Interpreting results of observational research. Problem with confounders can be tackled.
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Confounding Factors, Epidemiologic↗
Biomedical subjects
M Sutton
Publications and source records attributed to M Sutton.
Are increases in cigarette taxation regressive?
Using the latest published data from Tobacco Advisory Council surveys, this paper re-evaluates the question of whether or not increases in cigarette taxation are regressive in the United Kingdom. The extended data set shows no evidence of increasing price-elasticity by social class as found in a major previous study. To the contrary, there appears to be no clear pattern in the price responsiveness of smoking behaviour across different social classes. Increases in cigarette taxation, while reducing smoking levels in all groups, fall most heavily on men and women in the lowest social class. Men and women in social class five can expect to pay eight and eleven times more of a tax increase respectively, than their social class one counterparts. Taken as a proportion of relative incomes, the regressive nature of increases in cigarette taxation is even more pronounced.
Adult↗
Evaluation of the tilt test in an adult emergency medicine population.
STUDY OBJECTIVE: To evaluate the usefulness of the tilt test in identifying significantly dehydrated or occultly bleeding adult patients in an emergency department. DESIGN: Prospective. SETTING: Urban ED. TYPES OF PARTICIPANTS: Two hundred two ill adult patients with complaints suggestive of dehydration and/or occult blood loss and a control sample of 21 healthy individuals. INTERVENTION: Orthostatic measurements were taken from blood samples from the ill and healthy patients. The estimates of the degree of dehydration measured or calculated were total body water deficit percentage (based on measured serum osmolality), ratio of blood urea nitrogen to creatinine, creatinine, and hematocrit. Multiple historical and physical examination variables related to dehydration or occult bleeding were recorded. MEASUREMENTS AND MAIN RESULTS: Multiple analysis of variance testing of the historical and examination variables in the 166 dehydrated patients revealed the absence of syncope (P = .037) and the lack of axillary sweat (P = .026) to be significantly associated with an increased level of dehydration. Regression analysis of the orthostatic measurements and age with the estimates of dehydration found that orthostatic change in heart rate (P = .0165) and age (P = .0047) demonstrated a very small (r2 = .098) association with the level of dehydration. Orthostatic changes in systolic blood pressure and diastolic blood pressure demonstrated no statistically significant association with level of dehydration. There was wide variation in the tilt test measurements in samples from both the healthy and the ill patients: heart rate, 6.8 +/- 7.8 versus 13.2 +/- 10.5; systolic blood pressure, -2.5 +/- 8.0 versus -8.3 +/- 12.8 mm Hg; and diastolic blood pressure, 5.3 +/- 9.9 versus 0.6 +/- 8.6 mm Hg, respectively. The only parameter that attained statistical significance between the 36 blood-loss patients and the healthy patients was change in systolic blood pressure (P = .001); however, this was not clinically significant (-10.7 +/- 13.7 versus -2.5 +/- 8.0 mm Hg, respectively). CONCLUSION: It appears impossible to define a "positive" tilt test that would adequately identify patients with clinically significant dehydration or blood loss; this is due to the large variance in patients' orthostatic measurements both in a healthy and in an ill state and the lack of a significant correlation of orthostatic measurements to a level of dehydration. Lack of axillary sweat, no complaint of syncope, and younger age all indicate greater degrees of dehydration.
Adolescent↗
Acquired methemoglobinemia from amyl nitrate inhalation.
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Adult↗
The Senegal DNA haplotype is associated with the amelioration of anemia in African-American sickle cell anemia patients.
We have previously determined that in African sickle cell anemia (SS) patients three different beta-like globin gene cluster haplotypes are associated with different percent G gamma (one of the two types of non-alpha chains comprising hemoglobin F [HbF]), mean percent HbF, and percent dense cells. We report now that in adult New York SS patients, the presence of at least one chromosome with the Senegal haplotype is associated with higher Hb levels (1.2 g/dL higher) than is found for any other non-Senegal haplotype (P less than .004). The percent reticulocytes and the serum bilirubin levels were lower in these patients. When the effect of alpha-gene number was analyzed by examining a sample of SS patients with concomitant alpha-thalassemia, the same results were obtained. Because the HbF level is significantly higher among the Senegal haplotype carriers in this sample, the inhibitory effect on sickling of this Hb variant may be one of the reasons for the haplotype effect. We conclude that the Senegal beta-like globin gene cluster haplotype is associated with an amelioration of the hemolytic anemia that characterizes sickle cell disease.
Adult↗
Polymerase chain reaction amplification applied to the determination of beta-like globin gene cluster haplotypes.
