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Biomedical subjects

M Francis

Publications and source records attributed to M Francis.

At least 55 records · Page 3Linked to original sources

Conventional heart rate variability analysis of ambulatory electrocardiographic recordings fails to predict imminent ventricular fibrillation.

OBJECTIVES: The purpose of this report was to study heart rate variability in Holter recordings of patients who experienced ventricular fibrillation during the recording. BACKGROUND: Decreased heart rate variability is recognized as a long-term predictor of overall and arrhythmic death after myocardial infarction. It was therefore postulated that heart rate variability would be lowest when measured immediately before ventricular fibrillation. METHODS: Conventional indexes of heart rate variability were calculated from Holter recordings of 24 patients with structural heart disease who had ventricular fibrillation during monitoring. The control group consisted of 19 patients with coronary artery disease, of comparable age and left ventricular ejection fraction, who had nonsustained ventricular tachycardia but no ventricular fibrillation. RESULTS: Heart rate variability did not differ between the two groups, and no consistent trends in heart rate variability were observed before ventricular fibrillation occurred. CONCLUSIONS: Although conventional heart rate variability is an independent long-term predictor of adverse outcome after myocardial infarction, its clinical utility as a short-term predictor of life-threatening arrhythmias remains to be elucidated.

Adult↗

Caffeine and other predictors of bone density among pre- and perimenopausal women.

We evaluated the influence of dietary, anthropomorphic, and hormonal factors on bone density in a cross-sectional sample of 281 pre- and perimenopausal women age 50-60 years living in Massachusetts. The sample included only women who had intact ovaries and were not currently using estrogen. Information on diet was obtained through a semiquantitative food frequency questionnaire. We measured bone density using single-photon absorptiometry in the non-dominant arm in two sites: the midshaft and the ultradistal radius. We observed no important associations between midshaft bone density and dietary variables but found linear relations between ultradistal radius bone density and body mass index [b = 1.10 gm/cm2 per kg/m2, standard error (SE) = 0.56], follicle-stimulating hormone (FSH) (b = -0.36 gm/cm2 per IU/liter, SE = 0.15), and several nutrients: calcium (b = 0.012 gm/cm2 per mg/day, SE = 0.007), retinol (b = 0.002 gm/cm2 per IU/day, SE = 0.0008), vitamin C (b = 0.025 gm/cm2 per mg/day, SE = 0.013), and vitamin D (b = 0.040 gm/cm2 per IU/day, SE = 0.018). We could not clearly distinguish the independent contribution of these micronutrients, however, because many were commonly ingested together in the form of supplements. Caffeine was inversely associated with bone density (b = -0.035, SE = 0.017) independent of dietary, anthropometric, and hormonal factors. Analyses of individual caffeinated beverages revealed consistent inverse associations for coffee (b = -3.42 gm/cm2 per cups/day, SE = 1.49), tea (b = -2.85 gm/cm2 per cups/day, SE = 1.56), and caffeinated cola (b = -14.0 gm/cm2 per cans/day, SE = 5.1), but not for decaffeinated coffee or decaffeinated cola [corrected]. [ABSTRACT TRUNCATED AT 250 WORDS)

Anthropometry↗

Scores on field independence and performance in snooker.

The purpose of this study was to compare the scores on the Group Embedded Figures Test, a measure of field dependence, for 25 male intermediate-level snooker players with scores of 25 intermediate-level sportsmen engaged in soccer, rugby, field hockey, and tennis and to examine the relation between scores on field dependence and performance on a snooker decision-making test. All the snooker players also took a test of decision making in snooker. The snooker players scored significantly more field independent than the sports-science majors on the Group Embedded Figures Test. A Pearson correlation of 0.78 was obtained between scores on the Group Embedded Figures Test and the decision-making test. As there may be an association between scores on field dependence and decision making in snooker, further research should examine sports like lawn bowls and pool where decisions are made in a static environment.

Attention↗

Cancer epidemiology among styrene-butadiene rubber workers.

