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Biomedical subjects

C Robertson

Publications and source records attributed to C Robertson.

At least 109 records · Page 6Linked to original sources
PubMed1999

Effect of tamoxifen on lipoprotein(a) and insulin-like growth factor-I (IGF-I) in healthy women.

Studies in breast cancer patients have shown that tamoxifen decreases circulating levels of lipoprotein(a) (Lp(a)), an independent risk factor for premature coronary heart disease, and insulin-like growth factor-I (IGF-I), a promising surrogate biomarker for breast cancer. Since a common hormone regulatory pathway has been suggested for both biomarkers, we measured Lp(a) levels for 6 months in 68 healthy women participating in a chemoprevention trial of tamoxifen and correlated its changes with IGF-I. After 1 month, mean Lp(a) levels decreased by 23% with tamoxifen and increased by 6% with placebo (P = 0.033). No further change was observed after 2 and 6 months. Women with abnormal values at baseline (i.e. > 30 mg/dl) showed the highest reduction. The mean levels of IGF-I decreased by 23.5% with tamoxifen and remained stable with placebo, but the changes induced by tamoxifen in Lp(a) and IGF-I levels were uncorrelated. Our results support the observation that tamoxifen may be a suitable preventive option for women with multiple disease risk factors.

Adult↗
PubMed1999

Prediction of response to primary chemotherapy for operable breast cancer.

The use of primary systemic cytotoxics leads to a high remission rate in patients with breast cancer. Response was identified as an important variable associated with survival. Thus, features which predict response, are potentially relevant for planning treatments and improving survival. Retrospectively, we investigated several histopathological features (expression of oestrogen and progesterone receptors, Mib1, bcl-2, c-erbB-2, and p53) prior to two programmes of either sequential preoperative chemotherapy (doxorubicin plus cyclophosphamide) and radiotherapy (Group A), or preoperative chemotherapy (5-fluorouracil, folinic acid and vinorelbine) alone (Group B) in patients with operable breast cancer. After three courses, patients with a partial or complete response were given a further three courses, which was followed for patients in Group A by radiotherapy 50 Gy plus a boost of 10 Gy. All patients were submitted to surgery after completion of preoperative treatment and pathology material from 73 patients (median age, 49 years, range, 30-70; performance status, 0-1; 68 T2, 5 T3) was obtained. The overall response rate according to radiological and clinical evaluation was 59% (68% for Group A and 49% for Group B). 12 of 14 patients with p53-positive tumours and 31 of 59 with p53-negative tumours responded (P = 0.04). 6 of 7 patients with elevated c-erbB-2 had a response compared with 37 of 66 patients in the group with c-erbB-2 negative tumours (P = 0.03). Mib1 expression decreased substantially (> or = 50%) in 25 patients during treatment, of whom 20 responded compared with 21 of 48 patients with a lower decrease (P = 0.04). Response was observed in 28 of 37 patients with high baseline Mib1 (> 20%) and in 15 of 36 patients in the low Mib1 group (P = 0.05). Finally, 32 of 44 tumours with low expression of progesterone receptors responded compared with 11 of 29 tumours with high receptors expression (P = 0.05). These markers might be useful for tailoring primary and postsurgical systemic treatments.

Adult↗
PubMed1999

Larynx cancer in Slovakia and the role of anatomical subsites.

During the time period 1968-92, 6958 laryngeal cancers (6602 in men and 356 in women) were diagnosed in Slovakia and notified to the National Cancer Registry. We analysed long-term trends in incidence, mortality and survival. Mortality and incidence rates in Slovakian men rose rapidly until 1980 and more slowly subsequently. The mortality-to-incidence ratio initially was 40% and increased to 70% in the period 1985-88. A log-linear model showed that the more recent generations experienced the slowest increase in incidence. Incidence and mortality rates in women remained stable and did not exceed 1 per 100,000. The 5-year survival probability from invasive larynx cancer was 47%. Survival rates had shown no particular trend by year and age at diagnosis. The main finding was that 5-year survival from supraglottis cancer is 20% poorer than survival from glottis cancer. Supraglottis is the prevalent larynx subsite in countries with high larynx, oropharynx and oesophagus incidence rates. This supports the hypothesis that supraglottis cancer is more strongly linked to a synergistic effect of smoking and alcohol than glottis cancer.