We report here on the application of the polymerase chain reaction (PCR) technique for the determination of the beta-like gene cluster haplotypes. Seven fragments containing each one of the following polymorphic sites--Xmnl 5' to the G gamma gene, HindIII in the IVSII of G gamma and A gamma gene, HincII 3' and inside the gamma gene, Hinfl 5' of the beta gene, and HpaI 3' of the beta gene--are amplified using the PCR technique. Each amplified fragment is subsequently digested with the appropriate enzyme, analyzed by electrophoresis on agarose gel containing ethidium bromide, and visualized under ultraviolet light. This technique has the advantages of rapidity, safety, and cost-effectiveness.
DNA-Directed DNA Polymerase↗
Symphysis-fundus measurements in screening for small-for-dates infants: a community based study in Gloucestershire.
Symphysis-fundus charts were introduced into 50 general practitioner antenatal clinics and the hospital antenatal clinics of two obstetricians in Gloucestershire in February 1985 for a 12-month period. Of the 1139 charts analysed, the sensitivity of one or more low fundal height measurements in predicting birthweight below the tenth centile for gestational age was 51% with a specificity of 88%. In the 319 charts with four or more measurements after 26 weeks gestation a sensitivity of 65% was recorded in predicting birthweight below the tenth centile, rising to 91% in the prediction of birthweight below the fifth centile; the specificity was correspondingly 81% and 80%. The sensitivity of the test varied inversely with maternal body mass index. The mean absolute difference in pairs of observations between general practitioners, midwives and an observer was 1.5 cm. Measurement of symphysis-fundus distance is not a precise diagnostic tool but it does provide an improvement on abdominal palpation in the prediction of small-for-dates infants. The findings of this study support the use of serial symphysis-fundus measurements in community antenatal clinics. Referral for ultrasound investigation is recommended when the measurement is low.
Anthropometry↗
Cardiovascular adaptations to transfusion/chelation therapy of homozygote sickle cell anemia.
The effect of transfusion/chelation therapy on the cardiovascular adaptations to chronic anemia in pediatric and young adult patients with homozygous sickle cell disease is uncertain. This study compares left ventricular (LV) function indexes and thoracoabdominal aortic systolic and diastolic blood flow in nontransfused and transfused patients with homozygous sickle cell disease. The study population consisted of 29 nontransfused patients with homozygous sickle cell disease, ages 0.4 to 20.9 years (group 1) and 11 chronically transfused/chelated patients, ages 4.0 to 21.8 years (group 2). The mean total hemoglobin concentration in group 2 was 28% greater than that in group 1. The mean duration of transfusion/chelation therapy in group 2 was 3.7 years. The percent of predicted LV end-diastolic and end-systolic dimensions were significantly greater than the respective controls in both groups. There was no significant difference in percent of predicted LV end-diastolic dimension (group 1, 120 +/- 12%; group 2, 120 +/- 12%) or percent of predicted LV end-systolic dimension (group 1, 120 +/- 12%; group 2, 117 +/- 8) between the groups. The percent of LV shortening fraction was similar in study groups and control subjects. Aortic systolic blood flow (cc/min/m2) for group 1 (2,426 +/- 841) and 2 (2,374 +/- 1.004) were significantly greater than corresponding control values (1,683 +/- 442, 1,736 +/- 430, respectively). Aortic diastolic blood flow was significantly greater than corresponding control values for both group 1 (699 +/- 313 vs 488 +/- 212) and group 2 (1,080 +/- 607 vs 588 +/- 219).(ABSTRACT TRUNCATED AT 250 WORDS)
Adaptation, Physiological↗
Brain infarction in sickle cell anemia: magnetic resonance imaging correlates.
Brain infarction is a well-known but poorly understood complication of sickle cell disease. Seventy-three sickle cell disease patients underwent neurological examinations and high-field, heavily T2-weighted axial cranial magnetic resonance image (MRI) scanning. Eighteen of the 73 had a history of stroke, defined as an acute, focal neurological sign lasting longer than 1 hour; in the event of a convulsive onset, an MRI abnormality as a correlate was necessary. Sixteen of the 18 stroke patients demonstrated focal MRI abnormalities consistent with arterial borderzone infarctions. Fifty-five of the 73 patients had no history of stroke. Six of the 55 (11%) had focal MRI abnormalities suggesting previous subclinical stroke. Five of these lesions were in borderzone regions. The distinguishing feature in 21 of the 22 patients with MRI abnormalities was the predilection for lesions in the high cortical convexity, in the general regions of arterial borderzones between the major cerebral arteries and adjacent deep white matter. The pattern of MRI lesions suggests two pathogenetic mechanisms: (1) proximal large-vessel disease with inadequate cerebral perfusion (distal field insufficiency syndrome) and (2) distal small-vessel disease (sludging syndrome).
Adolescent↗
Insulin autoantibodies at diagnosis of insulin-dependent diabetes: effect on the antibody response to insulin treatment.
