The prehospital 12-lead EKG: starting outside the emergency department.
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Electrocardiography↗
Biomedical subjects
D Collins
Publications and source records attributed to D Collins.
Rapid differentiation of bovine and human tubercle bacilli based on a characteristic mutation in the bovine pyrazinamidase gene.
Bovine tuberculosis (TB) caused by Mycobacterium bovis is an important veterinary disease that can also afflict humans. Although M. bovis shares an almost identical genome with M. tuberculosis, subtle differences in host specificity and several biochemical parameters can be used to distinguish the two closely related species. The current method for distinguishing M. bovis from M. tuberculosis relies on tedious testing of biochemical parameters, including natural resistance to pyrazinamide and defective pyrazinamidase (PZase) activity of M. bovis strains. In this study, we report the development of a rapid PCR-single-strand conformation polymorphism (SSCP) assay to differentiate M. bovis from M. tuberculosis strains, based on the detection of a single characteristic point mutation in the PZase gene (pncA) of M. bovis. Eighty-seven of 89 M. bovis strains could be distinguished from M. tuberculosis strains. Surprisingly, two animal isolates which were initially identified as M. bovis were shown to be M. africanum because they had a wild-type pncA sequence with positive PZase. These two M. africanum strains contain multiple (three and six) copies of insertion sequence IS6110, a feature they have in common with M. tuberculosis. The implication of this finding for the taxonomy of M. tuberculosis complex is discussed in relation to host preference and epidemiology. The development of a rapid PCR-SSCP test for distinguishing M. bovis from M. tuberculosis will be useful for monitoring the spread of bovine TB to humans in areas where bovine TB is endemic and for directing the treatment of human TB caused by M. bovis.
Amidohydrolases↗
Carotid atherosclerosis in men with low levels of HDL cholesterol.
BACKGROUND AND PURPOSE: A low HDL cholesterol (HDL-C) frequently occurs in conjunction with a desirable LDL cholesterol (LDL-C) and is a risk factor for coronary heart disease (CHD). Additionally, the presence of carotid atherosclerosis is a strong and independent predictor of morbidity and mortality in patients with CHD. This article describes the prevalence and correlates of sonographically detected carotid atherosclerosis in men with low levels of HDL-C and CHD but without elevated levels of LDL-C or total cholesterol. METHODS: High-resolution B-mode ultrasonography was used to quantify intima-media wall thickness (IMT) in the common and internal carotid arteries and at the carotid artery bifurcation in 202 randomly selected male veterans with CHD and low levels of HDL-C who are participating in the VA HDL Intervention Trial. Ultrasonographic measurement of carotid artery wall stiffness was determined in a subset of 94 of these individuals. RESULTS: The mean maximum and single greatest carotid artery IMT measurements were 1.41 and 2.58 mm, respectively. The prevalence of ultrasound-detected carotid atherosclerosis as defined by a mean maximum IMT > or = 1.3 mm was 58.9% and by single maximum IMT > or = 1.5 mm was 87.1%. IMT was associated with increased age, lower extremity arterial disease, systolic blood pressure, and ultrasonographically measured carotid artery stiffness. CONCLUSIONS: Men with low levels of HDL-C and CHD but without elevated LDL-C or total cholesterol have a very high prevalence of ultrasound-detected carotid artery atherosclerosis.
Aged↗
The emperor's new shift.
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Medical Staff, Hospital↗
Stabilization of granulocyte colony-stimulating factor and structurally analogous growth factors by anionic phospholipids.
