Is 'bedside medicine' returning to oncology?
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Humans↗
Biomedical subjects
M Watson
Publications and source records attributed to M Watson.
Canadian experiences in telehealth: equalizing access to quality care.
The Canadian Conference "TExpo'98: Interactive Health" focused on four telehealth themes: community needs, Canadian experiences, industry perspectives, and access/security/interoperability issues. Health and socioeconomic needs have been the driving force behind telehealth initiatives; telelearning is one of the major Canadian initiatives. To encourage Canadian telehealth initiatives, the federal government is building a national health infrastructure. One element in this framework is concerned with empowering the public, strengthening health care services, and ensuring accountability. Technological advancements and innovative partnerships among health communities, government, users, professional bodies, and industry are critical to continued growth. Key issues including access, evaluation, implementation, privacy, confidentiality, security, and interoperability are of universal concern to participants. Research that examines the benefits and costs of telehealth is needed.
Canada↗
Apical microleakage of radiolabeled lysozyme over time in three techniques of root canal obturation.
The three methods of obturation assessed in this study were lateral condensation (80 teeth), Thermafil (40 teeth), and McSpadden (40 teeth). All teeth were prepared to the master apical file 30 and widened coronally by Gates Glidden burs before being randomly assigned to experimental groups to be filled by each technique; they were then sealed with nail polish, except for the apical 1 mm. Quantitative evaluation of apical microleakage for each technique was obtained after periods of 1 day, 7 days, 14 days, and 28 days of immersion in a lysozyme solution labeled with radioactive iodine by preparing horizontal sections of the teeth and measuring the level of radioactivity in each section using a gamma counter. Initial (1-day) leakage was least in the Thermafil group and was significantly different from the other techniques. Leakage was greatest in the laterally condensed samples. By the end of the study (28th day) values for lateral condensation were lowest, but were significantly different only for the McSpadden group. For all techniques leakage was most significant in the first 3 mm from the apex and was very low below this level so that all methods can be considered as giving a hermetic seal below 3 mm.
Analysis of Variance↗
K-ras mutations, rectal crypt cells proliferation, and meat consumption in patients with left-sided colorectal carcinoma.
It has been suggested that N-nitroso compounds derived from meat may increase the risk of K-ras mutations in the human colon. We sought evidence of associations between red meat consumption, frequency and type of K-ras mutations in resected tumours, and the rate of crypt cell proliferation (CCP) in the normal mucosa of patients with left-sided colorectal carcinoma. Meat consumption was assessed by food frequency questionnaire, and CCP was determined in rectal biopsies obtained prior to surgery. K-ras mutations in the resected tumours were determined using a PCR-based oligonucleotide hybridization assay. Fifteen K-ras mutations were detected in tumours from 43 patients; 13/15 in codon 12, 3/15 in codon 13, and 1/15 in both codons 12 and 13. All mutations were G-->A or G-->T transitions. There was no statistically significant difference between intakes of red meat in patients with a K-ras mutation (92.4 +/- 9.7 g/day) and those without (82.3 +/- 7.7 g/day). Rectal CCP was significantly higher in patients than in healthy controls, but there was no correlation with meat consumption or K-ras mutation. These data do not support the hypothesis that meat consumption is a risk factor for acquisition of K-ras mutations during colorectal carcinogenesis.
Aged↗
Magnetic resonance spectroscopy in the evaluation of neurotoxicity following cranial irradiation for childhood cancer.
In order to evaluate the role of proton MR spectroscopy (1H-MRS) in the diagnosis and assessment of long-term radiation-related neurotoxicity, 14 children who had received cranial irradiation for the treatment of childhood leukaemia (n = 6) or brain tumours (n = 8) underwent 1H-MRS, MRI and neuropsychological assessment. Short-term effects at 2 months following treatment were studied in a further three patients. MRI abnormalities were observed in nine patients. No statistically significant differences between patients and controls (n = 17) were seen in any of the calculated 1H-MRS metabolite ratios, in any of the three patient groups. On multivariate logistic regression analysis there was a correlation between the choline/water ratio and a low IQ. It is concluded that any systematic radiation-induced changes in the 1H MRS metabolites must be below the detection threshold of this study.
Adolescent↗
Neonatal tachyarrhythmias.
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Electrocardiography↗
Hemoglobin adducts from acrylonitrile and ethylene oxide in cigarette smokers: effects of glutathione S-transferase T1-null and M1-null genotypes.