The standardized mortality ratios for some cancers of the lymphohaematopoietic system were high in an early cohort analysis. Since the presence of large numbers of unexposed workers could conceal risks within a cohort, a case-control study was designed to examine the relationship between estimated exposures and the occurrence of these cancers. The results suggested that the risk for leukaemia was associated with exposure to butadiene and with work in specific areas. Modelling, using rank scores, indicated an increase in the risk for leukaemia with increasing exposure score. Use of cases validated by review of hospital records and selection of a new set of controls did not change the findings. The data indicated that comparison of scores within the same time frame improved the model and increased the estimated odds ratio, suggesting that exposure time or dose rate may prove to be the important variable for risk. Exact measurements from the companies involved showed significant correlations between assigned ranks and level of exposure derived from personal monitoring for butadiene but not for styrene. Thus, use of the measured values might be expected to show an association between leukaemia and exposure to butadiene. The standardized mortality ratio for leukaemia among long-term workers hired before 1960 who had worked in the three plants where the geometric mean butadiene level was three to five times higher than those in the other plants is 1.8 times higher than that of the US population. An appropriate algorithm for comparing cases and controls on the bases of the measured samples is being developed.

Butadienes↗

Preliminary assessment of the Dex Frame for assisting children with specific learning difficulties.

A device called the Dex Frame has recently been marketed as an aid for children with specific learning difficulties. Using a test of reading speed and a test of reading accuracy we have attempted to evaluate the device. Two groups of children with learning difficulties were used, one having sole use of the device and being allowed to carry it with them and a second group who only used the device when attending for remedial tuition and assessment. The results show that no significant improvement occurred in reading performance of the groups with learning difficulties using the Dex Frame as compared with a control group. The teachers of the groups did, however, feel that on an individual basis some children (< 10%) expressed that they felt more comfortable using the device.

Audiovisual Aids↗

A YAC contig across the fragile X site defines the region of fragility.

The fragile X syndrome is a common cause of mental retardation and is associated with a fragile site at Xq27.3 (FRAXA). Recently, evidence has been presented for the role of methylation and genomic imprinting in the expression of the disease. We have identified a site of methylation in patients by long range restriction mapping of the region. In this paper we present a YAC contig of this area, localise the CpG sequences which are methylated, and show by in situ hybridisation that the site of fragility lies within this region.

Base Sequence↗

Identification and characterization of a protective immunodominant B cell epitope of pertactin (P.69) from Bordetella pertussis.

Epitopes defined by monoclonal antibodies (mAb) specific for the Bordetella pertussis outer membrane protein P.69 (pertactin) were mapped using a series of amino- and carboxy-terminal deletion mutants expressed in Escherichia coli. mAb were found to bind predominantly to a region of pertactin spanning a (Pro-Gln-Pro)5 repeat motif and one mAb was found to bind to another region spanning a (Gly-Gly-Xaa-Xaa-Pro)5 repeat motif. To localize further the mAb-binding sites, a panel of synthetic peptides, a series of 94 overlapping hexameric peptides, and a P.69 30-amino acid fusion to a hepatitis B core protein (HBcAg-69), were synthesized. This combined approach has identified the binding site for the mAb BBO5: Pro-Gly-Pro-Gln-Pro-Pro; mAb BBO7, E4A8 and E4D7: Ala-Pro-Gln-Pro-Pro-Ala-Gly-Arg; and mAb BPE3: Thr-Leu-Trp-Tyr-Ala-Glu-Ser-Asn-Ala-Leu-Ser-Lys-Arg. We have used a non-lethal murine respiratory model of B. pertussis infection to investigate the ability of a peptide containing the epitope of the mAb BBO5 to elicit protective immunity. Immunization of mice with the HBcAg-69 protein prevented growth of B. pertussis in the lungs compared to mice receiving HBcAg alone, and protection correlated with high titers of anti-P.69 antibodies.

Amino Acid Sequence↗

Criteria for the accurate interpretation of changes in left ventricular ejection fraction and cardiac volumes as assessed by rest and exercise gated radionuclide angiography.

