Prevention Conference V: Beyond secondary prevention: identifying the high-risk patient for primary prevention: medical office assessment: Writing Group I.
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Cardiovascular Diseases↗
Biomedical subjects
T Pearson
Publications and source records attributed to T Pearson.
Volume-regulated anion channels do not contribute extracellular adenosine during the hypoxic depression of excitatory synaptic transmission in area CA1 of rat hippocampus.
We investigated whether volume-regulated anion channels (VRACs) contributed to the accumulation of extracellular adenosine during hypoxia in area CA1. The rapid hypoxic depression of the fEPSP was greatly attenuated by the selective adenosine A1 receptor antagonist DPCPX (50 nM), but not affected by the VRAC blockers tamoxifen (10-30 microM) or DNDS (1 mM). Our data argue against the efflux of adenosine per se or its precursor ATP through VRACs as making a significant contribution to extracellular adenosine during the early stages of hypoxia.
Adenosine↗
The wearing of facial protection in high-risk environments.
The term Universal Precautions (UP) originates from the Centre for Disease Control (CDC) in Atlanta (Taylor 1993). The precautions recognise that it is safer for all patients to be treated as potentially infective, whatever their status in life. The basic aim of UP is to lower the level of contact with blood or body fluids. This reduces the risk to all personnel of contact with blood born viruses and pathogenic organisms carried in other body fluids (Wicker 1991). The precautions recognise that there are high risk environments rather than high risk patients.
Acquired Immunodeficiency Syndrome↗
Switch recombination in a transfected plasmid occurs preferentially in a B cell line that undergoes switch recombination of its chromosomal Ig heavy chain genes.
Ab class switching is induced upon B cell activation in vivo by immunization or infection or in vitro by treatment with mitogens, e. g. LPS, and results in the expression of different heavy chain constant region (CH) genes without a change in the Ab variable region. This DNA recombination event allows Abs to alter their biological activity while maintaining their antigenic specificity. Little is known about the molecular mechanism of switch recombination. To attempt to develop an assay for enzymes, DNA binding proteins, and DNA sequences that mediate switch recombination, we have constructed a plasmid DNA substrate that will undergo switch recombination upon stable transfection into the surface IgM+ B cell line (I.29 mu), a cell line capable of undergoing switch recombination of its endogenous genes. We demonstrate that recombination occurs between the two switch regions of the plasmid, as assayed by PCRs across the integrated plasmid switch regions, followed by Southern blot hybridization. Nucleotide sequence analysis of the PCR products confirmed the occurrence of S mu-S alpha recombination in the plasmid. Recombination of the plasmid in I.29 mu cells does not require treatment with inducers of switch recombination, suggesting that recombinase activity is constitutive in I.29 mu cells. Recombination does not require high levels of transcription across the switch regions of the plasmid. Fewer recombination events are detected in four different B and T cell lines that do not undergo switch recombination of their endogenous genes.
Animals↗
Heterothermal acclimation: an experimental paradigm for studying the control of thermal acclimation in crabs.
A method for the study of the control of the attainment of thermal acclimation has been applied to the crabs, Cancer pagurus and Carcinus maenas. Crabs were heterothermally acclimated by using an anterior-posterior partition between two compartments, one at 8 degrees C and the other at 22 degrees C. One compartment held a three-quarter section of the crab including the central nervous system (CNS), eye stalks, and ipsilateral legs; the other held a quarter section including the contralateral legs. Criteria used to assess the acclimation responses were comparisons of muscle plasma membrane fatty acid composition and "fluidity." In both species, the major fatty acids of phosphatidylcholine were 16:0, 18:1, 20:5, and 22:6, whereas phosphatidylethanolamine contained significantly less 16:0 but more 18:0; these fatty acids comprised 80% of the total. Differences in fatty acid composition were demonstrated between fractions obtained from the ipsilateral and contralateral legs from the same heterothermally acclimated individual. In all acclimation states (except 22CNS, phosphatidylcholine fraction), membrane lipid saturation was significantly increased with acclimation at 22 degrees as compared with 8 degrees C. Membrane fluidity was determined by using 1,3-diphenyl-1,3,5 hexatriene (DPH) fluorescence polarization. In both species, membranes from legs held at 8 degrees were more fluid than from legs held at 22 degrees C irrespective of the acclimation temperature of the CNS. Heterothermal acclimation demonstrated that leg muscle membrane composition and fluidity respond primarily to local temperature and were not predominately under central direction. The responses between 8 degrees C- and 22 degrees C-acclimated legs were more pronounced when the CNS was cold-acclimated, so a central influence cannot be excluded.
