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Biomedical subjects

L Robertson

Publications and source records attributed to L Robertson.

At least 19 recordsLinked to original sources

Prognostic significance of the metastasis-inducing protein S100A4 (p9Ka) in human breast cancer.

The calcium-binding protein S100A4 is capable of inducing metastasis in rodent models for breast cancer. We now show that rabbit antibodies to recombinant rat S100A4 recognize specifically human S100A4 using Western blotting techniques and use them to assess the prognostic significance of S100A4 in primary tumors from a group of 349 patients treated between 1976 and 1982 for stage I and stage II breast cancer. The antibody stains normal breast tissue heterogeneously, but stains positively 41% of the carcinomas, leaving the remaining 59% as negatively stained. In addition to the carcinoma cells, some host stromal cells and lymphocytes are also stained, but these have been discounted in subsequent analyses. There is an association of staining of carcinomas for S100A4 with some tumor variables considered to be associated with poor prognosis for patients: tumor present in axillary lymph nodes (borderline P = 0.058), staining for c-erbB-3 (P = 0.002), cathepsin D (P = 0.024), and c-erbB-2 (P = 0.048). The association of staining for S100A4 with patient survival has been evaluated using life tables and analyzed using generalized Wilcoxon statistics. Eighty percent of the S100A4-negative patients but only 11% of the S100A4-positive patients are alive after 19 years of follow-up, and this association is highly significant (P < 0.0001); the former have a median survival of >228 months and the latter 47 months. The other tumor variables that show significant association with survival time are nodal status (P < 0.0001), tumor size (P = 0.0035), histological grade (P = 0.013), staining for c-erbB-2 (P = 0.0015), estrogen receptor (P = 0.028), and p53 (P = 0.032). Analysis of the association of patients with carcinomas staining for S100A4 and their survival in subgroups defined by these other tumor variables shows that in each subgroup, staining for S100A4 is associated with poorer survival. Patients whose tumors stain for S100A4 and possess involved lymph nodes (P < 0.0001), which are fixed to the chest wall (P = 0.015) or which stain for c-erbB-2 (P = 0.050), show a significant reduction in survival times over those with only S100A4-staining tumors. Patients with involved lymph nodes, or staining for c-erbB-2 in the S100A4-negative group fail to show any significant reduction in survival times. Multivariate regression analysis for 137 patients shows that staining for S100A4 is most highly correlated with patient deaths (P < 0.0001), but involved lymph nodes (P = 0.001), fixed tumors (P = 0.0002), and high histological grade (P = 0.022) are also significant independent prognostic variables. These results suggest that in this group of patients, the metastasis-inducing protein S100A4 is most tightly correlated with patient demise.

Adult↗

Life skills programmes for chronic mental illnesses.

BACKGROUND: Most people with schizophrenia have a pattern of illness characterised by remission and relapses. The illness can become chronic and disabling. The social disability can require a variety of psychological, nursing and occupational therapies. Life skills programmes, addressing the needs associated with independent functioning, are often a part of the rehabilitation process. OBJECTIVES: To compare the effectiveness of life skills programmes with standard care for people with chronic mental health problems. SEARCH STRATEGY: CINAHL (1982-1997), The Cochrane Library (Issue 2, 1997), The Cochrane Schizophrenia Group's Register of Trials (April 1998), EMBASE (1980-1997), MEDLINE (1966-1997) and PsycLIT (1974-1997) were methodically searched. Hand searches and scrutiny of references supplemented this process. SELECTION CRITERIA: All relevant randomised or quasi-randomised controlled trials for life skills programmes versus standard care involving those with serious mental illnesses. DATA COLLECTION AND ANALYSIS: Searches were inspected by two reviewers (LR, MN) with a third (JC) acting as arbitrator. Data were extracted in the same way. Where possible an intention-to-treat analysis was undertaken on dichotomous data and normally distributed continuous data. MAIN RESULTS: Two randomised controlled trials were included with a total of 38 participants. Data were sparse and no clear effects were demonstrated. REVIEWER'S CONCLUSIONS: If life skills training is to continue as part of rehabilitation programmes a large, well designed, conducted and reported pragmatic randomised trial is an urgent necessity. There may even be an argument for stating that maintenance of current practice, outside of a randomised trial, is unethical.

