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Biomedical subjects

P Elliott

Publications and source records attributed to P Elliott.

At least 55 records · Page 3Linked to original sources
PubMed2000

Outdoor air concentrations of nitrogen dioxide and sulfur dioxide and prevalence of wheezing in school children.

We report analysis of data on outdoor air pollution and respiratory symptoms in children collected in the Czech part of the international Small Area Variations in Air pollution and Health (SAVIAH) Project, a methodological study designed to test the use of geographical information systems (GIS) in studies of environmental exposures and health at small area level. We collected the following data in two districts of Prague: (1) individual data on 3,680 children (response rate 88%) by questionnaires; (2) census-based socio-demographic data for small geographical units; (3) concentrations of nitrogen dioxide (NO2) and sulfur dioxide (SO2) measured by passive samplers in three 2-week surveys at 80 and 50 locations, respectively. We integrated all data into a geographical information system. Modeling of NO2 and SO2 allowed estimation of exposure to outdoor NO2 and SO2 at school and at home for each child. We examined the associations between air pollution and prevalence of wheezing or whistling in the chest in the last 12 months by logistic regression at individual level, weighted least squares regression at small area (ecological) level and multilevel modeling. The results varied by the level of analysis and method of exposure estimation. In multilevel analyses using individual data, odds ratios per 10 microg/m3 increase in concentrations were 1.16 (95% CI = 0.95-1.42) for NO2, and 1.08 (95% CI = 0.97-1.21) for SO2. While mapping of spatial distribution of NO2 and SO2 in the study area appeared valid, the interpolation from outdoor to personal exposures requires consideration.

Air Pollutants↗
PubMed2000

Surgery and post-operative radiotherapy for early stage cervical cancer.

The use of post-operative radiotherapy in the treatment of cervical cancer is controversial. The aim of this study was to document the results and toxicity of adjuvant irradiation in patients with Stage 1B and 2A cervical cancer. We performed a retrospective review of all patients treated with post-operative radiotherapy at Royal Prince Alfred Hospital between 1986 and 1993. Patient, tumour and treatment factors and late toxicity were recorded. Relapse-free and overall survival were calculated. Eighty-one patients form the study population. The median follow-up was 6.1 years. Fifty-eight patients (72%) had stage 1B cervical cancer and 23 (28%) stage 2A. The 5 year relapse-free and overall survival were 78% and 80% respectively. Six patients (7%) had late toxicity requiring inpatient medical treatment and 6 patients (7%) required surgery. The survival was comparable to other series reported in the literature. There was an incidence of 14% late toxicity requiring medical or surgical intervention which is greater than with hysterectomy or pelvic irradiation alone. Clinical prognostic factors should be used to select patients for either surgery or radiotherapy alone to minimise the increased toxicities associated with a combination of surgery and radiotherapy.

Adenocarcinoma↗
PubMed2000

Chlorination disinfection byproducts in water and their association with adverse reproductive outcomes: a review.

OBJECTIVES AND METHODS: Chlorination has been the major disinfectant process for domestic drinking water for many years. Concern about the potential health effects of the byproducts of chlorination has prompted the investigation of the possible association between exposure to these byproducts and incidence of human cancer, and more recently, with adverse reproductive outcomes. This paper evaluates both the toxicological and epidemiological data involving chlorination disinfection byproducts (DBPs) and adverse reproductive outcomes, and makes recommendations for future research. RESULTS AND CONCLUSIONS: Relatively few toxicological and epidemiological studies have been carried out examining the effects of DBPs on reproductive health outcomes. The main outcomes of interest so far have been low birth weight, preterm delivery, spontaneous abortions, stillbirth, and birth defects--in particular central nervous system, major cardiac defects, oral cleft, and respiratory, and neural tube defects. Various toxicological and epidemiological studies point towards an association between trihalomethanes (THMs), one of the main DBPs and marker for total DBP load, and (low) birth weight, although the evidence is not conclusive. Administered doses in toxicological studies have been high and even though epidemiological studies have mostly shown excess risks, these were often not significant and the assessment of exposure was often limited. Some studies have shown associations for DBPs and other outcomes such as spontaneous abortions, stillbirth and birth defects, and although the evidence for these associations is weaker it is gaining weight. There is no evidence for an association between THMs and preterm delivery. The main limitation of most studies so far has been the relatively crude methodology, in particular for assessment of exposure. RECOMMENDATIONS: Large, well designed epidemiological studies focusing on well defined end points taking into account relevant confounders and with particular emphasis on exposure characterisation are ideally needed to confirm or refute these preliminary findings. In practice, these studies may be impracticable, partly due to the cost involved, but this is an issue that can be put right--for example, by use of subsets of the population in the design of exposure models. The studies should also reflect differences of culture and water treatment in different parts of the world. To identify the specific components that may be of aetiological concern and hence to fit the most appropriate exposure model with which to investigate human exposure to chlorinated DBPs, further detailed toxicological assessments of the mixture of byproducts commonly found in drinking water are also needed.