Although serial left ventricular ejection fraction and volumetric measurements using gated radionuclide angiography are commonly used to evaluate clinical changes and therapeutic outcomes in individual patients, criteria are not available for accurately interpreting whether a change in any of these hemodynamic measurements is clinically meaningful. Accordingly, the magnitude of inherent variability among sequential measurements of hemodynamic variables assessed by gated radionuclide angiography was investigated in a double-blind placebo-controlled fashion in 39 patients during two placebo periods separated by 6 weeks. All patients analyzed had remained clinically stable during the study period. Although the mean values for all hemodynamic variables between the two placebo periods were minimally changed, the differences in individual patients were striking. Criteria were developed to allow meaningful interpretation of changes in hemodynamic variables by estimating the likelihood that an observed change is due to variability alone. On the basis of this analysis of placebo radionuclide angiographic data, variation due to chance alone is unlikely to account for all variability if a change observed between the two rest gated studies in a patient is greater than or equal to 7% units for left ventricular ejection fraction, greater than or equal to 45 ml/m2 for end-diastolic volume index, greater than or equal to 35 ml/m2 for end-systolic volume index, greater than or equal to 20 ml/m2 for stroke volume index and greater than or equal to 1.25 liters/min per m2 for cardiac index. An observed 4% unit change in left ventricular ejection fraction (increase or decrease) after a medical intervention in an individual patient occurs by random variation greater than 25% of the time.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Volume↗

Regulatory implications of airborne respirable free silica variability in underground coal mines.

The respirable dust standard for respirable free crystalline silica in underground coal mines is expressed as milligrams per cubic meter (mg/m3) of respirable dust and is determined by the silica content of the dust. The Mine Safety and Health Administration (MSHA) regulates silica exposure by determining and enforcing compliance with the respirable dust standard for each active mine section. The MSHA strategy for regulation is examined in the context of respirable free crystalline silica and dust data. Deficiencies of the strategy include the same enforcement efforts regardless of compliance history, inappropriate treatment of data, and emphasis on short-term variability of silica content. These deficiencies result in inadequate enforcement in chronically dusty mines, "game playing" with optional samples, and an overall approach that does not focus on the long-term impact of silica exposure on lung health. Alternative approaches include enforcement efforts proportional to compliance history, use of a moving average silica content, and more statistically sound approaches to data interpretation.

Air Pollutants, Occupational↗

Absence of demonstrable phospholipid turnover in B cells stimulated by low mitogenic concentrations of dextran-anti-immunoglobulin conjugates.

Previously we have demonstrated that when anti-immunoglobulin (Ig) is conjugated to high molecular weight dextran (Dex) it stimulates B cell activation at pg/ml concentrations in the absence of detectable phosphoinositide hydrolysis or increases in intracellular ionized calcium. To study carefully whether anti-Ig-Dex recruited a phosphoinositide-dependent pathway of activation, we stimulated B cells that were labeled with 32P and [3H]glycerol with anti-Ig-Dex conjugates at concentrations ranging from 1-1 x 10(-4) micrograms/ml. Thirty seconds to thirty minutes after stimulation lipids were extracted and analyzed by thin layer chromatography and spots correlating with known lipid standards were isolated and counted. There was a four- and tenfold increase in the ratio of 32P/3H incorporated into phosphatidic acid (a metabolite of diacylglycerol) and phosphatidylinositol, respectively, when cells were stimulated with 0.1-1.0 microgram/ml of anti-Ig-Dex for 30 min. Below 1 ng/ml there was no detectable increase in the turnover of these metabolites despite the fact that in parallel cultures B cells were stimulated to proliferate by this concentration of anti-Ig-Dex. To determine whether a cAMP-dependent pathway was recruited by low concentrations of conjugates, we evaluated cAMP levels from B cells that were stimulated with anti-Ig-Dex for 5-60 min using a radioimmunoassay. While cholera toxin stimulated a 50-100-fold increase in the levels of cAMP, we observed no alteration in cAMP in anti-Ig-stimulated cells. These results support and extend our previous findings by demonstrating that B cell activation that is induced by cross-linking of surface Ig may not stimulate phosphoinositide-dependent or cAMP-dependent pathways of activation. Possible alternative mechanisms of activation will be discussed.

