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Biomedical subjects

R Pugh

Publications and source records attributed to R Pugh.

At least 19 recordsLinked to original sources
PubMed2000

Estrogen receptor (ER) and progesterone receptor (PgR), by ligand-binding assay compared with ER, PgR and pS2, by immuno-histochemistry in predicting response to tamoxifen in metastatic breast cancer: a Southwest Oncology Group Study.

Results of estrogen receptor (ER) and progesterone receptor (PgR) ligand-binding assays (LBAs) are strongly correlated with ER and PgR by immuno-histochemistry (IHC). To investigate whether ER and PgR by IHC are also strongly correlated with tamoxifen response, time to treatment failure (TTF) and overall survival (OS), the results of the 2 methods were directly compared in 205 patients with ER(+) metastatic breast cancer treated with daily tamoxifen (Southwest Oncology Group protocol 8228) with 9 years median follow-up. pS2, another estrogen-regulated molecule, was also analyzed. Tumors were scored for IHC from 0 to 5, according to the proportion of positively stained cells. These IHC scores for both ER and PgR were significantly associated with LBA levels (p < 0.001). There was a significant direct relationship between higher IHC ER, PgR and pS2 and increasing response to tamoxifen. TTF and OS were also significantly longer for patients with higher ER or PgR, but not pS2, IHC scores. Low, intermediate and high ER or PgR categories showed similar differences in response rates whether defined by LBA or IHC. In logistic regression models which included ER, PgR and pS2 by IHC; ER and PgR by LBA; and menopausal status, only ER (IHC) and pS2 (IHC) retained significance for predicting tamoxifen response (p = 0. 02 and p = 0.005, respectively), along with menopausal status (for PgR by IHC, p = 0.09). Increasing ER and PgR by IHC, as by LBA, are thus significantly associated with a progressively better response and longer survival in ER(+) metastatic breast cancer. pS2 is also predictive in this setting.

Antineoplastic Agents, Hormonal↗
PubMed1998

A comparison of artificial saliva and pilocarpine in the management of xerostomia in patients with advanced cancer.

This was a crossover study comparing a mucin-based artificial saliva (Saliva Orthana) and pilocarpine hydrochloride (Salagen) in the management of xerostomia in patients with advanced cancer. The pilocarpine was found to be more effective than the artificial saliva in terms of mean change in visual analogue scale scores for xerostomia (P = 0.003). Furthermore, more patients reported that it had helped their xerostomia, and more patients wanted to continue with it after the study. However, the pilocarpine was found to be associated with more side-effects than the artificial saliva (P < 0.001). These side-effects were usually reported as being mild. Of the patients who used both treatments, 50% preferred the artificial saliva, and 50% preferred the pilocarpine. The commonest reason for preferring the artificial saliva was the fact that it was a spray, rather than a tablet.

Adult↗
PubMed1998

HER-2 expression and response to tamoxifen in estrogen receptor-positive breast cancer: a Southwest Oncology Group Study.

HER-2/neu is a growth factor receptor, the expression of which has been associated with a more aggressive breast tumor biology and resistance to some types of chemotherapy. Preliminary laboratory and clinical data have led to claims that HER-2/neu expression is also associated with resistance to tamoxifen. Therefore, to test the hypothesis that HER-2/neu expression is associated with a poorer response to tamoxifen, a shorter time to treatment failure (TTF), and worse survival in estrogen receptor (ER)-positive metastatic breast cancer, we examined 205 paraffin-embedded blocks of tumors from patients enrolled on Southwest Oncology Group 8228 for HER-2/neu expression. Tumors were ER positive (ER level > 3 fmol/mg cytosolic protein in either primary tumors or metastases), and patients had not received any prior therapy for metastatic disease. All patients were treated with daily tamoxifen. The study began in 1982, and median follow-up of patients who are still alive is now 9 years. Membrane staining for HER-2/neu was evaluated by immunohistochemistry using antibody TAB 250 and was scored according to the proportion of cells staining positive; tumors were deemed positive if > 1% of the cells stained for HER-2/neu. HER-2/neu positivity was associated with lower ER values (P = 0.04) and low bcl-2 (P = 0.01). HER-2/neu positivity was not significantly associated with response rate (negative versus positive, 57 versus 54%; P = 0.67), TTF (median, 8 versus 6 months; P = 0.15), or survival (median, 31 versus 29 months; P = 0.36). There was also no significant evidence of a progressive relationship between an increasing proportion of cells expressing HER-2/neu and a shorter TTF or survival. HER-2/neu expression in ER-positive metastatic breast cancer is not significantly associated with a poorer response to tamoxifen or a more aggressive clinical course. Earlier suggestions to the contrary may have been due to failure to rigorously exclude ER-negative tumors, which are much less likely to respond to tamoxifen and more likely to have high HER-2/neu levels.

