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Biomedical subjects

D Dunlop

Publications and source records attributed to D Dunlop.

At least 19 recordsLinked to original sources
PubMed2006

A phase III trial of docetaxel/carboplatin versus mitomycin C/ifosfamide/cisplatin (MIC) or mitomycin C/vinblastine/cisplatin (MVP) in patients with advanced non-small-cell lung cancer: a randomised multicentre trial of the British Thoracic Oncology Group (BTOG1).

BACKGROUND: Phase III studies suggest that non-small-cell lung cancer (NSCLC) patients treated with cisplatin-docetaxel may have higher response rates and better survival compared with other platinum-based regimens. We report the final results of a randomised phase III study of docetaxel and carboplatin versus MIC or MVP in patients with advanced NSCLC. PATIENTS AND METHODS: Patients with biopsy proven stage III-IV NSCLC not suitable for curative surgery or radiotherapy were randomised to receive four cycles of either DCb (docetaxel 75 mg/m(2), carboplatin AUC 6), or MIC/MVP (mitomycin 6 mg/m(2), ifosfamide 3 g/m(2) and cisplatin 50 mg/m(2) or mitomycin 6 mg/m(2), vinblastine 6 mg/m(2) and cisplatin 50 mg/m(2), respectively), 3 weekly. The primary end point was survival, secondary end points included response rates, toxicity and quality of life. RESULTS: The median follow-up was 17.4 months. Overall response rate was 32% for both arms (partial response = 31%, complete response = 1%); 32% of MIC/MVP and 26% of DCb patients had stable disease. One-year survival was 39% and 35% for DCb and MIC/MVP, respectively. Two-year survival was 13% with both arms. Grade 3/4 neutropenia (74% versus 43%, P < 0.005), infection (18% versus 9%, P = 0.01) and mucositis (5% versus 1%, P = 0.02) were more common with DCb than MIC/MVP. The MIC/MVP arm had significant worsening in overall EORTC score and global health status whereas the DCb arm showed no significant change. CONCLUSIONS: The combination of DCb had similar efficacy to MIC/MVP but quality of life was better maintained.

Adult↗
PubMed2005

Phase II study of gemcitabine and cisplatin in locally advanced/metastatic oesophageal cancer.

Palliative chemotherapy for inoperable/metastatic oesophageal cancer has limited activity. This study assesses the feasibility and activity of gemcitabine and cisplatin in this group of patients. In total, 42 patients with locally advanced/metastatic squamous or adenocarcinoma of the oesophagus were treated with gemcitabine 1250 mg m(-2) days 1 and 8 and cisplatin 75 mg m(-2) day 1 in a 21-day cycle. Interim safety analysis was carried out after the first 19 patients suggested significant toxicity. The dose of gemcitabine was subsequently reduced to 1000 mg m(-2). Patients were assessed for toxicity and response. The median number of treatment cycles per patient was 4 (range 1-6). Grade 3-4 neutropenia occurred in 37% of cycles; however, there was only one episode of neutropenic fever. Nonhaematological toxicities included fatigue, nausea and vomiting. Among 32 patients eligible for response, there were three complete responses and 16 partial responses (overall response rate of 45%); nine patients had stable disease. Median survival was 11 months. The response rate appears to be greatest in those with squamous carcinoma compared to adenocarcinoma (71 vs 33%, P=0.036). The combination of gemcitabine and cisplatin in this schedule has manageable toxicity and significant activity in patients with locally advanced/metastatic oesophageal cancer and is worthy of further study.

Adult↗
PubMed2004

Phase II study of ISIS 3521, an antisense oligodeoxynucleotide to protein kinase C alpha, in patients with previously treated low-grade non-Hodgkin's lymphoma.

