Search PubMed⌕ Search

Biomedical subjects

D C Mitchell

Publications and source records attributed to D C Mitchell.

At least 37 records · Page 2Linked to original sources

A simplified technique for the cryopreservation of vein allografts.

OBJECTIVES: we assessed the effects of cryopreservation on smooth-muscle cell injury in human vein. MATERIALS AND METHODS: long saphenous vein was collected during surgery and cryopreserved. Smooth-muscle cell damage was assessed after thawing by in situ detection of fragmented DNA. The presence of cryoprotectant (10% dimethyl sulphoxide, DMSO), cooling and warming rates, and the rate of cryoprotectant removal after thawing were examined. RESULTS: control veins exhibited damage in 8.5% (95% confidence interval (CI) 4.7 to 13.4%,n=13) of smooth-muscle cells compared with 27.7% (95% CI 23.2 to 32.4%, n=115) in vein frozen in 10% DMSO (p=0.001). In the presence of DMSO, damage to smooth-muscle cells was independent of the rates of cooling (p=0.72) and warming (p=0.45). The rate of dilution to remove the cryoprotectant after thawing also had no effect on cell damage (p=0.64). In the absence of cryoprotectant, cell damage was doubled to approximately 50% by slow rather than rapid warming (p=0.01). CONCLUSION: cooling rate, and the presence of a cryoprotectant, has little effect on smooth-muscle damage, provided that the tissue is warmed rapidly. Slow warming, in the absence of DMSO, causes substantial damage. These results suggest that simplified methods of vein cryopreservation are feasible.

Confidence Intervals↗

Nutritional guidance is needed during dietary transition in early childhood.

OBJECTIVE: To assess dietary nutritional quality during dietary transition to a modified adult-style diet in the second year of life. DESIGN: A total of 55 children from 12 to 18 months old and their parents were studied. Dietary intake and indices of growth were measured monthly. Dietary data were collected monthly and tabulated using the Minnesota Nutrient Data System. Data were evaluated using repeated-measures analysis of variance, time trend, and correlational analyses. RESULTS: Mean energy intake increased from 12 to 18 months of age (926+/-24 kcal to 1062+/-33 kcal) with contributions from energy-yielding macronutrients remaining relatively constant. Throughout the study, fat intakes were below 30% of energy for 22% to 33% of the sample. Micronutrient intake patterns were diverse with intake for some nutrients (vitamins A, C, B(6), B(12), and D and calcium) remaining above recommended levels despite changes over the course of the study. Folate intakes increased from 79% of the recommended value at 12 months old to approximately 100% at 18 months old. Zinc and vitamin E intakes were well below recommended levels throughout the study, and iron decreased markedly from 96% of the recommended level at 12 months old to 76% at 18 months old. APPLICATIONS/CONCLUSIONS: These data show that intakes of some key nutrients are low during the period of dietary transition in early childhood, and intakes for some nutrients actually decrease despite increases in energy intake. Furthermore, because a considerable portion of children studied were consuming low-fat diets, it is clear that many parents are not following the only pediatric nutrition recommendations that currently exist. These findings argue strongly for the development of dietary guidance that not only addresses fat restriction, but also assists parents in selecting diets that support optimum growth and development in young children.nutrient intake, infants, dietary density.

Diet↗

Effect of protein hydration on receptor conformation: decreased levels of bound water promote metarhodopsin II formation.

Neutral solutes were used to investigate the effects of osmotic stress both on the ability of rhodopsin to undergo its activating conformation change and on acyl chain packing in the rod outer segment (ROS) disk membrane. The equilibrium concentration of metarhodopsin II (MII), the conformation of photoactivated rhodopsin, which binds and activates transducin, was increased by glycerol, sucrose, and stachyose in a manner which was linear with osmolality. Analysis of this shift in equilibrium in terms of the dependence of ln(Keq) on osmolality revealed that 20 +/- 1 water molecules are released during the MI-to-MII transition at 20 degrees C, and at 35 degrees C 13 +/- 1 waters are released. At 35 degrees C the average time constant for MII formation was increased from 1.20 +/- 0.09 ms to 1.63 +/- 0.09 ms by addition of 1 osmolal sucrose or glycerol. The effect of the neutral solutes on acyl chain packing in the ROS disk membrane was assessed via measurements of the fluorescence lifetime and anisotropy decay of 1,6-diphenyl-1,3,5-hexatriene (DPH). Analysis of the anisotropy decay of DPH in terms of the rotational diffusion model showed that the angular width of the equilibrium orientational distribution of DPH about the membrane normal was progressively narrowed by increased osmolality. The parameter fv, which is proportional to the overlap between the DPH orientational probability distribution and a random orientational distribution, was reduced by the osmolytes in a manner which was linear with osmolality. This study highlights the potentially opposing interplay between the effect of membrane surface hydration on both the lipid bilayer and integral membrane protein structure. Our results further demonstrate that the binding and release of water molecules play an important role in modulating functional conformational changes for integral membrane proteins, as well as for soluble globular proteins.