Activities of Daily Living↗

Patch incorporation in diaphragmatic hernia.

BACKGROUND/PURPOSE: Biomaterial insertion often is required for closure of congenital diaphragmatic hernia (CDH). The optimal biomaterial remains uncertain. This study was designed to compare a commonly used patch (polytetrafluoroethylene) with a recently available fabric, fluorinated polyester. The aim of this study was to determine the clinical performance, histological tissue-polymer interaction, bacterial adhesion, and shrinkage rates of biomaterial inserted endoscopically into a CDH lamb model. METHODS: Polytetrafluoro-ethylene (PTFE) and fluorinated polyester (FP) were randomised for laparoscopic patch insertion into 12 lambs. All lambs (age <4 weeks) underwent 3-port laparoscopy, surgical creation of diaphragmatic hernia, and sutured patch placement. Two PTFE and 2 FP lambs were killed at 1-, 3-, and 6-month intervals postoperatively. Postmortem examination histopathology, electron microscopy, and specific bacterial broth immersion (Escherichia coil, Staphylococcus aurens, and epidermidis) were performed. RESULTS: All 12 lambs completed the study with intact patches that were fully peritonised. One abdominal adhesion was noted in a FP lamb at 6 months. FP was comparatively easier to insert, manipulate, and suture endoscopically. Histopathology findings showed that PTFE patches created a strong peripheral foreign body reaction with dystrophic calcification, whereas FP was well incorporated with intrapatch fibroblastic activity and neovascularsation. No significant difference in resistance to bacterial adhesion of relevant organisms was noted between the materials. Graft shrinkage for FP was 7% in one direction only, evident by 3 months. CONCLUSIONS: Fluorinated polyester has advantages in this laparoscopic lamb model. It shows rapid and sustained incorporation with intrapatch neovascularisation when compared with polytetrafluoro-ethylene's significant foreign body reaction. It was preferred for its endoscopic handling and suturing properties. The laparoscopic techniques used may contribute to the general lack of adhesions, and insufficient data are available to comment on the comparative effect of the materials on adhesion formation. No difference was demonstrated in resistance to bacterial adherence in the harvested materials.

Animals↗

Molecular characterization of the vanD gene cluster and a novel insertion element in a vancomycin-resistant enterococcus isolated in Canada.

A single vanD-containing Enterococcus faecium strain (N97-330) was isolated in Canada. The vanD-containing region was cloned and sequenced. Although the proteins have more than 96% identity to a previously described vanD region in BM4339, the vanS(D) gene contains a frameshift mutation that leads to a predicted truncated protein. Furthermore, sequence analysis of the ddl gene revealed the presence of an IS982-like element (ISEfm1) which interrupted the D-Ala-D-Ala ligase. This suggested the constitutive expression of the vanD operon, which was confirmed. Pulsed-field gel electrophoresis fingerprinting demonstrated that BM4339 was not related to N97-330 (>15 band differences). Both strains contained multiple copies of the IS982-like element.

Amino Acid Sequence↗

Medical complications after stroke: a multicenter study.

BACKGROUND AND PURPOSE: This prospective, multicenter study was performed to determine the frequency of symptomatic complications up to 30 months after stroke using prespecified definitions of complications. METHODS: We recruited 311 consecutive stroke patients admitted to hospital. Research nurses reviewed their progress on a weekly basis until hospital discharge and again at 6, 18, and 30 months after stroke. RESULTS: Complications during hospital admission were recorded in 265 (85%) of stroke patients. Specific complications were as follows: neurological-recurrent stroke (9% of patients), epileptic seizure (3%); infections-urinary tract infection (24%), chest infection (22%), others (19%); mobility related-falls (25%), falls with serious injury (5%), pressure sores (21%); thromboembolism-deep venous thrombosis (2%), pulmonary embolism (1%); pain-shoulder pain (9%), other pain (34%); and psychological-depression (16%), anxiety (14%), emotionalism (12%), and confusion (56%). During follow-up, infections, falls, "blackouts, " pain, and symptoms of depression and anxiety remained common. Complications were observed across all 3 hospital sites, and their frequency was related to patient dependency and duration after stroke. CONCLUSIONS: Our prospective cohort study has confirmed that poststroke complications, particularly infections and falls, are common. However, we have also identified complications relating to pain and cognitive or affective symptoms that are potentially preventable and may previously have been underestimated.

