Search PubMed⌕ Search

Biomedical subjects

D White

Publications and source records attributed to D White.

At least 91 records · Page 5Linked to original sources
PubMed1999

An epidemiological review of red cell transfusions in cancer chemotherapy.

OBJECTIVE: The objective of this chart review was to determine the frequency of transfusion and prevalence of anemia (hemoglobin result < 100 g/L) in patients receiving chemotherapy. DESIGN: This study was a retrospective review of medical charts. SETTING: Patients receiving chemotherapy were included from 12 tertiary care comprehensive cancer centres across Canada. MAIN OUTCOME MEASURE: The primary study outcome measure was red blood cell transfusion rate, controlling for patient variables. RESULTS: The 616 patients included had started chemotherapy in January-June 1992. For each subject, data collection finished 4 weeks after the end of the first regimen or after a maximum follow-up period of 26 weeks. Seventy-two patients (12%; 95% confidence interval 9.5% to 14.5%) were transfused for anemia (reasons other than blood loss), and 28% (95% confidence interval 24.5% to 31.5%) of the subjects were anemic during treatment. The univariate analyses of transfusion for anemia yielded significant associations with prognostic factors. In the multivariate analyses, platinum (odds ratio [OR] = 6.69) and anthracycline (OR = 3.56) chemotherapy, baseline hemoglobin (OR = 0.96) and disease stage (OR = 1.72) were statistically significant contributors. CONCLUSION: In this patient cohort, red blood cell transfusion was infrequent (12%). However, patient groups at high risk of transfusion could be identified, with platinum-based chemotherapy being the most significant contributing factor. The information obtained from this multicentre study may prove helpful in developing supportive care guidelines for the management of chemotherapy-related anemia requiring transfusion.

Adolescent↗
PubMed1999

Quality here, there and everywhere: the application of a multi-dimensional learning tool to learning disability health services.

The following paper examines the applicability of Maxwell's Multi-dimensional Quality Evaluation model to community learning disability health services. The model defines seven dimensions against which the quality of any given service can be measured: effectiveness, efficiency, economy, equity, access to services, appropriateness and social acceptability. A number of examples in relation to community learning disability services are discussed.

Community Mental Health Services↗
PubMed1998

Genetics of polycystic ovary syndrome.

We have found evidence for the involvement of two major genes in the aetiology of PCOS. The results of both linkage and association studies suggest that CYP11a (coding for P450 cholesterol side chain cleavage) and the insulin VNTR regulatory polymorphism are important genes in the aetiology of PCOS and may explain, in part, the heterogeneity of the syndrome. Differences in expression of CYP11a could account for variation in androgen production in women who have polycystic ovaries and those subjects who are homozygous for III alleles at the insulin gene VNTR locus are more likely to be hyperinsulinaemic. It is likely that other genes are involved in the aetiology of PCOS. Recent results lend weight to the idea that PCOS represents a complex trait in which several genes--but perhaps a relatively small number of key genes--contribute, in conjunction with nutritional factors, to the observed clinical and biochemical heterogeneity.

Androgens↗
PubMed1998

Life-supporting pig-to-primate renal xenotransplantation using genetically modified donors.

BACKGROUND: In order to circumvent the complement-mediated hyperacute rejection of discordant xenografts, a colony of pigs transgenic for the human regulator of complement activity, human decay-accelerating factor (hDAF), has been produced. METHODS: Seven kidneys from hDAF transgenic pigs and six kidneys from nontransgenic control pigs were transplanted into cynomolgus monkeys; both native kidneys were removed during the same operation. The recipient animals were immunosuppressed with cyclosporine, steroids, and cyclophosphamide. RESULTS: In the transgenic group, the median survival time was 13 days (range, 6-35 days); the median survival time in the control group was 6.5 days (range, 0.3-30 days). There were no cases of hyperacute rejection in the transgenic group, and the two longest-surviving kidneys in this group showed no evidence of rejection on histological examination. In contrast, all control kidneys underwent antibody-mediated rejection, one demonstrating hyperacute rejection and the others acute vascular rejection. CONCLUSION: This study demonstrates that (i) a kidney from an hDAF transgenic pig can support the life of a primate for up to 35 days (and also shows the basic physiological compatibility between the pig and nonhuman primate); (ii) nontransgenic kidneys are not routinely hyperacutely rejected; and (iii) the presence of hDAF on the kidney confers some protection against acute vascular rejection. Improved immunosuppression and immunological monitoring may enable extended survival.