BACKGROUND: The purpose of this study was to assess the efficacy and safety of ISIS 3521, an antisense phosphorothioate oligonucleotide to protein kinase C alpha in patients with relapsed low-grade non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Twenty-six patients received ISIS 3521 (2 mg/kg/day) as a continuous infusion over 21 days of each 28-day cycle. RESULTS: The median age of the patients was 53 years (range 37-77). Histological subtypes were low-grade follicular lymphoma (n = 22) and B-cell small lymphocytic lymphoma (n = 4). Twenty-one (81%) had stage III/IV disease. The median number of previous lines of chemotherapy was two (range one to six). A total of 87 cycles of ISIS 3521 were administered. Twenty-three patients were assessable for response. Three patients achieved a partial response. No complete responses were observed. Ten patients had stable disease. Grade 3-4 toxicity was as follows: neutropenia (3.8%) and thrombocytopenia (26.9%). CONCLUSIONS: ISIS 3521 has demonstrated anti-tumour activity in patients with relapsed low-grade NHL. There may be a potential role for this agent in combination with conventional chemotherapy for advanced low-grade lymphoma, and further trials are warranted.

Adult↗
PubMed2002

Impaction grafting of the femur in two-stage revision for infected total hip replacement.

We report the mid-term results of femoral impaction grafting which was used in 53 patients during the second stage of a two-stage revision for an infected total hip replacement. We reviewed all cases performed between 1989 and 1998. All patients underwent a Girdlestone excision arthroplasty, received local and systemic antibiotics and subsequently underwent reconstruction, using femoral impaction grafting. Four patients had further infection (7.5%), and four died within 24 months of surgery. One patient underwent revision of the stem for a fracture below its tip at ten months. This left 44 patients with a mean follow-up of 53 months (24 to 122). All had improved clinical scores and a satisfactory radiological outcome.

Adult↗
PubMed2000

A pilot study on the effects of exercise in patients with systemic lupus erythematosus.

OBJECTIVE: A pilot study was designed to assess the efficacy and safety of different exercise therapies on patient-reported fatigue and functional status. METHODS: Ten patients with systemic lupus erythematosus (SLE) were randomly placed in either an aerobic exercise group (group 1: n = 5) or a range of motion/muscle strengthening (ROM/MS) exercise group (group 2: n = 5). Outcome measures assessed at baseline and the end of the study were fatigue, functional status, disease activity, cardiovascular fitness, isometric strength, bone mineral density (BMD) of the lumbar spine and femoral neck, and parathyroid hormone and osteocalcin as representative bone biochemical markers for bone resorption and bone formation, respectively. RESULTS: Both aerobic and ROM/MS types of exercise were safe and did not worsen SLE disease activity. Patients in both exercise groups showed some improvement in fatigue, functional status, cardiovascular fitness, and muscle strength. Both groups showed increased bone turnover, but BMD was unchanged. Eighty percent of the patients met the compliance standard for the study. CONCLUSIONS: This pilot study shows the feasibility of exercise for SLE patients. The potential value of this approach shows promise in the routine management of these patients.

Activities of Daily Living↗
PubMed2000

Tirapazamine plus cisplatin versus cisplatin in advanced non-small-cell lung cancer: A report of the international CATAPULT I study group. Cisplatin and Tirapazamine in Subjects with Advanced Previously Untreated Non-Small-Cell Lung Tumors.

PURPOSE: A phase III trial, Cisplatin and Tirapazamine in Subjects with Advanced Previously Untreated Non-Small-Cell Lung Tumors (CATAPULT I), was designed to determine the efficacy and safety of tirapazamine plus cisplatin for the treatment of non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with previously untreated NSCLC were randomized to receive either tirapazamine (390 mg/m(2) infused over 2 hours) followed 1 hour later by cisplatin (75 mg/m(2) over 1 hour) or 75 mg/m(2) of cisplatin alone, every 3 weeks for a maximum of eight cycles. RESULTS: A total of 446 patients with NSCLC (17% with stage IIIB disease and pleural effusions; 83% with stage IV disease) were entered onto the study. Karnofsky performance status (KPS) was >/= 60 for all patients (for 10%, KPS = 60; for 90%, KPS = 70 to 100). Sixty patients (14%) had clinically stable brain metastases. The median survival was significantly longer (34.6 v 27. 7 weeks; P =.0078) and the response rate was significantly greater (27.5% v 13.7%; P <.001) for patients who received tirapazamine plus cisplatin (n = 218) than for those who received cisplatin alone (n = 219). The tirapazamine-plus-cisplatin regimen was associated with mild to moderate adverse events, including acute, reversible hearing loss, reversible, intermittent muscle cramping, diarrhea, skin rash, nausea, and vomiting. There were no incremental increases in myelosuppression, peripheral neuropathy, or renal, hepatic, or cardiac toxicity and no deaths related to tirapazamine. CONCLUSION: The CATAPULT I study shows that tirapazamine enhances the activity of cisplatin in patients with advanced NSCLC and confirms that hypoxia is an exploitable therapeutic target in human malignancies.

