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Biomedical subjects

A Gordon

Publications and source records attributed to A Gordon.

At least 91 records · Page 5Linked to original sources
PubMed1998

Topotecan for the treatment of advanced epithelial ovarian cancer: an open-label phase II study in patients treated after prior chemotherapy that contained cisplatin or carboplatin and paclitaxel.

PURPOSE: Topotecan, a topoisomerase I inhibitor, was evaluated in a multicenter, phase II study of women with epithelial ovarian carcinoma who relapsed after one or two prior regimens that included platinum and paclitaxel. PATIENTS AND METHODS: Topotecan 1.5 mg/m2 daily was administered as a 30-minute infusion for 5 consecutive days on a 21-day cycle. Eligibility criteria included bidimensionally measurable disease, Eastern Cooperative Oncology Group performance status of 2 or less, and adequate bone marrow, liver, and renal function. Efficacy was assessed by independent radiologic review. RESULTS: One hundred thirty-nine patients were treated; 81% were platinum resistant. Sixty-two patients had received one prior regimen and 77 patients had received two prior regimens. Nine patients were not assessable for response; however, all patients were included in the response analysis. The overall response rate was 13.7%; 12.4% in platinum-resistant and 19.2% in platinum-sensitive patients. Stable disease lasted at least 8 weeks in 27.3% of the patients. The median duration of response and time to progression were 18.1 and 12.1 weeks, respectively. The median survival was 47.0 weeks. Grade 4 neutropenia occurred in 82% of the patients (34% of the courses) and thrombocytopenia in 30% of the patients (9% of the courses). Infectious complications occurred in 6% of the courses. Nonhematologic toxicities were mild. There were no drug-related toxic deaths. CONCLUSION: As a single agent, topotecan has modest activity in women with advanced epithelial ovarian carcinoma who have progressed or not responded after one or two prior regimens with platinum and paclitaxel. Further investigation of combination regimens is indicated in the primary therapy for ovarian cancer based on the mechanism of action and tolerability.

Adult↗
PubMed1998

The effects of therapeutic touch on patients with osteoarthritis of the knee.

BACKGROUND: The purpose of this study was to determine if therapeutic touch, an alternative medicine modality, is effective in the treatment of osteoarthritis of the knee. METHODS: A single-blinded randomized control trial was conducted in a family practice center of a community hospital family practice residency program in Pennsylvania. The patients were between the ages of 40 and 80, had been given a diagnosis of osteoarthritis of at least one knee, had not had knee replacement, and had no other connective tissue disease. The patients were randomized to therapeutic touch, mock therapeutic touch, or standard care. The main outcome measures were pain and its impact, general well-being, and health status measured by standardized, validated instruments, as well as the qualitative measurement of a Depth interview. RESULTS: Twenty-five patients completed the study. The treatment group had significantly decreased pain and improved function as compared with the placebo and control groups. The qualitative Depth interview confirmed this result. CONCLUSION: Despite the small numbers, significant differences were found in improvement in function and pain for patients receiving therapeutic touch. A larger study is needed to confirm these results. Alternative therapies can neither be accepted nor rejected without being subjected to the scientific method.

Activities of Daily Living↗
PubMed1997

Skeletal muscle endurance training improves peripheral oxidative capacity, exercise tolerance, and health-related quality of life in women with chronic congestive heart failure secondary to either ischemic cardiomyopathy or idiopathic dilated cardiomyopathy.

Despite reported benefits of exercise training in men with chronic congestive heart failure (CHF) and in both men and women with coronary artery disease, the effects of training in women with CHF have not been throughly investigated. Therefore, 16 women (62 +/- 10 years [mean +/- SD]) with stable, moderate, chronic CHF (left ventricular ejection fraction 28 +/- 8%) were studied in a randomized crossover trial with 8 weeks of knee extensor endurance training and 8 weeks of nontraining. The effects of the exercise-based rehabilitation were assessed in skeletal muscle metabolic capacity, exercise tolerance, and quality of life. The compliance rate in training was 98% and no adverse events occurred during the study period. Training increased the activity of citrate synthase (44%, p <0.0001) and lactate dehydrogenase (23%, p <0.002) in the trained muscles, and an improved oxidative capacity in relation to the glycolytic capacity (23%, p <0.002) was found. Peak oxygen uptake (14%, p <0.0005) and peak work rate (43%, p <0.0001) during incremental exercise increased, and blood lactate concentration during standardized submaximal exercise and during the recovery phase decreased (17%, p <0.05). The distance ambulated during 6 minutes (p <0.03), and the overall (p <0.01), physical (p <0.05), and psychosocial (p <0.03) health-related quality of life improved. Because the skeletal muscle endurance training improved peripheral oxidative capacity, exercise tolerance, and the health-related quality of life without any adverse events, this mode of training can be recommended for women with chronic heart failure.

