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Biomedical subjects

G Francis

Publications and source records attributed to G Francis.

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

Cost and health related quality of life consequences of multiple sclerosis.

OBJECTIVES: To (i) quantify the cost of multiple sclerosis (MS) to the Canadian health care system and society; (ii) measure health utility in MS patients, and (iii) examine the influence of disability on patient utility and health care costs. MATERIALS AND METHODS: A comprehensive patient survey and chart review of relapsing MS patients in remission, relapse and recalling a relapse. RESULTS: Annual remission costs increased with EDSS level ($7596 at EDSS 1, $33 206 at EDSS 6). At all EDSS levels the largest costs were due to inability to work, which increased with EDSS. The average relapse cost for all EDSS levels was $1367. An inverse correlation was found between EDSS level and patient utility for patients in remission and relapse. The decrease in remission health utility from EDSS 1 to 6 was 0.24, which is 25% greater than the difference in health status between an average 25 and 85 year-old. CONCLUSIONS: This study demonstrates that MS produces substantial health care costs and reductions in patient quality of life and ability to work, losses that can be avoided or delayed if disease progression is slowed. These data provide health-care decision-makers with the opportunity to consider the full impact of MS when faced with budget allocation decisions.

Adult↗
PubMed1999

Ventilatory and heart rate responses to exercise : better predictors of heart failure mortality than peak oxygen consumption.

BACKGROUND: An abnormally low chronotropic response and an abnormally high ventilatory response (V(E)/V(CO2)) to exercise are common in patients with severe heart failure, but their relative prognostic impacts have not been well explored. METHODS AND RESULTS: Consecutive patients with heart failure referred for metabolic stress testing who were not taking beta-blockers or intravenous inotropes (n=470) were followed for 1.5 years. The chronotropic index was calculated while peak V(O2) and V(E)/V(CO2) were directly measured. Chronotropic index and peak V(O2) were considered abnormal if in the lowest 25th percentiles of the patient cohort, whereas V(E)/V(CO2) was considered abnormal if in the highest 25th percentile. For comparative purposes, a group of 17 healthy controls underwent metabolic testing as well. Compared with controls, heart failure patients had markedly abnormal ventilatory and chronotropic responses to exercise. In the heart failure cohort, there were 71 deaths. In univariate analyses, predictors of death included high V(E)/V(CO2) low chronotropic index, low V(O2), low resting systolic blood pressure, and older age. Nonparametric Kaplan-Meier plots demonstrated that by dividing the population according to peak V(E)/V(CO2) and peak V(O2), it is possible to identify low, intermediate, and very high risk groups. In multivariate analyses, the only independent predictors of death were high V(E)/V(CO2) (adjusted relative risk [RR] 3.20, 95% CI 1.95 to 5.26, P<0.0001) and low chronotropic index (adjusted RR 1.94, 95% CI 1.18 to 3.19, P=0.0009). CONCLUSIONS: The ventilatory and chronotropic responses to exercise are powerful and independent predictors of heart failure mortality.

Adolescent↗
PubMed1999

Myocardial oxygenation during high work states in hearts with postinfarction remodeling.

BACKGROUND: Postinfarction left ventricular remodeling (LVR) is associated with reductions in myocardial high-energy phosphate (HEP) levels, which are more severe in animals that develop overt congestive heart failure (CHF). During high work states, further HEP loss occurs, which suggests demand-induced ischemia. This study tested the hypothesis that inadequate myocyte oxygen availability is the basis for these HEP abnormalities. METHODS AND RESULTS: Myocardial infarction was produced by left circumflex coronary artery ligation in swine. Studies were performed in 20 normal animals, 14 animals with compensated LVR, and 9 animals with CHF. Phosphocreatine (PCr)/ATP was determined with 31P NMR and deoxymyoglobin (Mb-delta) with 1H NMR in myocardium remote from the infarct. Basal PCr/ATP tended to be decreased in postinfarct hearts, and this was significant in animals with CHF. Infusion of dobutamine (20 microg x kg-1 x min-1 IV) caused doubling of the rate-pressure product in both normal and LVR hearts and resulted in comparable significant decreases of PCr/ATP in both groups. This decrease in PCr/ATP was not associated with detectable Mb-delta. In CHF hearts, rate-pressure product increased only 40% in response to dobutamine; this attenuated response also was not associated with detectable Mb-delta. CONCLUSIONS: Thus, the decrease of PCr/ATP during dobutamine infusion is not the result of insufficient myocardial oxygen availability. Furthermore, in CHF hearts, the low basal PCr/ATP and the attenuated response to dobutamine occurred in the absence of myocardial hypoxia, indicating that the HEP and contractile abnormalities were not the result of insufficient oxygen availability.

