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Ian Smith

Publications and source records attributed to Ian Smith.

48 records · Page 3Linked to original sources
PubMed2003

In search of the good life: a cultural odyssey in the East and West.

In the first part of this article, the authors argue that any conception of well-being is culturally embedded and depends on how the notions of "well" and "being" are defined and practiced in different cultural communities. To support this argument, they conduct a comprehensive review of the empirical literature, which shows that members of individualistic and collectivistic cultures differ in their emotional experience of well-being. This difference has been traced to the indigenous psychology of selfhood in those cultures. In the second part of the article, the authors debunk the myth of infinite cultural variability, while retaining the basic insight concerning the cultural constitution of well-being. They develop a theoretical model of well-being, in which agency and communion are universal dimensions of well-being, and people in different cultures require different combinations of agency and communion to experience well-being. Following this theoretical development, the authors examine cultural impediments to the good life in individualistic and collectivistic cultures. The mutual incompatibility of agency and communion is ruled out as a possible cause of why it is so difficult to live the good life. Instead, the authors propose a dialectical synthesis of agency and communion as a way of dealing with this challenge of living the good life.

Affect↗
PubMed2002

Nurse led follow up and conventional medical follow up in management of patients with lung cancer: randomised trial.

OBJECTIVE: To assess the effectiveness of nurse led follow up in the management of patients with lung cancer. DESIGN: Randomised controlled trial. SETTING: Specialist cancer hospital and three cancer units in southeastern England. PARTICIPANTS: 203 patients with lung cancer who had completed their initial treatment and were expected to survive for at least 3 months. INTERVENTION: Nurse led follow up of outpatients compared with conventional medical follow up. OUTCOME MEASURES: Quality of life, patients' satisfaction, general practitioners' satisfaction, survival, symptom-free survival, progression-free survival, use of resources, and comparison of costs. RESULTS: Patient acceptability of nurse led follow up was high: 75% (203/271) of eligible patients consented to participate. Patients who received the intervention had less severe dyspnoea at 3 months (P=0.03) and had better scores for emotional functioning (P=0.03) and less peripheral neuropathy (P=0.05) at 12 months. Intervention group patients scored significantly better in most satisfaction subscales at 3, 6, and 12 months (P<0.01 for all subscales at 3 months). No significant differences in general practitioners' overall satisfaction were seen between the two groups. No differences were seen in survival or rates of objective progression, although nurses recorded progression of symptoms sooner than doctors (P=0.01). Intervention patients were more likely to die at home rather than in a hospital or hospice (P=0.04), attended fewer consultations with a hospital doctor during the first 3 months (P=0.004), had fewer radiographs during the first 6 months (P=0.04), and had more radiotherapy within the first 3 months (P=0.01). No other differences were seen between the two groups in terms of the use of resources. CONCLUSION: Nurse led follow up was acceptable to lung cancer patients and general practitioners and led to positive outcomes.

Aged↗
PubMed2002

Randomized, placebo-controlled trial of clodronate in patients with primary operable breast cancer.

PURPOSE: The development of bone metastases depends on tumor-induced osteoclastic resorption of bone, which may be inhibited by the antiosteolytic bisphosphonate clodronate. Given to patients with primary breast cancer, clodronate might reduce the subsequent incidence of bone metastases. PATIENTS AND METHODS: This double-blind, multicenter trial accrued 1,069 assessable patients with operable breast cancer between 1989 and 1995. All patients received surgery, radiotherapy, chemotherapy, and tamoxifen as required. Patients were randomized to receive oral clodronate 1,600 mg/d or a placebo for 2 years starting within 6 months of primary treatment. The primary end point was relapse in bone, analyzed on an intent-to-treat basis, during the medication period and during the total follow-up period (median follow-up, 2,007 days). Secondary end points were relapse in other sites, mortality, and toxicity. RESULTS: During the total follow-up period, there was a nonsignificant reduction in occurrence of bone metastases (clodronate, n = 63; placebo, n = 80; hazards ratio [HR], 0.77; 95% confidence interval [CI], 0.56 to 1.08; P =.127). During the medication period there was a significant reduction in the occurrence of bone metastases (clodronate, n = 12; placebo, n = 28; HR, 0.44; 95% CI, 0.22 to 0.86; P =.016). The occurrence of nonosseous metastases was similar (clodronate, n = 112; placebo, n = 128; P =.257), but there was a significant reduction in mortality (clodronate, n = 98; placebo, n = 129; P =.047) during the total follow-up period. CONCLUSION: Clodronate, given to patients with primary operable breast cancer, may reduce the occurrence of bone metastases, although this reduction was only significant during this medication period. There was a significant reduction in mortality.

Administration, Oral↗
PubMed2002

GTP cyclohydrolase I gene transfer augments intracellular tetrahydrobiopterin in human endothelial cells: effects on nitric oxide synthase activity, protein levels and dimerisation.