Acclimatization↗
Protein glycosylation mutants of procyclic Trypanosoma brucei: defects in the asparagine-glycosylation pathway.
We employed a genetic approach to study protein glycosylation in the procyclic form of the parasite Trypanosoma brucei. Two different mutant parasites, ConA 1-1 and ConA 4-1, were isolated from mutagenized cultures by selecting cells which resisted killing or agglutination by concanavalin A. Both mutant cells show reduced concanavalin A binding. However, the mutants have different phenotypes, as indicated by the fact that ConA 1-1 binds to wheat germ agglutinin but ConA 4-1 and wild type do not. A blot probed with concanavalin A revealed that many proteins in both mutants lost the ability to bind this lectin, and the blots resembled one of wild type membrane proteins treated with PNGase F. This finding suggested that the mutants had altered asparagine-linked glycosylation. This conclusion was confirmed by studies on a flagellar protein (Fla1) and procyclic acidic repetitive protein (PARP). Structural analysis indicated that the N- glycan of wild type PARP is exclusively Man5GlcNAc2 whereas that in both mutants is predominantly a hybrid type with a terminal N- acetyllactosamine. The occupancy of the PARP glycosylation site in ConA 4-1 was much lower than that in ConA 1-1. These mutants will be useful for studying trypanosome glycosylation mechanisms and function.
Animals↗
Fungal susceptibility testing.
The utility of antifungal susceptibility testing has not been broadly determined. Thus, susceptibility testing of fungal isolates is not recommended on a routine basis. For instance, susceptibilty testing may be considered for some Candida species and for patients with Pseudallescheria boydii infections. Testing of yeasts for susceptiblity to azoles is of particular value due to their variability in response to these agents. It may also be important to test the susceptibility of new fungal organisms not previously identified or known to cause human disease because in these situations there are no clinical reports of efficacy to guide the choice of antifungal therapy.
Antifungal Agents↗
Heterologous acclimation: a novel approach to the study of thermal acclimation in the crab Cancer pagurus.
The control of the attainment of acclimation in Cancer pagurus has been studied. Homologous (8 or 22 degrees C) and heterologous acclimation [central nervous system (CNS) and periphery of crabs simultaneously held at 8 or 22 degrees C] were used. The dependence of electrophysiological parameters of dactylopodite closer muscles of walking legs on nerve stimulation was determined between 6 and 26 degrees C. Muscle resting potential (RP) hyperpolarized linearly with increasing measurement temperatures and showed a 69% compensation between 8 and 22 degrees C on homologous acclimation. With the CNS temperature constant at 8 degrees C, the leg muscle RP showed a 72% compensation on heterologous acclimation to 8 and 22 degrees C; when CNS temperature was constant at 22 degrees C, leg muscle RP showed a 48% compensation on heterologous acclimation to 8 and 22 degrees C. In homologous acclimation, the shape of the excitatory junction potential vs. temperature relationship was characteristic of acclimation temperature. In heterologous acclimation, the shape of this plot was related to the temperature experienced by the leg and not by the CNS. Thus acclimation was principally dependent on local tissue temperature and was relatively independent of CNS or hormonal influences.
Acclimatization↗
Floppy pinnae in Siamese cats.