Adenosine Triphosphate↗
PubMed1999

Motion parallel to line orientation: disambiguation of motion percepts.

Four experiments demonstrate that lines indicating path of movement can generate rotational percepts in a multistable motion display that usually produces only horizontal or vertical motion percepts. The properties of the path-of-movement lines are predicted by a neural-network theory of visual perception. Experimental results validate the theory's predictions by demonstrating that movement of the display elements seems to follow an increasing luminance gradient in lines but not bars, and that illusory contours have similar effects. Experimental results also demonstrate that, in a choice between movement along lines drawn parallel or orthogonal to possible motion paths, observers more often see movement along the lines parallel to the motion path. These results suggest modifications to current computational and neurophysiological theories of motion perception.

Computer Graphics↗
PubMed1999

Spatial frequency and visual persistence: cortical reset.

Psychophysical studies show that the duration of visual persistence increases with spatial frequency of gratings. Previous theories ascribe this finding to differences between the spatial and temporal properties of sustained and transient pathways. This paper proposes an alternative account that explains persistence as a side-effect of excitatory feedback in neural circuits for contour extraction. Mechanisms to break excitatory feedback include inhibitory reset signals at stimulus offset. Simulations demonstrate how gratings with lower spatial frequency generate stronger inhibitory reset signals, thereby resulting in shorter persistence for lower spatial frequencies. Additional simulations account for interactions of spatial frequency with stimulus duration, effects of adaptation, and properties of residual traces, as opposed to visual persistence.

Adaptation, Ocular↗
PubMed1999

Java experiments for introductory cognitive psychology courses.

Interactive on-line experiments provide a unique and useful method for communicating material to students that is otherwise cumbersome and often confusing. The Java programming language is particularly suited for Internet-based programming applications of this sort because it bypasses many technical issues, including resource availability, security, and cross-platform compatibility. In most cases, topics appropriate to this medium of presentation should (1) not be easily demonstrated by other means, (2) represent an important finding in the field, and (3) be robust with respect to variations in both participants and equipment. The present paper outlines the integration of interactive experiments into an introductory cognitive psychology classroom, describing several experiments currently available on the World-Wide Web (WWW). Evaluation of the technical aspects of the technology as well as expansion of the format to other courses is discussed.

Cognitive Science↗
PubMed1998

Serotyping of HIV type 1 infections: definition, relationship to viral genetic subtypes, and assay evaluation. UNAIDS Network for HIV-1 Isolation and Characterization.

V3 serotyping refers to a system based on binding of antibody in patient sera to V3-loop peptides derived from HIV-1 env genetic subtypes. The V3x serotype represents reactivity of serum from an HIV-1-infected patient (regardless of viral genetic subtype), which reacts preferentially to a V3 peptide derived from the X subtype sequence. We have classified HIV-1 serotypes, determined the relationship between the HIV-1 V3 serotypes and viral genetic subtypes in a large study (n = 125), and evaluated the performance of three different V3 peptide-binding assays. Seven HIV-1 V3 serotypes were identified: A, B, B-Br, B-Th, C, D, and E. Serotypes B-Br and B-Th represent sera that react specifically to peptides derived from Brazilian B (B-Br, GWGR) and Thai B (B-Th, GPGQ) strains. The HIV-1 V3 B, C, and E serotypes correlated closely with their viral env genetic subtypes; 19-26 of 32 B sera (59-79%), 3-4 of 4 C sera (75-100%), and 19-22 of 23 E sera (83-96%) were identified as serotypes B, C, and E, respectively. In contrast, two major V3 serotypes were classified in A sera: A (14-18 of 36 [40-50%]) and C (12-19 of 36 [33-54%]). Similarly, two major V3 serotypes were classified in D sera: B (6-10 of 20 [30-50%]) and D (9-12 of 20 [45-60%]). Serotyping of subtype E sera showed the best concordance with genetic subtypes by all assays. Overall, HIV-1 V3 serotyping produced consistent results among three laboratories. However, HIV-1 V3 serotypes do not distinguish all HIV-1 genetic subtypes. The relative biological significance of the V3 serotypes remains to be elucidated.

