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PubMed2002

Searching for unrelated donor hematopoietic stem cells: availability and speed of umbilical cord blood versus bone marrow.

Unrelated donor (URD) umbilical cord blood (UCB) has several potential advantages over URD BM for hematopoietic stem cell transplantation. To examine the efficiency of donor identification for each of these URD stem cell sources, we reviewed the search processes for all pediatric and adult URD transplantation referrals to the University of Minnesota during a period of 1 year. Of 171 consecutive referrals for URD transplantation, 108 patients proceeded to a formal URD search with selection of at least 1 donor. Significantly more formal UCB searches(54%) than BM searches (21%) were performed for patients who required urgent transplantation (P < .01). At least one 4-6/6 HLA-antigen matched UCB graft but no suitable BM graft was identified for 21 of the 108 patients (19%). The median time required to obtain a URD BM donor (from formal search to clearance of a BM donor) was 49 days (range, 32-293 days) compared to a UCB search time (from formal search to a donor unit chosen) of only 13.5 days (range, 2-387 days). For patients undergoing both BM and UCB searches, 29 more days (95% confidence interval, 21-37 days) were required to identify and clear a URD BM donor than a UCB donor (P < .01). For the 76 patients who proceeded to transplantation, patients receiving UCB received a transplant a median of 25 days more rapidly than did those receiving BM (P < .01). These data confirm that the availability of banked cryopreserved URD UCB grafts allows transplantations for patients with no available BM donor and that URD UCB grafts areavailable considerably faster than are URD BM grafts. Faster availability is a particular advantage for patients requiring urgent transplantation. These unique features of UCB transplantation must be considered in comparisons of the outcomes of UCB versus BM transplant recipients and in the design of prospective trials comparing URD sources.

Adolescent↗

PubMed2003

A novel regional citrate anticoagulation protocol for CRRT using only commercially available solutions.

PURPOSE: To describe a citrate regional anticoagulation (CRA) protocol for patients with acute renal failure and contraindications to heparin who require continuous renal replacement therapy (CRRT), using only commercially available solutions, for units that do not want or cannot prepare extemporaneously made solutions. MATERIALS AND METHODS: Case report and series from a medical/surgical intensive care unit of a university teaching hospital. A CRA protocol was developed by using only commercially available solutions. Five dialysis-specific clinical parameters were identified to allow simplified measurement and control. RESULTS: There was a dramatic improvement of dialysis filter survival in the index patient that was seen in the subsequent patients receiving CRA. This was accompanied by excellent control of the clinical and biochemical parameters as well as nursing acceptance and ownership of the protocol. CONCLUSION: It is possible to provide safe and effective CRA with only commercially available solutions. The protocol is applicable to most patients requiring CRRT.

Adult↗

PubMed2001

The next step for emergency contraception: over-the-counter availability.

Emergency contraception to prevent pregnancy after episodes of unprotected sexual intercourse has existed since ancient times. Modern medicine began to use hormonal methods in the 1960s, and today emergency contraception is used regularly in many countries. In the United States, providers do not routinely prescribe it, nor do they adequately inform their patients that it is available. This occurs even though sufficient information exists on the safety and efficacy of this method. Because the effectiveness of emergency contraceptive pills relies heavily on prompt administration, better access for patients is essential. Recently, proponents of emergency contraception have attempted to better inform the public of this resource. In addition, two oral contraceptive products are now available and marketed specifically for emergency contraception. The purpose of this article is to discuss the safety and efficacy of emergency contraceptive pills and the potential for them to become available without a prescription.

Contraceptives, Postcoital↗

PubMed1983

Muscular exercise in type I-diabetics. I. Different metabolic reactions during heavy muscular work in dependence on actual insulin availability.