OBJECTIVES: Tetrahydrobiopterin (BH4) is an essential cofactor for endothelial nitric oxide synthase (eNOS) activity. BH4 levels are regulated by de novo biosynthesis; the rate-limiting enzyme is GTP cyclohydrolase I (GTPCH). BH4 activates and promotes homodimerisation of purified eNOS protein, but the intracellular mechanisms underlying BH4-mediated eNOS regulation in endothelial cells remain less clear. We aimed to investigate the role of BH4 levels in intracellular eNOS regulation, by targeting the BH4 synthetic pathway as a novel strategy to modulate intracellular BH4 levels. METHODS: We constructed a recombinant adenovirus, AdGCH, encoding human GTPCH. We infected human endothelial cells with AdGCH, investigated the changes in intracellular biopterin levels, and determined the effects on eNOS enzymatic activity, protein levels and dimerisation. RESULTS: GTPCH gene transfer in EAhy926 endothelial cells increased BH4 >10-fold compared with controls (cells alone or control adenovirus infection), and greatly enhanced NO production in a dose-dependent, eNOS-specific manner. We found that eNOS was principally monomeric in control cells, whereas GTPCH gene transfer resulted in a striking increase in eNOS homodimerisation. Furthermore, the total amounts of both native eNOS protein and a recombinant eNOS-GFP fusion protein were significantly increased following GTPCH gene transfer. CONCLUSIONS: These findings suggest that GTPCH gene transfer is a valid approach to increase BH4 levels in human endothelial cells, and provide new evidence for the relative importance of different mechanisms underlying BH4-mediated eNOS regulation in intact human endothelial cells. Additionally, these observations suggest that GTPCH may be a rational target to augment endothelial BH4 and normalise eNOS activity in endothelial dysfunction states.

3T3 Cells↗
PubMed2002

Lethal and sublethal effects of a granulovirus on the tomato moth Lacanobia oleracea.

A Scottish isolate of Lacanobia oleracea granulovirus (LoGV) was tested against larvae from a laboratory colony of L. oleracea (Lepidoptera: Noctuidae) using the peroral bioassay technique. The median lethal doses ranged from 10(1.38) occlusion bodies in first instar larvae to 10(7.45) in fifth instars. Sublethal effects on development and reproduction were observed among the survivors of virus challenge. Larvae dosed as first and second instars had faster developmental rates, and those dosed as fourth and sixth instars had reduced larval and pupal weights, compared to their respective controls. There was a 15% reduction in the number of eggs laid by adults that developed from infected larvae, but no reduction in egg viability. The F(1) generation did not show significantly greater mortality than controls, suggesting a lack of transovarial transmission. The significance of these results in terms of pest management of the tomato moth is discussed.

Animals↗
PubMed2002

Occult primary breast carcinoma presenting as axillary lymphadenopathy.

BACKGROUND: The objective of this study was to review the need for radiotherapy or not in patients with occult primary breast cancer presenting with axillary metastases treated with breast conservation usually with no surgery to the breast. METHODS: From 1975 to 2001, 58 patients were treated with axillary lymphadenopathy from a cryptic primary breast carcinoma. After clinical and radiological assessment, 29 patients retained a diagnosis of occult primary breast carcinoma. Clinical and pathological data were collected retrospectively on the 29 patients and survival was calculated from the date of initial diagnosis using the Kaplan-Meier method. The median follow-up was 44 months. RESULTS: Median age at diagnosis was 57 years (range 28-81 years). Sixteen patients had radiotherapy to the ipsilateral breast. Eleven patients received no local therapy to the ipsilateral breast and two patients had quadrantectomies which were negative for malignancy. Locoregional relapse occurred in 12.5% of patients who had received radiotherapy and 69% of those who had not received any radiotherapy (P=0.02). Fifty-seven per cent of patients having a local relapse were salvaged with further surgery. The eventual breast conservation rate was 93%. Patients who received radiotherapy to the breast had significantly improved relapse-free survival (HR=0.31; P=0.04) and local relapse-free survival (HR=0.09; P=0.004). There were no significant differences in overall survival between those patients who had breast irradiation and those who did not (HR 0.91; 95% CI 0.18-4.5). CONCLUSION: Occult primary carcinoma with axillary metastases can be treated successfully with breast preservation but radiotherapy to the breast is necessary to minimize the risk of locoregional recurrence.

Journal Article↗
PubMed2002

Cost considerations in the use of anaesthetic drugs.

Measuring the direct drug costs of an anaesthetic is relatively easy, but assessing increased expenditure in relation to clinical benefits and indirect costs is not. This review examines a number of papers that have attempted just such a task and tries to illustrate some of the difficulties inherent in this important area of cost-effective analyses.

Journal Article↗
PubMed2002

Neoadjuvant docetaxel in breast cancer: 3-year survival results from the Aberdeen trial.