Insulin autoantibodies (IAA) are frequently found in newly diagnosed untreated insulin-dependent diabetics. We evaluated whether the insulin antibody response over the first year of treatment with insulin was different in individuals with IAA v those without IAA. One hundred five previously untreated type I diabetics were randomly assigned to treatment with either pure porcine or mixed bovine/porcine insulin. Twenty-one in each group had detectable IAA at diagnosis. Percent binding rose in all patients after commencing insulin therapy and was significantly greater in those with IAA at diagnosis irrespective of the type of insulin administered. The elevated binding in the IAA positive patients at all time points was equivalent to the binding that could be attributed to the insulin autoantibodies. Two different mechanisms could explain this greater insulin antibody binding during insulin therapy in the IAA positive patients. First, there may be summation of binding due to insulin autoantibodies and binding due to insulin antibodies formed in response to the exogenous insulin. Alternatively, the insulin antibodies formed in response to exogenous insulin could replace the IAA, with those individuals positive for IAA at diagnosis having a proportionately greater antibody response to injected insulin. Irrespective of the mechanism, patients with IAA at diagnosis develop higher insulin antibody measurements when subsequently treated with exogenous insulin.
Autoantibodies↗
A preliminary behavioral investigation of PMMA, the 4-methoxy analog of methamphetamine.
The controlled-substance analog N-monomethyl-1-(4-methoxyphenyl)-2-aminopropane (PMMA) may be viewed as being either the 4-methoxy analog of methamphetamine or the N-methyl analog of 1-(4-methoxyphenyl)-2-aminopropane (PMA). Because of its abuse potential, PMMA was examined with regard to (a) its stimulus properties in rats trained to discriminate either 1.0 mg/kg of (+)amphetamine or (+/-)DOM from saline, (b) its toxicity (isolated and aggregated) in mice relative to (+/-)PMA, and (c) its locomotor stimulant activity in mice relative to (+/-)amphetamine, (+/-)methamphetamine, and (+/-)PMA. Racemic PMMA produced neither DOM-like nor, unlike PMA, amphetamine-like stimulus effects. There was no significant difference between the 24-hr isolated (LD50 = 63 mg/kg) and aggregated (LD50 = 53 mg/kg) toxicity, and PMMA did not produce significant locomotor stimulation at doses of up to 30 mg/kg. The present results suggest that while PMMA may produce central effects it does not appear to behave as a simple amphetamine-like agent.
Amphetamine↗
DNA methylation in hereditary persistence of fetal hemoglobin (HPFH-2).
Recent studies show that the region of DNA brought into close proximity to the fetal gamma-globin genes in deletional forms of hereditary persistence of fetal hemoglobin (HPFH) is selectively hypomethylated (and presumably active) in normal erythroid tissue. This region is normally located approximately 100 kilobases (kb) 3' to the fetal genes. The continued expression of fetal hemoglobin in adult life in these forms of HPFH has been ascribed to the effect of this erythroid-specific region in altering local chromosomal structure and allowing transcription. Because transcriptional activity is often associated with hypomethylation, we have examined the methylation status of the gamma-globin genes and the truncated psi beta gene on the HPFH chromosome to determine whether juxtaposition of this erythroid-specific region results in a generalized hypomethylation of the globin gene region upstream of the deletion breakpoint. Genomic DNA purified from nucleated red blood cells (nRBC) from a patient with HPFH-2/beta O thalassemia was digested with Msp I or Hpa II, and the methylation pattern determined on the HPFH chromosome by using secondary cleavage with restriction enzymes which span the deletion breakpoint. These studies show that in nRBC the HPFH-2 chromosome is hypomethylated in the 3'-juxtaposed region (3'JR) and in the region of the gamma-globin genes. In contrast, Msp I sites near the truncated psi beta-globin gene remain methylated, suggesting that only a subset of CpG sites upstream from the 3'JR become hypomethylated in HPFH-2. This subset of sites corresponds to those which are normally hypomethylated when fetal genes are active. The continued high level of fetal globin expression is, therefore, not associated with a generalized hypomethylation upstream from the deletion junction.
DNA↗
Early postoperative changes in left ventricular chamber size, architecture, and function in aortic stenosis and aortic regurgitation and their relation to intraoperative changes in afterload: a prospective two-dimensional echocardiographic study.