Acrylonitrile (ACN) is used to manufacture plastics and fibers. It is carcinogenic in rats and is found in cigarette smoke. Ethylene oxide (EO) is a metabolite of ethylene, also found in cigarette smoke, and is carcinogenic in rodents. Both ACN and EO undergo conjugation with glutathione. The objectives of this study were to examine the relationship between cigarette smoking and hemoglobin adducts derived from ACN and EO and to investigate whether null genotypes for glutathione transferase (GSTM1 and GSTT1) alter the internal dose of these agents. The hemoglobin adducts N-(2-cyanoethyl)valine (CEVal), which is formed from ACN, and N-(2-hydroxyethyl)valine (HEVal), which is formed from EO, and GST genotypes were determined in blood samples obtained from 16 nonsmokers and 32 smokers (one to two packs/day). Smoking information was obtained by questionnaire, and plasma cotinine levels were determined by immunoassay. Glutathione transferase null genotypes (GSTM1 and GSTT1) were determined by PCR. Both CEVal and HEVal levels increased with increased cigarette smoking dose (both self-reported and cotinine-based). CEVal and HEVal levels were also correlated. GSTM1 and GSTT1 genotypes had little effect on CEVal concentrations. GSTM1 null genotypes had no significant impact on HEVal. However, HEVal levels were significantly elevated in GSTT1-null individuals when normalized to smoking status or cotinine levels. The ratio of HEVal:CEVal was also elevated in GSTT1-null smokers (1.50 +/- 0.57 versus 0.88 +/- 0.24; P = 0.0002). The lack of a functional GSTT1 is estimated to increase the internal dose of EO derived from cigarette smoke by 50-70%.
Acrylonitrile↗
Knowledge and attitudes of hospital staff to occupational exposure to bloodborne viruses.
In order to assess awareness of occupational risk of exposure to bloodborne viruses a questionnaire was sent to 245 health care workers, representing a 10% sample of employees with patient contact in a large teaching hospital in Scotland, stratified by occupational group. One hundred and eight questionnaires (44%) were returned. Seventy per cent of respondents in laboratory and clinical areas described themselves as having sufficient knowledge for their own area of practice, but many gave incorrect answers or expressed uncertainty about the infectivity of HIV and hepatitis B and hepatitis C viruses. Ninety-four respondents were unaware that a regimen containing more than one antiretroviral drug is now recommended for post exposure prophylaxis of HIV infection, 37 thought they had been at risk of bloodborne viral infection and had contacted the occupational health department for advice, and 68 respondents disagreed with guidelines from the United Kingdom's General Medical Council on testing of patients for bloodborne viruses. The results indicate a need for educational initiatives for new and existing staff.
Attitude of Health Personnel↗
Sequence and analysis of chromosome 4 of the plant Arabidopsis thaliana.
The higher plant Arabidopsis thaliana (Arabidopsis) is an important model for identifying plant genes and determining their function. To assist biological investigations and to define chromosome structure, a coordinated effort to sequence the Arabidopsis genome was initiated in late 1996. Here we report one of the first milestones of this project, the sequence of chromosome 4. Analysis of 17.38 megabases of unique sequence, representing about 17% of the genome, reveals 3,744 protein coding genes, 81 transfer RNAs and numerous repeat elements. Heterochromatic regions surrounding the putative centromere, which has not yet been completely sequenced, are characterized by an increased frequency of a variety of repeats, new repeats, reduced recombination, lowered gene density and lowered gene expression. Roughly 60% of the predicted protein-coding genes have been functionally characterized on the basis of their homology to known genes. Many genes encode predicted proteins that are homologous to human and Caenorhabditis elegans proteins.
Animals↗
Influence of psychological response on survival in breast cancer: a population-based cohort study.