Animals↗
PubMed1998

p53 binds to a constitutively nucleosome free region of the mdm2 gene.

The mdm2 oncogene is a p53 responsive gene which contains both a p53 independent and a p53 dependent promoter (P1 and P2 respectively). We have utilized ligation mediated PCR genomic footprinting in order to investigate the intra-nuclear binding of p53 to the mdm2 P2 promoter. The DNase I protection pattern in nuclei from murine cells lacking p53 has been compared to the protection pattern in cells containing a temperature sensitive p53-Val135. At 32 degrees C p53-Val135 assumes a wild-type conformation while at 37 degrees C this p53 is conformationally mutant. We observed clear wild-type p53 dependent protection of the putative p53 response elements (REs) as well as protection of the adjacent TATA box. Interestingly the protection pattern observed with purified wild-type p53 on naked DNA showed less nucleotide sequence protection than the protection observed to be p53 dependent in nuclei. Constitutive DNase I hypersensitivity at both the mdm2 P1 and P2 promoters was detected by indirect Southern blot analysis. DNase I hypersensitivity reflects altered chromatin conformations resulting, most likely, from the absence of nucleosomes. Taken together our findings suggest that the mdm2 P2 promoter is maintained in a nucleosome free state which is pre-primed for transcriptional activation by p53.

Animals↗
PubMed1998

A clinical score to reduce unnecessary antibiotic use in patients with sore throat.

OBJECTIVE: To validate a score based on clinical symptoms and signs for the identification of group A Streptococcus (GAS) infection in general practice patients with score throat. DESIGN: A single throat swab was used as the gold standard for diagnosing GAS infection. Clinical information was recorded by experienced family physicians on standardized encounter forms. Score criteria were identified by means of logistic regression modelling of data from patients enrolled in the first half of the study. The score was then validated among the remaining patients. SETTING: University-affiliated family medicine centre in Toronto. PATIENTS: A total of 521 patients aged 3 to 76 years presenting with a new upper respiratory tract infection from December 1995 to February 1997. OUTCOME MEASURES: Sensitivity, specificity and likelihood ratios for identification of GAS infection with the score approach compared with throat culture. Proportion of patients prescribed antibiotics, throat culture use, and sensitivity and specificity with usual physician care and with score-based recommendations were compared. RESULTS: A score was developed ranging in value from 0 to 4. The sensitivity of the score for identifying GAS infection was 83.1%, compared with 69.4% for usual physician care (p = 0.06); the specificity values of the 2 approaches were similar. Among patients aged 3 to 14 years, the sensitivity of the score approach was higher than that of usual physician care (96.9% v. 70.6%) (p < 0.05). The proportion of patients receiving initial antibiotic prescriptions would have been reduced 48% by following score-based recommendations compared with observed physician prescribing (p < 0.001), without any increase in throat culture use. CONCLUSIONS: An age-appropriate sore throat score identified GAS infection in children and adults with sore throat better than usual care by family physicians, with significant reductions in unnecessary prescribing of antibiotics. A randomized trial comparing the 2 approaches is recommended to determine the ability of the score approach to reduce unnecessary prescribing of antibiotics during routine clinical encounters.

Adolescent↗
PubMed1998

Isolation of antiSLIP1-reactive boar sperm P68/62 and its binding to mammalian zona pellucida.