Adult↗
PubMed1997

The increasing efficacy of breast cancer treatment.

Breast cancer is the commonest malignancy in women and although identification of this multi-system disease has increased, the survival rates have not dramatically altered over the past four decades. Optimium treatment of patients with breast cancer is a subject of great debate and traditionally may be divided into surgery, radiotherapy, chemotherapy and hormone manipulation. Halsted's radical mastectomy, although initially superseded by more mutilating surgery involving removal of tumour, breast, pectoral muscles and axillary contents, has given way to more conservative surgery and breast conservation, so now removal of the tumour with a marginal of healthy tissue is possible. Additional loco-regional radiotherapy has added to the increasing number of treatment options available to both doctor and patient. Systemic adjuvant therapy, primarily hormonal therapy, is used with the aim of decreasing the incidence of recurrence and distant tumour development. Through the process of randomized controlled trials these new therapeutic treatments have shown to be effective in the treatment of locoregional disease. Surgery in patients with advanced systemic disease is limited, however radiotherapy is of considerable importance and can be used to treat or palliate sites of metastases. In recent years trials have assessed chemotherapeutic regimens. However, limited number of patients and adequate randomization have hindered the confident acceptance of these results. Cyclophosphamide, methotrexate and 5 fluorouracil still remain the standard chemotherapeutic regimen, however many new drugs are currently undergoing trials and these or combinations of these may prove to be of future clinical use. Dramatic advances in cell and molecular biology have allowed the development of novel breast cancer therapies. Specific oncogenes and loss of tumour suppressor genes have been associated with decrease patient survival, with the presence of lymph node metastases and with decreased relapse free survival. Growth factor receptor blockers and tyrosine kinase inhibitors may be developed to specifically eradicate breast cancer cells. Immunotherapy and gene therapy may produce effective therapies. Trials utilizing cytokines and trials increasing the immunogenicity of tumours have already reported promising results. Surgery, chemotherapy, radiotherapy and hormone manipulation are the major treatment arms of breast cancer therapy. However, breast cancer still accounts for 20 percent of all female cancer deaths and the overall survival of patients has remained relatively static over the past forty years. From our increasing understanding of the pathological processes involved in the development and spread of breast cancer, new pharmaceutical, immunological and gene therapies may dramatically increase the cure rate of this serious disease.

Breast Neoplasms↗
PubMed1997

Improved ventilation and decreased sympathetic stress in chronic heart failure patients following local endurance training with leg muscles.

BACKGROUND: Two-legged knee extensor training activates only about half the muscle mass used in traditional cycle ergometer training. With such an exercise model it is possible to achieve a substantial local training effect in spite of a restricted circulatory capacity. The present study sought to investigate the systemic effects of such local training on ventilation and neurohumoral activity in patients with moderate heart failure. METHODS AND RESULTS: Thirteen male patients with chronic heart failure (age 56 +/- 3 years, EF 28 +/- 3%) performed two-legged knee extensor exercises (about 4 kg of working muscle) for 15 minutes 3 times a week during 8 weeks at 65-75% of peak VO2 of a two-legged kick and were compared to a non-training control group (n = 7, age 62 +/- 3, EF 27 +/- 3%). Before and after the training period VO2, VCO2 and the minute ventilation (1/min) were determined at rest and at submaximal and maximal workloads. Also measured before and after training were two-legged knee extensor peak exercise capacity (W), strength (Nm), a 6-minute walking test (m), quadriceps femoris citrate synthase activity, plasma catecholamines, vasoactive amines and blood lactate during submaximal knee extension exercise, and perceived health-related quality of life. After training, VO2 and VCO2 were reduced at submaximal exercise by 20-30% (P < .01) but were unchanged at peak exercise. With training, the two-legged knee extensor peak exercise capacity increased by 38% (P < .01). The 6-minute walking gait velocity increased by 12% (P < .01) and skeletal muscle citrate synthase activity by 28% (P < .01). Training improved the quality of life (P < .01). After training, VO2 (P < .001), VCO2 (P < .001) and minute ventilation (P < .001) were reduced at the workload corresponding to the maximal workload before training. The ratio minute ventilation/VO2 was reduced (P < .05) after training at the before-training maximal workload. No change was observed in the control group with regard to two-legged peak exercise capacity or peak VO2. Plasma NPY was reduced both at rest and at submaximal exercise by 35% (P < .01), whereas noradrenaline was reduced only during exercise (P < .05). CONCLUSIONS: Local muscle training is effective in stable chronic heart failure and can improve, in addition to exercise capacity and quality of life, the ventilatory response, and decrease the sympathetic stress.