The present study focussed on the impact of heavy muscular work upon metabolic homeostasis in insulin dependent (type I) diabetics in situations involving a certain degree of hyper- and hypoinsulinemia. 20 juvenile type I-diabetics were compared with 6 nondiabetic healthy subjects. The diabetics were studied in states of hypo-(trial A) and hyperinsulinemia (trial B) at the start of the exercise. Differences in insulin availability resulted from the different times that had elapsed from the last insulin injection (3 hours in trial A and 1 hour in trial B) before the ergometer test started at 7 a.m. Six diabetics out of 20 patients were studied in both trials A and B to establish the reproducibility of metabolic reactions to the exercise. Bicycle ergometer tests were carried out in the upright position at 5 graded steps of 50 W, 75 W, 100 W, 125 W and a load near to exhaustion. Rest periods of five minutes were allowed between these work periods for taking blood samples before and after each work load. Plasma glucose, FFA, glycerol, lactate, alanine, IRI and HCP concentrations were investigated. The blood pressure at rest and during exercise was measured, and the physical working capacity (PWC170) was calculated according to Wahlund on the basis of the heart rate response to exercise. The results of the exercise tests reflect clearly the different metabolic reactions to heavy muscular work despite the relatively slight differences in insulin availability at the start: --Exhausting muscular work during the hypoinsulinemic state resulted in hyperglycemia and exaggerated lipolysis. --Heavy muscular work in a hyperinsulinemic state resulted in a reduced blood glucose level and antilipolytic reactions in comparison to nondiabetics. These findings suggest the great necessity of an adequate insulin availability during heavy muscular work in juvenile type I-diabetics.

Aerobiosis↗

PubMed2000

Availability and accessibility of evidence-based information resources provided by medical libraries in Australia.

This article reports on the results of an exploratory survey of the availability and accessibility of evidence-based information resources provided by medical libraries in Australia. Although barriers impede access to evidence-based information for hospital clinicians, the survey revealed that Medline and Cinahl are available in over 90% of facilities. In most cases they are widely accessible via internal networks and the Internet. The Cochrane Library is available in 69% of cases. The Internet is widely accessible and most libraries provide access to some full-text, electronic journals. Strategies for overcoming restrictions and integrating information resources with clinical workflow are being pursued. State, regional and national public and private consortia are developing agreements utilising on-line technology. These could produce cost savings and more equitable access to a greater range of evidence-based resources.

Australia↗

PubMed2005

Ground-based and remotely sensed nutrient availability across a tropical landscape.

Tropical soils often are assumed to be highly weathered and thus nutrient-depleted, but this prediction applies primarily to geomorphically stable surfaces. Topography complicates the assumption of nutrient depletion, because erosion can enhance the supply of nutrients to tropical ecosystems. Consequently, understanding nutrient availability across landscapes requires a spatially explicit assessment of the relative strength of depletion and enhancement. We document the relationship between foliar nutrients and topographic position across a 20-km(2), 4- to 5-million-year-old eroded landscape in Kaua'i, Hawai'i, and use this relationship to build a bottom-up map of predicted nutrient availability across this landscape. Only approximately 17% of the landscape is nutrient-poor, mostly on stable uplands; nutrient availability on slopes and valley bottoms is much higher, in some cases similar to the most fertile montane forests in the Hawaiian Islands. This pattern was corroborated by top-down remote sensing of area-integrated canopy phosphorus concentrations.

Ecosystem↗

PubMed1998

Phosphate availability affects the thylakoid lipid composition and the expression of SQD1, a gene required for sulfolipid biosynthesis in Arabidopsis thaliana.