Adult↗
PubMed1999

Frequency of fractures in women with systemic lupus erythematosus: comparison with United States population data.

OBJECTIVE: To describe the frequency of self-reported fractures in a large population-based cohort of women with lupus, to compare the frequency of self-reported fractures between lupus patients and women of similar age in the general population by use of data from the 1994 National Health Interview Survey (NHIS), and to describe the associated risk factors for fracture in women with lupus. This study is a secondary analysis of data collected to assess cardiovascular risk in women with lupus. METHODS: Fractures and associated risk factors were ascertained by self report in this retrospective cohort study of 702 living women with lupus who were followed up for 5,951 person-years. Self-reported fractures were verified in a subset of patients. A Weibull regression model was used to assess risk factors associated with time from lupus diagnosis to fracture in the univariate and multivariate analyses. Age-specific standard morbidity ratios (SMRs) were calculated to determine whether fracture occurrence was greater than expected in women with lupus. RESULTS: Eighty-six (12.3%) of 702 women reported at least 1 fracture following the diagnosis of lupus. The sites of the first fracture were the leg (n = 32), foot (n = 16), arm (n = 15), spine (n = 9), rib (n = 7), hip (n = 2), pelvis (n = 2), hand (n = 1), shoulder (n = 1), and finger (n = 1). Fracture risk was increased in the lupus cohort compared with women of similar age from the United States population, using weighted data from the 1994 NHIS (SMR 4.7; 95% confidence interval 3.8, 5.8). Variables in the univariate analysis that were significantly associated (P < 0.05) with time from lupus diagnosis to fracture were older age at lupus diagnosis, longer disease duration, longer duration of corticosteroid use, less use of oral contraceptives, and menopause status. In the multivariate analysis, independent determinants of time from lupus diagnosis to fracture were older age at lupus diagnosis and longer duration of corticosteroid use. CONCLUSION: Fractures occurred in 12.3% of lupus patients who were followed up for 5,951 person-years. There was nearly a 5-fold increase in fracture occurrence in the women with lupus compared with women from the US population. Older age at lupus diagnosis and longer use of corticosteroids were associated with time from lupus diagnosis to fracture. With increased life expectancy of lupus patients, fracture occurrence is a major threat to the health of these women. Prevention strategies must be directed toward minimizing the occurrence of fractures in these patients.

Adrenal Cortex Hormones↗
PubMed1999

Free leptin, bound leptin, and soluble leptin receptor in normal and diabetic pregnancies.

We measured serum levels of free leptin, bound leptin, and soluble leptin receptor by specific RIA methods in 20 normal and 19 insulin-dependent diabetes mellitus subjects at 20 and 30 weeks gestation and postpartum, and analyzed the data using hierarchical statistical models. Total leptin levels rise from 20-30 weeks gestation (688 +/- 58 to 785 +/- 62 pmol/L, mean +/- SEM; P = 0.009). There is a significant postpartum fall to 445 +/- 47 pmol/L (P < 0.001). This rise is caused by the rise in the bound leptin levels, as there is no significant change in free leptin levels between 20 and 30 weeks (P = 0.17). There is a significant postpartum fall in free leptin levels (P < 0.001). Insulin requirements rise in the third trimester, but despite this there was no significant difference in free or bound leptin levels between the normal and diabetic subjects at any stage [free leptin, 223 +/- 35 and 266 +/- 24, 237 +/- 45 and 223 +/- 27, and 109 +/- 16 and 104 +/- 24 (P = 0.34); bound leptin, 410 +/- 73 and 428 +/- 54, 501 +/- 78 and 562 +/- 71, and 330 +/- 47 and 271 +/- 46 (P = 0.84); for normals and diabetics at 20 and 30 weeks gestation and postpartum, respectively]. Diabetic subjects, however, had significantly higher soluble leptin receptor levels at all stages (P << 0.001), which rose further in the third trimester from 3742 +/- 268 (mean +/- SEM) to 4134 +/- 239 pmol/L, whereas in the normal group there was a fall from 3149 +/- 169 to 2712 +/- 123 (P = 0.05). There is a linear relationship between the soluble leptin receptor levels and the body mass index in the diabetic group only. We conclude that there is no significant difference in free or bound leptin levels between the normal and insulin-dependent diabetic subjects either during pregnancy or postpartum, but female insulin-dependent diabetic subjects have significantly higher soluble leptin receptor levels. We speculate that high soluble leptin receptor levels might be implicated in the development of the leptin resistance in this group.