Over the past 30 years there has been an increased use of neoadjuvant (or primary) chemotherapy for treating patients with breast cancer. However, while it is clear that chemotherapy given in the adjuvant setting after surgery does prolong patients' overall and disease-free survival, the evidence that chemotherapy in the neoadjuvant setting also increases survival remains unproven. In the Aberdeen study, 162 patients with large and locally advanced breast cancer underwent 4 cycles of CVAP (cyclophosphamide/vincristine/doxorubicin/prednisone) primary chemotherapy. Patients with a complete or partial response were then randomized to either 4 further cycles of CVAP or 4 cycles of docetaxel (100 mg/m2). It was shown that the addition of sequential docetaxel (100 mg/m2) to CVAP neoadjuvant chemotherapy resulted in a significantly enhanced clinical response rate (94% vs. 64%) and a substantially increased complete histopathological response rate (34% vs. 16%) when compared to patients receiving CVAP alone. Furthermore, patients receiving docetaxel had an increased breast conservation rate (67% vs. 48%) and an increased survival at a median follow-up of 3 years. It is important to note that this was a small study, and the survival results should be interpreted with caution. The results are encouraging, however, and further studies are urgently required.

Adult↗
PubMed2002

Coordinate expression of apoptosis-associated proteins in human breast cancer before and during chemotherapy.

PURPOSE: Induction of apoptosis is a key factor in the response of tumors to chemotherapy. Laboratory studies have established many of the factors that regulate and execute apoptosis, but the significance of these in human tumors is poorly understood. Therefore, the relationship between key components of this machinery was examined in primary human breast carcinomas before and 24 h after the initiation of chemotherapy. EXPERIMENTAL DESIGN: Apoptosis was measured using the terminal deoxynucleotidyl transferase-mediated nick end labeling assay, and proliferation was assessed using the anti-Ki67 antibody MIB-1. Monospecific polyclonal antibodies were used for immunohistochemical detection of Bcl-2, Bax, XIAP, activated (cleaved) caspase 3 and 6, and cleaved DNA Fragmentation Factor-40 (DFF40) using paraffin-embedded tissues. RESULTS: Before treatment, a significant correlation was found between apoptosis and proliferation (r = 0.64, P < 0.0001), between caspases 3 and 6 (r = 0.49, P = 0.004) and between cleaved DFF40 and active caspases 3 (r = 0.66, P < 0.0001) or 6 (r = 0.47, P = 0.006). Before treatment, expression of inhibitor of apoptosis protein, XIAP, also correlated positively with cleaved caspase 3 (r = 0.64, P < 0.0001), caspase 6 (r = 0.36, P = 0.04), and DFF40 (r = 0.61, P = 0.0001). At 24 h after chemotherapy, significant increases in apoptosis and decreases in proliferation were observed, with the degree of increase in apoptosis inversely associated with decrease in proliferation. Chemotherapy-induced increases in Bax were correlated with increases in cleaved DFF40 (r = 0.54, P = 0.0008), but no other variables showed significant change at 24 h after initiation of chemotherapy. CONCLUSION: The pretreatment biomarker relationships suggest parallel cleavage and activation of these executioner proteins in breast cancer and that XIAP may maintain cell survival in the face of caspase activation. The findings provide in vivo evidence in human breast cancer that chemotherapy induces an apoptotic program characterized by up-regulation of Bax and cleavage of caspase substrate DFF40.

Adult↗
PubMed2002

Comparison of two dentifrices with respect to efficacy for the control of plaque and gingivitis, and with respect to extrinsic tooth staining: a six-month clinical study on adults.

The objective of this six-month, double-blind clinical study, conducted in harmony with American Dental Association guidelines, was to provide a comparison between Colgate Total Toothpaste and Crest Gum Care Toothpaste with respect to their levels of efficacy for the control of supragingival dental plaque and gingivitis, and with respect to the levels of tooth staining associated with their use. Adult male and female subjects from the Edinburgh, Scotland area were entered into the study and stratified into two treatment groups which were balanced for age, sex, baseline Quigley-Hein Plaque Index scores and baseline Löe-Silness Gingival Index scores. Subjects received an oral prophylaxis, and were instructed to brush their teeth twice daily (morning and evening) for one minute with their assigned dentifrice, using a soft-bristled toothbrush. Examinations for plaque, gingivitis and extrinsic tooth staining were conducted after three months' and again after six months' use of the study dentifrices. One-hundred and nine (109) subjects complied with the protocol and completed the entire six-month clinical study. At both the three- and six-month study examinations, the Colgate Total Toothpaste group exhibited statistically significantly less plaque, gingivitis and extrinsic tooth staining compared to the Crest Gum Care Toothpaste group. At the six-month examination, the magnitude of these differences exceeded 18% for all six parameters measured (18.7% for Plaque Index, 60.5% for Plaque Severity Index, 22.2% for Gingival Index, 85.1% for Gingivitis Severity Index, 45.3% for stain intensity, and 46.3% for stain area). Thus, the results of this six-month clinical study support the conclusion that Colgate Total Toothpaste provides a statistically significant, substantive advantage in efficacy for the control of plaque and gingivitis over Crest Gum Care Toothpaste, while, at the same time, providing better control against the development of extrinsic tooth staining.

Adult↗