Adult↗
PubMed1997

The use of mapping in public health and planning health services.

The availability of relatively inexpensive, user-friendly geographical information systems, with a steadily extending range of analytic and other facilities, provides a powerful tool for the analysis and display of the increasing number of health-related data sets, and for their greater accessibility. Relationships between several sets of variables can become immediately apparent from a map in a way that is much more difficult to comprehend from a table or description. It is also easy to define ad hoc areas, such as the area adjacent to a possible toxic point source or to a main road, in terms of unit postcodes and Census output areas, to determine standardized rates for mortality and hospital admissions. Apart from the geographical information system itself, the basic requirements are access to relevant data sets including Census data, and to the central postcode directory, which provides grid references for unit postcodes and permits matching of postcoded health events to Census output areas.

Catchment Area, Health↗
PubMed1997

Topotecan versus paclitaxel for the treatment of recurrent epithelial ovarian cancer.

PURPOSE: Topotecan and paclitaxel were evaluated in a randomized, multicenter study of patients with advanced epithelial ovarian carcinoma who had progressed during or after one platinum-based regimen. PATIENTS AND METHODS: Patients received either topotecan (1.5 mg/m2) as a 30-minute infusion daily for 5 days every 21 days (n = 112) or paclitaxel (175 mg/m2) infused over 3 hours every 21 days (n = 114). Patients had bidimensionally measurable disease and were assessed for efficacy and toxicity. RESULTS: Response rate was 23 of 112 (20.5%) in topotecan-treated patients and 15 of 114 (13.2%) in paclitaxel-treated patients (P = .138). Disease stabilization for at least 8 weeks was noted in 30% of patients with topotecan and 33% of patients with paclitaxel. Median durations of response to topotecan and paclitaxel were 32 and 20 weeks, respectively (P = .222) and median times to progression were 23 and 14 weeks, respectively (P = .002). Median survival was 61 weeks for topotecan and 43 weeks for paclitaxel (P = .515). Response rates for topotecan and paclitaxel were 13.3% versus 6.7% (P = .303) in resistant patients (not responded to prior platinum-based therapy or progressed within 6 months of an initial response) and 28.8% versus 20.0% (P = .213) in sensitive patients (progressed > 6 months after response). Neutropenia was significantly more frequent on the topotecan arm 79% versus paclitaxel arm 23% (P < .01). It was short-lasting and noncumulative in both arms. Nonhematologic toxicities were generally mild (grades 1 to 2) for both agents. CONCLUSION: Topotecan has efficacy at least equivalent to paclitaxel manifested by the higher response rate and significantly longer time to progression.

Adult↗
PubMed1997

Crosstalk of the heart and periphery: skeletal and cardiac muscle as therapeutic targets in heart failure.

Heart failure syndrome is initiated as the body's metabolic needs temporarily exceed the pumping capacity of the heart. In most cases, this phenomenon tends to occur during physical exercise. Although not always subjectively recognized, limited exercise capacity remains the clinical hallmark of congestive heart failure. It can be measured objectively as reduced skeletal muscle performance and maximal whole-body oxygen uptake, which are not necessarily explained by central haemodynamic abnormalities. In fact, the initial cardiac condition sets forth a series of peripheral adaptations that are potentially life-saving during acute decompensation but become disadvantageous and symptom-generating in stable heart failure. Inodilator drugs were theoretically ideal to revert the adverse haemodynamic crosstalk between the heart and periphery. However, these drugs failed to improve prognosis in congestive heart failure, whereas drugs that did so showed typically unimpressive haemodynamic effects. Exercise therapy has recently emerged as a safe and effective way to enhance physical performance and subjective well-being in congestive heart failure. A dual therapeutic approach is suggested, consisting of exercise training to improve the periphery and the use of cardioprotective drugs to limit cardiac cellular damage from neurohormonal activation.

Adrenergic beta-Antagonists↗
PubMed1997

A double-blind, placebo-controlled pilot study of carbamazepine for the treatment of alcohol dependence.