Chlorine↗
PubMed2000

Risk of mortality, cancer incidence, and stroke in a population potentially exposed to cadmium.

OBJECTIVES: To follow up mortality and cancer incidence in a cohort potentially exposed to cadmium and to perform a geographical (ecological) analysis to further assess the health effects of potential exposure to cadmium. METHODS: The English village of Shipham has very high concentrations of cadmium in the soil. A previous cohort study of residents of Shipham in 1939 showed overall mortality below that expected, but a 40% excess of mortality from stroke. This study extends the follow up of the cohort for mortality to 1997, and includes an analysis of cancer incidence from 1971 to 1992, and a geographical study of mortality and cancer incidence. Standardised mortality and incidence ratios (SMRs and SIRs) were estimated with regional reference rates. Comparisons were made with the nearby village of Hutton. RESULTS: All cause cohort mortality was lower than expected in both villages, although there was excess cancer incidence in both Shipham (SIR 167, 95% confidence interval (95% CI) 106 to 250) and Hutton (SIR 167, 95% CI 105 to 253). There was an excess of mortality from hypertension, cerebrovascular disease, and nephritis and nephrosis, of borderline significance, in Shipham (SMR 128, 95% CI 99 to 162). In the geographical study, all cause mortality in Shipham was also lower than expected (SMR 84, 95% CI 71 to 100). There was an excess in genitourinary cancers in both Shipham (SIR 160, 95% CI 107 to 239) and Hutton (SIR 153, 95% CI 122 to 192). CONCLUSION: No clear evidence of health effects from possible exposure to cadmium in Shipham was found despite the extremely high concentrations of cadmium in the soil.

Cadmium Poisoning↗
PubMed2000

Lack of multicellular drug resistance observed in human ovarian and prostate carcinoma treated with the proteasome inhibitor PS-341.

Almost all known conventional cytotoxic anticancer drugs are less effective in killing tumor cells grown as multicellular spheroids than in killing tumor cells grown as monolayer cell cultures. This "multicellular resistance" reflects the relative intrinsic drug-resistant phenotype of most solid tumors growing in vivo and is due to factors such as limited drug penetration or reduced fractions of proliferating cells. Proteasome inhibitors such as PS-341, a dipeptide boronic acid analogue, represent an interesting new class of potential anticancer drugs, which are entering early-phase clinical trials. PS-341 has been found to have good broad-spectrum cytotoxic activity in the 60-monolayer cell line National Cancer Institute screen. However, because its relative potency has not been tested in spheroid systems, we analyzed the activity of PS-341 in a spheroid/solid tumor context using four different human ovarian carcinoma cell lines and three prostate carcinoma cell lines, respectively. We found, with one exception, that PS-341 showed equal or greater activity in spheroids than in the respective monolayer cell cultures, even in a prostate cancer spheroid model with a very low growth fraction. PS-341 induced apoptotic cell death in carcinoma cells in both culture systems. We also noted a decrease in XIAP protein, a member of the inhibitor of apoptosis (IAP) family of apoptosis inhibitors, and phosphorylation of Bcl-XL in PS-341-treated ovarian carcinoma cells. Furthermore, DNA fragmentation, a hallmark of apoptosis (in this case, induced by PS-341), was completely inhibited by the caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (Z-VAD). Taken together, the results indicate that unlike most other known anticancer cytotoxic drugs, PS-341 appears to be as effective in killing tumor cells grown in the form of multicell spheroids as in killing tumor cells grown in monolayer cell culture. Hence, this compound has the potential to circumvent multicellular drug resistance and, as such, may show promising activity against solid tumors with low growth fractions in vivo, which are frequently intrinsically resistant to conventional cytotoxic anticancer drugs.

Antineoplastic Agents↗
PubMed1999

Investigation of excess environmental risk around putative sources: Stone's test with covariate adjustment.