Recombinant granulocyte colony-stimulating factor (rhG-CSF) interacts with liposomes composed of the anionic phospholipid dioleoylphosphatidylglycerol (DOPG), and this interaction enhances the stability of the protein [Collins, D., & Cha, Y. (1994) Biochemistry 33, 4521-4526]. In the present studies, we have examined the interaction of rhG-CSF with phospholipids other than DOPG. Fluorescence spectroscopy of rhG-CSF with a variety of lipid vesicles demonstrated that rhG-CSF inserts into bilayers of anionic, but not zwitterionic, phospholipids. Isothermal titration calorimetry of the interaction between DMPG and rhG-CSF indicates that the binding is saturable and involves 10 lipids/rhG-CSF. Studies of phosphatidylglycerols with varying alkyl chain lengths determined that the stabilization of rhG-CSF by anionic phospholipids required a certain alkyl chain length; no stabilization was observed with lipids of shorter chain length. Also investigated was the stabilization of other growth factors, which are structurally similar to rhG-CSF, by anionic phospholipids. These proteins include recombinant porcine somatotropin (rpSt), recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF), recombinant human interleukin 4 (rhIL-4), and recombinant human interleukin 2 (rhIL-2). The helical secondary structure of the proteins was recoverable after heating and cooling in the presence of anionic phospholipids as observed by circular dichroism; the presence of zwitterionic lipids did not induce this effect. Results of these investigations concluded that a group of structurally similar proteins interact preferentially with anionic phospholipids and that the complexation of the growth factors with vesicles composed of anionic phospholipids improves the stability of the proteins under conditions where they normally denature.
Calorimetry, Differential Scanning↗
The Veterans Affairs High-Density Lipoprotein Intervention Trial: baseline characteristics of normocholesterolemic men with coronary artery disease and low levels of high-density lipoprotein cholesterol. Veterans Affairs Cooperative Studies Program High-Density Lipoprotein Intervention Trial Study Group.
This report describes the baseline characteristics of the 2,531 patients with coronary artery disease enrolled in the Veterans Affairs Cooperative Studies Program High Density Lipoprotein Intervention Trial. The population is characterized by a large percentage of elderly patients, diabetic patients, and patients with the clinical characteristics of the insulin-resistance syndrome.
Adult↗
Fate of cationic liposomes and their complex with oligonucleotide in vivo.
The present studies describe the biodistribution of cationic liposomes and cationic liposome/oligonucleotide complex following intravenous injection into mice via the tail vein. (111)In-diethylenetriaminepentaacetic acid stearylamide ((111)In-DTPA-SA) was used as a lipid-phase radiolabel. Inclusion of up to 5 mol% DTPA-SA in liposomes composed of 3beta-(N-(N',N'-dimethylaminoethane)carbamoyl)cholesterol (DC-Chol) and dioleoylphosphatidylethanolamine (DOPE) did not influence liposome formation or size, nor the binding/uptake or fusion of the cationic liposomes with CHO cells in vitro. Moreover, nuclear delivery of oligonucleotide to CHO cells was unaffected by the probe. The biodistribution of liposomes with increasing concentration of DC-Chol (1:4-4:1, DC-Chol/DOPE, mol/mol) at 24 h post-injection revealed no dependence on lipid composition. Uptake was primarily by liver, and accumulation in spleen and skin was also observed. Comparatively little accumulation occurred in lung. Clearance of injected liposomes by liver was very rapid (approximately 84.5% of the injected dose by 7.5 h post-injection). Liposome uptake by liver and spleen were equally efficient in the dose range of 3.33 to 33.33 mg/kg body weight, yet possible saturation of liver uptake at a dose of 66.80 mg/kg may have allowed for increased spleen accumulation. Preincubation of cationic liposomes with phosphorothioate oligonucleotide induced a dramatic yet transient accumulation of the lipid in lung which gradually redistributed to liver. Similar results were observed when monitoring iodinated oligonucleotide in the complex. Immuno-histochemical studies revealed large aggregates of oligonucleotide within pulmonary capillaries at 15 min post-injection, suggesting the early accumulation in lung was due to embolism. Immuno-histochemical studies further revealed labeled oligonucleotide to be localized primarily to Kupffer cells at 24 h post-injection. Immuno-electron microscopy revealed localization of oligonucleotide primarily to the lumen of pulmonary capillaries at 15 min post-injection. Immuno-electron microscopy revealed localization of oligonucleotide primarily to the lumen of pulmonary capillaries at 15 min post-injection, and to phagocytic vacuoles of Kupffer cells at 24 h post-injection. By these methods, nuclear delivery of oligonucleotide in vivo was not observed. Increasing concentration of mouse serum inhibited cellular binding/uptake of cationic liposomes in vitro, without or with complexed oligonucleotide. We therefore postulate that interaction with plasma components, including opsonin(s), inhibits cellular uptake of the injected liposomes as well as the liposome/oligonucleotide complex, and mediates rapid uptake by Kupffer cells of the liver. These results are relevant to the design of cationic liposomes for efficient delivery of nucleic acid in vivo.