Adult↗
PubMed1998

Heat shock proteins hsp27 and hsp70: lack of correlation with response to tamoxifen and clinical course of disease in estrogen receptor-positive metastatic breast cancer (a Southwest Oncology Group Study).

In this study, we tested the hypothesis that heat shock proteins (hsps) 27 and 70 are associated with clinical resistance to tamoxifen. hsp27 is, like progesterone receptor, an estrogen-regulated protein. hsp70 is also of interest because of its interaction with estrogen receptors and because hsp70 is a component of the molecular chaperone machinery functioning in the assembly and trafficking of steroid receptors. In addition, hsps in general help protect cells against noxious stimuli and stress, and their expression has been linked to drug resistance. The study involved 205 tumors from estrogen receptor-positive tamoxifen-treated breast cancer patients with metastatic disease. All patients received daily tamoxifen as initial therapy for metastatic disease. The study began in 1982, and follow-up is now 9 years. hsp27 and hsp70 were detected by immunohistochemistry and scored according to the nuclear and/or cytoplasmic content. Expression of hsp27 or hsp70 was unrelated to estrogen receptor content, progesterone receptor content, menopausal status, age, and presence of visceral disease. Cytoplasmic and nuclear hsp27 positivities were weakly and inversely related to each other (P = 0.05). There was a significant association between cytoplasmic hsp27 and cytoplasmic hsp70 content (P < 0.001), as well as between nuclear hsp70 and nuclear hsp27 content (P = 0.001). Cytoplasmic and nuclear hsp70 were also associated (P = 0.02). However, increased hsp27 and hsp70 expression (nuclear or cytoplasmic) was not significantly associated with response to tamoxifen, time to treatment failure, or survival. Thus, this study clarifies the lack of clinical utility of hsp27 and hsp70 in predicting the response to tamoxifen in an estrogen receptor-positive breast cancer population.

Adult↗
PubMed1997

Increased intensification and total dose of cyclophosphamide in a doxorubicin-cyclophosphamide regimen for the treatment of primary breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-22.