Stone (Statistics in Medicine, 7, 649-660 (1988)) proposed a method of testing for elevation of disease risk around a point source. Stone's test is appropriate to data consisting of counts of the numbers of cases, Yi say, in each of n regions which can be ordered in increasing distance from a point source. The test assumes that the Yi are mutually independent Poisson variates, with means mu i = Ei lambda i where the Ei are the expected numbers of cases, for example based on appropriately standardized national incidence rates, and the lambda i are relative risks. The null hypothesis that the lambda i are constant is then tested against the alternative that they are monotone non-increasing with distance from the source. We propose an extension to Stone's test which allows for covariate adjustment via a log-linear model, mu i = Ei lambda i exp (sigma jp = 1 xij beta j), where the xij are the values of each of p explanatory variables in each of the n regions, and the beta j are unknown regression parameters. Our methods are illustrated using data on the incidence of stomach cancer near two municipal incinerators.

Air Pollutants↗
PubMed1999

Transmural myocardial blood flow distribution in hypertrophic cardiomyopathy and effect of treatment.

Verapamil alleviates symptoms in patients with hypertrophic cardiomyopathy (HCM), but the underlying mechanism of improvement remains speculative. Baseline and dipyridamole myocardial blood flow (MBF) were measured in 15 HCM patients (14 men, 42 +/- 10 years), before and after 4 weeks of verapamil SR 480 mg daily, using 15O labelled water the positron emission tomography (PET). Subendocardial (endo) and subepicardial (epi) MBF was measured in the septum (thickness 25.4 +/- 5.8 mm). Pre-treatment baseline whole heart MBF was 1.02 +/- 0.28 ml/min/g and 1.01 +/- 0.30 ml/min/g on treatment (p = ns). Dipyridamole MBF was 1.39 +/- 0.31 ml/min/g off treatment and 1.23 +/- 0.34 ml/min/g on treatment (p = ns). Coronary flow reserve (dipyridamole/resting MBF) was 1.45 +/- 0.52 and 1.30 +/- 0.51, respectively (p = ns). At baseline, the septal endo/epi MBF ratio was uniform off and on treatment (1.13 +/- 0.18 vs 1.18 +/- 0.21, p = ns). Before treatment, the endo/epi ratio following dipyridamole decreased to 0.93 +/- 0.24 (p < 0.01 vs baseline) and 5/15 (33%) patients had a ratio < 0.8 which would suggest subendocardial underperfusion. During treatment, the endo/epi ratio following dipyridamole was no more different from baseline (1.06 +/- 0.24, p = ns vs baseline) and 2/14 (14%) patients had an endo/epi < 0.8. PET can be successfully used to determine transmural MBF in vivo in patients with hypertrophied ventricles. Despite symptomatic improvement, high dose verapamil therapy does not increase total MBF in patients with HCM but may improve septal transmural MBF distribution during dipyridamole in some patients.

Adult↗
PubMed1999

Ionic mechanisms underlying excitatory effects of serotonin on embryonic rat motoneurons in long-term culture.

The actions of serotonin were investigated on motoneurons isolated from embryonic day 14 rat spinal cord and enriched by metrizamide density gradient centrifugation. Trophic support was provided by a spinal cord glial monolayer, ciliary neurotrophic factor and heat-inactivated serum. Cultures were maintained for 17-83 days and investigated using whole-cell patch-clamp recording. Serotonin evoked slow depolarizations (6.2+/-0.7 or 9.3+/-1.3 mV in the presence of 6-cyano-7-nitroquinoxaline-2,3-dione and strychnine, EC50 8.2 nM), which were reversibly blocked by 0.1 microM ketanserin. Serotonin generated synaptic potentials in motoneurons, lowered the threshold for repetitive firing and changed the slope of the current intensity-firing frequency relationship. The inward current evoked by serotonin (-147+/-15.2 pA) was ascribed to a complex ionic mechanism, which varied amongst neurons in the sampled population. It was due to closure of barium-sensitive potassium channels, effects on Ih and increase in a separate mixed cation current which comprised both transient voltage-sensitive and sustained components. We conclude that serotonergic responses develop in motoneurons cultured under these conditions in the absence of serotonergic input, sensory neurons or many interneurons.

Aging↗
PubMed1999

Treatment outcome in Australian veterans with combat-related posttraumatic stress disorder: a cause for cautious optimism?