Animals↗
Correlates and consequences of diffuse atherosclerosis in men with coronary heart disease. Veterans Affairs High-Density Lipoprotein Intervention Trial Study Group.
BACKGROUND: Peripheral atherosclerosis is a strong and independent predictor of mortality even in patients with known coronary heart disease. However, the prevalence, correlates, and potential adverse effects on quality of life associated with combined coronary heart disease and clinically evident cerebrovascular or lower-extremity atherosclerosis are not known. Identification of patients with "diffuse atherosclerosis" may enhance treatment of modifiable risk factors and alter therapeutic strategies. METHODS: We conducted a cross-sectional analysis of 2531 men younger than 73 years with coronary heart disease, low-density lipoprotein cholesterol levels of 3.62 mmol/L (140 mg/dL) or less, and high-density lipoprotein cholesterol level of 1.03 mmol/L (40 mg/dL) or less who were participating in Department of Veterans Affairs Cooperative Study 363 (the Veterans Affairs High-Density Lipo-protein Intervention Trial. Baseline demographic, medication, comorbidity, and atherosclerotic risk factor data were assessed by means of a standardized questionnaire. All plasma lipid levels were determined after a 12-hour fast by a central standardized lipid laboratory. Health status was determined by baseline reported symptoms, medical comorbidities, and the Psychological General Well-being Index. Clinically evident diffuse atherosclerosis was defined as a documented history of lower-extremity atherosclerosis or cerebrovascular disease. RESULTS: The mean age of all participants was 63.5 years. The mean plasma lipid values were as follows: total cholesterol, 4,52 mmol/L (174.6 mg/dL); high-density lipo-protein cholesterol, 0.81 mmol/L (31.5 mg/dL); low-density lipoprotein cholesterol, 2.88 mmol/L (111.2 mg/dL); and triglycerides, 1.81 mmol/L (160.6 mg/dL). Diffuse atherosclerosis was present in 525 (21%). Lower-extremity atherosclerosis was reported in 10%, while cerebrovascular disease was present in 13%. After controlling for other variables, the following factors were associated with the presence of diffuse atherosclerosis: increased age, being unmarried, being retired, having less than a high school education, increased alcohol use, hypertension, cigarette smoking, and diabetes. There was no association between lipid levels and the presence of diffuse atherosclerosis. After adjustment for age, race, and comorbidities, men with diffuse disease still had a reduced quality of life compared with men without diffuse atherosclerosis, as defined by having a greater number of clinical symptoms, lower psychological well-being scores, and more advanced or complicated coronary heart disease. CONCLUSIONS: Clinically evident diffuse atherosclerosis is common in men with coronary heart disease and low levels of high-density lipoprotein cholesterol. Because diffuse atherosclerosis is associated with a reduced quality of life and several modifiable risk factors, early detection and aggressive risk factor intervention appear justified.
Adult↗
Tryptophan depletion and aggressive responding in healthy males.