Single-step purification of boar sperm P68/62 that is cross-reactive with a polyclonal antibody against sulfolipidimmobilizing protein 1 (SLIP1) was achieved by chromatofocusing. This method is useful for obtaining P68/62 in quantity. The two proteins, P68 and P62, were antigenically related, since the antibody generated specifically against the 68-kDa band reacted with both the 68- and 62-kDa bands. Like rat testis SLIP1, purified boar sperm P68/62 bound to sulfogalactosylglycerolipid (SGG) and inhibited sperm-egg binding in a dose-dependent manner when added exogenously to sperm-egg coincubates. This inhibitory effect occurred at the level of the zona pellucida (ZP), and further studies showed that biotinylated boar sperm P68/62 bound to the ZP of unfertilized mouse eggs. Furthermore, biotinylated boar sperm P68/62 bound to isolated ZP of unfertilized eggs from other species, including pig, rat, cat, dog, and human, as well as to ZP of intact fertilized mouse eggs and preimplantation embryos of various developmental stages, although the degree of its binding to the ZP of intact eight-cell embryos, morulae, and blastocysts was much lower than that of fertilized eggs and two-cell embryos. These results suggest that P68/62 of capacitated sperm must act together with other sperm surface proteins/molecules that regulate zona binding specificity within homologous species and in unfertilized eggs. Together with our previous findings, we suggest that rather than being a true ZP receptor, sperm P68/62 may be involved in the initial step of sperm-ZP binding that is adhesive in nature.

Animals↗
PubMed1998

RAS, FMS and p53 mutations and poor clinical outcome in myelodysplasias: a 10-year follow-up.

The molecular mechanisms underlying the development and evolution of myelodysplastic syndrome (MDS) are largely unknown. The increasing number of blast cells in the bone marrow correlate with poor prognosis and risk of developing acute leukemia. Such progression is frequently associated with increasing chromosomal abnormalities and genetic mutations. A cohort of 75 MDS patients were investigated for RAS, FMS and p53 mutations, and these molecular findings were related to cytogenetics, clinical status, transformation to acute leukemia, prognostic scores and survival. A mutation incidence of 57% (43/75) was found, with 48% (36/75) RAS mutations, 12% (9/75) FMS mutations and 8% (4/50) p53 mutations. The mutation status for RAS and FMS was related to MDS subgroup, increasing with poor-risk disease. The highest incidence was in the chronic myelomonocytic leukemia (CMML) subgroup. The most frequent RAS mutations were of codon 12 and a predominance of FMS codon 969 mutations was observed. A statistically significant increased frequency of transformation to AML was observed in MDS patients harboring RAS or FMS mutations (P < 0.02). Patients with oncogene mutations had a significantly poorer survival compared with those without mutations at 2 years and at the end of the period of follow-up (P < 0.02). Multivariate analysis including mutation, age, gender, diagnosis (FAB), cytogenetics and International score shows that the International score and mutation and age is the best predictive model of a poor outcome, (P < 0.0001). When the analysis was undertaken without the International score, mutation and gender was the best predictor of poor survival (P = 0.005). This study shows that oncogene mutation, indicative of genetic instability, is associated with disease progression and poor survival in MDS.

Adult↗
PubMed1998

Educating young people about drugs: a systematic review.

AIMS: To assess the effectiveness of interventions directed at the prevention or reduction of use of illicit substances by young people or those directed at reducing harm caused by continuing use. DESIGN: A systematic review was conducted. Reports were identified through electronic and hand searching and contact with known workers in the area. Studies were included if they reported evaluations of interventions targeting illicit drug use and provided sufficient detail of the intervention and design of the evaluation to allow judgements to be made of their methodological soundness. Meta-analyses were conducted combining the data of the methodologically sound studies. PARTICIPANTS AND SETTINGS TARGETED BY INTERVENTIONS: Evaluations of interventions were included if their targeted audience included young people aged between 8 and 25 years. Identified evaluations were delivered in a range of settings including: schools and colleges; community settings; the family; medical/therapeutic settings; mass media. MEASUREMENTS: Data extracted from each report included details of design, content and theoretical orientation of intervention, setting of the intervention, target audience, methods, population size, subject refusal rates, rates of attrition, outcome measures, length of follow-up and findings, including statistical power. FINDINGS: The majority of studies identified were evaluations of interventions introduced in schools and targeting alcohol, tobacco and marijuana simultaneously. These studies were methodologically stronger than interventions targeting other drugs and implemented outside schools. Meta-analyses showed that the impact of evaluated interventions was small with dissipation of programme gains over time. Interventions targeting hard to reach groups have not been evaluated adequately. CONCLUSIONS: Effort needs to be directed towards the development of improved evaluative solutions to the problems posed by these groups. There is still insufficient evidence to assess the effectiveness of the range of approaches to drugs education; more methodologically sound evaluations are required. There is also a need to target interventions to reflect the specific needs and experiences of recipients.