Animals↗

The morbidity of secondary vascular access. A lifetime of intervention.

OBJECTIVES: to examine the outcome and incidence of access-related procedures in patients who dialyse via PTFE secondary access grafts. DESIGN: retrospective case note study. RESULTS: recipients of secondary access procedures face a lifetime of haemodialysis access interventions. In total, 639 access-related procedures were performed on the 72 patients studied. At the end of the study five patients were wholly reliant on central venous catheters for dialysis access. Patients with secondary access grafts have little hope of transplantation; only six of 72 patients received a transplant after a secondary access procedure. CONCLUSION: the increasing number of patients coming to synthetic access-graft procedures and the morbidity of such procedures mean that surgeons should adopt strategies to minimise the use of grafts and limit the number of interventions performed. Careful planning will also reduce the number of central line placements and help to reduce the morbidity associated with long-term haemodialysis. Increasing resources will be required to meet the rising demand for secondary access provision.

Adult↗

Self-selected diets of lactating women often fail to meet dietary recommendations.

OBJECTIVE: To assess longitudinally nutrient intakes of lactating women during the postpartum period. DESIGN: Dietary data from lactating women were collected by means of 2-day food records at 3 and 6 months postpartum. Intake of energy and selected nutrients was tabulated and compared with dietary standards. SUBJECTS: The 52 lactating women enrolled in the study lived in a university community, were apparently healthy, had a body mass index within normal range, were successfully nursing a term infant, and planned to nurse for at least 6 months. STATISTICAL ANALYSES PERFORMED: Paired t tests and Stuart-Maxwell chi(2) analyses. RESULTS: Mean energy intakes were below the Recommended Dietary Allowance. Mean intakes of most nutrients met or exceeded recommended standards except for zinc and vitamins D and E at both 3 and 6 months postpartum. Calcium and folate intakes were also below standards at 6 months. Although mean iron intake exceeded the standard at both measurement times, there was a significant decline from 3 to 6 months. Relative frequencies of mothers meeting various percentages of standards differed significantly from 3 to 6 months for calcium; iron; folate; and vitamins E, D, and B-6. At 6 months, significant increases were noted in the number of women reporting calcium, folate, and vitamin B-6 intakes at less than one half of the recommended amounts. APPLICATIONS/CONCLUSIONS: Guidance for lactating women should stress food sources of nutrients likely to be limited in their diets: calcium; zinc; folate; and vitamins E, D, and B-6.

Adult↗

What to consider when conducting a cost-effectiveness analysis in a clinical setting.

More data are needed providing strong evidence that nutrition services are cost-effective. Economic evaluations, such as cost-effectiveness analyses, are excellent practice-based research projects. We conducted a cost-effectiveness analysis in a clinical setting to compare the cost-effectiveness of lipid-lowering medications plus diet therapy (medication + diet) with diet therapy alone (diet alone) for treating patients with hypercholesterolemia. Twenty-five adults with hypercholesterolemia (13 receiving medication + diet, 12 receiving diet alone) either participated in an 8-week, home-based, step 1 intervention or were counseled about diet and lifestyle by their care provider. Diet, cost, and laboratory data were collected at baseline, at 9 months, and at 19 months after participation in the intervention (follow-up). Cost per unit change in outcome was evaluated for each group. The diet-alone group made only small changes in dietary intake, changes that were smaller in magnitude than those made by the medication + diet group. Nevertheless, at 9 months, costs per unit change in total serum cholesterol level and low-density lipoprotein cholesterol (LDL-C) level were approximately $24 and $83 less, respectively, for the diet-alone group. At follow-up, however, the cost per unit change in LDL-C level was approximately $17 less for the medication + diet group, which can be explained by the medication + diet group's greater decrease in LDL-C level. The following elements should be considered when conducting a cost-effectiveness analysis of medical nutrition therapy: effectiveness of the nutrition intervention, adequate sample size, confounding variables, compliance with diet and drug therapy, direct and indirect costs of care, and follow-up evaluation.

Adult↗

Molecular order and dynamics in bilayers consisting of highly polyunsaturated phospholipids.