Alcohol Drinking↗
PubMed1999

The views and outcomes of consenting and non-consenting patients receiving ECT.

BACKGROUND: Current mental health legislation in the UK makes provision for the use of certain treatments in severely ill patients who are unable, or unwilling, to give informed consent. Under the terms of this legislation, electroconvulsive therapy (ECT) may be used, usually to treat severely depressed patients. A number of organizations have challenged this practice, stating that ECT should only be given with fully informed consent: it has been implied that patients receiving compulsory ECT (given without the patient's consent, under the terms of mental health legislation) find the treatment damaging and unhelpful. METHODS: A series of 150 patients receiving ECT in Aberdeen was studied. A proportion of the series (approximately 7%) received compulsory ECT. The views and treatment outcomes of compulsory patients were compared with those of patients giving informed consent for treatment. RESULTS: More than 80% of patients in both consenting and compulsory groups considered ECT to have helped them. Clinical outcome did not differ between the groups. Patients' views showed marked concordance with independent medical evaluation of outcome. CONCLUSIONS: Outcome following ECT in non-consenting patients is equivalent to that seen in consenting patients whether rated by the patients themselves or by clinicians. Overall outcome is good, with more than 80% of patients benefiting from treatment. A ban on compulsory ECT would deny the access of seriously ill patients to an effective and acceptable treatment.

Adult↗
PubMed1999

A comprehensive assessment of satisfaction with care: preliminary psychometric analysis in an oncology institute in Italy.

BACKGROUND: Little is known about patients' perception of the quality of the care they receive in oncology hospitals. We developed a 61-item comprehensive assessment of satisfaction with care (CASC) to evaluate the competence of hospital physicians and nurses, as well as aspects of care organisation and hospital environment. The aims of this study were to define the structure of the CASC and assess the internal consistency and convergent and discriminant validity of its scales. PATIENTS AND METHODS: Three hundred ninety-five consecutive cancer patients discharged from an oncology institute in Italy were asked to complete the CASC at home and return it in a self-addressed envelope. RESULTS: Two percent of the patients refused to participate and 25% failed to return the questionnaire. Separate factor analyses of the CASC sub-scales disclosed the perceived extent of doctors' and nurses' availability, coordination, human quality, technical competence, provision of psychosocial care and information, as well as the patients' general satisfaction, perception of the organisation of their care, access and comfort. Multi-trait scaling analysis was carried out on item-grouping resulting from factor analyses. High levels of internal consistency and convergent validity were obtained but discriminant validity could be improved. CONCLUSIONS: Results of present psychometric testing of the CASC forecast adequate properties. This will be confirmed by repeating these analyses in a cross-cultural setting.

Adult↗
PubMed1999

Secretory leukocyte proteinase inhibitor is preferentially increased in patients with acute respiratory distress syndrome.

Inappropriate release of proteases from inflammatory and stromal cells can lead to destruction of the lung parenchyma. Antiproteinases such as alpha-1-proteinase inhibitor (alpha1-Pi), secretory leukocyte proteinase inhibitor (SLPI) and elastase-specific inhibitor (elafin) control excess production of human neutrophil elastase. In the present study, the concentrations of alpha1-Pi, SLPI and elafin found in bronchoalveolar lavage (BAL) fluid from control subjects, patients at risk of developing acute respiratory distress syndrome (ARDS) and patients with established ARDS were determined. Levels of all three inhibitors were raised in patients compared with normal subjects. SLPI was increased in the group of patients who were at risk of ARDS and went on to develop the condition, compared with the "at-risk" group who did not progress to ARDS (p=0.0083). Alpha1-Pi and elafin levels were similar in these two populations. In patients with established ARDS, both alpha1-Pi and SLPI levels were significantly increased, compared to patients at risk of ARDS who did (p=0.0089) or did not (p=0.0003) progress to ARDS. The finding of increased antiproteinases shortly before the development of acute respiratory distress syndrome provide further evidence for enhanced inflammation prior to clinical disease.