BACKGROUND: The psychological response to breast cancer, such as a fighting spirit or an attitude of helplessness and hopelessness toward the disease, has been suggested as a prognostic factor with an influence on survival. We have investigated the effect of psychological response on disease outcome in a large cohort of women with early-stage breast cancer. METHODS: 578 women with early-stage breast cancer were enrolled in a prospective survival study. Psychological response was measured by the mental adjustment to cancer (MAC) scale, the Courtauld emotional control (CEC) scale, and the hospital anxiety and depression (HAD) scale 4-12 weeks and 12 months after diagnosis. The women were followed up for at least 5 years. Cox's proportional-hazards regression was used to obtain the hazard ratios for the measures of psychological response, with adjustment for known clinical factors associated with survival. FINDINGS: At 5 years, 395 women were alive and without relapse, 50 were alive with relapse, and 133 had died. There was a significantly increased risk of death from all causes by 5 years in women with a high score on the HAD scale category of depression (hazard ratio 3.59 [95% CI 1.39-9.24]). There was a significantly increased risk of relapse or death at 5 years in women with high scores on the helplessness and hopelessness category of the MAC scale compared with those with a low score in this category (1.55 [1.07-2.25]). There were no significant results found for the category of "fighting spirit". INTERPRETATION: For 5-year event-free survival a high helplessness/hopelessness score has a moderate but detrimental effect. A high score for depression is linked to a significantly reduced chance of survival; however, this result is based on a small number of patients and should be interpreted with caution.
Aged↗
Severe adverse impact on sexual functioning and fertility of bone marrow transplantation, either allogeneic or autologous, compared with consolidation chemotherapy alone: analysis of the MRC AML 10 trial.
BACKGROUND: Data relating to the impact of bone marrow transplantation (BMT) on sexual functioning are equivocal; some studies have shown no major impact whereas others demonstrate a significant adverse effect on sexual health in patients treated with BMT. Further clarification is required to facilitate treatment choices and follow-up management of patients. METHODS: A cross-sectional study of sexual health and infertility was conducted in 479 patients with acute myeloid leukemia (AML) in first complete remission (CR) who were entered into the UK MRC AML 10 trial comparing allogeneic BMT (Allo-BMT), autologous BMT (A-BMT), and intensive consolidation chemotherapy (CCT). Assessment was made by patient questionnaire via the treating centers for completion and returned directly to the coordinating center. RESULTS: Both Allo-BMT and A-BMT were observed to have severe, highly significant adverse effects on the patients' sexual health. Significantly more BMT patients than CCT patients reported a decrease in interest in sex (48% vs. 24%), sexual activity (53% vs. 35%), pleasure from sex (36% vs. 18%), and ability to have sex (38% vs. 18%) (P < 0.001 in each case). Hormonal disorders and infertility also were more common in BMT patients than in CCT patients. These differences were more apparent in women and remained after adjustment for age. CONCLUSIONS: These results indicate a need to consider quality of life parameters when reviewing treatment options and to instigate effective proactive management strategies for dealing with sexual health problems in leukemia survivors.
Acute Disease↗
Sugar printing rheumatic diseases: a potential method for disease differentiation using immunoglobulin G oligosaccharides.
OBJECTIVE: To look for oligosaccharide structural variants of IgG that may be unique to specific rheumatic diseases. METHODS: Using normal-phase high-performance liquid chromatography technology, a comparison was made of the oligosaccharide pools released from serum IgG from patients with systemic lupus erythematosus (SLE) (n = 10), ankylosing spondylitis (AS) (n = 10), primary Sjögren's syndrome (n = 6), juvenile chronic arthritis (JCA) (n = 13), psoriatic arthritis (n = 9), rheumatoid arthritis (RA) (n = 5), and healthy control individuals (n = 19). RESULTS: The oligosaccharide pools were resolved into 13 peaks and the relative proportions of the peaks in each disease group was significantly different from that in healthy controls (P < 0.0001-0.05). A characteristic serum IgG oligosaccharide profile, or sugar print, for each of the rheumatic diseases was found. The sugar prints exhibited a range of glycosylation patterns whereby all RA (P < 0.0001) and JCA (P < 0.006) patients had predominantly agalactosyl structures, while SLE (P < 0.03-0.0001) and AS (P < 0.025-0.0001) patients had predominantly digalactosyl structures. CONCLUSION: The data suggest that each disease is associated with a specific mechanism that gives rise to alterations in the normal glycosylation pattern of IgG. Sugar printing of IgG is therefore a potential means for the differentiation of rheumatic diseases and may provide insight into disease pathogenesis.
Adult↗
Inhibition of cytokinesis by asbestos and synthetic fibres.