The time-resolved fluorescence emission and decay of fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene (DPH) was used to characterize equilibrium and dynamic bilayer structural properties of symmetrically substituted phosphatidylcholines (PCs) with acyl chains containing no, one, four, or six double bonds and mixed-chain phosphatidylcholines with a saturated sn-1 chain and one, four, or six double bonds in the sn-2 chain. Both the Brownian rotational diffusion (BRD) model and the wobble-in-cone model were fit to all differential polarization data, and the descriptions of the data provided by the BRD model were found to be statistically superior. Global analysis of differential polarization data revealed two statistically equivalent solutions. The solution corresponding to a bimodal orientational distribution function, f(theta), was selected based on the effects of temperature on f(theta) and previous measurements on fixed, oriented bilayers. The overall equilibrium acyl chain order in these bilayers was analyzed by comparing the orientational probability distribution for DPH, f(theta) sin theta, with a random orientational distribution. Orientational order decreased and probe dynamics increased in mixed-chain species as the unsaturation of the sn-2 chain was increased. The degree of orientational order dropped dramatically in the dipolyunsaturated species compared with the mixed-chain phosphatidylcholines, which contained a polyunsaturated sn-2 chain. In terms of both orientational order and probe dynamics, the differences between the highly polyunsaturated species and the monounsaturated species were much greater than the differences between the monounsaturated species and a disaturated PC.

Diphenylhexatriene↗

Effect of cholesterol on molecular order and dynamics in highly polyunsaturated phospholipid bilayers.

The effect of cholesterol on phospholipid acyl chain packing in bilayers consisting of highly unsaturated acyl chains in the liquid crystalline phase was examined for a series of symmetrically and asymmetrically substituted phosphatidylcholines (PCs). The time-resolved fluorescence emission and decay of fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene (DPH) was used to characterize equilibrium and dynamic structural properties of bilayers containing 30 mol % cholesterol. The bilayers were composed of symmetrically substituted PCs with acyl chains of 14:0, 18:1n9, 20:4n6, or 22:6n3, containing 0, 1, 4, or 6 double bonds, respectively, and mixed-chain PCs with a saturated 16:0 sn-1 chain and 1, 4, or 6 double bonds in the sn-2 chain. DPH excited-state lifetime was fit to a Lorentzian lifetime distribution, the center of which was increased 1-2 ns by 30 mol % cholesterol relative to the cholesterol-free bilayers. Lifetime distributions were dramatically narrowed by the addition of cholesterol in all bilayers except the two consisting of dipolyunsaturated PCs. DPH anisotropy decay was interpreted in terms of the Brownian rotational diffusion model. The effect of cholesterol on both the perpendicular diffusion coefficient D perpendicular and the orientational distribution function f(theta) varied with acyl chain unsaturation. In all bilayers, except the two dipolyunsaturated PCs, 30 mol % cholesterol dramatically slowed DPH rotational motion and restricted DPH orientational freedom. The effect of cholesterol was especially diminished in di-22:6n3 PC, suggesting that this phospholipid may be particularly effective at promoting lateral domains, which are cholesterol-rich and unsaturation-rich, respectively. The results are discussed in terms of a model for lipid packing in membranes containing cholesterol and PCs with highly unsaturated acyl chains.

Cholesterol↗

Venous allografts prepared from stripped long saphenous vein. Is there a need for antibiotic sterilisation?

AIM: Can useful lengths of vein be retrieved from varicose vein stripping procedures; is it necessary to sterilise this tissue prior to use as vein allografts? METHOD: Stripped long saphenous vein was retrieved at operation. Vein samples were cultured using direct plate inoculation and enrichment culture. Further samples were immersed in two low concentration antibiotic solutions and recultured. Smooth muscle viability was assessed after antibiotic immersion and storage by cryopreservation. RESULTS: High quality vein could be retrieved by vein stripping. Vein segments grew skin commensals on enrichment culture despite negative cultures with standard media plate inoculation (Chi-squared = 53.34 1 d.f. p < 0.001). Low concentration antibiotic solutions sterilised processed vein. Smooth muscle cell viability was reduced by cryopreservation, Mann-Whitney p = 0.008 (control 98% S.E. 0.93 vs. cryopreserved 64% S.E. 6.58), but prior exposure to antibiotics did not compound this effect. CONCLUSION: Useful lengths of vein grafts can be retrieved from varicose vein stripping procedures. Venous segments are frequently contaminated by skin commensals. Enrichment culture is required to detect contamination. Low concentration antibiotics sterilise venous-tissue without affecting smooth muscle cell viability.

Anti-Bacterial Agents↗

Time and cost for recruiting older adults.