Adult↗
PubMed1998

Do clinical breast examination skills improve during medical school?

PURPOSE: To assess the effects of stage of training, gender, and specialty interest on medical students' breast cancer knowledge, attitudes, and clinical breast examination (CBE) skills as a case study of the progression of physical examination skills during medical education. METHOD: In 1996, questionnaires assessing breast cancer knowledge and attitudes were administered to 493 premedical and first-, second-, and third-year medical students at Northwestern University Medical School. Silicone breast models were used to evaluate the CBE proficiency of a subset of 151 students. RESULTS: Breast cancer knowledge was positively correlated with stage of training (r = .62), with significant differences between all levels (p < .001). In contrast, first-year medical students attained the highest mean lump-detection sensitivity (61.5%), followed by second-year (53.9%) and third-year (43.5%) students (p < .001, first- vs third-year students; p < .10, second- vs third-year students). There was no significant difference in specificity among the four stages. CONCLUSIONS: The results suggest that breast cancer knowledge and attitudes are not related to CBE proficiency, which is a practiced tactile skill. The decline in lump-detection sensitivity with increased stage of training may demonstrate the need for increased attention to palpation skills during the clinical years. These findings are consistent with those of earlier reports that suggest the need for the reinforcement of physical examination skills during clinical education.

Breast Neoplasms↗
PubMed1997

Factors influencing hematologic toxicity of radioimmunotherapy with 131I-labeled anti-carcinoembryonic antigen antibodies.

BACKGROUND: Several investigators have reported a considerable variability in the observed hematologic toxicity after radioimmunotherapy (RAIT) with monoclonal antibodies (MoAb) given at similar amounts of radioactivity based on body surface area and/or similar radiation absorbed doses given to the red marrow. The authors investigated various factors potentially affecting hematologic toxicity after RAIT with 131I-labeled anti-carcinoembryonic antigen (CEA) MoAb to identify the statistically significant factors from those commonly perceived clinically to substantially contribute to this toxicity. METHODS: Ninety-nine patients who received 131I-labeled anti-CEA MoAb for the treatment of CEA-producing cancers were assessed for platelet and white blood cell toxicity based on the common Radiation Therapy Oncology Group criteria. Multivariate regression analysis was used to identify the statistically significant factors affecting toxicity among the following variables: red marrow dose, baseline platelet and white blood cell counts, bone and/or marrow metastases, prior chemotherapy or radiotherapy, timing of prior chemotherapy or radiotherapy in relationship to RAIT, type and number of prior chemotherapeutic regimens, age, sex, antibody form, and cancer type. RESULTS AND CONCLUSIONS: Red marrow dose, baseline platelet or white blood cell counts, multiple bone and/or marrow metastases, and chemotherapy 3-6 months before RAIT were the only four significant factors affecting hematologic toxicity according to multivariate analysis. The identification of bone and/or marrow metastases and recent chemotherapy as significant factors for hematologic toxicity could be important in the design of future clinical trials.

Adolescent↗
PubMed1997

Carpal tunnel decompression under local anaesthetic and tourniquet control.