This study investigated treatment outcome in combat-related posttraumatic stress disorder (PTSD). Participants were 419 Australian Vietnam veterans who completed a 12-week hospital-based program. A comprehensive protocol assessed PTSD, comorbidity, and social functioning at admission and at 3 and 9 months posttreatment. Overall, the group showed significant improvements in core PTSD symptoms, anxiety, depression, alcohol abuse, social dysfunction, and anger. Changes occurred mostly between admission and 3 months posttreatment, with gains maintained at 9 months. Ratings by patients and their partners indicated perceived improvement and strong satisfaction with treatment. Nevertheless, treatment gains were variable and, for most veterans, considerable pathology remained following the programs. The current study provides grounds for cautious optimism in the treatment of combat-related PTSD.

Alcoholism↗
PubMed1999

Haemodynamic effects of rapacuronium in adults with coronary artery or valvular disease.

We have assessed the haemodynamic effects of rapacuronium (Org 9487) in adults undergoing cardiac surgery and compared these with vecuronium and placebo. We studied 56 adult patients undergoing coronary artery bypass grafting or valve replacement surgery using a fentanyl-based anaesthetic technique. A pulmonary artery flotation catheter was inserted before induction of anaesthesia. After induction, tracheal intubation and stabilization of haemodynamic measurements, subjects were allocated randomly to receive rapacuronium 1.5 mg kg-1 vecuronium 0.1 mg kg-1 or saline placebo. Haemodynamic measurements were made before drug administration and 1, 3, 5 and 10, and if possible, 15 min after administration. Rapacuronium was associated with statistically significant increases in heart rate (17%) and cardiac index (15%) and decreases in mean arterial pressure (11%) and systemic vascular resistance (18%), whereas vecuronium and placebo were associated with significant decreases in heart rate only (14-15%) (P < 0.05). No cutaneous signs of histamine release were observed. Clinically, the results were within acceptable limits. Our results suggest that administration of rapacuronium may be associated with significant changes in heart rate and arterial pressure in patients undergoing coronary artery bypass grafting.

Adult↗
PubMed1999

A national facility for small area disease mapping and rapid initial assessment of apparent disease clusters around a point source: the UK Small Area Health Statistics Unit.

BACKGROUND: Reports of disease clusters are often received by district health authorities and are, in some cases, associated with concerns about a pollution source. The Small Area Health Statistics Unit (SAHSU) has developed a Rapid Inquiry Facility, which will produce an estimated relative risk for any given condition for the population within defined areas around a point source, relative to the population in a local reference region. The system can also facilitate the production of annual reports and other health studies for Departments of Public Health Medicine through the creation of ward-level maps to illustrate disease variation across small areas. METHODS: The facility uses routinely collected morbidity, mortality and population data at a small area scale, together with the computing facilities and expertise necessary to run such analyses quickly and efficiently. Using this facility SAHSU can supply a report within three working days. To aid interpretation, smoothed small area maps that account for sampling variability in the observed data can also be produced. RESULTS: The paper reports on two case studies where the pilot system has been utilized by health authorities for both point source analyses and small area disease mapping. CONCLUSIONS: We believe that this facility would be of considerable use to districts. The local knowledge and expertise of the local public health specialist is essential in the interpretation and presentation of the facility's output. Feedback from public health specialists is helping SAHSU refine the output of the facility, so as to make the information presented as comprehensive and as useful as possible.

Data Interpretation, Statistical↗
PubMed1999

Arrhythmia vulnerability assessment using magnetic field maps and body surface potential maps.

Magnetic field maps and body surface potential maps can be used to measure cardiac activity. The ability of magnetic and potential body surface maps to identify patients' vulnerable to recurrent sustained ventricular arrhythmia (VA) were compared. Magnetic field maps (MFM) and body surface potential mapping (BSPM) were obtained from 76 normal (N) subjects, 15 myocardial infarct (MI) patients, and 15 VA patients. QRST integral maps were calculated for each subject and nondipolar content was determined using Karhunen-Loeve transform eigen-maps. Although differences in nondipolar content were significant between the normal and patient groups (P = 2.4 x 10(-5) for BSPM and P = 6.0 x 10(-8) for MFM), differences in nondipolar content between MI and VA patients using QRST integral BSPM and MFM maps were not significant. The trajectory of the location of the maxima and minima on the map area during the QRS and ST-T intervals were also constructed. Discrimination between MI and VA patients was based on intergroup differences in the amount of fragmentation of the trajectory plots. The ST-T trajectory plots were significantly more fragmented (P < 0.0001 and P < 0.05 for MFM and BSPM, respectively) for VA than for MI patients. The ST-T interval MFM and BSPM trajectory plots enabled separation of MI and VA patients with accuracies of 83% and 73%, respectively. These results suggest that repolarization MFM and BSPM extrema trajectory plots can be used effectively as a means of identifying patients at risk for VA.