OBJECTIVES: The purpose of this study was to examine the time requirements and costs of recruiting older adults for participation in a medical center-/university-sponsored, home-based nutrition education study. A two-step recruitment strategy consisting of an introductory letter followed by a telephone call was used. DESIGN: A random selection of 1300 individuals aged 60 to 74 years was drawn from a patient database of a large, rural, tertiary care hospital to receive introductory letters and recruitment telephone calls. One week after the mailing, potential subjects were contacted by trained interviewers and asked to participate in a home-based nutrition education study. PARTICIPANTS: Men and women, aged 60 to 74 years, whose names appeared in a rural, tertiary care hospital database. MEASUREMENTS: Recruitment rate, time required for recruitment by telephone, and cost of the combined mailing and telephone recruitment effort. RESULTS: Of the 1300 individuals selected, 1077 (83%) people were contacted by phone and 223 (17%) people were unable to be reached. A total of 2895 calling attempts were required to determine the recruitment status of those identified as potential participants. Of those reached by phone, the recruitment rate was 45%. The total cost (mailing, telephone, and database management) per recruited subject was $8.56. CONCLUSION: This study has helped to establish the costs of recruitment for home-based education interventions using a two-step strategy of an introductory mailing and follow-up telephone interview.

Aged↗

The effect of changes in dietary fat on the food group and nutrient intake of 4- to 10-year-old children.

OBJECTIVE: To determine how young children changed their overall diet when they changed their fat intake after 3 months of participating in a nutrition education demonstration study designed to lower low-density lipoprotein cholesterol and cardiovascular risk. METHODS: Three 24-hour dietary recalls were collected from 303 4- to 10-year-old children at baseline and 3 months later. At both times, mean number of servings from food groups, grams of fat contributed from food groups, and intake of calories and nutrients were calculated and compared among quartiles of children formed according to change in their percent of calories from total fat after 3 months. RESULTS: Children who reduced their percent of calories from total fat most (ie, by an average of 8.5%) after 3 months consumed fewer servings from meats, eggs, dairy, fats/oils, and breads but tended to increase their number of servings from lower-fat foods within those food groups, particularly from dairy foods. These children also increased their mean intake of fruits, vegetables, and desserts, and maintained average intakes of all nutrients (except vitamin D) in excess of two thirds of the respective recommended dietary allowance. CONCLUSIONS: Young children who reduced their percent of calories from total fat in accordance with the current National Cholesterol Education Program recommendations accomplished this by reducing their overall intake of higher-fat foods, replacing higher-fat foods with lower-fat foods within several food groups, particularly within the dairy group (eg, drinking skim milk instead of whole milk) and by consuming more servings of fruits, vegetables, and very-low-fat desserts. These behaviors did not compromise their mean calorie or nutrient intakes, showing that it is possible for young children to lower their fat intake safely to reduce their risk of future heart disease.

Child↗

Extracorporeal circuit sterility after 168 hours.

One of the most important tasks of the perfusionist is the proper assembly of the extracorporeal circuit (ECC) prior to the initiation of cardiopulmonary bypass (CPB). The ECC is usually assembled, primed and debubbled 30 minutes to one hour prior to the patient entering the operating room. But there are occasions when the ECC may have been set up and the previously scheduled procedure cancelled. Perfusionists in this situation have found themselves in a quandary; dispose of the ECC because of required nursing compliance and the sterility question, or keep it and use it later because of the economic impact on the "bottom line". Some hospitals may have satisfactorily answered the question of ECC sterility after 24 hours without observation, but the few reported papers regarding this issue, and our desire to save these circuits, inspired us to find out if they were in fact sterile after having been open for a long period of time. The purpose of this study was to evaluate ECC sterility using an open reservoir oxygenator, over a time period of seven days. After obtaining 792 bacterial cultures from three sites within the ECC, the study was terminated. There were no positive bacterial cultures during the study period. Assuming there is no deliberate contamination, pump circuits assembled in an unused operating room can be maintained sterile for a period of seven days.

Bacteria↗

Primary alcohols modulate the activation of the G protein-coupled receptor rhodopsin by a lipid-mediated mechanism.

The visual pigment rhodopsin is a prototypical member of the G protein-coupled receptor superfamily. In this study, we have investigated the effect of a series of n-alcohols on the formation of metarhodopsin II (MII), the photoactivated conformation of rhodopsin, which binds and activates transducin. When rhodopsin was photolyzed in the presence of several n-alcohols, increased MII formation was observed in the order ethanol > butanol > hexanol, whereas longer chain n-alcohols inhibited MII formation with decanol > octanol. The magnitude of the stimulatory effects was greater in a more highly unsaturated phospholipid. Alcohols, which enhanced MII formation also increased phospholipid acyl chain packing free volume, while those that decreased this bilayer property inhibited MII formation. An apparent discontinuity in the effect of these alcohols results when their potency is calculated in terms of the total aqueous alcohol concentration. In sharp contrast, a continuous variation in their behavior is observed, when their potency is calculated in terms of the amount of alcohol partitioned in the membrane. Our findings strongly support a lipid-mediated mechanism of action for alcohols on rhodopsin and, by analogy, for other G protein-coupled receptors.