Bronchoalveolar Lavage Fluid↗
PubMed1999

Simultaneous modelling of time trends and regional variation in mortality rates.

BACKGROUND: We seek to model the regional component of the variance in the mortality rates in the UK and to ascertain if there is evidence that this regional variance is increasing in recent periods. METHODS: Age Period Cohort (APC) models, based on the local 'curvatures', are used in each region to describe the changes in the trends in the mortality rates. This is extended to a multilevel model to estimate the regional component of the variance in the rates and to estimate the effect of regional differences in the trends in the rates. We show how the use of a multilevel APC model can help to distinguish the cohort and period trends in the mortality rates from the cohort and period effects on the regional variance in these rates. RESULTS: For both sexes, but particularly for females, a reduction in the rate of decrease in mortality was found around 1960. In addition, particularly for females, cohorts born after 1930 appear to show reductions in mortality at an increased rate. It is demonstrated that there is evidence that the between-region variation in the rates has not remained constant and that it is much less now than it was at the beginning of the data series. Further, there is evidence that the trends in the rates are not the same in all regions and that while there is a convergence of the rates in many regions, Scotland, in particular, stands out as a region which contributes most to the regional variation in mortality rates. CONCLUSION: Evidence of regional variation in mortality rates has been found with a suggestion of a decrease over the period of the study though with some stability since 1951.

Adolescent↗
PubMed1999

Psychological distress in cancer patients attending the European Institute of Oncology in Milan.

BACKGROUND: The determination of the extent and specific features of the psychological distress to be expected in a cancer centre may influence the choice of interventions to be implemented for addressing these problems. This study was aimed at estimating the prevalence of psychological distress in patients attending a second reference cancer centre in Milan (Italy), and at identifying associated factors. PATIENTS AND METHODS: 190 consecutive patients were assessed within 3 days of hospital discharge using the Hospital Anxiety and Depression Scale. RESULTS: Major depressive disorders or generalised anxiety disorders were estimated in 16% of the patients. Only 2 of these patients were referred to the psycho-oncology unit, hence the psychological distress of many patients was not considered during their hospital stay. In the multiple regression analysis, independent predictors of psychological distress were female gender, experience of disturbance in family and social life due to illness, nausea and vomiting, and perception of being in a poor state of health (R(2) = 0.31, p value < 0.001), while physical functioning, fatigue and pain, significant factors in univariate analysis (p < 0. 05), sociodemographic and clinical factors were not predictors. CONCLUSIONS The psycho-oncology team should focus on helping doctors and nurses identify the patients' psychological problems, dealing with them or making a referral.

Adult↗
PubMed1999

Effect of blood tamoxifen concentrations on surrogate biomarkers in a trial of dose reduction in healthy women.

PURPOSE: Tamoxifen administered at 20 mg/d has been shown to decrease breast cancer incidence in at-risk women by 50%, but toxicity may limit its broad use, particularly in postmenopausal women. Because toxicity may be dose-dependent, we studied the biologic activity of low concentrations of tamoxifen to determine the plausibility of a dose reduction. PATIENTS AND METHODS: We measured the blood concentrations of tamoxifen and its main metabolites in a dose titration study in 105 healthy women (placebo, tamoxifen 10 mg on alternate days, tamoxifen 10 mg/d, and tamoxifen 20 mg/d). Drug levels measured after 2 months of treatment were correlated with the changes in surrogate biomarkers of different diseases, including lipid profile, blood cell count, fibrinogen, antithrombin III, osteocalcin, and insulin-like growth factor I, a promising surrogate biomarker of breast cancer. RESULTS: The means (+/- SD) for tamoxifen and N-desmethyltamoxifen (metabolite X) concentrations (ng/mL) were dose-related, being, respectively, 0 and 0 with placebo, 26.8 +/- 15.1 and 43.7 +/- 22.5 with 10 mg every other day, 51.2 +/- 24.1 and 90.7 +/- 48.0 with 10 mg/d, and 136.0 +/- 52.7 and 230.6 +/- 75.0 with 20 mg/d of tamoxifen. At variance, the biomarker changes were of comparable magnitude at any drug concentration except for platelet count and triglycerides levels, the latter showing a trend to an increase with increasing tamoxifen concentrations. CONCLUSION: An 80% reduction in blood concentrations does not seem to affect the activity of tamoxifen on biomarkers of cardiovascular or breast cancer risk and may in fact have a more favorable safety profile. Additional studies are warranted to determine the most appropriate dose of this agent.