In order to study the effect of decreasing plasma tryptophan levels on aggressive responding in a controlled laboratory setting, we administered two doses (25 g and 100 g) of a tryptophan-free amino acid mixture to ten healthy male subjects after 24 h of a low tryptophan diet. Subjects were screened for current or past psychiatric, or non-psychiatric medical illness. Aggressive responding on a free-operant laboratory measure of aggression (the Point Subtraction Aggression Paradigm) and plasma tryptophan levels were measured before and after drinking the amino acid mixture. There was a significant increase in aggressive responding 5 h after the 100 g mixture and a significant increase in aggressive responding 6 h after the 25 g mixture compared to a baseline day when no drink was administered. There was also a significant decrease in plasma tryptophan at 5 hours after ingestion compared to baseline for both doses of amino acid mixture. This study supports the hypothesis that tryptophan depletion increases aggressive responding in healthy males in a laboratory setting, probably by decreasing brain serotonin.
Adult↗
Research design and mental practice.
Research design is the basis from which study outcomes are obtained. Unfortunately, a multitude of methodological design combinations has historically been used to examine the phenomenon of mental practice relative to motor behaviour. The present paper contends that these varied methodological combinations obscure efforts to produce a solid foundation of mental practice evidence. The paper presents an overview of the implemented mental practice research designs via a methodological components model and illustrates how this model can be used to clarify design issues of past mental practice research, and plan more effective future studies. Analysis of past research demonstrates the need for a balanced emphasis between study design and study outcome, and suggests a more explicit methodological focus in order to promote more effectively designed mental practice studies in the future.
Humans↗
Soft tissue sarcoma of the extremity.
A retrospective review of 33 cases of soft tissue sarcoma of the extremity presenting over a 10 year period was undertaken. The history, patterns of referral, diagnostic investigations, procedures undertaken and outcomes were studied. We found there was a frequent delay in diagnosis and sometimes misinterpretation of biopsy specimens. Patients were seen by a variety of specialists from disciplines such as general surgery, plastic surgery, orthopaedic surgery and rheumatology. Considerable progress has been made in the treatment of soft tissue sarcomas, often allowing local control of the tumour without amputation. We believe there should be early referral of patients having these tumours to a centre where a combined multidisciplinary approach can be undertaken.
Adolescent↗
The efficacy of SNOMED, Read Codes, and UMLS in coding ambulatory family practice clinical records.
This study was initially developed as a traditional quantitative study to determine the level of match of identified clinical terms in three (3) clinical vocabularies. To address concerns raised by a review of the literature and our own experience, a supplemental study to collect qualitative data was added. Dictated progress notes from a stratified sample of patient visits over a period of four (4) years were used to obtain a representative sample of terms. A total of 144 progress notes were selected taking into consideration the usual demographics plus additional variables. From the 144 clinical notes, 864 terms were extracted and evaluated by level of match. The within-term effect was highly significant (F = 58.69, p < or = .001), indicating significant differences in the mean level of match for the three coding systems. Qualitative findings suggest that this and other published studies may not answer questions about the "efficacy of available clinical vocabularies in coding ambulatory family practice clinical records", and additional studies are needed which must be carefully structured and utilize a standardized procedure.
Family Practice↗
Isolation of small, primitive human hematopoietic stem cells: distribution of cell surface cytokine receptors and growth in SCID-Hu mice.