Alcohols↗

A role for phospholipid polyunsaturation in modulating membrane protein function.

Visual transduction is one of the best characterized G protein--coupled signalling systems. In addition, about 50% of the disk membrane phospholipid acyl chains are 22:6n-3, making this system ideal for determining the role of polyunsaturation in modulating membrane-signalling systems. The extent of formation of metarhodopsin II (MII), the G protein--activating photointermediate of rhodopsin, was studied in phospholipid vesicles composed of a variety of phosphatidylcholines, differing in their acyl chain composition at the sn-2 position. The amount of MII formed increased progressively with the level of acyl chain unsaturation at the sn-2 position. The effect of added cholesterol was to reduce the amount of MII formed. The acyl chain packing free volume of the rhodopsin containing lipid vesicles was characterized by a fractional volume parameter fv derived from measurements of the time-resolved fluorescence anisotropy decay of the hydrophobic membrane probe 1,6-diphenyl-1,3,5-hexatriene. The relationship among sn-2 acyl chain unsaturation, cholesterol content, and MII formation is explained on the basis of variation in fv with bilayer lipid composition and a novel model for the packing of phospholipids containing polyenoic acyl chains, such as 22:6n-3.

Fats, Unsaturated↗

Amphotericin B responsive Scedosporium apiospermum infection in a patient with acute myeloid leukaemia.

A 71 year old man with newly diagnosed acute myelomonocytic leukaemia developed a soft tissue infection of his foot during his first course of chemotherapy. Scedosporium apiospermum was isolated from the lesion, which resolved rapidly on treatment with intravenous amphotericin B despite being resistant in vitro to this agent. This observation suggests that sensitivity testing of S apiospermum should be interpreted with caution and that clinical response may be a better indicator of outcome.

Aged↗

The dietary intake of children with IDDM.

OBJECTIVE: To assess the dietary intake of children with IDDM and to determine whether the intake meets the current nutritional recommendations for children with IDDM. RESEARCH DESIGN AND METHODS: A total of 66 children with IDDM who were < 10 years of age were recruited from two suburban Pennsylvania hospitals. To collect dietary intake data, subjects were asked, via telephone interview, to complete three random-day 24-h dietary recalls. Data were analyzed for the content of nutrients and other food components by a computerized database program. Intakes were expressed as a 3-day average intake for each subject. RESULTS: Overall mean intake of protein and cholesterol approximated the current recommendations. The mean intake of saturated fat exceeded recommendations, while fiber intake was less than the recommended level. Many of the children consumed levels of saturated fat well above recommendations. Energy, vitamin, and mineral intakes were adequate for the overall sample. However, from 10 to 40% of the sample had an inadequate intake of vitamin D, vitamin E, and zinc. The percentage of those with inadequate intakes of these nutrients decreased with age. CONCLUSIONS: These data suggest that, on average, among this sample of children with IDDM aged < 10 years, adherence to the current nutritional recommendations for children with IDDM was adequate, but some individual children had intakes that were not consistent with the recommendations for optimal management of IDDM.

Child↗

Effect of ethanol on metarhodopsin II formation is potentiated by phospholipid polyunsaturation.

The role of phospholipids in modulating the effect of ethanol on membrane receptor activation was investigated by studying the extent of metarhodopsin II (MII) formation in vesicles formed POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) and PDPC (1-palmitoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine) and in native rod outer segment disk membranes as a function of ethanol concentration. The equilibrium concentration of MII, the G protein-activating form of photoactivated rhodopsin, was found to increase as a function of ethanol concentration in all three bilayers. Phospholipid composition had a marked effect on ethanol potency, with the presence of polyunsaturated phospholipid acyl chains increasing ethanol potency by 40%. The effects of ethanol on lipid acyl chain packing in POPC and PDPC were investigated using frequency domain anisotropy decay measurements of the fluorescent membrane probe 1,6-diphenyl-1,3,5-hexatriene. Enhanced formation of MII due to the presence of ethanol was correlated with the effects of ethanol on acyl chain packing properties. These findings support a phospholipid-mediated mechanism for the action of ethanol in modulating integral membrane receptor conformation.

Cell Membrane↗