Amino Acid Sequence↗
PubMed1998

In vivo differentiation of astrocytic brain tumors and isolated demyelinating lesions of the type seen in multiple sclerosis using 1H magnetic resonance spectroscopic imaging.

We used computer pattern recognition of proton magnetic resonance spectroscopic image data to differentiate between brain tumors and large, isolated, demyelinating lesions of the type seen in multiple sclerosis. Leave-one-out linear discriminant analyses correctly classified resonance profiles from five acute demyelinating lesions, 20 low-grade astrocytomas, 22 anoplastic astrocytomas, and 24 glioblastomas. Classification of nonacute lesions will require further development, as the metabolic profiles of demyelinating lesions evolve over time.

Adult↗
PubMed1998

The impact of initial surgical management on outcome in young patients with differentiated thyroid cancer.

BACKGROUND/PURPOSE: It is generally believed that differentiated thyroid cancer (DTC) in young patients has an excellent prognosis. This calls into question the need for more extensive surgical ablation of the thyroid gland with attendant risks of surgical complications. The purpose of this report was to investigate both the incidence of surgical morbidity and the impact of surgery on locoregional recurrence of disease. METHODS: The authors reviewed the clinical course of patients under 22 years of age treated for DTC within Department of Defense hospitals since 1950. Data were available for determination of surgical morbidity in 126 and for outcome in 105. RESULTS: The incidence of postoperative hypocalcemia was 17% and of recurrent laryngeal nerve injury 3%. Factors predictive of morbidity were (1) more extensive thyroid surgery (P = .023), and (2) the presence of gross tumor invasion (P = .022). The incidence of neck recurrence was analyzed among a cohort of 90 patients. A total of 19 (21%) patients had a local recurrence. The median time to recurrence was 24 months. The factor predictive of recurrence was the presence of gross invasion (P = .0001). A strong trend toward locoregional recurrence was found among patients with metastatic disease to more than five cervical nodes (P < .08). The primary operations on the thyroid and regional nodes were not significant predictors of neck recurrence. Among these 19 patients there have been no deaths, but 25% had persistent disease at a mean follow-up of 12.6 years. CONCLUSIONS: The incidence of surgical morbidity does increase with more extensive surgery. Outcome is predicted primarily by the initial extent of disease.

Adolescent↗
PubMed1998

The effect of insulin-like growth factor-I (IGF-I) on protein turnover in the meat-type chicken (Gallus domesticus).

Insulin-like growth factor-I (IGF-I) effects on chicken growth and development are poorly understood. This study examined the effect of IGF-I on protein synthesis rates in various tissues in the male broiler chicken. At three weeks of age, osmotic minipumps were subcutaneously implanted in the scapular area. Chickens were infused with either chicken IGF-I (450 micrograms/kg BW/day) or saline. After treatment for 5 days, the chickens received a flooding dose of [3H]-phenylalanine, and were sacrificed 20 min later. Wing vein blood samples were taken at 0, 5, 10 and 20 min post-injection. The following tissues were removed and frozen for analysis: pectoralis muscle, gastrocnemius muscle, heart, liver, and small intestine. In vivo total protein synthesis measurements were made using the double-label technique. Contractile protein degradation was evaluated using intracellular free 3-methylhistidine concentrations in skeletal muscle. There were no significant differences in absolute or relative body growth rates over the treatment period. Skeletal muscle (pectoralis and gastrocnemius) weights were significantly decreased with IGF-I treatment, while heart weight was significantly increased. Plasma insulin levels were significantly lower in IGF-treated chickens compared to that in control birds. There was no effect of IGF-I on protein synthesis rates in any of the tissues examined. Intracellular free 3-methylhistidine concentrations were higher in both the gastrocnemius (17%) and pectoralis muscles (25%) of chickens treated with IGF-I. This data demonstrates that IGF-I may have an indirect effect to regulate muscle protein turnover rates.