Carbamazepine, chemically related to the tricyclic antidepressants, has multiple clinical actions. It is a potent anticonvulsant, mild sedative, and mood stabilizer. It is nonaddictive and has little toxicity when clinical and laboratory monitoring is performed. It has proven efficacy in the treatment of acute alcohol withdrawal. Kindling and protracted withdrawal are the theoretical rationale for the mechanism of its action in the treatment of alcohol dependence. This 12-month double-blind placebo-controlled pilot study of 29 subjects evaluated the efficacy of carbamazepine for the treatment of alcohol dependence. Subjects were randomly assigned to either placebo or carbamazepine. A baseline assessment and bimonthly follow-up for 12 months assessed demographic variables, mood and functioning, treatment compliance, drinking behaviors, biological markers of drinking, and medication toxicity. Despite the small sample size, compliance difficulties after 4 months and a sizable drop-out rate, there were treatment effects favoring carbamazepine. Univariate analyses showed a decrease in drinks per drinking day and maximum number of heavy drinking days in a row at 2 and 4 months of follow-up. Survival analysis revealed a significant delay in time to first episode of heavy drinking, and close to a trend level of significance for time to first drink. There were significant time, but not time by treatment group, effects on multiple measures of mood. These pilot results are encouraging and support carbamazepine as a possible pharmacologic tool in the treatment of alcohol dependence.

Adult↗
PubMed1997

Efficacy and safety of topotecan in the treatment of advanced ovarian carcinoma.

Topotecan (Hycamtin; SmithKline Beecham Pharmaceuticals, Philadelphia, PA) has emerged as a promising new chemotherapy drug for patients with refractory and progressive stage III and IV epithelial ovarian carcinoma. A semisynthetic analog of camptothecin, topotecan exerts its antitumor effects through inhibition of the nuclear enzyme topoisomerase I. Phase I trials found antitumor activity in many topotecan dosing schedules, one of which involved the administration of topotecan daily as a 30-minute infusion for 5 consecutive days, with the cycle repeated every 21 days. With this schedule, the maximum tolerated dose was found to be 1.5 mg/m2/d. In a series of phase II investigations in platinum-resistant ovarian cancer patients, response rates have ranged from 13% to 25%. In addition, a number of patients exhibit prolonged disease stabilization, with overall rates of nonprogression ranging from 37% to 81%. Activity in paclitaxel-resistant patients is also seen, with a multicenter phase II trial showing a response rate of 13% among first-line paclitaxel failures and 14.3% among second-line failures. A phase III trial compared topotecan and paclitaxel as second-line therapies in 226 advanced ovarian cancer patients who had been previously treated with platinum-containing regimens. Preliminary data show that patients treated with topotecan evidenced a higher response rate (23% v 14%), longer response duration (32 weeks v 20 weeks), and significantly longer time to progression (23 weeks v 14 weeks; P = .002). Additional schedules are still being evaluated, with a phase II trial of prolonged infusion of relatively low-dose topotecan over 21 days demonstrating a 37% response rate in 16 patients. All phase II and III trials analyzed thus far indicate that topotecan is well tolerated with an acceptable toxicity profile, with myelosuppression as the dose-limiting toxicity. Hematologic toxicities are predictable, of short duration, and noncumulative. Mild to moderate nonhematologic toxicities are manageable. These findings demonstrate that topotecan is a viable new second-line or salvage treatment for patients with advanced ovarian cancer who are refractory or resistant to prior chemotherapy, including platinum-based agents and/or paclitaxel.

Antineoplastic Agents↗
PubMed1996

Markedly improved skeletal muscle function with local muscle training in patients with chronic heart failure.