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Animals↗
Visual half-field Stroop effects with spatial separation of words and color targets.
Past inconsistencies in the occurrence of differential visual half-field Stroop effects were addressed in two experiments using a visual half-field presentation technique incorporating brief displays (100 ms) and a fixation task designed to ensure proper eye fixation at display onset. Experiment 1 used displays in which distractor words and color targets were presented in contralateral visual fields. Experiment 2 compared contralateral with ipsilateral displays where words and color targets appeared one above the other in the same visual field. Stroop effects were larger whenever a word occupied the right as opposed to the left visual field, regardless of whether the color target was left or right. Results are consistent with the idea that words are processed more efficiently or automatically in right visual field/left hemisphere presentations.
Analysis of Variance↗
Elevated lipoprotein(a) levels in South Asians in North America.
This report demonstrates that South Asians living in North America have elevated levels of Lp(a) compared with North American whites. Elevated Lp(a) levels may account, in part, for the tendency of South Asians to develop premature coronary heart disease (CHD).
Adult↗
Fertility, pregnancy and the management of myeloproliferative disorders.
The management of pregnant patients with chronic myeloproliferative disorders (MPD) is a difficult problem. Patients with essential thrombocythaemia (ET), and, less frequently, those with chronic myeloid leukaemia (CML) or polycythaemia vera (PV), present at a childbearing age. Pregnancy itself does not appear to affect adversely the natural course and prognosis of the MPD. However, fertility might be reduced, and an adverse outcome of pregnancy due to thrombotic or bleeding complications is a matter of concern. It ET, first-trimester abortion is the most frequent complication but increased perinatal mortality and premature delivery are also observed. Placental infarction due to thrombosis seems to be the most consistent event. Maternal thrombotic or haemorrhagic complications are rare but are more common than seen in normal pregnancy. The outcome of pregnancy seems to be positively influenced by aspirin, at least in some cases. The value of cytoreduction and/or heparin prophylaxis has not been established but may have a role in selected cases. In CML, the potential adverse effects of hyperleukocytosis, and sometimes thrombocytosis, generally make myelosuppressive treatment essential. In PV, the number of reported pregnancies is low. Maintaining the PCV below 0.45 is of the utmost importance relating to the outcome of pregnancy. Although cytoreductive drugs should generally be avoided, if possible, until at least after the first trimester of pregnancy, interferon-alpha seems to be the drug of choice when myelosuppression is indicated. In summary, the available information about pregnancy occurring during the course of an MPD indicates that successful management of pregnancy is possible. However, optimal management of these patients is poorly defined and agreed protocols are not available. In view of these problems, it is timely to consider the establishment of a national or European registry to monitor prospectively the management offered to pregnant women found to have an MPD.
Abnormalities, Drug-Induced↗
Effects of reducing dietary saturated fatty acids on plasma lipids and lipoproteins in healthy subjects: the DELTA Study, protocol 1.
