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Biomedical subjects

D Grant

Publications and source records attributed to D Grant.

At least 37 records · Page 2Linked to original sources

Small bowel transplantation.

Small bowel transplantation has become the treatment of choice for patients with chronic gut failure whose illness cannot be maintained on home parenteral nutrition. Outcomes have improved as a result of refinements in patient selection, surgical techniques, and the prevention, diagnosis, and treatment of graft rejection. Early listing is important because of the shortage of organ donors. Rejection rates are still 50% or more, despite the use of potent immune suppression. Sepsis rates are also higher for patients who have had small bowel transplantation than for those who have received other organs because of bacterial translocation from the gut secondary to preservation injury and graft rejection. Graft and patient survival rates after small bowel transplantation are comparable to rates after lung transplantation. Successful transplant recipients resume unrestricted oral diets.

Chronic Disease↗

Spirometric pulmonary function in healthy preschool children.

The purpose of this study was to evaluate spirometric lung function in normal children ages 3 to 6 yr. Spirometric measurements were obtained at nursery and daycare centers by experienced pediatric pulmonary function technicians. Of 307 children recruited, 259 fulfilled our criteria as normal. Of these, 82.6% (214) were able to perform technically acceptable and reproducible maneuvers during a testing session limited to 15 min. The regression model with log-transformed parameters of pulmonary function and height had the best correlations. After accounting for height in the model, other physical traits and health questionnaire items did not contribute significantly. PEFR, FVC, FEV1, and FEF25-75 all increased with increasing height; correlation coefficients were 0.73, 0.93, 0.92, and 0.67, respectively. The group mean coefficients of variation for replicate measurements of PEFR, FVC, FEV1, and FEF25-75 were 7.8%, 2.5%, 2.7%, and 8.3%, respectively. There was a significant decrease in the ratio FEV1/FVC with increasing height; the mean predicted FEV1/FVC was 0.97 at 90 cm height and 0.89 at 125 cm height. In conclusion, reproducible spirometry can be obtained in the majority of preschool children and has the potential to improve our assessment and management of pulmonary disease.

Child↗

The impact and management of cancer-related fatigue on patients and families.

Fatigue has been identified as both a chronic and recurrent problem for individuals diagnosed with and treated for cancer, yet there is little information on how to manage the impact of fatigue. Describing what happens to individuals and their families as a result of fatigue and identifying what individuals do to manage or reduce the impact of fatigue are essential elements in determining multidimensional nursing interventions. The purpose of this pilot study was to examine the impact of fatigue on individuals with cancer of the lung and their families, and explore how they managed as a result of the fatigue. A semi-structured interview guide was used with 22 lung cancer patients and 14 family members six weeks post completion of radiation therapy. Results indicated that fatigue was not reported as a major concern by many of the participants in this study. For those who did experience fatigue, it was considered an inconvenience and a frustration that had to be dealt with for a limited time period. Some patients appeared to gradually adjust and accommodate to the fatigue and were not really aware of the changes that took place over time. Over half of the family members felt more of the impact of fatigue than did their loved ones. Family subtly assumed or took over responsibilities and activities the patient could no longer perform. The symptom of fatigue has been well documented in the cancer experience as both a chronic and recurrent problem for individuals diagnosed with and treated for cancer. The emphasis of previous work has been on deriving a conceptual definition of fatigue, achieving consensus on a definition, and developing theoretical frameworks to guide further study of this complex construct. Fatigue has been conceptualized as a multidimensional phenomenon, attributable to multiple causes and having a negative effect on quality of life (Piper, 1993; Tiesinga, Dasson, & Halfens, 1996). Describing what happens to individuals and their families as a result of fatigue and identifying what individuals do to manage or reduce the effects caused by the fatigue are essential elements in determining multidimensional nursing interventions.

Adaptation, Psychological↗

Soybean genomic survey: BAC-end sequences near RFLP and SSR markers.

We are building a framework physical infrastructure across the soybean genome by using SSR (simple sequence repeat) and RFLP (restriction fragment length polymorphism) markers to identify BACs (bacterial artificial chromosomes) from two soybean BAC libraries. The libraries were prepared from two genotypes, each digested with a different restriction enzyme. The BACs identified by each marker were grouped into contigs. We have obtained BAC- end sequence from BACs within each contig. The sequences were analyzed by the University of Minnesota Center for Computational Genomics and Bioinformatics using BLAST algorithms to search nucleotide and protein databases. The SSR-identified BACs had a higher percentage of significant BLAST hits than did the RFLP-identified BACs. This difference was due to a higher percentage of hits to repetitive-type sequences for the SSR-identified BACs that was offset in part, however, by a somewhat larger proportion of RFLP-identified significant hits with similarity to experimentally defined genes and soybean ESTs (expressed sequence tags). These genes represented a wide range of metabolic functions. In these analyses, only repetitive sequences from SSR-identified contigs appeared to be clustered. The BAC-end sequences also allowed us to identify microsynteny between soybean and the model plants Arabidopsis thaliana and Medicago truncatula. This map-based approach to genome sampling provides a means of assaying soybean genome structure and organization.