Photosynthetic membranes of higher plants contain specific nonphosphorous lipids like the sulfolipid sulfoquinovosyl diacylglycerol in addition to the ubiquitous phospholipid phosphatidylglycerol. In bacteria, an environmental factor that drastically affects thylakoid lipid composition appears to be the availability of phosphate. Accordingly, we discovered an increase in the relative amount of sulfolipid and a concomitant decrease in phosphatidylglycerol in Arabidopsis thaliana grown on medium with reduced amounts of phosphate, as well as in the pho1 mutant of A. thaliana deficient in phosphate transport. To investigate the molecular basis of the observed change in lipid composition, we isolated a cDNA of A. thaliana, designated SQD1, that encodes a protein involved in sulfolipid biosynthesis as suggested by three lines of evidence. First, the cDNA shows high sequence similarity to bacterial sqdB genes known to be essential for sulfolipid biosynthesis; second, the SQD1 gene product is imported into chloroplasts where sulfolipid biosynthesis takes place; and third, transgenic plants expressing SQD1 in antisense orientation show a reduction in sulfolipid content. In the pho1 mutant as well as in wild-type plants grown under reduced phosphate availability, increased amounts of SQD1 mRNA and SQD1 protein are detected, suggesting that the increase in sulfolipid content under phosphate limitation is the result of an increased expression of at least one gene required for sulfolipid biosynthesis in A. thaliana. It is suggested that a certain amount of anionic thylakoid lipid is maintained by substituting sulfolipid for phosphatidylglycerol under reduced phosphate availability.

Amino Acid Sequence↗

PubMed1996

Intracellular assembly of inducible NO synthase is limited by nitric oxide-mediated changes in heme insertion and availability.

Cytokines induce the mouse macrophage cell line RAW 264.7 to express cytokine-inducible nitric oxide synthase (iNOS), which is active only in dimeric form. Because dimerization of purified iNOS subunits requires tetrahydrobiopterin, heme, and L-arginine, we investigated if availability of these factors also influences intracellular assembly of dimeric iNOS. Following exposure to cytokines, iNOS protein was found to accumulate in a near linear manner over 16 h of further culture. In contrast, dimeric iNOS accumulated at a slower rate that continuously decreased during culture, resulting in only 25% of the accumulated iNOS protein being in dimeric form by 16 h. Further experiments argued against dimer instability or L-arginine and tetrahydrobiopterin availability as factors limiting iNOS dimer accumulation. Blocking cellular NO synthesis with Nomega-nitro-L-arginine methyl ester (L-NAME) greatly increased iNOS dimer assembly, indicating NO synthesis limited iNOS dimerization. NO synthesis was found to prevent an increase in soluble heme level that was associated with iNOS induction in Nomega-nitro-L-arginine methyl ester-treated cells and also diminished heme insertion into iNOS. These NO-related defects were not reversed by adding heme precursors or hemin to the activated cell cultures. Measurement of iron release from activated cells demonstrated that endogenous NO synthesis substantially increased the release of 59Fe to the medium. These observations suggest that iNOS dimerization is limited to a large extent by iNOS NO synthesis. NO appears to limit intracellular assembly of dimeric iNOS by preventing heme insertion and decreasing heme availability.

Aminolevulinic Acid↗

PubMed1997

Nutrient deprivation of cultured rat hepatocytes increases the desferrioxamine-available iron pool and augments the sensitivity to hydrogen peroxide.

Primary cultures of rat hepatocytes were subjected to amino acid and serum deprivation for 4 h. This treatment augmented the sensitivity to ensuing hydrogen peroxide exposure for 30 min. The by nutrient deprivation-increased autophagocytosis was confirmed by transmission electron microscopy and uptake of the lysosomotropic weak base acridine orange within the intracellular acidic vacuolar apparatus. The desferrioxamine-available pool of iron increased 2.5-fold during deprivation, compared with control cells. Furthermore, amino acid deprivation increased the cellular protein turnover, measured by radioactive labeling with -3H-Leu. Exposure to 40 microM ascorbic acid specifically decreased the turnover of ferritin, as estimated by enzyme-linked immunosorbent assay, and prevented an increase of the desferrioxamine-available iron pool, resulting in protection against hydrogen peroxide-induced cell killing. Thus, hepatocytes with nutrient deprivation-enhanced autophagocytosis contain a larger pool of catalytically active iron than control cells. This iron pool is mainly derived from the turnover (autophagocytosis) of cytosolic ferritin and is probably situated in the lysosomes. Furthermore, nutrient-deprived cells show augmented sensitivity to hydrogen peroxide-induced oxidative stress, since the enhanced availability of iron in low molecular weight form results in an increased potential of intralysosomal Fenton chemistry, that may cause lysosomal rupture with release of potent hydrolytic enzymes.