Adult↗
PubMed1999

Electrocardiographic changes in 1000 highly trained junior elite athletes.

OBJECTIVES: To evaluate the spectrum of electrocardiographic (ECG) changes in 1000 junior (18 or under) elite athletes. METHODS: A total of 1000 (73% male) junior elite athletes (mean (SD) age 15.7 (1.4) years (range 14-18); mean (SD) body surface area 1.73 (0.17) m2 (range 1.09-2.25)) and 300 non-athletic controls matched for gender, age, and body surface area had a 12 lead ECG examination. RESULTS: Athletes had a significantly higher prevalence of sinus bradycardia (80% v 19%; p<0.0001) and sinus arrhythmia (52% v 9%; p<0.0001) than non-athletes. The PR interval, QRS, and QT duration were more prolonged in athletes than non-athletes (153 (20) v 140 (18) milliseconds (p<0.0001), 92 (12) v 89 (7) milliseconds (p<0.0001), and 391 (27) v 379 (29) milliseconds (p = 0.002) respectively). The Sokolow voltage criterion for left ventricular hypertrophy (LVH) and the Romhilt-Estes points score for LVH was more common in athletes (45% v 23% (p<0.0001) and 10% v 0% (p<0.0001) respectively), as were criteria for left and right atrial enlargement (14% v 1.2% and 16% v 2% respectively). None of the athletes with voltage criteria for LVH had left axis deviation, ST segment depression, deep T wave inversion, or pathological Q waves. ST segment elevation was more common in athletes than non-athletes (43% v 24%; p<0.0001). Minor T wave inversion (less than -0.2 mV) in V2 and V3 was present in 4% of athletes and non-athletes. Minor T wave inversion elsewhere was absent in non-athletes and present in 0.4% of athletes. CONCLUSIONS: ECG changes in junior elite athletes are not dissimilar to those in senior athletes. Isolated Sokolow voltage criterion for LVH is common; however, associated abnormalities that indicate pathological hypertrophy are absent. Minor T wave inversions in leads other than V2 and V3 may be present in athletes and non-athletes less than 16 but should be an indication for further investigation in older athletes.

Adolescent↗
PubMed1999

Magnesium in drinking water supplies and mortality from acute myocardial infarction in north west England.

OBJECTIVES: To examine whether higher concentrations of magnesium in drinking water supplies are associated with lower mortality from acute myocardial infarction at a small area geographical level; to examine if the association is modified by age, sex, and socioeconomic deprivation. DESIGN: Small area geographical study using 13,794 census enumeration districts. Water constituent concentrations (magnesium, calcium, fluoride, lead) measured at water supply zone and assigned to enumeration districts. SETTING: 305 water supply zones in north west England. SUBJECTS: Resident population of 1,124,623 men and 1,372,036 women (1991 census) aged 45 years or more. MAIN OUTCOME MEASURE: Mortality from acute myocardial infarction, International Classification of Diseases, ninth revision (ICD-9) 410. Subsidiary analysis examined deaths from ischaemic heart disease, ICD 410-414. RESULTS: There were 21,339 male and 17,883 female deaths from acute myocardial infarction in 1990-92. Drinking water magnesium concentrations in water zones ranged from 2 mg/l to 111 mg/l (mean (SD) 19 (20) mg/l, median 12 mg/l); 24% of variation in magnesium concentrations was within zone and 76% was between zone. The relative risk of mortality from acute myocardial infarction (standardised for age, sex, and Carstairs deprivation quintile) for a quadrupling of magnesium concentrations in drinking water (for example, 20 mg/l v 5 mg/l) was 1.01 (95% confidence interval (CI) 0.99 to 1.03). When adjusted for north-south and east-west trends in mortality from acute myocardial infarction and for drinking water calcium, fluoride, and lead concentrations, this relative risk was 1.01 (95% CI 0.96 to 1.06). There was no evidence of a protective effect for acute myocardial infarction even among age, sex, and deprivation groups that were likely to be relatively magnesium deficient. For ischaemic heart disease mortality there was an apparent protective effect of magnesium and calcium (with calcium predominating in the joint model), but these were no longer significant when the geographical trends were incorporated. CONCLUSIONS: No evidence was found of an association between magnesium concentrations in drinking water supplies and mortality from acute myocardial infarction. These results do not support the hypothesis that magnesium is the key water factor in relation to mortality from heart disease.

Age Factors↗