PURPOSE: The National Surgical Adjuvant Breast and Bowel Project (NSABP) initiated a randomized trial (B-22) to determine if intensifying but maintaining the total dose of cyclophosphamide (Cytoxan, Bristol-Myers Squibb Oncology, Princeton, NJ) in a doxorubicin (Adriamycin, Pharmacia, Kalamazoo, MI)-cyclophosphamide combination (AC), or if intensifying and increasing the total dose of cyclophosphamide improves the outcome of women with primary breast cancer and positive axillary nodes. PATIENTS AND METHODS: Patients (N = 2,305) were randomized to receive either four courses of standard AC therapy (group 1); intensified therapy, in which the same total dose of cyclophosphamide was administered in two courses (group 2); or intensified and increased therapy, in which the total dose of cyclophosphamide was doubled (group 3). The dose and intensity of doxorubicin were similar in all groups. Disease-free survival (DFS) and overall survival were determined using life-table estimates. RESULTS: There was no significant difference in DFS (P = .30) or overall survival (P = .95) among the groups through 5 years. At 5 years, the DFS of women in group 1 was similar to that of women in group 2 (62% v 60%, respectively; P = .43) and to that of women in group 3 (62% v 64%, respectively; P = .59). The 5-year survival of women in group 1 was similar to that of women in group 2 (78% v 77%, respectively; P = .86) and to that of women in group 3 (78% v 77%, respectively; P = .82). Grade 4 toxicity increased in groups 2 and 3. Failure to note a difference in outcome among the groups was unrelated to either differences in amount and intensity of cyclophosphamide or to dose delays and intervals between courses of therapy. CONCLUSION: Intensifying or intensifying and increasing the total dose of cyclophosphamide failed to significantly improve either DFS or overall survival in any group. It was concluded that, outside of a clinical trial, dose-intensification of cyclophosphamide in an AC combination represents inappropriate therapy for women with primary breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

bcl-2, p53, and response to tamoxifen in estrogen receptor-positive metastatic breast cancer: a Southwest Oncology Group study.

PURPOSE: To test the hypothesis that high bcl-2 expression and accumulation of p53 protein, both of which should inhibit apoptosis, are associated with a poorer tamoxifen response and a more aggressive clinical course in estrogen receptor (ER)-positive metastatic breast cancer. METHODS: A total of 205 paraffin-embedded tumor blocks were evaluated for nuclear p53 (a marker of p53 inactivation) and cytoplasmic bcl-2 by immunohistochemistry (IHC). All patients received tamoxifen as initial therapy for metastatic disease. The study began in 1982 and follow-up duration of the 24 patients last known alive is 8 years. RESULTS: Response to tamoxifen and time to treatment failure (TTF) were not significantly associated with p53 status, although patients with higher p53 had a worse survival (P = .008; median, 36 v 20 months). Higher bcl-2 expression was associated with higher levels of ER (P = .02), better response to tamoxifen (62% v 49%; P = .07), longer TTF (median, 9 v 5 months; P = .002), and better survival (median, 40 months v 25 months; P = .009). In multivariate analyses, including ER, progesterone receptor (PgR), and p53, high bcl-2 remained significantly associated with a longer TTF (P = .007) and survival (P = .07). p53 status was a significant factor for shorter survival (P = .05), but not for TTF (P = .61). CONCLUSION: p53 status, as determined by IHC is not significantly associated with response to tamoxifen, although tumors with altered p53 protein are inherently more aggressive. Contrary to expectation, high bcl-2 identifies a relatively indolent phenotype of ER-positive metastatic breast cancer, in which patients experience a better clinical response to tamoxifen and a longer survival.

Adult↗
PubMed1997

Scottish general practice registrars--their views on psychotherapy training.

BACKGROUND: Psychological problems constitute between 10% and 30% of general practice workload. In 1993, the Royal Colleges of General Practitioners and Psychiatrists published guidelines on the psychiatric component of vocational training for general practice, recognizing the need for training in the psychological aspects of patient care and knowledge of the psychotherapies. Little is known as to how much these guidelines have been followed. AIM: To determine Scottish general practice registrars' views on whether the above training objectives had been met. METHOD: An anonymous self-report questionnaire was sent to all general practice registrars in west and south-east Scotland one month before the end of their trainee year with a 95% response rate. This provided basic descriptive information on the population surveyed and their attitudes to psychotherapy training. RESULTS: Altogether, 53% had spent time in psychiatry and half of these had had access to a consultant psychotherapist, but only 9% had been involved in using a psychological approach to treatment. A total of 51% disagreed that they had had enough psychotherapy experience, and 44% did not feel confident in assessing patients for psychotherapy, 15% saying that lack of knowledge would prevent them from referring patients. Of the whole sample, 88% felt that further psychotherapy training would be helpful. CONCLUSION: The majority of general practice registrars in Scotland did not feel that training objectives had been met regarding the attainment of skills in the psychotherapies.