BACKGROUND: Reduced heart pump function and skeletal muscle abnormalities are considered important determinants for the low physical exercise capacity in chronic heart failure. Because of reduced ventricular function, traditional physical rehabilitation may cause underperfusion and low local work intensity, thereby producing suboptimal conditions for skeletal muscle training. HYPOTHESIS: The study was undertaken to determine the effects of local exercise training, designed as one- or two-legged knee extensor training, on exercise capacity in patients with moderate chronic heart failure. Because such exercise models use only about one quarter to half the muscle mass used in cycle ergometer training, the influence of a restricted circulatory capacity should therefore be limited. Further, we aimed to determine whether or not chronic heart failure skeletal musculature abnormalities are counteracted with such training. METHODS: Fourteen patients with chronic heart failure [age 58 +/- 3 years, ejection fraction (EF) 28 +/- 4%] were randomized to two different training protocols three times a week for 8 weeks and compared with a nontraining control group (n = 7, age 62 +/- 3, EF 27 +/- 3%). Group 2L (n = 7) underwent simultaneous two-legged knee extensor training (about 4 kg working muscle) for 15 min at 65-75% of VO2 max of the two-legged kick. Group 1L (n = 7) trained each leg at a time for 15 min of continuous one-legged dynamic knee extensor work with the same training load per muscle mass, that is, at 35% of VO2 max of the two-legged kick (about 2 kg working muscle). Peak VO2 of two-legged knee extensor exercise (l/min), two-legged endurance (W), and strength (Nm) were determined before and after the training period. The activity of citrate synthase (CS) was estimated in tissue samples from the quadriceps femoris muscle. RESULTS: Peak VO2 did not change with training. Two-legged knee extensor endurance exercise capacity increased by an average of 40-50% (p < 0.01) in all training patients in both the 2L and 1L groups, while no change was observed in the control group. Depressed skeletal muscle CS activity increased by 25-35% in both training groups (p < 0.01). Strength increased by 16% in the 2L group after training (p < 0.05), while no change was seen in the 1L and control groups. CONCLUSIONS: Skeletal muscle changes in stable moderate chronic heart failure are not entirely irreversible. A major factor contributing to these changes and to exercise limitation is deconditioning. Local muscle training is efficient and can at least partially improve skeletal muscle function in these patients. Different degrees of local activation, that is, one- or two-legged knee extensor exercise, do not seem to differ in terms of their effect on exercise capacity. Depressed skeletal muscle oxidative capacity adapts to such physical training with increased activity to an extent not different from that for healthy volunteers.

Adaptation, Physiological↗
PubMed1996

Improved quality of life in chronic heart failure patients following local endurance training with leg muscles.

BACKGROUND: Despite reported benefits of exercising for chronic heart failure patients, limited data are available on quality of life and the effects of different modes of training. This study assessed the effects of local endurance training with knee extensor muscles on exercise tolerance and health-related quality of life in male patients with moderate, chronic heart failure. METHODS AND RESULTS: Twenty-one patients (mean age, 60 years; range, 43-73 years) in New York Heart Association functional classes II-III (ejection fraction, 28 +/- 11%) were randomized to two training groups and one control group. Both training groups performed the same relative quantity of dynamic work with knee extensor muscles 3 days a week for 8 weeks. However, the quantity of muscle mass trained at one time and, consequently, the load on the integrated circulation differed between the groups (two-and one-leg training). Exercise capacity and perceived quality of life were assessed before and after the training or control period. Exercise tolerance increased (P < .01) in both training groups with significantly (P < .01) better improvement in submaximal exercise capacity in the two-leg group. There was no improvement in the control group. Coping capacity did not differ from the reference range and did not change during the study. Global health-related quality of life was depressed at baseline. Training improved (P < .05) health-related quality of life. Compared with the control group, the improvement of health-related quality of life subscales was more pronounced in the two-leg training group (P < .02-.005) as compared to the one-leg training group (not significant to P < .05). CONCLUSIONS: Local muscle endurance training has beneficial effects on exercise tolerance and health-related quality of life in patients with moderate, chronic heart failure. As two-leg training showed a tendency toward better improvement in submaximal exercise capacity and in quality of life than one-leg training, the effects on quality of life appear to be exercise-related in addition to a possible placebo-related effect. Also, the effect appears to be related to the extent of muscle trained at one time.

Adult↗
PubMed1996

Relationship between p53 status and radiosensitivity in human tumour cell lines.

We examined the relationship between p53 levels before and after irradiation, radiation-induced cell cycle delays, apoptotic cell death and radiosensitivity in a panel of eight human tumour cell lines. The cell lines differed widely in their clonogenic survival after radiation, (surviving fraction at 2 Gy: SF2=0.18-0.82). Constitutive p53 protein levels varied from 2.2 +/- 0.4 to 6.3 +/- 0.3 optical density units (OD) per 10(6) cells. p53 after irradiation (6 Gy) also varied between the cell lines, ranging from no induction to a 1.6-fold increase in p53 levels 4 h after treatment. p53 function was also assessed by G1 cell cycle arrest after irradiation. The cellular response to radiation, measured as G0/G1 arrest, and the induction of apoptosis were in good agreement. However, a trace amount of DNA ladder formation was found in two cell lines lacking G1 arrest. Overall cellular radiosensitivity correlated well with the level of radiation-induced G1 arrest (correlation coefficient r=0.856; P=0.0067), with p53 constitutive levels (r=0.874, P=0.0046), and with p53 protein fold induction (r=-0.882, P=0.0038). Our data suggest that (1) the constitutive p53 level, (2) G1 arrest after irradiation, or (3) the p53 protein response to radiation may be good predictive tests for radiosensitivity in some cell types.

Apoptosis↗