We prospectively studied 16 patients with isolated aortic stenosis and eight with isolated aortic regurgitation undergoing aortic valve replacement, using two-dimensional echocardiography preoperatively, intraoperatively, and 41 +/- 7 days postoperatively to calculate the intraoperative change in afterload, quantify the postoperative changes in left ventricular chamber size, architecture, load and function, determine whether the postoperative left ventricular remodeling correlated with the intraoperative change in afterload in aortic stenosis and aortic regurgitation, and assess whether preoperative afterload excess precluded postoperative improvement in left ventricular function. Preoperative left ventricular mass, end-systolic meridional and circumferential wall stresses, ejection fraction, and stress-shortening relations in patients with aortic stenosis and aortic regurgitation were similar. However, our patients with aortic regurgitation had severe systolic dysfunction, with ejection fraction less than 55% in all but one patient, compared with only 10 of 16 patients with aortic stenosis. Left ventricular end-diastolic volume, mass/volume ratio, and chamber shape were significantly different in patients with aortic stenosis and aortic regurgitation (174 +/- 64 vs 294 +/- 140 ml, p less than .01; 1.81 +/- 0.63 vs 1.14 +/- 0.18, p less than .01; and 0.59 +/- 0.09 vs 0.69 +/- 0.09, p less than .05, respectively). Intraoperative end-systolic meridional and circumferential stresses fell significantly in patients with aortic stenosis but remained unchanged in those with aortic regurgitation. The changes in left ventricular volume and ejection fraction during early postoperative remodeling (6 weeks) correlated with the intraoperative change in afterload in patients with aortic stenosis. In contrast, there was no intraoperative change in afterload in patients with aortic regurgitation and no significant changes in left ventricular volume, architecture, or function at 6 weeks or at 6 months. The differences in left ventricular remodeling and changes in function between patients with aortic stenosis and aortic regurgitation in the early postoperative period most probably relates to the major difference in intraoperative reduction in afterload, although a contributory role may have been played by the preoperative left ventricular dysfunction in those with aortic regurgitation that was underestimated by measurement of ejection fraction.
Adult↗
Chronic corticosterone administration in rats: behavioral and biochemical evidence of increased central dopaminergic activity.
Chronic corticosteroid treatment in humans in frequently complicated by behavioral changes. The present study suggests that chronic steroid administration in rats has distinct neurochemical consequences which are behaviorally relevant. Ten male Sprague-Dawley rats received 7 daily injections of corticosterone, following which they exhibited increased caudate homovanillic acid as well as an attenuated decline in vertical and ambulatory movement (functional measures of dopamine activity) compared to placebo-treated rats. A subgroup of steroid-treated rats which was more behaviorally responsive to corticosterone also showed increased caudate 5-hydroxyindole acetic acid and decreased prefrontal cortex dopamine and serotonin. These results are discussed in relation to the known behavioral side effects of chronic corticosteroid administration in man and the psychiatric manifestations of naturally occurring states of hypercortisolemia.
Animals↗
A thermolabile variant of alpha-L-fucosidase--clinical and laboratory findings.
A family with two sibs affected clinically with the severe infantile form of fucosidosis is described. Biochemical studies revealed a relatively high residual activity (34-60% of normal) with markedly decreased thermostability. The importance of including thin layer chromatography for urinary oligosaccharides in the diagnostic workup for such patients is emphasized.
Chromatography, Thin Layer↗
Effects of aerobic training on primary dysmenorrhea symptomatology in college females.
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Adolescent↗
Neuroendocrine and personality variables in dysthymic disorder.
In an attempt to characterize a subgroup of depressed patients diagnosed as having dysthymic disorder, the authors gave them two commonly used biological tests for depression and several personality inventories and compared the results with those from age- and sex-matched normal control subjects. There were no significant differences between the 11 early-onset dysthymic disorder patients and the 11 controls on the dexamethasone suppression test or the thyrotropin-releasing hormone test. The personality questionnaires, however, showed that the dysthymic disorder patients were significantly more neurotic, extrapunitive, and intrapunitive and had significantly lower self-esteem than the control subjects.
Adult↗
Relationship between the movement characteristics of human spermatozoa and their ability to penetrate cervical mucus and zona-free hamster oocytes.
In a group of normospermic donors exhibiting hamster oocyte penetration scores of 0-100%, multiple regression analysis indicated that only 20% of the variation in fertilizing potential could be explained by differences in the movement characteristics of the spermatozoa following incubation in vitro. When the movement characteristics of the spermatozoa in semen were considered this figure was reduced to 6.8% as a result of significant differences in the motility patterns exhibited by the seminal and post-incubation sperm populations. A much closer relationship was observed between the movement characteristics of human spermatozoa in semen and their ability to penetrate cervical mucus. When differences in motile sperm densities were taken into account, 76% of the variation in cervical mucus penetration could be accounted for by the existence of linear correlations with certain aspects of sperm movement (multiple R = 0.874). Of the various attributes of sperm motility measured (linear velocity of progression, frequency of rotation, amplitude of sperm head displacement, % rolling and % yawing), a failure to exhibit an adequate amplitude of lateral sperm head displacement was consistently found to be the most significant factor determining the success of sperm-cervical mucus interaction (R2 = 0.53).
Animals↗