Using high-resolution timelapse microscopy, we have followed individual phagocytized fibres through the later stages of division in MeT-5A human mesothelial cells and LLC-MK(2)monkey epithelial cells. The fibres used were crocidolite and chrysotile asbestos, fibrous glass (MMVF), and refractory ceramic fibres (RCF). Long fibres (15-80 microm) trapped within the cleavage furrow can partially or completely block cytokinesis. Cells proceed in one of three ways: (1) eventual completion of cytokinesis; (2) incomplete cytokinesis, resulting in two cells joined by a fibre-containing intercellular channel; or (3) failure of cytokinesis, resulting in a binucleate or trinucleate cell. Two factors associated with fibre-induced bi/trinucleation are: (1) an initial association between the fibre and the forming daughter nuclei, which is sometimes lost over time, and (2) disintegration of the midbody. The studies suggest that delay of cytokinesis by interzonal fibres can result in bi/trinucleation through the loss of midbody/intercellular bridge proteins that are required for completion of cytokinesis.
Animals↗
XR3054, structurally related to limonene, is a novel inhibitor of farnesyl protein transferase.
In this report, a novel inhibitor of farnesyl protein transferase (FPTase) is described. The compound, XR3054, is structurally similar to farnesol, a component of the reaction in which FPTase catalyses transfer of farnesol pyrophosphate to the CAAX recognition motif on proteins. The compound was selected initially because of its ability to inhibit in vitro farnesylation of CAAX recognition peptides with an IC50 of 50 microM. The farnesylation of p21 ras was reduced in a dose-dependent manner in the presence of XR3054. Similarly XR3054 was able to reduce the anchorage-independent growth of V12 H-ras transformed NIH 3T3 cells in a focus formation assay in soft agar, with an IC50 value of 30 microM, whilst not affecting the anchorage-independent growth of v-raf transformed cells. XR3054 reduced the phosphorylation of p42 mitogen activated protein (MAP) kinase in parental NIH 3T3 cells and V12 H-ras transformed NIH 3T3 cells, but constitutively active v-raf transformed cells showed no reduction in phosphorylation of ERK2 in the presence of XR3054. XR3054 inhibited the proliferation of the prostatic cancer cell lines LnCAP and PC3 and the colon carcinoma SW480 and HT1080 (IC50 values of 12.4, 12.2, 21.4 and 8.8 microM, respectively) but was relatively inactive when tested against a panel of breast carcinoma cell lines. The activity did not relate to the presence of mutant or wild-type ras in the cell lines tested. In conclusion XR3054 inhibits ras farnesylation, MAP kinase activation and anchorage-independent growth in NIH 3T3 transformed with v12 H-ras. Since the antiproliferative effect of the compound is not related to the ras phenotype, XR3054 may also have effects on other cell signalling mechanisms.
Alkyl and Aryl Transferases↗
Circuits with surface modifying additive alter the haemodynamic response to cardiopulmonary bypass.
OBJECTIVE: Blood contact with synthetic surfaces during cardiopulmonary bypass (CPB), inevitably results in the activation of a variety of interrelated pathways of inflammation and coagulation that may contribute to postoperative complications in cardiac surgery patients. The objective of this trial was to evaluate clinical events and complement activation related to the use of a novel biomaterial, into which a surface modifying additive had been incorporated into the polymer used to prepare the bypass circuit. METHODS: A prospective, double-blind trial was carried out with 34 patients randomized to surgery, with either a standard circuit or a circuit treated ('tip to tip') with the surface modifying additive. Variables recorded included perioperative haemodynamics, volume replacement, alpha-agonist and inotrope use. Terminal complement complex (SC5b-9) was measured using an ELISA. RESULTS: Upon initiation of bypass, there was a decrease in mean arterial pressure (MAP) in the control group, not seen in the test group (P = 0.0005, ANOVA). There was a decrease in the total volume of replacement fluid given intraoperatively in the test group as compared with the control group (total plus prime; control 5.3 +/- 1.2 L, test 4.4 +/- 1.9 L, P = 0.03, Mann-Whitney test). There was a trend to decreased need for inotrope infusion in the test group after CPB (test 1/17, control 6/17, Fisher exact test; P = 0.085). No difference was seen in the generation of terminal complement complex between the groups either during or after CPB. CONCLUSIONS: The decrease in blood pressure in the control group, upon the initiation of CPB, did not occur in patients undergoing CPB with the circuit prepared with the surface modifying additive. The decrease in blood pressure was likely associated with the increase in total administered fluids intraoperatively (approximately 1 l/patient) and perhaps the trend towards higher use of inotropes in the control patients as opposed to the test patients. These haemodynamic changes did not appear to be related to complement activation early in CPB.