Animals↗
PubMed1998

Pregnancy outcomes among women with and without diabetic microvascular disease (White's classes B to FR) versus non-diabetic controls.

The objective of this paper is to evaluate the impact of contemporary management on the maternal and neonatal outcomes of pregnancies complicated by diabetes in women with microvascular disease versus women without microvascular disease. The study population consisted of two hundred and eighty-eight (288) pregnant women with pregestational diabetes and one hundred and fifty (150) healthy pregnant controls. Diabetic women were grouped according to the presence (n = 103) or absence of diabetic microvascular disease (n = 185). Data were collected regarding diabetes management, level of glycemic control, and the development of antenatal complications. Maternal and neonatal outcomes were compared among the three groups. Women in the diabetes groups were stratified according to mean blood glucose levels and glycosylated hemoglobin during each trimester. There was no significant difference found between the two diabetes groups in terms of preterm labor, polyhydramnios, pyelonephritis, and growth restriction. The only maternal complications that occurred with increased incidence among women with microvascular disease were acute hypertensive complications (51.6 vs. 32.9%; p<0.05). However, when the diabetes groups were compared to healthy controls, a significant difference was seen in all maternal and neonatal complications. Preterm delivery, polyhydramnios, and large-for-gestational-age (LGA) infants were associated with poor third-trimester metabolic control as compared with others in satisfactory metabolic controls: 30.8 vs. 11.4% for preterm delivery; 17.3 vs. 5.1% for polyhydramnios; 51.9 vs. 33.9% for LGA; p<0.05. Congenital malformations were associated with poor first-trimester glucose control (5.8 vs. 1.3% anomalies in well-controlled women). Furthermore, major congenital malformations were also significantly increased in the offspring of women with diabetic microvascular disease 6.8%, as compared to 1.69% in diabetic women without microvascular disease; p<0.01. The incidence of hypertensive complications did not differ between the two diabetic groups. Pregestational diabetic women with and without microvascular disease can be counseled to anticipate comparably favorable pregnancy outcomes, although maternal and neonatal complications may exceed that experienced by pregnant women without diabetes mellitus.

Adult↗
PubMed1998

A computational and perceptual account of motion lines.

To indicate motion in a static drawing, artists often include lines trailing a moving object. The use of these motion lines is notable because they do not seem to be related to anything in the optic array. The dynamic behavior of a neural-network model for contour detection is analyzed and it is shown that it generates trails of oriented responses behind moving stimuli. The properties of the oriented response trails are shown to correspond to motion lines. The model generates trails of different orientations depending on the speed and length of the movement, and thereby predicts different uses of two types of motion lines. The model further predicts that motion lines should bias real motion in some situations. An experiment relating motion lines to ambiguous motion percepts demonstrates that motion lines contribute to motion percepts.

Humans↗
PubMed1998

Improved correlation between scores on the expanded disability status scale and cerebral lesion load in relapsing-remitting multiple sclerosis. Results of the application of new imaging methods.