Antineoplastic Agents, Hormonal↗
PubMed1998

Double-blind, placebo-controlled trial to assess the efficacy and tolerability of mepartricin in the treatment of BPH.

BACKGROUND: Mepartricin, a semisynthetic polyene derivative with a favorable effect on urethro-prostatic function, was clinically evaluated, adopting the diagnostic and research criteria recommended by the First International Consultation on BPH. METHODS: A multicenter, randomized, double-blind, parallel-group study compared mepartricin 40 mg/daily to placebo in the treatment of 196 patients with newly diagnosed BPH and mild-to-moderate symptomatology. International Prostate Symptom Score (I-PSS), quality of life (QoL) index and maximum urinary flow-rate (Qmax) were determined every 4 weeks for 6 months; postvoiding volume, prostate volume, and prostate-specific antigen (PSA) were assessed after 3 and 6 months of therapy. RESULTS: Mepartricin was shown to determine a statistically significant improvement over placebo in I-PSS and QoL index from month 2 onwards, and a significant linear increase in Qmax over the study period. At month 6, the improvement in the mepartricin and placebo groups in I-PSS, QoL index, and Qmax was 6.3 (standard error (SE) 0.51) and 4.2 (SE 0.60) points (P = 0.003), 0.99 (SE 0.14) and 0.62 (SE 0.12) points (P = 0.036), and 2.7 (SE 0.46) and 1.2 (SE 0.46) ml/sec (P = 0.051), respectively. No significant differences were noted in postvoiding residual volume, prostate volume, or PSA. Mepartricin tolerability was good, showing no adverse events on sexual function. CONCLUSIONS: Mepartricin proved to be an effective treatment of benign prostatic hyperplasia, determining an improvement in symptoms, quality of life, and peak urinary flow.

Aged↗
PubMed1998

Biologic activity of tamoxifen at low doses in healthy women.

BACKGROUND: Results of a clinical trial recently completed in the United States indicate that administration of tamoxifen (20 mg/day) to women at risk can reduce breast cancer incidence by approximately 50% but is associated with an increased risk of developing endometrial cancer and venous thromboembolic events. Since these adverse effects may be dose related, we investigated the effect of tamoxifen on several biomarkers when the drug was given at doses lower than those currently in use. METHODS: In two sequential experiments, 127 healthy hysterectomized women aged 35-70 years were randomly assigned to one of the following four treatment arms: placebo (n = 31) or tamoxifen at 20 mg/day (n = 30) (first experiment); or tamoxifen at 10 mg/day (n = 34) or tamoxifen at 10 mg/ alternate days (n = 32) (second experiment). Baseline and 2-month measurements of the following parameters were compared: 1) total cholesterol (primary end point) and other surrogate markers of cardiovascular disease, e.g., low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, and lipoprotein(a); 2) blood cell count; 3) fibrinogen; 4) antithrombin III; 5) osteocalcin; and, 6) in a subgroup of 103 women, insulin-like growth factor-I (IGF-I), a possible surrogate marker for breast cancer. RESULTS: After adjustment for the baseline values, there were reductions in circulating levels of total cholesterol and IGF-I of the same magnitude in all three tamoxifen treatment arms. A similar pattern was observed for most of the other parameters. In the placebo arm, fibrinogen level, which showed a decrease, was the only parameter exhibiting change. CONCLUSIONS: Up to a 75% reduction in the conventional dose of tamoxifen (i.e., 20 mg/day) does not affect the activity of the drug on a large number of biomarkers, most of which are surrogate markers of cardiovascular disease. This study was hypothesis generating, and larger studies are warranted to assess the efficacy of tamoxifen at low doses.

