We describe two patients with ADEM in whom treatment with IV methylprednisolone coincided with deterioration in their clinical status. They were subsequently treated with IV immunoglobulin and exhibited dramatic clinical improvement, with return to their previous level of functioning.

Acute Disease↗
PubMed2000

Quantitative theories of metacontrast masking.

In metacontrast masking, the effect of a visual mask stimulus on the perceptual strength of a target stimulus varies with the stimulus-onset asynchrony (SOA) between them. As SOA increases, the target percept first becomes weaker, bottoms out at an intermediate SOA, and then increases for still larger SOAs. As a result, a plot of target percept strength against SOA produces a U-shaped masking curve. Theories have proposed special mechanisms to account for this curve, but new mathematical analyses indicate that it is a robust characteristic of a large class of neurally plausible systems. The author describes 3 quantitative methods of accounting for the U-shaped masking effect and analyzes 4 previously published mathematical models of masking. The models produce the masking curve through mask blocking, whereby a strong internal representation of the target blocks the mask's effects.

Cognition↗
PubMed2000

The RAFFT as a screening tool for adolescent substance use disorders.

The objective of this study was to measure the sensitivity and specificity of the RAFFT, a screening instrument for problematic adolescent substance use. Two hundred and twenty-six adolescent patients, aged 13 to 18, who were referred to an emergency room or an ambulatory evaluation clinic were included. Patients answered the five questions of the RAFFT before a comprehensive psychiatric assessment was completed. Diagnoses were made according to DSM-IV. The best results were obtained with two positive answers on the RAFFT: a sensitivity of 89% and a specificity of 69% in the screening for substance abuse or dependence. The RAFFT performed well in this highly selected patient population.

Adolescent↗
PubMed2000

Perceived motion in complementary afterimages: verification of a neural network theory.

Steady fixation of a regular pattern like a bar grating or concentric circles leads to a complementary afterimage at pattern offset. The afterimage has the appearance of shimmering lines that are locally orthogonal to the orientations of the inducing image. Additionally, the afterimage includes motion running parallel to the orientation of the afterimage lines. We argue that this afterimage motion supports the existence of a cue to motion that is based on the spatial organization of oriented responses. This cue was previously proposed after analysis of a neural network model of visual perception. We test predictions of the model on various types of complementary afterimage inducing stimuli. When a contrast or size gradient is included in the inducing image, the afterimage motion moves toward the higher part of the gradient, in agreement with the model. Implications of this cue for computational and neurophysiological theories of motion perception are discussed.

Figural Aftereffect↗