A postal survey within the North West Region (UK) revealed that 66% of the consultant orthopaedic surgeons did not use local anaesthesia routinely for carpal tunnel decompression. This prospective study was set up to assess the effectiveness, safety and patient tolerance of performing this procedure using local anaesthesia and upper arm tourniquet control. Eight-six carpal tunnel decompressions were performed on 75 consecutive and unselected patients with confirmed carpal tunnel syndrome over a 6-month period. Completed questionnaires were obtained before discharge. None or only slight discomfort was experienced for all aspects of the operation in at least 94%. None of the patients reported severe and unbearable discomfort. At review, 3 months postoperatively, all patients with the exception of two reported complete resolution of preoperative symptoms. The use of local anaesthesia and a tourniquet is safe, effective and well-tolerated in carpal tunnel decompressions.

Adult↗
PubMed1997

Phase II trial of the oral platinum complex JM216 in non-small-cell lung cancer: an EORTC early clinical studies group investigation.

BACKGROUND: JM216 is a new oral platinum complex with dose-limiting toxicity myelosuppression, now undergoing phase II evaluation. PATIENTS AND METHODS: JM216 was evaluated as first line therapy in non-small-cell lung cancer. Seventeen patients received 120 mg/m2/day for five days repeated every three weeks. RESULTS: Toxicity was manageable, the commonest side-effects being nausea, vomiting, diarrhoea, constipation and asthenia. Myelososuppression was generally grade < 2 and there were no cases of neutropenic sepsis or bleeding. Thirteen patients were fully evaluable for response. No sustained objective responses were reported. One patient was reported as stable disease had a partial response after three courses but was progressing again after four. An additional five patients had stable disease (46.2%). CONCLUSIONS: Although some patients may have had useful palliation, JM216 did not appear to have significant antitumour activity in non-small-cell lung cancer.

Administration, Oral↗
PubMed1997

Predictors of decline in manual performance in older adults.

OBJECTIVE: To determine factors that predict decline in manual performance using a multivariate model of determinants of functional limitation. DESIGN: Longitudinal observational study. SETTINGS: Ambulatory general medicine clinics, residences of homebound individuals, and a continuing care retirement community. PARTICIPANTS: Subjects were 485 persons more than 60 years of age and included continuing care retirement community (CCRC) residents (n = 215), chronically homebound older persons (n = 65), and ambulatory older adults (n = 205). Mean age at baseline was 78 years. MEASUREMENT: Independent variables included demographics, physician measures of upper-extremity joint impairment, comorbidities derived from physical examination and chart abstract, self-assessed arthritis pain, depression, and anxiety. The major dependent variable was 2-year decline in timed manual performance below a threshold associated with need for long-term care services. RESULTS: The proportion of subjects who exceed a Timed Manual Performance Test threshold of 350 seconds increased slowly from baseline through Year 4 for all age groups but rose rapidly from Year 4 to Year 6 for the oldest group (> 85 years at baseline). Using a discrete survival model, we found that age, education, grip strength, and psychological status predicted crossing the manual performance threshold within a 2-year period. CONCLUSIONS: The findings, coupled with earlier findings that upper extremity joint impairment predicted both grip strength and manual performance, suggest that joint impairment may be an important risk factor for future functional limitation. Since diminished hand function has been shown to predict dependency, development and testing of interventions to maintain or restore upper extremity joint function and reduce pain would appear to be a high research priority.

Age Factors↗
PubMed1997

Improving transfusion practices in a busy teaching hospital.

A retrospective audit of blood transfusions was carried out in Cardiff Royal Infirmary (CRI) to investigate how efficiently blood was requested and used by the various clinical directorates. Excessive crossmatch/transfusion (C/T) ratios were found for a number of operations. In an attempt to improve practices, a pilot study was carried out between the Department of Haematology and the largest single requesting group, the Orthopaedic Directorate. As a result of a preliminary retrospective audit, crossmatch guidelines were revised, with more reliance on the group and antibody screen (G & S) for low-risk operations. A subsequent prospective audit showed major reductions in crossmatch requests and a general decrease in C/T ratios to very efficient levels without any patient morbidity. Blood was freed for urgent use elsewhere, and significant cost improvements resulted. This study, using the orthopaedic surgery department as a model, shows the value of inter-departmental audit and supports the experience of other centres using similar methods to make considerable savings in the amount of blood crossmatched unnecessarily.