Animals↗

Characteristics of self-reported hearing problems in a community survey.

The Cardiff Health Survey included a question asking whether the respondents had any difficulties with their hearing and, if so, to specify the biggest difficulty. This self-completed questionnaire was administered to 4,266 individuals randomly sampled from the electoral register of Cardiff in 1986. 14.7% of those responding indicated a hearing disability; and the main specific disabilities listed are described. The commonest complaints were of difficulties hearing the television and radio, and with general conversation. A number of other specific complaints were reported similar to those found in previous studies with the 'Problems Questionnaire'. Age, social class, general health, smoking and the individual's attitudes were found to influence the pattern of response.

Age Factors↗

The inverse relationship between baseline left ventricular ejection fraction and outcome of antiarrhythmic therapy: a dangerous imbalance in the risk-benefit ratio.

Each year, millions of prescriptions are written for antiarrhythmic drug suppression of ventricular arrhythmias. A large portion of these prescriptions are written for patients with asymptomatic, complex ventricular arrhythmias and organic heart disease, termed "potentially malignant" or "potentially lethal." Since arrhythmia suppression in this population is of unproven benefit, we performed the following study: A total of 246 patients (42% with significant left ventricular dysfunction) had complex ventricular arrhythmias, and were treated with one of eight antiarrhythmic drugs (Vaughan Williams classes IA, IB, IC, II, and III). The extent of arrhythmia suppression and the development of serious complications resulting from therapy after 2 weeks was of primary interest. A total of 82 of 246 (33%) maintained adequate (protocol definition) suppression of both ventricular premature beats (VPBs) as well as nonsustained ventricular tachycardia (VT) for 2 weeks, mostly in patients with left ventricular ejection fraction (LVEF) greater than or equal to 40% (p = 0.04 versus LVEF less than 40%). Life-threatening complications of antiarrhythmic therapy occurred most frequently in the 61 patients with an LVEF less than 30% compared to the 185 patients with LVEF greater than or equal to 30% (15% versus 2.1%, p = 0.0005). Suppression of VT was achieved nearly twice as commonly in patients with an LVEF greater than or equal to 30% than in those with an LVEF less than 30% (67% versus 36%; p = 0.0008). Life-threatening complications occurred seven times as frequently in patients presenting with nonsustained VT and an LVEF less than 30% (18% versus 2.3%; p = 0.003).(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Arrhythmia Agents↗

The effect of autocorrelation on the estimation of workers' daily exposures.

Daily 8-hr time-weighted average (TWA) measurements may not be independent since production rates, maintenance schedules, work practices, and ventilation can result in trends where consecutive values are correlated (autocorrelation). A sampling program which involves collection of measurements on consecutive days, therefore, can result in biased estimates of the mean and variance of the exposure distribution if a high degree of autocorrelation exists. Three simulated data sets were examined to assess the effects of autocorrelation on the estimation of exposure distributions. Results indicated that about 30% of estimated mean values from a highly-autocorrelated series were outside the 95% confidence interval observed for an uncorrelated series. Three data sets obtained from actual workplaces were found to have relatively little autocorrelation. This suggests that for workplaces such as those analyzed here, a random sampling program may not be necessary, and sequential sampling may produce accurate estimates of the parameters of the exposure distribution.

Air Pollutants, Occupational↗

The natural history of benign and potentially malignant ventricular arrhythmias with special reference to nonsustained ventricular tachycardia.