Algorithms↗

Genome organization in dicots: genome duplication in Arabidopsis and synteny between soybean and Arabidopsis.

Synteny between soybean and Arabidopsis was studied by using conceptual translations of DNA sequences from loci that map to soybean linkage groups A2, J, and L. Synteny was found between these linkage groups and all four of the Arabidopsis chromosomes, where GenBank contained enough sequence for synteny to be identified confidently. Soybean linkage group A2 (soyA2) and Arabidopsis chromosome I showed significant synteny over almost their entire lengths, with only 2-3 chromosomal rearrangements required to bring the maps into substantial agreement. Smaller blocks of synteny were identified between soyA2 and Arabidopsis chromosomes IV and V (near the RPP5 and RPP8 genes) and between soyA2 and Arabidopsis chromosomes I and V (near the PhyA and PhyC genes). These subchromosomal syntenic regions were themselves homeologous, suggesting that Arabidopsis has undergone a number of segmental duplications or possibly a complete genome duplication during its evolution. Homologies between the homeologous soybean linkage groups J and L and Arabidopsis chromosomes II and IV also revealed evidence of segmental duplication in Arabidopsis. Further support for this hypothesis was provided by the observation of very close linkage in Arabidopsis of homologs of soybean Vsp27 and Bng181 (three locations) and purple acid phosphatase-like sequences and homologs of soybean A256 (five locations). Simulations show that the synteny and duplications we report are unlikely to have arisen by chance during our analysis of the homology reports.

Acid Phosphatase↗

Immunoplatelet counting: a proposed new reference procedure.

Given the high degree of interoperator error and poor precision of manual platelet counting, it has recently been proposed that an immunoplatelet counting method could become the new reference procedure. Platelets are identified immunologically with a suitable monoclonal antibody, and the platelet count is derived from the ratio of fluorescent platelet events to collected red blood cell (RBC) events that are also counted by a reliable and calibrated standard impedance counter (RBC ratio). In this study, we have set up a rapid and simple method for immunoplatelet counting and simultaneously compared the RBC ratio with the bead ratio derived from two different preparations of commercial calibration beads (Trucount and FlowCount beads). Comparison of the level of imprecision of the RBC ratio with either the manual count or bead ratios revealed a superior coefficient of variation of < 5% even in samples with a platelet count < 20 x 10(9)/l. The RBC ratio correlated extremely well with the existing manual phase reference method (r2 = 0.93) and especially well with three different commercial impedance counters and a dual-angle optical counter (r2 = 0.98-0.99). However, at < 100 x 10(9)/l, the correlation of the RBC ratio with the dual-angle optical count (ADVIA 120) (r2 = 0.96) was superior to all impedance counters. This suggests that automated optical counting methods may be more accurate at determining platelet counts in thrombocytopenic samples. As the RBC ratio is rapid, cheap and relatively easy to perform, we propose that this method could replace the manual count as a new international reference method.

Calibration↗

New quantitative parameters on a recently introduced automated blood cell counter--the XE 2100.

The XE 2100 (Sysmex Corporation) is a cell counter that furthers the technology of fluorescent flow cytometry developed from the earlier range of Sysmex analysers. The new diagnostic features are a nucleated red cell count (NRBC), the ability to measure platelets by impedance as well as an 'optical' platelet count using a fluorescence dye and an immature granulocyte (IG) count. The NRBC count was highly correlated (r = 0.97) with the manual reference count. For counts below 100 x 109/l the 'optical' method and the immunocount gave good a correlation (r = 0.97) optical and impedance counts were also well correlated (r = 0.89). The use of the 'optical' platelet count significantly improves the reliability of low platelet counts. The IG count correlated with visual counts (r = 0.81) and allows the detection of immature cells at an earlier stage in the laboratory process. The introduction of fluorescent flow cytometric analysis allows extended quantification of additional cell populations and so potentially improves screening and monitoring of various pathological conditions.

Adult↗

Gastrointestinal transplantation: An update.

Gastrointestinal transplantation is a life-saving option for patients who have chronic intestinal failure and cannot tolerate total parenteral nutrition (TPN). Early referral is important because of the scarcity of donors and the increased risk of complications in debilitated recipients. One-year patient survival rates range from 50% to 70%. Despite the use of intense immune suppression, most patients experience at least 1 episode of graft rejection. More than 80% of the survivors are able to stop TPN and resume an unrestricted oral diet. Patients with functioning grafts have a good quality of life.

Adult↗

All major regions of FtsK are required for resolution of chromosome dimers.

Resolution of chromosome dimers, by site-specific recombination between dif sites, is carried out in Escherichia coli by XerCD recombinase in association with the FtsK protein. We show here that a variety of altered FtsK polypeptides, consisting of the N-terminal (cell division) domain alone or with deletions in the proline-glutamine-rich part of the protein, or polypeptides consisting of the C-terminal domain alone are all unable to carry out dif recombination. Alteration of the putative nucleotide-binding site also abolishes the ability of FtsK to carry out recombination between dif sites.

