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Biomedical subjects

D Collins

Publications and source records attributed to D Collins.

At least 37 records · Page 2Linked to original sources
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

The fall and rise of cost sharing in Kenya: the impact of phased implementation.

The combined effects of increasing demand for health services and declining real public resources have recently led many governments in the developing world to explore various health financing alternatives. Faced with a significant decline during the 1980s in its real per capita expenditures, the Kenya Ministry of Health (MOH) introduced a new cost sharing programme in December 1989. The programme was part of a comprehensive health financing strategy which also included social insurance, efficiency measures, and private sector development. Early implementation problems led to the suspension in September 1990 of the outpatient registration fee, the major revenue source at the time. In 1991, the Ministry initiated a programme of management improvement and gradual re-introduction of an outpatient fee, but this time as a treatment fee. The new programme was carried out in phases, beginning at the national and provincial levels and proceeding to the local level. The impact of these changes was assessed with national revenue collection reports, quality of care surveys in 6 purposively selected indicator districts, and time series analysis of monthly utilization in these same districts. In contrast to the significant fall in revenue experienced over the period of the initial programme, the later management improvements and fee adjustments resulted in steady increases in revenue. As a percentage of total non-staff expenditures, fiscal year 1993-1994 revenue is estimated to have been 37% at provincial general hospitals, 20% at smaller hospitals, and 21% at health centres. Roughly one third of total revenue is derived from national insurance claims. Quality of care measures, though in some respects improved with cost sharing, were in general somewhat mixed and inconsistent. The 1989 outpatient registration fee led to an average reduction in utilization of 27% at provincial hospitals, 45% at district hospitals, and 33% at health centres. In contrast, phased introduction of the outpatient treatment fee beginning in 1992, combined with somewhat broader exemptions, was associated with much smaller decreases in outpatient utilization. It is suggested that implementing user fees in phases by level of health facility is important to gain patient acceptance, to develop the requisite management systems, and to orient ministry staff to the new systems.

Cost Sharing↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

New mouse model for polycystic kidney disease with both recessive and dominant gene effects.

In the course of studying the genetics of chlorambucil mutagenesis, we have uncovered a new model for autosomal polycystic kidney disease (PKD). In the homozygous condition, the gene, jcpk, causes a very severe disease characterized by cysts in all segments of the nephron. Death usually occurs before 10 days of age. Extrarenal involvement was also noted; enlarged bile ducts, pancreatic ducts, and gall bladder often accompanied the PKD. In addition, approximately 25% of the aged +/jcpk heterozygotes show evidence of glomerulocystic disease. This gene maps to Chromosome 10 between two DNA markers, D10Mit20 and D10Mit42. Because this gene causes extrarenal abnormalities and because it has a heterozygote effect, it may be an informative animal model for the commonly occurring human adult dominant PKD.

Animals↗
PubMed1995

The utilisation and economic evaluation of antibiotics prescribed in primary care.

This was an observational study of efficacy and resource utilisation over three years in a cohort of 917 patients who received at least one prescription for an oral antibiotic between January and March 1989 in a large rural primary care health centre in Tayside, Scotland. Three thousand, six hundred and sixty three prescriptions were issued (2286 to females) for; 1502 upper respiratory tract infections, 419 lower respiratory tract infections, 441 urinary tract infections, 177 skin and soft tissue infections, 97 gynaecological infections, 103 cases of acne and 71 other infections. Excluding acne, 14% of infections required more than one antibiotic to achieve a successful outcome. The highest success rates for antibiotics were amoxycillin (92%) and penicillin V (92%) in upper respiratory tract infections, erythromycin (90%) in lower respiratory tract infections and co-trimoxazole (83%) in urinary tract infections. The most cost-effective antibiotics were penicillin V for upper respiratory tract infection, erythromycin for lower respiratory tract infection and co-trimoxazole for urinary tract infection. Varying the value placed on general practitioners' time did not change the rank order of antibiotic cost-effectiveness. The efficacy and cost-effectiveness of the treatment of acute infections in primary care varies considerably with the antibiotic used as first choice. More expensive antibiotics might be justified in cost-effectiveness terms if they had high cure rates in clinical practice.

Adolescent↗
PubMed1994

Interactions of liposome bilayers composed of 1,2-diacyl-3-succinylglycerol with protons and divalent cations.

Bilayer liposomes were prepared by using pure DOSG (1,2-dioleoyl-3-succinylglycerol) or DPSG (1,2-dipalmitoyl-3-succinylglycerol) at pH 7.4 or above. These liposomes undergo destabilization upon incubation with acid. When calcein was used as an entrapped aqueous marker, half maximal content leakage was observed between pH 5.8-6.3. Differential scanning calorimetry showed that at pH 7.4, the chain-melting temperature (Tm) of DPSG was 60.4 degrees C, and increased with decreasing pH (Tm = 57.0 degrees C and 62.7 degrees C at pH 8.9 and 6.7, respectively). Below pH 6.7, extensive phase separation occurred as the major chain melting peak split into three peaks. These three peaks coalesced into one peak below pH 5. Freeze fracture electron micrographs of DOSG liposomes at pH 4 showed the formation of non-bilayer as well as hexagonal phase structures. The effects of divalent cations, such as Ca2+ and Mg2+, on the destabilization of DASG bilayers have also been studied. Differential scanning calorimetry studies of bilayers composed of DPSG showed that both Ca2+ and Mg2+ could increase the Tm of DPSG with increasing concentrations. However, under identical conditions Mg2+ was more effective than Ca2+ in increasing the Tm of DPSG. X-ray diffraction indicated that both Ca2+ and Mg2+ could induce DPSG bilayers to undergo a complete lamellar to hexagonal phase transition. There was a size-dependency on the plasma stability of DOSG liposomes. DOSG liposomes that were smaller in size were more stable in plasma than the larger ones. After incubation with plasma, DOSG liposomes became less acid-sensitive. DOSG immunoliposomes entrapping diphtheria toxin A chain were used as a model for cytoplasmic delivery of the novel pH-sensitive liposomes. The delivery activity was comparable to that of the conventional pH-sensitive liposomes containing unsaturated phosphatidylethanolamine. Our data indicate that the mechanism of liposome destabilization involves extensive bilayer phase separation as well as the formation of non-bilayer structures.

Calorimetry, Differential Scanning↗
PubMed1994

Interaction of recombinant granulocyte colony stimulating factor with lipid membranes: enhanced stability of a water-soluble protein after membrane insertion.

The interaction of recombinant granulocyte colony stimulating factor (rhG-CSF) with lipid vesicles was studied. In the presence of dioleoylphosphatidylglycerol (DOPG) vesicles, the intrinsic fluorescence of rhG-CSF exhibits dramatic changes. In particular, tryptophan fluorescence is greatly enhanced and the emission maximum shifted to lower wavelengths. The presence of DOPG vesicles causes the protein tryptophans to become inaccessible to iodide, a water-soluble quencher of tryptophan fluorescence, yet accessible to quenching via energy transfer to pyrenyl decanoic acid, a lipid-soluble fluorescent probe. The data suggest that rhG-CSF inserts into lipid vesicles composed of DOPG. The driving force for the insertion may be a conformational change induced by the low pH at the lipid-water interface of DOPG vesicles. The DOPG-inserted form of rhG-CSF retains biological activity and shows remarkable stability, even under high-temperature conditions which lead to denaturation of rhG-CSF alone. Membrane insertion of G-CSF may be involved in the in vivo activity of this important cytokine.

Decanoic Acids↗