Ambulatory ECG recordings are routinely used to identify patients at increased risk of sudden cardiac death and to monitor changes in ventricular arrhythmias during antiarrhythmic drug therapy. The arrhythmia frequency established during the initial baseline has previously been reported to change during a second placebo monitoring period in patients with non-life-threatening ventricular arrhythmias, but the extent to which this applies to patients with nonsustained ventricular tachycardia has not been examined. To extend these observations to patients with potentially lethal ventricular arrhythmias, we studied 53 patients enrolled in one of two investigational antiarrhythmic drug trials that introduced a second single-blind placebo period (placebo-pulse) an average of 16 months after successful arrhythmia suppression. Thirty-eight of the 53 patients had runs of nonsustained ventricular tachycardia recorded during the initial baseline (placebo I) period, with 63% averaging greater than or equal to 10 runs per day. There was a marked reduction in the arrhythmia frequencies between the two placebo periods: 55% for ventricular premature beats, and 77% for pairs (p less than 0.001, respectively). Of the 38 patients with nonsustained ventricular tachycardia, there was a 72% reduction (892 +/- 531 vs 245 +/- 18 runs of VT/day, placebo I vs II; p = 0.0001), with 32% having total suppression of nonsustained ventricular tachycardia during the second placebo period. The results of this trial extend our previous observations of long-term spontaneous changes in arrhythmia frequency to patients with symptomatic, potentially lethal ventricular arrhythmia and support the recommendation for periodic reassessment of baseline arrhythmia frequency to determine the continued need for antiarrhythmic therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Arrhythmia Agents↗

Hepatic macrophage function in schistosomal glomerulopathy.

Hepatic fibrosis in the pathogenesis of schistosomal glomerulopathy cannot be explained by any positive influence of hepatocellular injury. In order to examine the potential role of impairment of hepatic macrophage function, the t1/2 plasma clearance of 99mTc-sulphur colloid was studied in 30 patients with schistosomal glomerulopathy, ten normal volunteers, ten cases of uncomplicated intestinal schistosomiasis, ten non-schistosomal cirrhotic patients and ten non-schistosomal nephrotic patients. Liver and renal biopsies were obtained from appropriate groups and examined by light microscopy and glomerular immunofluorescence. There was a significant correlation between t1/2 of sulphur colloid clearance and proteinuria, mesangial hypercellularity, and predominance of IgA glomerular deposits. These data indicate that hepatic macrophage dysfunction is an important factor in the pathogenesis of schistosomal glomerulopathy, and that IgA plays a major role in advanced glomerular lesions. The degree of impairment of hepatic macrophage function may influence the pattern and severity of glomerular lesions depending upon the affection of IgA clearance mechanisms.

Adult↗

Asymptomatic telephone ECG transmissions as an outpatient surveillance system of ventricular arrhythmias: relationship to quantitative ambulatory ECG recordings.

Although ambulatory ECG recordings provide quantitative information in the follow-up of patients with ventricular arrhythmias, they are performed infrequently, potentially missing serious arrhythmias in the unmonitored periods. Telephone ECG systems offer "real-time" ECG information, theoretically functioning as an arrhythmia surveillance system. Thus we incorporated frequent telephone ECG transmissions in two antiarrhythmic drug protocols. The first investigation was designed to show the relationship of telephone and ambulatory ECGs in patients with frequent ventricular tachycardia (VT). The second protocol selected patients with "nonlife-threatening" frequent premature ventricular complexes (PVCs) in whom a second placebo period was instituted to simulate the clinical situation of asymptomatic arrhythmia increase. In both drug trials there was a strong linear relationship between the log-transformed PVC counts of telephone ECG and concomitant PVC, couplet, and VT frequencies on ambulatory ECG. In the VT population, greater than or equal to 1 PVC on telephone ECG reflected the presence of VT on ambulatory ECG (sensitivity 87%; specificity 77%). In the second study, telephone ECG transmissions with PVCs on three consecutive transmissions reflected the change from less than or equal to 10 PVCs/hour to greater than or equal to 40 PVCs/hour on ambulatory ECG within 48 hours. These data support the concept that daily surveillance by means of telephone ECG provides arrhythmia information of qualitative clinical relevance.

Ambulatory Care↗