Accidental Falls↗

Evaluating the financial impact of clinical trials in oncology: results from a pilot study from the Association of American Cancer Institutes/Northwestern University clinical trials costs and charges project.

PURPOSE: Medical care for clinical trials is often not reimbursed by insurers, primarily because of concern that medical care as part of clinical trials is expensive and not part of standard medical practice. In June 2000, President Clinton ordered Medicare to reimburse for medical care expenses incurred as part of cancer clinical trials, although many private insurers are concerned about the expense of this effort. To inform this policy debate, the costs and charges of care for patients on clinical trials are being evaluated. In this Association of American Cancer Institutes (AACI) Clinical Trials Costs and Charges pilot study, we describe the results and operational considerations of one of the first completed multisite economic analyses of clinical trials. METHODS: Our pilot effort included assessment of total direct medical charges for 6 months of care for 35 case patients who received care on phase II clinical trials and for 35 matched controls (based on age, sex, disease, stage, and treatment period) at five AACI member cancer centers. Charge data were obtained for hospital and ancillary services from automated claims files at individual study institutions. The analyses were based on the perspective of a third-party payer. RESULTS: The mean age of the phase II clinical trial patients was 58.3 years versus 57.3 years for control patients. The study population included persons with cancer of the breast (n = 24), lung (n = 18), colon (n = 16), prostate (n = 4), and lymphoma (n = 8). The ratio of male-to-female patients was 3:4, with greater than 75% of patients having stage III to IV disease. Total mean charges for treatment from the time of study enrollment through 6 months were similar: $57,542 for clinical trial patients and $63,721 for control patients (1998 US$; P =.4) CONCLUSION: Multisite economic analyses of oncology clinical trials are in progress. Strategies that are not likely to overburden data managers and clinicians are possible to devise. However, these studies require careful planning and coordination among cancer center directors, finance department personnel, economists, and health services researchers.

Aged↗

Dental nerve blocks. Toothache remedies for the acute-care setting.

Ideally, tooth pain is managed by a competent dentist, who can provide definitive care. However, timely access to such care may not be available late at night, on weekends, or in rural practice settings. This article introduces primary care physicians to dental nerve blocks that can be learned without extensive training and use in the acute-care setting to provide temporary relief of oral, dental, and facial pain.

Humans↗

Plasma estradiol FSH and LH concentration after dominant follicle aspiration in the cow.

This work investigates the estrogenic role of the dominant follicle with regard to regulation of plasma FSH and LH concentration. Eight Holstein-Friesian cows were used for aspiration of the dominant follicle using ultrasound guidance during the early, mid and late stages of the luteal phase. Blood samples were collected at 15-min intervals from 4 h before until 7 h after aspiration. Plasma progesterone concentration increased from 0.7 to 7.2 ng mL-1 from early to mid luteal phase and then fell slightly to 5.9 ng mL-1 in the late luteal phase, but remained unaffected by follicle puncture. The follicular aspirate contained a thousandfold higher estradiol, than plasma concentration but its estradiol:progesterone ratio remained at around 2 at each stage of the luteal phase. Aspiration caused plasma estradiol concentration to fall from 1.4 to 0.7, 1.8 to 1.0 and 1.7 to 0.8 pg mL-1 in the early, mid and late stages of the luteal phase, respectively (P < 0.05). At the same time, mean plasma FSH concentration was increased from 1.1 to 1.8, 1.7 to 2.9 and 0.8 to 1.9 ng mL-1 (P < 0.05), respectively. The results suggest that estradiol secreted from dominant follicles selectively regulates gonadotropin secretion, since aspiration of the dominant follicle at any stage of the cycle affected circulating FSH but did not appear to influence the mean LH concentration.

Animals↗

Is there an increased clinical severity of patients with eating disorders under managed care?