Adolescent↗
PubMed1998

Isoflurane concentrations using uncompensated vaporisers within circle systems.

In a series of studies designed to investigate the need for a temperature-compensated vaporiser for use in a circle system, we first studied temperature changes within and isoflurane concentration delivered by a Komesaroff vaporiser during bench tests using different gas flows. Agent temperature and vapour concentration decreased as predicted by the Antoine equation. Using the vaporiser within a circle system during clinical anaesthesia, we then studied 20 patients breathing spontaneously and a further 10 patients receiving controlled ventilation, measuring the temperature of the agent within the vaporiser and the concentration of agent inspired by a the patient. In clincial use with the frest gas flows of 1-3.min-1, the inspired agent concentration did not decrease despite the decrease in temperature of the liquid isoflurane in the vaporiser.

Anesthesia, Closed-Circuit↗
PubMed1998

Respiratory feedback effects on vaporisers in circle systems.

We studied a group of spontaneously breathing patients anaesthetised for routine orthopaedic surgery using a circle system and isoflurane in a Komesaroff vaporiser within the circle. We observed and recorded: (1) the change in inspired isoflurane concentration caused by changing the fresh gas flow, (2) the increased respiration produced by surgical stimulus and the resulting increase in isoflurane concentration, (3) the respiratory depression produced by opioids and the consequent decrease in isoflurane concentration. We consider this regulation of anaesthetic uptake by the patient to be beneficial.

Analgesics, Opioid↗
PubMed1998

Controlled ventilation using isoflurane with an in-circle vaporiser.

We studied 19 patients anaesthetised for routine surgery using isoflurane delivered from a Komesaroff vaporiser mounted within a circle system. Their lungs were ventilated using a Penlon Nuffield ventilator attached to the circle system by a trunk of tubing. Fresh gas flow rates of 1, 2 or 31.min-1 were used. The inspired agent concentration was measured using a Datex Ultima multigas analyser and was found to be stable and easily controlled.

Anesthesia, Closed-Circuit↗
PubMed1998

Molecular cloning and characterization of a radial spoke head protein of sea urchin sperm axonemes: involvement of the protein in the regulation of sperm motility.

Monoclonal antibodies raised against axonemal proteins of sea urchin spermatozoa have been used to study regulatory mechanisms involved in flagellar motility. Here, we report that one of these antibodies, monoclonal antibody D-316, has an unusual perturbating effect on the motility of sea urchin sperm models; it does not affect the beat frequency, the amplitude of beating or the percentage of motile sperm models, but instead promotes a marked transformation of the flagellar beating pattern which changes from a two-dimensional to a three-dimensional type of movement. On immunoblots of axonemal proteins separated by SDS-PAGE, D-316 recognized a single polypeptide of 90 kDa. This protein was purified following its extraction by exposure of axonemes to a brief heat treatment at 40 degrees C. The protein copurified and coimmunoprecipitated with proteins of 43 and 34 kDa, suggesting that it exists as a complex in its native form. Using D-316 as a probe, a full-length cDNA clone encoding the 90-kDa protein was obtained from a sea urchin cDNA library. The sequence predicts a highly acidic (pI = 4.0) protein of 552 amino acids with a mass of 62,720 Da (p63). Comparison with protein sequences in databases indicated that the protein is related to radial spoke proteins 4 and 6 (RSP4 and RSP6) of Chlamydomonas reinhardtii, which share 37% and 25% similarity, respectively, with p63. However, the sea urchin protein possesses structural features distinct from RSP4 and RSP6, such as the presence of three major acidic stretches which contains 25, 17, and 12 aspartate and glutamate residues of 34-, 22-, and 14-amino acid long stretches, respectively, that are predicted to form alpha-helical coiled-coil secondary structures. These results suggest a major role for p63 in the maintenance of a planar form of sperm flagellar beating and provide new tools to study the function of radial spoke heads in more evolved species.