Few well-controlled diet studies have investigated the effects of reducing dietary saturated fatty acid (SFA) intake in premenopausal and postmenopausal women or in blacks. We conducted a multicenter, randomized, crossover-design trial of the effects of reducing dietary SFA on plasma lipids and lipoproteins in 103 healthy adults 22 to 67 years old. There were 46 men and 57 women, of whom 26 were black, 18 were postmenopausal women, and 16 were men > or =40 years old. All meals and snacks, except Saturday dinner, were prepared and served by the research centers. The study was designed to compare three diets: an average American diet (AAD), a Step 1 diet, and a low-SFA (Low-Sat) diet. Dietary cholesterol was constant. Diet composition was validated and monitored by a central laboratory. Each diet was consumed for 8 weeks, and blood samples were obtained during weeks 5 through 8. The compositions of the three diets were as follows: AAD, 34.3% kcal fat and 15.0% kcal SFA; Step 1, 28.6% kcal fat and 9.0% kcal SFA; and Low-Sat, 25.3% kcal fat and 6.1% kcal SFA. Each diet provided approximately 275 mg cholesterol/d. Compared with AAD, plasma total cholesterol in the whole group fell 5% on Step 1 and 9% on Low-Sat. LDL cholesterol was 7% lower on Step 1 and 11% lower on Low-Sat than on the AAD (both P<.01). Similar responses were seen in each subgroup. HDL cholesterol fell 7% on Step 1 and 11% on Low-Sat (both P<.01). Reductions in HDL cholesterol were seen in all subgroups except blacks and older men. Plasma triglyceride levels increased approximately 9% between AAD and Step 1 but did not increase further from Step 1 to Low-Sat. Changes in triglyceride levels were not significant in most subgroups. Surprisingly, plasma Lp(a) concentrations increased in a stepwise fashion as SFA was reduced. In a well-controlled feeding study, stepwise reductions in SFA resulted in parallel reductions in plasma total and LDL cholesterol levels. Diet effects were remarkably similar in several subgroups of men and women and in blacks. The reductions in total and LDL cholesterol achieved in these different subgroups indicate that diet can have a significant impact on risk for atherosclerotic cardiovascular disease in the total population.
Adult↗
Clinical predictors of oxidized low-density lipoprotein in patients with coronary artery disease.
Oxidized low-density lipoprotein (LDL) may play a key role in the initiation and progression of atherosclerosis. Risk factors for elevated levels of oxidized LDL are not well established and may be important in identifying individuals who may benefit from antioxidant supplementation or interventions to reduce oxidant stress. The purpose of this study was to determine if clinical parameters predict levels of oxidized LDL. We evaluated the relation between clinical parameters and oxidized LDL in 45 nonsmoking, nondiabetic patients (39 men and 6 women) with coronary artery disease. Oxidized LDL was assessed by measurement of conjugated dienes, lipid peroxides, and thiobarbituric reactive substances (TBARS) at 0 hours to evaluate baseline oxidant stress and postincubation with an oxidizing agent to assess the capacity of LDL for peroxidation. Results were lipid standardized and were not materially altered by multivariate adjustment. Significant predictors of increased oxidized LDL included female sex, family history of premature cardiovascular disease, increased percent body fat, increased body mass index, increased heart rate at rest, history of smoking, exercise <4 times per week, and no regular wine consumption. These data suggest that clinical parameters correlate with levels of oxidized LDL and may be useful in identifying patients at risk for increased oxidant stress.
Adult↗
Antioxidant nutrient supplementation reduces the susceptibility of low density lipoprotein to oxidation in patients with coronary artery disease.
OBJECTIVE: This study sought to determine the effect of antioxidant supplementation on the susceptibility of low density lipoprotein (LDL) to oxidation in patients with established cardiovascular disease (CVD). BACKGROUND: Data are inconsistent regarding the role of antioxidant nutrients in the prevention of CVD. METHODS: The study design was a 12-week, double-blind, placebo-controlled clinical trial. Patients with CVD (n = 45) were randomized to 1) placebo control; 2) 400 IU of vitamin E, 500 mg of vitamin C, 12 mg of beta-carotene (mid-dose); or 3) 800 IU of vitamin E, 1,000 mg of vitamin C, 24 mg of beta-carotene (high dose) daily. Reduced susceptibility of LDL to oxidation was estimated by an increase in lag phase (minutes). Baseline and 6- and 12-week measurements of lipoproteins and lag phase were obtained. Plasma levels of antioxidants were measured at baseline and 12 weeks. RESULTS: Concentrations of alpha-tocopherol, vitamin C and beta-carotene significantly increased in the mid- and high dose groups during the trial. Lag phase significantly increased from baseline (190.1 +/- 63.8 min [mean +/- SD]) to 12 weeks (391.1 +/- 153.0 min) in the high dose group (p < 0.01). A nonsignificant increase in lag phase in the mid-dose group was observed during the same time interval. A dose response was found for mean percent change from baseline to 12 weeks for lag phase for the placebo, mid- and high dose groups (p = 0.004 for trend). CONCLUSIONS: A high dose combination of antioxidant nutrients reduces the susceptibility of LDL to oxidation in patients with CVD and may be useful in secondary prevention.