Human CD34+ cells were subfractionated into three size classes using counterflow centrifugal elutriation followed by immunoadsorption to polystyrene cell separation devices. The three CD34+ cell fractions (Fr), Fr 25/29, Fr 33/37, and Fr RO, had mean sizes of 8.5, 9.3 and 13.5 microns, respectively. The majority of cells in the large Fr RO CD34+ cell population expressed the committed stage antigens CD33, CD19, CD38, or HLA-DR and contained the majority of granulocyte-macrophage colony-forming units (CFU-GM), burst-forming units-erythroid (BFU-E), and CFU-mixed lineage (GEMM). In contrast, the small Fr 25/29 CD34+ cells were devoid of committed cell surface antigens and lacked colony-forming activity. When seeded to allogeneic stroma, Fr RO CD34+ cells produced few CFU-GM at week 5, whereas cells from the Fr 25/29 CD34+ cell population showed a 30- to 55-fold expansion of myeloid progenitors at this same time point. Furthermore, CD34+ cells from each size fraction supported ontogeny of T cells in human thymus/liver grafts in severe combined immunodeficient (SCID) mice. Upon cell cycle analyses, greater than 97% of the Fr 25/29 CD34+ cells were in G0/G1 phase, whereas greater proportions of the two larger CD34+ cell fractions were in active cell cycle. Binding of the cytokines interleukin (IL)-1 alpha, IL-3, IL-6, stem cell factor (SCF), macrophage inhibitory protein (MIP)-1 alpha, granulocyte colony-stimulating factor (G-CSF), and granulocyte-macrophage (GM)-CSF to these CD34+ cell populations was also analyzed by flow cytometry. As compared with the larger CD34+ cell fractions, cells in the small Fr 25/29 CD34+ cell population possessed the highest numbers of receptors for SCF, MIP1 alpha, and IL-1 alpha. Collectively, these results indicate that the Fr 25/29 CD34+ cell is a very primitive, quiescent progenitor cell population possessing a high number of receptors for SCF and MIP1 alpha and capable of yielding both myeloid and lymphoid lineages when placed in appropriate in vitro or in vivo culture conditions.
Animals↗
Distribution of lipids in 8,500 men with coronary artery disease. Department of Veterans Affairs HDL Intervention Trial Study Group.
In the present study we measured fasting lipid profiles in over 8,500 community-living men with coronary artery disease (CAD) to determine the distribution of lipid abnormalities in this population: 81% were white and 16% black; mean age 62.9 +/- 8 years; mean total cholesterol 214 +/- 41 mg/dl; low-density lipoprotein (LDL) cholesterol 140 +/- 37 mg/dl; high-density lipoprotein (HDL) cholesterol 39 +/- 11 mg/dl; and triglycerides 190 +/- 142 mg/dl. After adjusting for age, the only significant difference between blacks and whites was a higher HDL cholesterol in blacks (45 vs 38 mg/dl, p < 0.003). With use of cut points established by the National Cholesterol Education Program, 87% of subjects had high LDL cholesterol (> or = 100 mg/dl), 38% had low HDL cholesterol (< 35 mg/dl), and 33% had high triglycerides (> 200 mg/dl). We estimated that 42% of men with CAD would be definite candidates for cholesterol-lowering medication according to the National Cholesterol Education Program guidelines and that 41% of those in whom cholesterol-lowering medication would not be definitely indicated had low levels of HDL cholesterol. We conclude that (1) black men with CAD have substantially higher HDL cholesterol than white men, (2) almost 90% of male patients with CAD are candidates for dietary intervention and > 40% may need medications to lower LDL cholesterol, and (3) 40% of patients without a definite indication for cholesterol-lowering medications have low levels of HDL cholesterol.
Adult↗
Fusion of cationic liposomes with mammalian cells occurs after endocytosis.
The interaction of cationic liposomes prepared using either dioleoyltrimethylammonium propane (DOTAP) or 3 beta-(N-(N',N'-dimethylaminoethane)carbamoyl)cholesterol (DC-CHOL) with model membranes and with cultured mammalian cells was examined using an assay developed for monitoring virus-cell fusion (Stegmann et al. (1993) Biochemistry 32, 11330-11337). Lipid mixing between cationic liposomes and liposomes composed of DOPE/dioleoylphosphatidylglycerol (DOPG) or dioleoylphosphatidylcholine (DOPC)/DOPG was insensitive to pH in the range of pH 4.5-7.0 and was not affected by sodium chloride concentration in the range of 0-150 mM. Lipid mixing was dependent on dioleoylphosphatidylethanolamine (DOPE), since cationic liposomes prepared using dioleoylphosphatidylcholine (DOPC) were incapable of lipid mixing with DOPC/DOPG liposomes. The interaction of cationic liposomes with Hep G-2 and CHO D- cells was also studied. For both cell types, liposome-cell lipid mixing was rapid at 37 degrees C, beginning within minutes and continuing for up to 1 hour after uptake. The extent of lipid mixing was decreased at 15 degrees C, especially at later (> or = 20 min) time points. This suggests that at least part of the observed lipid mixing occurred after reaching cellular lysosomes. No lipid mixing was seen at 4 degrees C. Monensin inhibited lipid mixing between cationic liposomes and the cells, despite having no effect on liposome uptake. Inhibition of endocytic uptake of liposomes, either by incubation in hypertonic media or by depletion of cellular ATP with sodium azide and 2-deoxyglucose abolished liposome-cell fusion in both cell types. These data demonstrate that binding to the cell surface is insufficient for cationic liposome-cell fusion and that uptake into the endocytic pathway is required for fusion to occur.