We hypothesized that a better correlation between MRI and clinical measures of neurological disability using the expanded disability status scale (EDSS) in multiple sclerosis could be obtained by assessing lesion load only in and around the corticospinal tracts, since the EDSS is weighted towards motor and ambulatory deficits. Multiple sclerosis lesions in cerebral MRIs from 39 patients with relapsing-remitting multiple sclerosis were manually painted using a three-dimensional computer display tool and mapped into a standardized three-dimensional coordinate space. Total lesion load was then measured. A mask to expose only the corticospinal tract was extracted from an MRI atlas and used to measure lesion load in the corticospinal tract. To account for the residual anatomical variability among the different MRI volumes after stereotaxic transformation, the corticospinal tract mask was dilated to various degrees and the lesion load remeasured. Spearman's rank correlation coefficient was used to calculate the correlation between the EDSS and total lesion load and corticospinal tract lesion load and between the EDSS subscores and total lesion load and corticospinal tract lesion load. Spearman's rank correlation coefficient between the EDSS and total lesion load was 0.6, probably reflecting the rather broad EDSS range represented in the study. The highest correlation of 0.67 was between the EDSS and corticospinal tract lesion load, dilated with a blurring kernel of 8-10 mm. The pyramidal subscore alone showed a weaker correlation with total lesion load, and with corticospinal tract lesion load, than did the overall EDSS, possibly reflecting the narrow range of disability in these subscores in patients with EDSS scores of 1-6.5. The imperfect correlation between the EDSS and corticospinal tract lesion load suggests that factors other than cerebral T2-weighted lesion volume are important determinants of disability.

Brain↗
PubMed1998

The Mayo Clinic-Canadian Cooperative trial of sulfasalazine in active multiple sclerosis.

OBJECTIVE: To determine whether sulfasalazine is better than placebo in slowing disability progression in MS. METHODS: In this randomized, double-blind, placebo-controlled phase III trial, 199 patients with active relapsing-remitting (n = 151) or progressive (n = 48) MS were evaluated at 3-month intervals for a minimum of 3 years (94% completed 3 years of follow-up; mean follow-up, 3.7 years). MRI studies were performed at 6-month intervals on a subset of 89 patients. RESULTS: Sulfasalazine failed to slow or prevent disability progression as measured by the primary outcome (confirmed worsening of the Expanded Disability Status Scale [EDSS] score by at least 1.0 point on two consecutive 3-month visits). Sulfasalazine influenced favorably a number of secondary outcomes during the first 18 months of the trial (e.g., annualized relapse rate, proportion of relapse-free patients; progressive subgroup only: rate of EDSS progression at 1 and 2 years, median time to EDSS progression) but these positive findings were not sustained into the second half of the trial. CONCLUSIONS: Sulfasalazine does not prevent EDSS score progression in the subset of MS patients studied by this protocol. Treatments may improve relapse-related outcomes in MS, at least temporarily, without providing sustained slowing of EDSS progression. Phase III MS trials should be of sufficient length to determine a meaningful impact on disease course.

Adult↗
PubMed1998

The short-term effects of digoxin in patients with right ventricular dysfunction from pulmonary hypertension.

OBJECTIVE: Studies on the effects of digoxin in patients with right ventricular failure and normal left ventricular function have not been performed. We evaluated the short-term effects of digoxin administration in patients with primary pulmonary hypertension on hemodynamics, neurohormones, and baroreceptor responsiveness. DESIGN: This was a prospective study with patients serving as their own controls. SETTING: University Hospital Intensive Care Unit with central monitoring. PATIENTS: Seventeen patients with primary pulmonary hypertension and symptomatic heart failure were enrolled. INTERVENTIONS: Following baseline hemodynamics, neurohormonal samples were drawn and the heart rate response to change in blood pressure following a challenge of phenylephrine and nitroprusside were recorded. One mg of intravenous digoxin was given and the measurements repeated after 2 hours. RESULTS: Following digoxin there was a significant increase in cardiac output (3.49+/-1.2 to 3.81+/-1.2 L/min., p=0.028), a significant fall in norepinephrine (680+/-89 to 580+/-85 pg/ml, p=.013), and a significant increase in atrial natriuretic peptide (311+/-44 to 421+/-9 pg/ml, p=0.01). All of the patients had changes in heart rate and blood pressure following phenylephrine and nitroprusside challenge, but there was no significant difference in the change in heart rate response to change in blood pressure when rechallenged after digoxin treatment. CONCLUSION: Digoxin produces a modest increase in cardiac output in patients with pulmonary hypertension and right ventricular failure, as well as a significant reduction in circulating norepinephrine. No detectable effects of digoxin on baroreceptor responsiveness were apparent. The use of digoxin in pulmonary hypertension is warranted.

Adult↗