Animals↗

PubMed1999

Post-transcriptional regulation of the arginine transporter Cat-1 by amino acid availability.

The regulation of the high affinity cationic amino acid transporter (Cat-1) by amino acid availability has been studied. In C6 glioma and NRK kidney cells, cat-1 mRNA levels increased 3.8-18-fold following 2 h of amino acid starvation. The transcription rate of the cat-1 gene remained unchanged during amino acid starvation, suggesting a post-transcriptional mechanism of regulation. This mechanism was investigated by expressing a cat-1 mRNA from a tetracycline-regulated promoter. The cat-1 mRNA contained 1.9 kilobase pairs (kb) of coding sequence, 4.5 kb of 3'-untranslated region, and 80 base pairs of 5'-untranslated region. The full-length (7.9 kb) mRNA increased 5-fold in amino acid-depleted cells. However, a 3.4-kb species that results from the usage of an alternative polyadenylation site was not induced, suggesting that the cat-1 mRNA was stabilized by cis-acting RNA sequences within the 3'-UTR. Transcription and protein synthesis were required for the increase in full-length cat-1 mRNA level. Because omission of amino acids from the cell culture medium leads to a substantial decrease in protein synthesis, the translation of the increased cat-1 mRNA was assessed in amino acid-depleted cells. Western blot analysis demonstrated that cat-1 mRNA and protein levels changed in parallel. The increase in protein level was significantly lower than the increase in mRNA level, supporting the conclusion that cat-1 mRNA is inefficiently translated when the supply of amino acids is limited, relative to amino acid-fed cells. Finally, y(+)-mediated transport of arginine in amino acid-fed and -starved cells paralleled Cat-1 protein levels. We conclude that the cat-1 gene is subject to adaptive regulation by amino acid availability. Amino acid depletion initiates molecular events that lead to increased cat-1 mRNA stability. This causes an increase in Cat-1 protein, and y(+) transport once amino acids become available.

3' Untranslated Regions↗

PubMed1983

Availability of iron from chicken meat and liver given to rats.

The concentration and distribution of iron in 59Fe-labelled chicken leg and breast meat and liver were determined by gel filtration. In all samples approximately 50% of the Fe was insoluble (haemosiderin) and the haemoproteins (haemoglobin and myoglobin) constituted from 15% (liver) to 25% (leg meat) of the total Fe. Ferritin accounted for from 12% (leg meat) to 27% (liver) of the total Fe. A technique was developed which enabled the time-course of the passage of 59Fe-labelled whole and fractionated meat and liver through the gastrointestinal tract of Fe-replete and Fe-deficient rats to be followed and it was found that the rate of stomach emptying appeared to be a function of the viscosity of the meal. In Fe-replete rats approximately 71% of a meal of raw chicken meat had left the stomach within 1 h of administration and by 2 h the stomach was almost empty and much of the unabsorbed 59Fe was in the ileum. By 4 h the ileum and colon contained almost equal amounts of 59Fe. Between different test meals there were only slight differences in gastrointestinal distribution and these reflected the different rates of stomach emptying. Stomach emptying was slower in Fe-deficient compared with Fe-replete rats. In Fe-replete, but not Fe-deficient, rats it was found that the amount of 59Fe lost (absorbed) from the gastrointestinal tract 2 h after administration of a test meal was not significantly different from the value found using a 7 d faecal collection technique. Comparison of the 2 h absorption values for several test meals indicated that 59Fe absorption from raw whole meat was significantly higher than from the soluble extract and the residue after extraction (haemosiderin). Heat treatment caused a significant decrease in the absorption of Fe in whole meat and the soluble meat extract but a significant increase in the liver absorption values. It is suggested that denatured haemoproteins are less available for absorption than their native forms but that heating increases the availability of the Fe of haemosiderin or ferritin or both. Isolated muscle ferritin was poorly absorbed but on the addition of excess bovine serum albumin the absorption of the Fe was markedly increased. It is concluded that, to estimate the Fe availability of a food such as chicken meat or liver one must not only take account of the concentration and type of each Fe-containing compound present but also such factors as their possible synergistic effects, the presence of chelating agents, the extent of cooking and the concentration and type of proteinaceous digestion products.