Attitude of Health Personnel↗
PubMed1996

Tinnitus coping style and its relationship to tinnitus severity and emotional distress.

The structure of the Tinnitus Coping Style Questionnaire (TCSQ) is examined in a sample of 108 tinnitus sufferers. Factor analysis of the TCSQ items identified two coping styles that were termed "effective coping" and "maladaptive coping". It is shown that "maladaptive coping," but not "effective coping," is related to reports of subjective tinnitus severity and emotional distress. The clinical implications of these findings are discussed.

Adaptation, Psychological↗
PubMed1995

The relationship between locus of control, tinnitus severity, and emotional distress in a group of tinnitus sufferers.

One hundred and nine tinnitus sufferers attending a specialist out-patient clinic completed questionnaires assessing the following: locus of control of behaviour, anxiety (STAI), depression (BDI) and tinnitus severity. Anxiety and depression were found to be correlated with tinnitus severity, as was locus of control, with "internals" reporting their tinnitus to be less severe than "externals." Partial correlations indicated that locus of control did not directly affect tinnitus severity, but rather, this effect was mediated by the effect of locus of control on anxiety and depression.

Adult↗
PubMed1995

Patients' reports of the effect of alcohol on tinnitus.

One hundred chronic sufferers attending a tinnitus outpatient clinic completed self-report questionnaires assessing the quantity of alcohol they consumed weekly and its effect on tinnitus. The results showed a mixed effect of alcohol on tinnitus with 22% of the sample reporting that drinking worsened tinnitus, 62% reporting no effect of alcohol on tinnitus and 16% reporting that alcohol improved tinnitus. The reported effect of alcohol on tinnitus significantly influenced the reported change in the level of alcohol intake since tinnitus onset, with significantly more units of alcohol being consumed by those sufferers who reported that alcohol improved their tinnitus. However, for the sample as a whole, drinking behaviour was not significantly different to that of the general population.

Adult↗
PubMed1994

Estimating numbers of homeless and homeless mentally ill people in north east Westminster by using capture-recapture analysis.

OBJECTIVES: To use routinely collected data to provide a reliable estimate of the size and psychiatric morbidity of the homeless population of a given geographical area by using capture-recapture analysis. DESIGN: A multiple sample, log-linear capture-recapture method was applied to a defined area of central London during 6 months. The method calculates the total homeless population from the sum of the population actually observed and an estimate of the unobserved population. Data were collected from local agencies used by homeless people. SUBJECTS: Homeless people in north east Westminster residing in bed and breakfast accommodation and hotels or sleeping rough who had contacted statutory or voluntary agencies in the area. RESULTS: 2150 contacts by 1640 homeless people were recorded. The estimated unobserved population was 3293, giving a total homeless population for the period of around 5000 (SD 1250). Mental health problems were significantly less prominent in the unobserved compared with the observed population (23% (754) v 40% (627), P < 0.0001). For both groups the prevalence varied greatly with age and sex. CONCLUSIONS: Capture-recapture techniques can overcome problems of ascertainment in estimating populations of homeless and homeless mentally ill people. Prevalences of mental illness derived from surveys that do not correct for ascertainment are likely to be falsely inflated while at the same time underestimating the total size of the homeless mentally ill population. Population estimates derived from capture-recapture techniques may usefully provide a good basis for including homeless populations in capitation calculations for allocating funds within health services.

Adult↗
PubMed1992

Selective memory for sensory and affective information in chronic pain and depression.