Adult↗
PubMed1998

The role of N-acetylation polymorphisms in smoking-associated bladder cancer: evidence of a gene-gene-exposure three-way interaction.

Arylamines are known bladder carcinogens and are an important constituent of tobacco smoke. The handling of arylamines in the body is complex and includes metabolism by NAT1 and NAT2, enzymes that play a role in both activation and detoxification of arylamines and their congeners. Both NAT1 and NAT2 are polymorphic, with alleles that have been shown to correlate with higher or lower enzyme activity. To explore the combined role of these genes and exposure on bladder cancer risk, we examined the NAT1 and NAT2 genotype in a case-control study of bladder cancer in which detailed exposure histories were available on all 230 cases and 203 frequency-matched controls. Using PCR-RFLP genotyping, we determined NAT2 genotype for the five most common alleles, NAT2*4, NAT2*5, NAT2*6, NAT2*7, NAT2*14 (frequently referred to as WT, M1, M2, M3, and M4, respectively). Similarly, the NAT1 genotype was determined for the four most common alleles NAT1*3, NAT1*4, and NAT1*11, and the putative high-activity allele, NAT1*10. No association between NAT2 genotype and bladder cancer risk was found whether genotype was considered alone or in combination with smoking, in either stratified or logistic regression analysis that adjusted for age, sex, and race. Stratified and logistic regression analysis both demonstrated an increased risk for individuals carrying the NAT1*10 allele among smokers. There was evidence of a gene-dosage effect, such that those who were homozygous for the NAT1*10 allele had the highest risks. There was also evidence of a statistically significant gene-environment interaction, such that bladder cancer risk depends on both NAT1 genotype and smoking exposure. Interestingly, although NAT2 genotype did not influence risk either alone or in combination with smoking exposure, there was evidence of a statistically significant gene-gene-environment three-way interaction. Bladder cancer risk from smoking exposure is particularly high in those who inherit NAT2 slow alleles in combination with one or two copies of the NAT1*10 allele. A biological mechanism for this finding is suggested.

Acetylation↗
PubMed1998

Prevention of breast cancer with tamoxifen: preliminary findings from the Italian randomised trial among hysterectomised women. Italian Tamoxifen Prevention Study.

BACKGROUND: Tamoxifen is a candidate chemopreventive agent in breast cancer, although the drug may be associated with the development of endometrial cancer. Therefore we did a trial in hysterectomised women of tamoxifen as a chemopreventive. METHODS: In October, 1992, we started a double-blind placebo-controlled, randomised trial of tamoxifen in women (mainly in Italy) who did not have breast cancer and who had had a hysterectomy. Women were randomised to receive tamoxifen 20 mg per day or placebo, both orally for 5 years. The original plan was to follow the intervention phase by 5 years' follow-up. In June, 1997, the trialists and the data-monitoring committee decided to end recruitment primarily because of the number of women dropping out of the study. Recruitment ended on July 11, 1997, and the study will continue as planned. The primary endpoints are the occurrence of and deaths from breast cancer. This preliminary interim analysis is based on intention-to-treat. FINDINGS: 5408 women were randomised; participating women have a median follow-up of 46 months for major endpoints. 41 cases of breast cancer occurred so far; there have been no deaths from breast cancer. There is no difference in breast-cancer frequency between the placebo (22 cases) and tamoxifen (19) arms. There is a statistically significant reduction of breast cancer among women receiving tamoxifen who also used hormone-replacement therapy during the trial: among 390 women on such therapy and allocated to placebo, we found eight cases of breast cancer compared with one case among 362 women allocated to tamoxifen. Compared with the placebo group, there was a significantly increased risk of vascular events and hypertriglyceridaemia among women on tamoxifen. INTERPRETATION: Although this preliminary analysis has low power, in this cohort of women at low-to-normal risk of breast cancer, the postulated protective effects of tamoxifen are not yet apparent. Women using hormone-replacement therapy appear to have benefited from use of tamoxifen. There were no deaths from breast cancer recorded in women in the study. It is essential to continue follow-up to quantify the long-term risks and benefits of tamoxifen therapy.