Adult↗
Cardiovascular disease in African American and white physicians: the Meharry Cohort and Meharry-Hopkins Cohort Studies.
Differences in cardiovascular disease (CVD) were studied in a cohort of medical students from the classes of 1958-65 of Meharry Medical College (n = 435), all African Americans, and the classes of 1957-64 of Johns Hopkins University (n = 580), all white. At baseline, African Americans were older (27 vs. 24 years, p = 0.001), more likely to smoke (71 vs. 47 percent), had greater body mass index (24 vs. 23 kg/m), and had higher systolic blood pressure (120 vs. 116 mmHg). At follow-up (23-35 years later), African American physicians had higher CVD risk (RR = 1.65, 95% CI = 1.3-2.41), higher incidence of coronary artery disease (1.4 times), and much higher case fatality (51.5 vs. 9.4 percent). Risk factor levels in youth can predict CVD events several years later; predictors may differ between racial groups. Best predictors were cigarette smoking, cholesterol, and paternal history in white physicians, and blood pressure in African American physicians.
Adult↗
Novel mutations and polymorphisms in the Fanconi anemia group C gene.
Fanconi anemia (FA) is an autosomal recessive disorder associated with hypersensitivity to DNA cross-linking agents and bone marrow failure. At least four complementation groups have been defined, and the FA group C gene (FAC) has been cloned. We have screened 76 unrelated FA patients of diverse ethnic and geographic origins and from unknown complementation groups for mutations in the FAC gene either by chemical cleavage mismatch analysis or by single-strand conformational polymorphism (SSCP). Five mutations were detected in four patients (5.3%), including two novel mutations (W22X and L496R). Nine polymorphisms were detected, seven of which have not been described previously (663A-->G, L190F, IVS6 + 30C-->T, I312V, V449M, Q465R, and 1974G-->A). Six of the nine polymorphisms occurred in patients or controls from the Tswana or Sotho chiefdoms of South Africa and were not found in 50 unrelated European controls. Restriction site assays were established for all 8 pathogenic mutations identified in the FAC gene to date and used to screen a total of 94 unrelated FA patients. This identified only one other group C patient, who was homozygons for the mutation IVS4 + 4A-->T. This study indicates that the proportion of FA patients from complementation group C is generally likely to be less than 10%. Guidelines for the selection of FA patients for FAC mutation screening are proposed.
Cell Cycle Proteins↗
Evidence of a healthy estrogen user survivor effect.
We examined the relation between menopausal estrogen use and all-cause and cause-specific mortality in a cohort of over 49,000 women followed between 1979 and 1989 in the Breast Cancer Detection Demonstration Project (BCDDP) Follow-Up Study. We found a lower all-cause mortality rate among women who took estrogens [rate ratio (RR) = 0.7; 95% confidence interval (CI) = 0.7-0.8], particularly current users (RR = 0.3; 95% CI = 0.2-0.4), than among women who never took them. Additional analyses, however, revealed that women who had recently stopped taking estrogens had a higher all-cause mortality rate than women who had never taken them (RR = 1.4; 95% CI = 1.2-1.7). Women who had recently stopped taking estrogens also had higher mortality rates from circulatory disease (RR = 1.3; 95% CI = 1.0-1.8) and cancer (RR = 1.6; 95% CI = 1.2-2.2) than women who never took them. The most likely explanation for these results is that women stop taking estrogens when they develop symptoms of serious illness. As a consequence of this "healthy estrogen user survivor effect," nonexperimental studies are susceptible to overestimating the benefits of menopausal estrogen use, particularly current use, on mortality.
Aged↗