OBJECTIVES: We sought to examine possible differences in medical status at presentation in 1996, compared to 1991, of adolescents with eating disorders (EDs) at a hospital-based multidisciplinary care program to reflect the increasing market penetration of managed care. DESIGN: Charts were reviewed for all new patients scheduled in a hospital-based outpatient ED program in 1996 and 1991. The 92-item standardized data extraction form included information on demographics, indicators of illness severity at the first visit, and subsequent hospitalization. The need for primary care referral was verified using billing records. Data were analyzed with Student's t-test, Chi-square, Fisher's exact, and Mann-Whitney U tests using SPSS 7.5. RESULTS: Of the 153 total patients, 133 kept their intake appointment and 130 (98%) of these had charts available for review. The age, racial/ethnic characteristics, and average length of disordered eating behaviors were not significantly different over the 5-year period. Referral from a primary care clinician was more commonly required in 1996 than 1991 (59% vs. 11%; p < .0001). Eighteen percent of the patients seen in 1996 were admitted from the initial appointment for medical stabilization, compared to 1.5% in 1991 (p = .002). Comparing 1996 to 1991, a similar number of patients had symptoms consistent with anorexia nervosa, whereas fewer patients in 1996 gave a history of bingeing and purging (22% vs. 40%; p = .027). There were no significant differences in indicators of illness severity, treatment by primary care clinician prior to referral, or hospitalization rates for those patients with and without managed care. CONCLUSIONS: Patients in 1996 were more likely to require referrals, were less likely to have symptoms consistent with bulimia nervosa, and were more likely to be admitted for medical stabilization. There were no differences in patient presentation characteristics or initial hospitalization rates based on their managed care status. Further research is needed to investigate the changes in illness severity at presentation and to assess the role that managed care plays in the treatment of patients with eating disorders.

Adolescent↗

Direct analysis of the secretions of the potato cyst nematode Globodera rostochiensis.

Secretions were induced from second (invasive) stage juveniles (J2s) of the potato cyst nematode Globodera rostochiensis by exposing them to 5-methoxy-N,N-dimethyl tryptamine oxalate (DMT). Secretions were collected from J2s in sufficient quantity to allow direct analysis. Gel electrophoresis followed by monochromatic silver staining demonstrated the presence of at least 10 proteins. The presence of several enzymes, including superoxide dismutase and proteases, was demonstrated using Western blots and activity assays. Antisera raised against the secretions recognized bands on Western blots consistent in molecular mass with those identified on silver stained gels. The antisera recognized structures implicated in the production of secretions including the subventral gland cells and surface of J2s.

Animals↗

Infections in patients with chronic lymphocytic leukemia treated with fludarabine.

BACKGROUND: Fludarabine, a purine analogue with activity in chronic lymphocytic leukemia, is usually well tolerated. Although serious infections after fludarabine therapy have been described, a systematic analysis of the risk factors for such infections in chronic lymphocytic leukemia is lacking. OBJECTIVE: To determine the risk factors for major infection in patients with chronic lymphocytic leukemia treated with fludarabine. DESIGN: Retrospective review of medical records. SETTING: Cancer center. PATIENTS: 402 patients with chronic lymphocytic leukemia not previously treated or treated with chlorambucil (with or without prednisone) who received fludarabine (30 mg/m2 of body surface area per day for 5 days) with or without prednisone at 4-week intervals. RESULTS: Infections occurred more often in previously treated (144 of 248 [58%]) than in previously untreated (53 of 154 [34%]) patients (P < 0.001). Listeriosis or pneumocystosis occurred in 12 of 170 (7%) previously treated patients receiving fludarabine plus prednisone, 0 of 78 previously treated patients receiving fludarabine alone, and 2 of 154 (1%) previously untreated patients receiving fludarabine plus prednisone (P = 0.003). Univariate analysis identified previous chemotherapy, advanced disease, failure to respond to fludarabine, elevated serum beta2-microglobulin level (P < 0.001), low serum albumin level (P = 0.024), elevated serum creatinine concentration (P = 0.008), and low granulocyte count (P = 0.003) as risk factors for infection. Multivariate analysis identified Rai stage III or IV (odds ratio, 1.98 [95% CI, 1.17 to 3.94]), previous treatment (odds ratio, 2.24 [CI, 1.43 to 3.51]), and elevated serum creatinine concentration (odds ratio, 1.98 [CI, 1.09 to 3.67]) as statistically significant independent risk factors for major infection. A baseline granulocyte count of more than 1000 cells/microL was protective (odds ratio, 0.54 [CI, 0.29 to 0.99]). Five (26%) of 19 patients with a CD4 count less than 50 cells/mL developed cutaneous zoster compared with 9 (6%) of 139 patients with a CD4 count greater than 50 cells/mL (P = 0.01). CONCLUSIONS: Fludarabine used in previously treated patients with chronic lymphocytic leukemia may be associated with infections involving T-cell dysfunction, such as listeriosis, pneumocystosis, mycobacterial infections, and opportunistic fungal and viral infections. Prophylaxis or presumptive therapy should be initiated in the appropriate setting.