Amino Acid Sequence↗
PubMed1998

Patient education for discharge after coronary bypass surgery in the 1990s: are patients adequately prepared?

Short hospitalizations for patients undergoing coronary artery bypass grafting (CABG) require continuous nursing evaluation of patients' discharge education. Six institutions collaborated in surveying 300 postoperative patients with CABG to identify learning priorities and patients' perceptions of the effectiveness of discharge education. Data analysis from the self-administered questionnaire demonstrated consistent patient priorities across institutions. Differences in teaching methods and content did not affect perceived preparedness or importance scores. Regional experience demonstrates that variable teaching efforts meet patients' priorities and provide high overall patient preparedness for discharge. Patients with the shortest hospitalizations had higher preparedness scores.

Adult↗
PubMed1998

Reducing adverse drug events and medication errors using rapid cycle improvement.

The article describes Fairview Health System's participation in the Institute for Healthcare Improvement Breakthrough Series on adverse drug events and medication errors. Fairview commissioned an interdisciplinary team to design, plan, and lead activities focused on reducing adverse drug events and medication errors. This team managed, facilitated, or led 15 separate projects, each focusing on a specific aspect of the medications process. Specific systems improvements were identified, leading to reductions in errors or adverse events. As a result of this effort, Fairview has committed to a long-term plan to reduce the risk of adverse drug events and medication errors to the lowest possible rate.

Anticoagulants↗
PubMed1998

Effect of interferon gamma on intrahepatic haemodynamics of the cirrhotic rat liver.

Sublethal injury of the liver with carbon tetrachloride (CCl4) induces the modulation of hepatic stellate cells to their myofibroblast (MFB) phenotype. Pretreatment or concomitant treatment with interferon gamma (IFNgamma) has been shown to inhibit this phenomenon. The aim of this study was to investigate the influence of IFNgamma treatment (50000 IU s.c. each day for 5 days) in rats with an established cirrhosis. Cirrhosis was induced with nine doses of CCl4. Comparison of biopsies before and after treatment with IFNgamma showed that the number of MFB present, identified by their alpha-smooth muscle actin immunoreactivity, was markedly reduced. Pressure-flow curves were constructed in isolated perfused liver preparations from IFNgamma-treated and saline-treated cirrhotic rats and analysed to obtain the extrapolated zero-flow intercept (Po, an index of hepatic vascular distensibility) and the vasodilator-induced change in resistance at a flow rate of 1 mL/min per g (deltaR1, an indication of the level of intrinsic vascular tone). In IFNgamma-treated rats, portal venous pressure measured in vivo was significantly reduced compared with controls (11.9+/-1.2 vs 16.0+/-0.5 mmHg, P< 0.05), Po was lower (2.03+/-0.18 vs 2.87+/-0.32 mmHg, P<0.05) and deltaR1 was decreased (0.39+/-0.15 vs 1.02+/-0.19 mmHg/mL per min per g, P< 0.05). The findings indicate that treatment with IFNgamma is effective in reducing MFB density in established CCl4-cirrhosis in the rat and results in a marked improvement in intrahepatic haemodynamics.

Animals↗
PubMed1998

The aadA gene of plasmid R100 confers resistance to spectinomycin and streptomycin in Myxococcus xanthus.

Plasmids with the aadA gene from plasmid R100, which confers resistance to the aminoglycosides spectinomycin and streptomycin in Escherchia coli, can be introduced into wild-type Myxococcus xanthus, strain DK1622, by electroporation. Recombinant M. xanthus strains with integrated plasmids carrying the aadA gene acquire resistance to high levels of these antibiotics. Selection for aadA in M. xanthus can be carried out independently of, or simultaneously with, selection for resistance to kanamycin. The kinds and frequencies of recombination events observed between integrative plasmids with aadA and the M. xanthus chromosome are similar to those observed after the transformation of yeast. Cleavage of integrative plasmid DNA at a site adjacent to a region of homology between the plasmid and the M. xanthus genome favors the targeted disruption of M. xanthus genes by allele replacement.

Anti-Bacterial Agents↗