Blood Banks↗
PubMed1996

Predictors of change in walking velocity in older adults.

OBJECTIVE: To determine factors that predict change in walking velocity in older people using a multivariate model. DESIGN: Longitudinal observational study. SUBJECTS: A total of 588 persons older than age 60, including subjects residing in a continuing care retirement community (CCRC) (n = 248), and homebound (n = 79) and ambulatory (n = 261) subjects. Mean age at baseline = 77. MEASUREMENT: Independent variables included demographics, physician measures of lower-extremity joint impairment and other musculoskeletal and neurological variables, comorbidities derived from physical examination and chart abstract, self-assessed arthritis pain, depression, and anxiety. The major dependent variables were 2- and 4-year decline in walking velocity below a threshold associated with nursing home placement. MAIN RESULTS: From baseline to Year 4, median walking velocity declined from 61.8 to 53.0 m/min, and the proportion of subjects above a threshold value of 11.5 m/min declined from 95.3% to 80.4%. Age, joint impairment, and weakness of quadriceps, measured at baseline, predicted 2-year and 4-year decline in walking velocity. CONCLUSIONS: The findings indicate that joint impairment and quadriceps strength contribute significantly to crossing a clinically significant threshold in walking velocity among older people over time. Future research is needed to determine whether these risk factors can be modified through preventive interventions such as muscle-strengthening exercises and pain medication.

Activities of Daily Living↗
PubMed1995

The determinants of walking velocity in the elderly. An evaluation using regression trees.

OBJECTIVE: To determine predictors of walking velocity in the elderly. METHODS: Five hundred thirty-two persons from 3 cohorts of elderly persons (retirement community, ambulatory care medical clinic, or chronically homebound population) performed a 10-foot (for the homebound subjects) or 50-foot (for all other subjects) walk time test and underwent a standardized interview, chart review, and clinical examination. The 73 independent variables that were evaluated included demographic, musculoskeletal, neurologic, psychologic, and other comorbidity items. Least-squares and least-absolute-deviation regression tree analyses were performed to determine the strongest predictive factors associated with walking velocity. RESULTS: Sampling cohort (homebound versus non-homebound), quadriceps strength, hip flexion strength, lumbosacral spine impairment, lower joint impairment, and education were found to be associated with walking velocity. Joint pain measures were not associated with walking velocity. CONCLUSION: Muscle strength variables are better predictors of walking velocity than are joint pain variables. Thus, clinical trials and observational studies using walking velocity as an outcome need to take into consideration the influence of muscle strength on this outcome variable.

Aged↗
PubMed1995

The prevalence and impact of arthritis in older persons.

OBJECTIVE: To review that what is known about the prevalence and impact of arthritis on disability and health care expenditures incurred by older persons. METHODS: The current prevalence estimates of osteoarthritis and osteoporosis in the US are examined, and what is known about the relationship of arthritis, broadly defined to disability, and the impact of arthritis-specific disability on home care and nursing home use by older persons are reviewed. RESULTS: Arthritis is a major contributor to disability among older people and is especially disabling for older women, who have higher prevalence rates and greater disability than their male counterparts. Studies of the relationship of arthritis to long-term care use indicate that arthritis can be a risk factor insofar as it can cause disability that results in homeboundedness, which, in turn is a risk factor for nursing home use. It is possible that previous analyses that included arthritis and disability as competing risk factors for nursing home use underestimate the contribution of arthritis because arthritis is a risk factor for disability; thus, the two variables may be strongly correlated. CONCLUSIONS: More study is needed to understand the contribution of sex to prevalence of arthritis and severity of arthritis-specific disability. The route through which arthritis affects long-term care use also needs careful longitudinal study. If arthritis is confirmed to be a major risk factor for disability that leads to long-term care use, the development and testing of interventions to prevent/minimize arthritis-specific disability should be a major research priority.

Age Factors↗