Analysis of Variance↗

Electrophysiological evidence against a neurotransmitter role of corticotropin-releasing hormone (CRH) in primary somatosensory cortex.

The possible neurotransmitter role of corticotropin-releasing hormone (CRH) was studied in the primary somatosensory cortex of the rat. Electrical activity of single neurones was recorded in layers II-VI of cortex, and in the region of the locus coeruleus. Iontophoresis and pressure ejection were employed to locally apply CRH, and changes in spontaneous, synaptically driven and iontophoretically driven firing were examined. In the cortex, of 62 neurones recorded most (51) were completely unaffected by high and prolonged current/pressure ejections of CRH. Depression of firing was occasionally seen (8 of 62), while a very few (3) were weakly excited. Of 25 cells studied with vibrissal stimulation to evoke excitatory synaptic responses, responses in two cells were depressed and in two they were enhanced. Activity that was evoked by iontophoretic ejection of excitatory amino acids, such as glutamate, was depressed in 6 of 40 cells (none were enhanced). Such effects as were seen were weak and often difficult to reproduce. The effect of CRH on depressions produced by GABA was also tested in four experiments. No effects on the amplitude or duration of the depressions were observed. In contrast recordings made in the midbrain, in the region of the locus coeruleus, resulted in over half the neurones (11 of 20) showing clear reproducible excitatory responses to CRH applications. Solutions used in the experiments were analysed using chromatography, radioimmunoassay and bioassay, and no significant degradation of the peptide was found compared with the synthetic standard (CRH (1-41)). The data provide evidence against CRH acting as a neurotransmitter or modulator in primary cortex, suggesting that the CRH which is localized in certain types of cortical cells is involved in other processes.

Animals↗

Quantitative coronary angiographic and intravascular ultrasound assessment of a new nonarticulated stent: report from the Advanced Cardiovascular Systems MultiLink stent pilot study.

OBJECTIVES: The purpose of this study was to evaluate the safety, feasibility, optimal deployment technique and 1-year clinical outcome for the Advanced Cardiovascular Systems (ACS) MultiLink stent. BACKGROUND: Optimal stent deployment assessed by quantitative coronary angiography and intravascular ultrasound (IVUS) is associated with improved clinical outcome. METHODS: Forty-nine consecutive patients with a discrete stenosis in a native coronary artery 3 to 4 mm in diameter were treated with the new, balloon-expandable ACS MultiLink stent. Stent expansion was assessed in all patients using quantitative coronary angiography and serial IVUS imaging after 8-, 12- and 16-atm inflations. Clinical follow-up was obtained at 30 days and 1 year. RESULTS: All 49 patients had successful placement of a MultiLink stent without death, emergency coronary artery bypass graft surgery or Q wave myocardial infarction. After placement of the MultiLink stent, the minimal lumen diameter increased from 1.24 to 2.98 mm (p < 0.001), and diameter stenosis decreased from 61% to 7% (p = 0.001). Minimal lumen cross-sectional area by IVUS increased progressively after 8, 12 and 16 atm (5.6 to 6.8 to 7.4 mm2, respectively, p < 0.001). However, only 64% of stents achieved a lumen/reference area ratio > or = 70%. No adverse clinical events occurred by 30 days, and by 1 year only one patient (2.0%) required revascularization of the stented artery. CONCLUSIONS: Treatment of stenoses in native coronary arteries with the MultiLink stent is associated with a high success rate and a low incidence of adverse events by 1 year, despite the fact that the majority of stents did not meet IVUS-defined criteria for "optimal stenting" derived from first-generation devices.

Aged↗

Dihydropyrimidine dehydrogenase pharmacogenetics in Caucasian subjects.