Mood congruity effects in induced mood states and affective disorders are well established. Recent evidence suggests that a similar process occurs in chronic pain patients, although the extent to which the memory bias is a consequence of the affective or sensory state of the subject in this group is unknown. In this study selective memory for sensory and affective pain-related information was investigated in depressed and non-depressed chronic pain patients and depressed psychiatric patients. A recall test comprising sensory, affective and neutral adjectives matched for frequency was followed by a recognition task, where the words of the recall test were randomized with an equal number of new adjectives matched for word type and frequency. Comparison of the three patient groups with normal controls revealed specific recall biases directly related to pain and depression in both chronic pain groups and the controls. Contrary to expectations, the depressed psychiatric patients failed to show a recall bias for affective adjectives: the possibility of cognitive avoidance as an explanation for this is discussed. Signal detection analysis of the recognition results suggested that selective memory in chronic pain and depression may to some extent be accounted for by differences in 'true memory', the contribution of response bias remaining less clear.

Adult↗
PubMed1990

Predictors of relatives' attendance at a state hospital workshop on schizophrenia.

A prospective research design was used to identify patient and family variables that would predict relatives' attendance at an educational workshop on schizophrenia at a state psychiatric hospital. Data were collected from patient charts and telephone interviews with relatives. Thirty-two percent of the 84 invited relatives attended the workshop. Significant predictors of attendance included relatives' proximity to the hospital, previous number of visits with the patient, knowledge about schizophrenia, and familiarity with the National Alliance for the Mentally Ill. The findings suggest that a substantial proportion of relatives of the seriously mentally ill desire information and help in coping with their ill family member. Relatives' participation might be further increased by conducting workshops at more convenient sites and encouraging attendance by those less knowledgeable about schizophrenia.

Adolescent↗
PubMed1988

Structural and immunochemical aspects of Brucella abortus endotoxins.

Smooth lipopolysaccharide (sLPS) of Brucella abortus, which is the most immunodominant component among the antigens of B. abortus isolated, has been used for diagnosis for decades. High yields of sLPS can be prepared by a modification of the procedures of Moreno et al. (J. Bacteriol. 138:361-369, 1979). Washed B. abortus cells can be disrupted by 21 freeze-quick thaw cycles and ultrasonication to separate non-membrane-bound material; then phenol extraction is performed 3 times and the phenol fraction is washed with H2O intensively. The membrane-bound sLPS can be fractionated into 3 to 5 groups according to the extent of dialysis and centrifugation. These membrane bound sLPS fractions show marked individual differences in their precipitin profile and chemical composition. Their protein content varies from 16% to 42% as determined by dye binding test and 17 to 60% by Lowry phenol method using bovine serum albumin as the standard, which indicates that these proteins associated with LPS may play important roles in the immunochemical interactions, solubility, and the heterogeneity of B. abortus lipopolysaccharides. Compared to previously published methods, a higher yield of sLPS, ranging from 3.6% to 7.7% of dried bacteria, is obtained. Group f5A, which has a standard bell shaped curve in the precipitin assay, is one of the major fractions in all three strains (1119.3, 19, 2308). The protein free sLPS (less than 1% of Lowry reactive component) can be prepared by pronase digestion. The immunochemical reactivity remains about the same before and after this treatment. The O-chains of the major fraction (f5A) of B. abortus (Strains 2308 and 19) membrane bound smooth lipopolysaccharide (sLPS) are obtained by hydrolysis of f5A native sLPS in 1% acetic acid at 100 degrees C for 2 hours. After hydrolysis, the O-chains are separated from the lipid A protein complex by centrifugation, and from small fragments by ultrafiltration of a molecular weight cut-off (MWCO) of 1.0 x 10(3). These carbohydrate haptens can be identified by precipitin-inhibition assay and further fractionated by both membrane filtration and dialysis. The size distributions of carbohydrate haptens of the endotoxins (f5A) ranged from several oligosaccharides up to 1.0 x 10(4) MWCO. Three major fractions of MWCO 8.0-10.0 x 10(3), 3.5-5.0 x 10(3), and less than 1.0 x 10(3) for both strains 2308 and 19 contain more than 85% of the total immunreactive materials.(ABSTRACT TRUNCATED AT 400 WORDS)

Brucella abortus↗