Cardiac Output↗
Hardy-Weinberg quality control.
An efficient test of deviation from Hardy-Weinberg frequencies with one degree of freedom was applied to 44 marker loci in a genome scan, and 7 loci had a significant excess of apparent homozygotes (chi2 (1) > 6) suggestive of typing error. In this example evidence for linkage did not increase when outliers were censored. Statistical quality control is an essential part of genotyping, and the effect of mistyping and map error should be considered in evaluating any genome scan.
Asthma↗
The impact of genetic counselling on risk perception and mental health in women with a family history of breast cancer.
The present study investigated: (1) perception of genetic risk and, (2) the psychological effects of genetic counselling in women with a family history of breast cancer. Using a prospective design, with assessment pre- and post-genetic counselling at clinics and by postal follow-up at 1, 6 and 12 months, attenders at four South London genetic clinics were assessed. Participants included 282 women with a family history of breast cancer. Outcome was measured in terms of mental health, cancer-specific distress and risk perception. High levels of cancer-specific distress were found pre-genetic counselling, with 28% of participants reporting that they worried about breast cancer 'frequently or constantly' and 18% that worry about breast cancer was 'a severe or definite problem'. Following genetic counselling, levels of cancer-specific distress were unchanged. General mental health remained unchanged over time (33% psychiatric cases detected pre-genetic counselling, 27% at 12 months after genetic counselling). Prior to their genetics consultation, participants showed poor knowledge of their lifetime risk of breast cancer since there was no association between their perceived lifetime risk (when they were asked to express this as a 1 in x odds ratio) and their actual risk, when the latter was calculated by the geneticist at the clinic using the CASH model. In contrast, women were more accurate about their risk of breast cancer pre-genetic counselling when this was assessed in broad categorical terms (i.e. very much lower/very much higher than the average woman) with a significant association between this rating and the subsequently calculated CASH risk figure (P = 0.001). Genetic counselling produced a modest shift in the accuracy of perceived lifetime risk, expressed as an odds ratio, which was maintained at 12 months' follow-up. A significant minority failed to benefit from genetic counselling; 77 women continued to over-estimate their risk and maintain high levels of cancer-related worry. Most clinic attenders were inaccurate in their estimates of the population risk of breast cancer with only 24% able to give the correct figure prior to genetic counselling and 36% over-estimating this risk. There was some improvement following genetic counselling with 62% able to give the correct figure, but this information was poorly retained and this figure had dropped to 34% by the 1-year follow-up. The study showed that women attending for genetic counselling are worried about breast cancer, with 34% indicating that they had initiated the referral to the genetic clinic themselves. This anxiety is not alleviated by genetic counselling, although women reported that it was less of a problem at follow-up. Women who continue to over-estimate their risk and worry about breast cancer are likely to go on seeking unnecessary screening if they are not reassured.
Adult↗
Seven novel mutations of the PKD2 gene in families with autosomal dominant polycystic kidney disease.
BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is genetically heterogeneous, with at least three chromosomal loci accounting for the disease. Mutations in the PKD2 gene on the long arm of chromosome 4 are expected to be responsible for approximately 15% of cases of ADPKD. METHODS: We report a systematic screening for mutations covering the 15 exons of the PKD2 gene in eight unrelated families with ADPKD type 2, using the heteroduplex technique. RESULTS: Seven novel mutations were identified and characterized that, together with the previously described changes, amount to a detection rate of 85% in the population studied. The newly described mutations are two nonsense mutations, a 1 bp deletion, a 1 bp insertion, a mutation that involves both a substitution and a deletion (2511AG-->C), a complex mutation in exon 6 consisting of a simultaneous 7 bp inversion and a 4 bp deletion, and the last one is a G-->C transversion that may be a missense mutation. Most of these mutations are expected to lead to the formation of shorter truncated proteins lacking the carboxyl terminus of PKD2. We have also characterized a frequent polymorphism, Arg-Pro, at codon 28 in this gene. The clinical features of these PKD2 patients are similar to the previously described, with the mean age of end-stage renal disease being 75.5 years (SE +/- 3.8 years). CONCLUSIONS: Our results confirm that many different mutations are likely to be responsible for the disease and that most pathogenic defects probably are point or small changes in the coding region of the gene.
Amino Acid Sequence↗