Animals↗

PubMed1996

Measurement of rapidly available glucose (RAG) in plant foods: a potential in vitro predictor of the glycaemic response.

The glycaemic index (GI) is an in vivo measurement based on the glycaemic response to carbohydrate-containing foods, and allows foods to be ranked on the basis of the rate of digestion and absorption of the carbohydrates that they contain. GI values are normalized to a reference amount of available carbohydrate and do no reflect the amounts of carbohydrate normally present in foods; for example, a food with a low content of carbohydrates will have a high GI value if that carbohydrate is digested and absorbed rapidly in the human small intestine. This is potentially confusing for a person wishing to control his or her blood glucose levels by the choice of foods. The rate and extent of starch digestion in vitro has been measured using a technique that classifies starch into three major fractions: rapidly digestible starch (RDS), slowly digestible starch (SDS) and resistant starch (RS). In addition, this technique gives a value for rapidly available glucose (RAG), which includes RDS, free glucose and the glucose moiety of sucrose. When the values for thirty-nine foods were expressed on the basis of the available carbohydrate content of these foods, highly significant (P < 0.001) positive correlations were observed between GI and both RDS and RAG. The measurement of RAG in vitro provides values for direct calculation of the amount of glucose likely to be rapidly absorbed in the human small intestine and, thus, to influence blood glucose and insulin levels. These values can be used to compare foods, as eaten, on an equal-weight basis. Food-table RAG values would allow simple calculation of the total amount of RAG provided by single foods, by whole meals and by whole diets. Studies are planned in which RAG and the glycaemic response in man will be measured for identical food products.

Dietary Carbohydrates↗

PubMed1987

Interactions between fats of differing chemical content: apparent availability of fatty acids.

1. Tallow (A) and rape oil (E) were obtained for evaluation. They were blended in the ratios A95:E5, A90:E10 and A80:E20. The three blends together with the two pure fats were each included at 40, 80 and 120 g/kg into a basal diet. 2. The experimental diets were evaluated for apparent availability (g/kg) of the fatty acids palmitic (C16:0), stearic (C18:0), oleic (C18:1) and linoleic (C18:2) using 6 replicates of a cage of two male broiler chicks 14 d old and 8 replicates of a cage of one Rhode Island cross cockerel approximately 1 year old. Diets were fed for 72 h then removed for 24 h. This was followed by a 48 h period when food was available ad libitum and a further 24 h starvation. A total collection of excreta was undertaken for the latter 72 h period. 3. Evaluation of apparent available fatty acid (AAFA g/kg fatty acid) was achieved by linear regression. 4. All results indicated a progressive increase in AAFA with both chicks and adults for C16:0 and C18:0 with increasing proportions of the more unsaturated rape oil in the fat blends and for C18:1 and C18:2 with chicks. 5. Evaluation of AAFA by quadratic regression indicated an additional effect of rate of inclusion for C16:0 and C18:0 with chicks and adults and for C18:1 with chicks.

Animals↗

PubMed2006

Prediction of slips: an evaluation of utilized coefficient of friction and available slip resistance.

The purpose of this study was to investigate the relationship between measures of floor surface slip resistance and an individual's peak utilized coefficient of friction (COFU) on the probability of a slip occurring during level walking. Video, kinematic and ground reaction force data were recorded simultaneously as subjects walked at a self-selected speed during conditions of normal and reduced floor surface slip resistance. Peak COFU during weight acceptance was calculated and the available floor surface slip resistance was measured using the variable incidence tribometer (VIT). Separate logistic regression analyses identified that knowledge of the available slip resistance (as measured by the VIT) in combination with an individual's peak COFU allowed for greater accuracy in classifying slip outcomes (89.5%; p = 0.004), while knowledge of only the available slip resistance reduced the accuracy of categorization to 78.9% (p = 0.021).