AIMS: Dihydropyrimidine dehydrogenase (DPD) catalyses the reduction of pyrimidines, including the anticancer agent 5-fluorouracil (5FU). Impaired 5FU degradation, through low DPD activity, has led to severe, life-threatening or fatal toxicity after administration of 5FU. Complete DPD deficiency is associated with the inherited metabolic disease thymine uraciluria. Several mutations in the gene encoding DPD have recently been identified, but the phenotype-genotype concordance of these alterations in the general population has not been reported. METHODS: Mononuclear cells were isolated from whole blood and DPD activity was determined after ex vivo incubation with 14C-5FU followed by h.p.1.c. analysis of 5FU metabolites. Analysis of mutations in the DPD gene at an exon splice site, codons 534, 543, and 732, and a deletion at base 1897 (deltaC1897) were performed in 30 subjects with the lowest and 30 subjects with the highest enzyme activity using PCR-RFLP. RESULTS: DPD activity was measured in 226 Caucasian subjects and was highly variable (range 19.1-401.4 pmol min(-1)mg(-1) protein). Mutations were frequently observed at codons 543 (allele frequency 28%), 732 (allele frequency 5.8%), and 534 (allele frequency 0.8%), but were not associated with low DPD activity. There were no splice site or deltaC1897 mutations found in this population. CONCLUSIONS: The five mutations analysed in this study are insufficient for identification of patients at risk for 5FU toxicity or thymine uraciluria. Both the splice site mutation and deltaC1897 are relatively rare in the general Caucasian population. Therefore, identification of further molecular alterations is required to facilitate the use of DPD analysis in genetic diagnosis and cancer therapeutics.

Alleles↗

Peri-operative dysrhythmias in patients undergoing major vascular surgery--a preliminary report.

The objective of this prospective study was to determine the nocturnal/diurnal distribution of peri-operative cardiac dysrhythmias in patients with coronary artery disease undergoing major vascular surgery. Eight patients with significant coronary artery disease undergoing major vascular surgery were studied. Continuous Holter monitoring was performed on each patient from approximately 1 h pre-operatively until 2-5 days post-operatively. Frequencies of isolated supraventricular and ventricular premature beats, and runs of supraventricular and ventricular premature beats were calculated for 6-h periods (00.00-06.00; 06.00-12.00; 12.00-18.00; 18.00-24.00 hours). Supraventricular tachycardia occurred significantly more frequently between 00.00 and 06.00 hours than during the other 6-h periods studied in the post-operative period following major vascular surgery.

Aged↗

Increased nuclear traffic chaos in hyphae of Aspergillus nidulans: molecular characterization of apsB and in vivo observation of nuclear behaviour.

Filamentous fungi are model microorganisms for studying nuclear migration in eukaryotic cells. Two genes, apsA and apsB (=anucleate primary sterigmata), were identified in Aspergillus nidulans that affect nuclear distribution in hyphae and specifically block conidiophore development at the metula stage when mutant. Here we describe the cloning, sequencing and molecular analysis of apsB. The gene encodes a 121 kDa coiled-coil, hydrophilic protein that was localized in the cytoplasm. No protein-protein interaction was detected between ApsB and ApsA, a membrane-associated, previously identified protein. An apsB null mutant was characterized by video epifluorescence microscopy using strains that express green fluorescent protein (GFP) in nuclei. With this novel approach, we have discovered a new mutant phenotype and have found that nuclei display an increased chaotic movement in older hyphal compartments that results in clustering and an uneven distribution of these organelles. These results suggest a regulatory role of ApsB in nuclear migration.

Amino Acid Sequence↗

Evaluation of semen from individual male domestic fowl by assessment of sperm: perivitelline interaction in vitro and in vivo.

1. Spermatozoa in semen samples from 8 individual male domestic fowls were shown to have a differential and characteristic ability to hydrolyse holes in the inner perivitelline layer from laid eggs in an in vitro assay. 2. The number of holes produced by samples of spermatozoa per unit area of inner perivitelline layer in vitro was linearly correlated with sperm ATP content (r = 0.85) and motility (r = 0.76). 3. The number of holes formed in the inner perivitelline layer in vitro was also linearly correlated with the numbers of holes formed in the inner perivitelline layer of eggs fertilised in vivo, in inseminated hens (r = 0.90); and was correlated logarithmically with the proportion of fertile eggs laid by these hens.

Animals↗