Animals↗
The detuning factor in the dynamics of interlimb rhythmic coordination.
Dynamical models of two coupled biological oscillators interpret the detuning term as an arithmetic difference between the uncoupled frequencies, delta omega = (omega 1-omega 2). This delta omega interpretation of detuning was addressed in four experiments in which human subjects oscillated pendulums in their right and left hands in 1:1 frequency locking in antiphase (Experiments 1-3) or inphase (Experiment 4). Differences between the uncoupled frequencies were manipulated through differences in the equivalent simple pendulum lengths, and the effects of this manipulation on the detuning of relative phase from pi or O and the standard deviation of relative phase SD phi were measured. In Experiment 1, the same values of omega i were satisfied by several different physical configurations. The experiment confirmed that the detuning term is related strictly to the uncoupled frequencies rather than to other physical characteristics of the oscillators. Experiments 2, 3 and 4 showed, however, that the particular dependency of fixed point drift and SD phi on delta omega depends on the particulars of omega 1 and omega 2. With variations in delta omega brought about by different omega 1 and omega 2 that always formed a constant ratio, fixed point drift related inversely to delta omega, and SD phi varied with delta omega in ways that depended on the magnitude of the constant ratio. These outcomes do not conform to expectations from models of coordination dynamics that interpret detuning as (omega 1-omega 2).
Adult↗
Dirithromycin increases ethinyl estradiol clearance without allowing ovulation.
OBJECTIVE: To use a novel, sensitive study design to detect a potential oral contraceptive (OC) and dirithromycin drug interaction by assessing the pharmacokinetics of the ethinyl estradiol (E2) component of a common OC and the potential failure of OC effectiveness. METHODS: In this nonblinded study, 20 healthy women using Ortho Novum 7/7/7-28 were selected for a three-OC-cycle study. Baseline measures included E2 and progesterone serum levels on days 21, 23, 25, and 27 of cycle one and days 1, 3, 5, and 7 of cycle two. During cycle two, 24-hour blood sampling and radioimmunoassay analysis for ethinyl E2 pharmacokinetics were performed on day 8 and pelvic ultrasound on day 13. Oral dirithromycin 500 mg/day for 14 days began on day 21 of cycle 2. After starting dirithromycin, cycle two and three serum E2, progesterone, and serial ethinyl E2 levels and pelvic ultrasound replicated the baseline schedule. Ovulation was assumed if E2 concentration was greater than 50 pg/mL, progesterone concentration was greater than 3 ng/mL, or if an ovarian cyst greater than 10 mm was present on ultrasound. RESULTS: Pharmacokinetic analysis demonstrated a small (7.6%) but statistically significant decrease (P = .03) in the mean ethinyl E2 24-hour area under the curve and an increase in apparent oral clearance. No woman ovulated, based on E2 levels and progesterone concentrations or ultrasound. CONCLUSION: Dirithromycin increased the apparent oral clearance of ethinyl E2. The clinical importance of the interaction may be negligible because no woman ovulated or had compromised OC effectiveness in this small series.
Adolescent↗
Using computer bulletin boards.
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Computer Communication Networks↗