Adult↗
PubMed1998

Age-period-cohort analysis of chronic disease rates. I: Modelling approach.

Age-Period-cohort models are widely used by epidemiologists to analyse trends in disease incidence and mortality. The interpretation of such models is fraught with difficulty in view of the exact linear dependency between the three variables. It is the purpose of this paper to review, compare and contrast some of the more common approaches to this problem based on Poisson regression and a linear model for the log rates. Also the results of using the different approaches on a single series of data on breast cancer incidence among females in Scotland from 1960-1989 are presented for comparison. Recommendations as to the merits and drawbacks of the approaches are also given in the conclusions. Models which are based upon the estimable contrasts such as local curvatures and deviations from linearity are most suitable.

Adolescent↗
PubMed1998

Age-period-cohort models of chronic disease rates. II: Graphical approaches.

In a companion article we have reviewed a number of available modelling approaches employed in estimating the influence of age, period and cohort effects on chronic disease rates. Here we review some of the graphical methods for displaying disease rates with a view to extracting information about the separate and joint effects of age, period and cohort. The more traditional displays such as line charts are compared to approaches based on smoothing and two- and three-dimensional plots which have recently been proposed. Other graphical techniques which are principally concerned with displaying interactions, such as biplots and correspondence analysis, are also considered. These techniques are illustrated with examples to compare the techniques revealing their strengths and weaknesses. It is clear that graphical approaches can be useful tools in understanding the behaviour of chronic disease time trends.

Adult↗
PubMed1998

Age at any birth and breast cancer risk.

This paper reviews previously published models of the effect of parity and age at any birth on breast cancer risk. It is shown that these models are conceptually similar and can be written within a general model. Various restrictions on the parameters of the general model yield the specific models. The models are applicable in case control studies and are illustrated using data from a case control study of breast cancer in Italy.

Age Factors↗
PubMed1998

Similar decreases in local tumor control are calculated for treatment protraction and for interruptions in the radiotherapy of carcinoma of the larynx in four centers.

PURPOSE: Data on patients with cancer of the larynx are analyzed using statistical models to estimate the effect of gaps in the treatment time on the local control of the tumor. METHODS AND MATERIALS: Patients from four centers, Edinburgh, Glasgow, Manchester, and Toronto, with carcinoma of the larynx and treated by radiotherapy were followed up and the disease-free period recorded. In all centers the end point was control of the primary tumor after irradiation alone. The local control rates at > or = 2 years, Pc, were analyzed by log linear models, and Cox proportional hazard models were used to model the disease-free period. RESULTS: T stage, nodal involvement, and site of the tumor were important determinants of the disease-free interval, as was the radiation schedule used. Elongation of the treatment time by 1 day, or a gap of 1 day, was associated with a decrease in Pc of 0.68% per day for Pc = 0.80, with a 95% confidence interval of (0.28, 1.08)%. An increase of 5 days was associated with a 3.5% reduction in Pc from 0.80 to 0.77. At Pc = 0.60 an increase of 5 days was associated with an 7.9% decrease in Pc. The time factor in the Linear Quadratic model, gamma/alpha, was estimated as 0.89 Gy/day, 95% confidence interval (0.35, 1.43) Gy/day. CONCLUSIONS: Any gaps (public holidays are the majority) in the treatment schedule have the same deleterious effect on the disease free period as an increase in the prescribed treatment time. For a schedule, where dose and fraction number are specified, any gap in treatment is potentially damaging.

Carcinoma↗