Accidental Falls↗

PubMed1994

Emotional availability in mother-twin dyads: effects on the organization of relationships.

The term "emotional availability" has evolved primarily in therapeutic contexts where it refers to the sensitive engagement of the therapist in the patient's narrative of life experiences and openness to the patient's emotional expressions (Emde 1980). In the therapeutic situation, emotional availability refers to the quality of the therapist in supporting the growth or development of the patient. It is anticipated that the outcome of the therapeutic experience will include an enhanced capacity for reciprocal emotional availability with others.

Child, Preschool↗

PubMed2006

Evidence-based treatment for opiate-dependent clients: availability, variation, and organizational correlates.

The majority of opiate-dependent clients entering substance abuse treatment are referred to "drug-free" (non-methadone) modalities. Given the known challenges of treating these clients in drug-free settings relative to the documented effectiveness of methadone maintenance, these analyses investigate the availability of various clinical and wraparound services for this population among a US sample of addiction treatment programs with and without methadone maintenance services (N = 763). Face-to-face interviews conducted in 2002-2003 gathered data on the number of opiate-dependent clients treated; organizational characteristics, including size, ownership, accreditation, and staffing; treatment practices, including methadone availability, use of other pharmacotherapies, and levels of care; and services offered, including vouchers, transportation, and other wraparound services. Facilities treating proportionately more opiate-dependent clients were significantly more likely to offer a variety of evidence-based services, regardless of methadone availability. Implications for referral linkages and quality of care are discussed.

Counseling↗

PubMed2001

Joints: if relevant. Do available textbooks contain adequate information about musculoskeletal examination skills for medical students?

The objective was to determine whether routinely available textbooks describe the core musculoskeletal examination skills for medical students. Textbooks were evaluated for content against a list of 27 core examination skills as perceived by rheumatologists, orthopaedic surgeons and general practitioners. The study took place in Newcastle upon Tyne, libraries of the rheumatology department, teaching hospital and medical school. The main outcome was the inclusion of a description of examination skills by available textbooks. Median score for each textbook was only 19 (range 1-24) of a possible 27 core skills. Screening examination was not included in general texts. General principles were well covered but detail was insufficient, particularly in texts aimed at students taking final examinations. It is not easy for students to access adequate information about core items of musculoskeletal examination from textbooks readily available to them. This may reflect a general view of the lack of importance of musculoskeletal clinical examination skills.

Journal Article↗

PubMed2004

A limiting factor for the progress of radionuclide-based cancer diagnostics and therapy--availability of suitable radionuclides.

Advances in diagnostics and targeted radionuclide therapy of haematological and neuroendocrine tumours have raised hope for improved radionuclide therapy of other forms of disseminated tumours. New molecular target structures are characterized and this stimulates the efforts to develop new radiolabelled targeting agents. There is also improved understanding of factors of importance for choice of appropriate radionuclides. The choice is determined by physical, chemical, biological, and economic factors, such as a character of emitted radiation, physical half-life, labelling chemistry, chemical stability of the label, intracellular retention time, and fate of radiocatabolites and availability of the radionuclide. There is actually limited availability of suitable radionuclides and this is a limiting factor for further progress in the field and this is the focus in this article. The probably most promising therapeutic radionuclide, 211At, requires regional production and distribution centres with dedicated cyclotrons. Such centres are, with a few exceptions in the world, lacking today. They can be designed to also produce beta- and Augeremitters of therapeutic interest. Furthermore, emerging satellite PET scanners will in the near future demand long-lived positron emitters for diagnostics with macromolecular radiopharmaceuticals, and these can also be produced at such centres. To secure continued development and to meet the foreseen requirements for radionuclide availability from the medical community it is necessary to establish specialized cyclotron centres for radionuclide production.

Astatine↗