Chromosomes, Bacterial↗

The use of herbal teas and remedies in Jamaica.

We investigated the prevalence of the use of herbs among adults and children in Jamaica in 1996. Two concurrent surveys were conducted in randomly selected urban and rural areas: among adults and among caretakers of young children. From over 90% of the selected households, all caretakers of children under 6 years and one randomly selected adult (18 years or older) were interviewed using structured questionnaires. The 457 adults reportedly used 156 types of herbs: a mean of 6 +/- 3 (mean +/- standard deviation) by the urban adults, and 10 +/- 6 by the rural adults (t-test, p < 0.001). Almost 100% of respondents had at some time used herbs for teas or for treating illnesses. The most common method of preparation was by infusion or boiling in water, then adding sugar. Urban respondents, women and those who were employed were more likely to buy medicines than to use herbal remedies. One hundred and sixty-seven caretakers of 203 children under 6 years were interviewed. The mean number of herbs given to each child was between 2 and 3. The most common herbs were introduced within the first 6 months of life. Many caretaker factors were associated with herbal use. Public health implications include the potential toxicity of some herbs, the possibility that herbal teas given to young children may displace more nutritious foods and delay presentation to health care facilities. The findings will allow policy makers to target those most likely to use herbal preparations or to give them to young children, and target herbs to be analyzed for toxic or beneficial properties.

Adolescent↗

The University of Toronto Liver Transplant Program: Toronto General Hospital, Hospital for Sick Children.

The University of Toronto Liver Transplant Program began in 1985 at a time when the procedure had already evolved from an experimental form of surgery to an accepted treatment for many forms of liver failure. The program was established not only to provide clinical care for patients but also to address academically the barriers that impeded success. The program brought together experts in medicine, surgery, pathology, and the basic sciences of immunology, virology and molecular biology. Significant advances over the past decade and a half in immunosuppressive drugs and monitoring, patient selection, and infectious management have contributed to markedly improved patient and graft survival rates. Nevertheless, we continue to face 2 major challenges: a growing scarcity of donor organs, a problem partially addressed through development of living-related liver donation, and recurrent viral hepatitis. We expect to remain on the forefront of ongoing research to provide solutions to these and other barriers to the full deployment of liver transplantation in the year 2000.

Adult↗

Peak cyclosporine levels (Cmax) correlate with freedom from liver graft rejection: results of a prospective, randomized comparison of neoral and sandimmune for liver transplantation (NOF-8).

BACKGROUND: Despite two decades of use, there are limited data on the best way to administer and monitor cyclosporine (CsA) for liver transplantation. The present study was undertaken (1) to determine whether treatment with a new formulation of CsA, Neoral, would improve the results of liver transplantation; and (2) to study the relationships between pharmacokinetic parameters and clinical outcomes after transplantation. METHODS: A double-blind, randomized, comparison of Sandimmune (SIM) with Neoral (NEO) was conducted at five Canadian centers in 188 consecutive adults undergoing primary orthotopic liver transplantation. Patients were induced with intravenous CsA then switched to NEO or SIM. Dose adjustments were made daily, or as needed, to reach a target trough CsA level of 350 ng/ml in both groups. Pharmacokinetic studies were performed on days 5, 10, 15, and 16 weeks after transplantation. RESULTS: The NEO group was slightly younger, with a median age of 50 years (range: 23-70) versus 55 years (range: 24-71) for SIM (P = 0.007); otherwise the two groups were well balanced. The NEO group stopped intravenous CsA earlier (5.8+/-2.6 days vs. 8.7+/-4.7 days, P<0.0001). This group required a lower median daily oral dose (7.5 mg/kg vs. 9.0 mg/kg, P<0.01) to maintain comparable trough CsA levels. Five SIM patients, but no NEO patients, discontinued the study due to the inability to reach target trough levels of CsA within the prescribed time (P<0.05). At 4 months, there were no differences between the two groups with respect to patient survival (93% NEO vs. 91% SIM), graft survival (90% NEO vs. 86% SIM), and rejection-free survival (54.1% NEO, 51.8% SIM). The incidence of serious adverse events was also similar and did not correlate with CsA pharmacokinetic profiles. The NEO group had a higher area under the drug concentration curve for the first 6 hr after the dosing interval (AUC0-6) and peak CsA levels (Cmax). There was a strong correlation between freedom from graft rejection during the first month after transplantation and (a) AUC0-6 and (b) Cmax at days 5 and 10 after transplantation, but only in the NEO group did this reach statistical significance. In contrast, there was a poor correlation between trough CsA and graft rejection. In patients on NEO, the concentration of CsA 2 hr after dosing (C2) closely reflected AUC0-6 (r2 = 0.93), whereas there was a poorer correlation in patients on SIM (r2 = 0.73) CONCLUSIONS: Cmax and/or AUC0-6 may provide better markers than trough levels for monitoring CsA-based immune suppression after orthotopic liver transplantation. Prospective studies are underway to determine whether dosing to C2, which provides a good estimation of Cmax, can be used to take full advantage of NEO's improved absorption profile.

Adult↗