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Biomedical subjects

M Middleton

Publications and source records attributed to M Middleton.

At least 19 recordsLinked to original sources
PubMed2006

Temozolomide in combination with celecoxib in patients with advanced melanoma. A phase II study of the Hellenic Cooperative Oncology Group.

BACKGROUND: There is now increasing evidence that a constitutive expression of cyclooxygenase (COX)-2 plays a role in the development and progression of malignant epithelial tumors. Expression of COX-2 is seen in 93% of melanomas, as determined by immunohistochemistry. Temozolomide (TMZ) has demonstrated activity against melanoma and has been investigated as single agent or in combination. We designed a phase II study to assess the efficacy and toxicity of the combination of TMZ and celecoxib (a COX-2 inhibitor) in patients with advanced melanoma. PATIENTS AND METHODS: From January 2003 to July 2004, 52 patients were enrolled in the study. Nineteen patients were M1a, six M1b and 27 M1c. Patients received TMZ 200 mg/m(2) per day p.o. for 5 consecutive days every 4 weeks and celecoxib 400 mg b.i.d. p.o. for a maximum of six cycles. Celecoxib was continued until progression. RESULTS: The median age was 63 years. There were 29 males and 23 females. Among 50 assessable patients, there were 11 (21.5%) objective responses including five complete responses and six partial responses. Twenty patients (38.5%) had stabilization of their disease, and 19 (36.5%) progressed. The median time to progression was 4.6 months and the median survival 9.5 months. Twenty-two patients (41.5%) completed all cycles of treatment. Median relative dose intensity of TMZ was 0.99 (range 0.6-1.2). Most commonly seen toxic effects included anemia (27.5%), neutropenia (17.5%), thrombocytopenia (33%), nausea/vomiting (75%), gastrointestinal (52%) and fatigue (46.5%). One patient discontinued due to severe toxicity. COX-2 was determined by immunohistochemistry and was expressed in all cases. CONCLUSION: The combination of TMZ and celecoxib is safe and potentially effective in the treatment of metastatic melanoma. Randomized studies are needed to explore the role of celecoxib in combination with chemotherapy or as maintenance treatment in these patients.

Antineoplastic Agents, Alkylating↗
PubMed2005

Two randomised phase II trials of subcutaneous interleukin-2 and histamine dihydrochloride in patients with metastatic renal cell carcinoma.

Histamine inhibits formation and release of phagocyte-derived reactive oxygen species, and thereby protects natural killer and T cells against oxidative damage. Thus, the addition of histamine may potentially improve the efficacy of interleukin-2 (IL-2). Two randomised phase II trials of IL-2 with or without histamine dihydrochloride (HDC) in patients with metastatic renal cell carcinoma (mRCC) were run in parallel. A total of 41 patients were included in Manchester, UK and 63 in Aarhus, Denmark. The self-administered, outpatient regimen included IL-2 as a fixed dose, 18 MIU s.c. once daily, 5 days per week for 3 weeks followed by 2 weeks rest. Histamine dihydrochloride was added twice daily, 1.0 mg s.c., concomitantly with IL-2. A maximum of four cycles were given. The Danish study showed a statistically significant 1-year survival benefit (76 vs 47%, P = 0.03), a trend towards benefit in both median survival (18.3 vs 11.4 months, P = 0.07), time to PD (4.5 vs 2.2 months, P = 0.13) and clinical benefit (CR + PR + SD) (58 vs 37%, P = 0.10) in favour of IL-2/HDC, whereas the UK study was negative for all end points. Only three patients had grade 4 toxicity; however, two were fatal. A randomised phase III trial is warranted to clarify the potential role of adding histamine to IL-2 in mRCC.

Adult↗
PubMed2003

Biological activity of serotonin conjugates from the seeds of Centaurea nigra.

Two serotonin conjugates, N-(trans-p-coumaroyl)-serotonin (1) and N-(trans-feruloyl)-serotonin (maoschamine, 2), isolated from the methanol extract of the seeds of Centaurea nigra, have been assessed for antibacterial and free radical scavenging activities. The general toxicity of 1 and 2 has also been determined by the brine shrimp lethality bioassay.

Animals↗
PubMed1998

The Development and Validation of Scales Assessing Students' Achievement Goal Orientations

Achievement goal theory has emerged as a major new direction in motivational research. A distinction is made among conceptually different achievement goal orientations including the goal to develop ability (task goal orientation), the goal to demonstrate ability (ability-approach goal orientation), and the goal to avoid the demonstration of lack of ability (ability-avoid goal orientation). Scales assessing each of these goal orientations were developed over an eight year period by a group of researchers at the University of Michigan. The results of studies conducted with seven different samples of elementary and middle school students are used to describe the internal consistency, stability, and construct validity of the scales. Comparisons of these scales with those developed by Nicholls and his colleagues provide evidence of convergent validity. Confirmatory factor analysis attests to the discriminant validity of the scales. Copyright 1998 Academic Press.

Journal Article↗
PubMed1998

G- and GM-CSF.

Explore the source record for details and available documents.

Fever↗
PubMed1998

A randomized phase II trial of interleukin 2 and interleukin 2-interferon alpha in advanced renal cancer.

A randomized phase II trial was performed to compare the efficacy and toxicity of interleukin 2 (IL-2) with an IL-2 and interferon alpha (IFN-alpha) regimen for the treatment of metastatic renal carcinoma. Sixty patients with recurrent renal cell carcinoma (RCC) who had previously undergone a nephrectomy were randomized to receive three cycles of IL-2 or IL-2 with IFN-alpha2b. Eighteen MU of IL-2 were administered subcutaneously on Mondays-Fridays for 3 weeks out of 4. Those patients randomized to receive the combination received the same regimen of IL-2 with 9 MU of IFN-alpha2b subcutaneously on Mondays, Wednesdays and Fridays for 3 weeks out of 4. Thirty patients were randomized to receive each arm. Twenty-nine were evaluable in each arm. Twenty-two patients received three cycles of IL-2 but only 14 patients received three cycles of IL-2/IFN-alpha because of the greater toxicity of the combination. The principal toxicities included nausea, fatigue and fever. There were no complete responses in either arm and only two patients who were treated with IL-2 attained a partial response. Twelve patients in each arm had stable disease and 15 patients in the IL-2 arm and 16 patients in the IL-2/IFN-alpha arm progressed through treatment. There were no significant differences in survival. Ten patients who received IL-2 are alive with a median follow-up of 266 days, whereas six patients who received IL-2/IFN-alpha are alive after a median of 278 days. The median survival from the time of identification of metastatic disease is 444 days in the IL-2 arm and 381 days in the IL-2/IFN-alpha arm. The IL-2/IFN-alpha combination is more toxic than IL-2 alone and this resulted in a reduced number of cycles of treatment. However, the median survival of the two groups was the same, suggesting that further evaluation of the IL-2/IFN-alpha combination should be confined to large prospective randomized clinical trials.

Adult↗
PubMed1998

Dose intensity in small cell lung cancer.

Evidence from preclinical models and from clinical trials describing the importance of dose intensity in securing a better treatment outcome is reviewed. Recent randomized trials have shown statistically significant survival benefits with higher-dose, accelerated chemotherapy regimens with and without granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor. The novel use of peripheral blood progenitor cells contained in whole blood autotransfusions, which allow a marked increase in dose intensity of an ifosfamide/carboplatin/etoposide regimen, could provide a much easier method of delivering dose-intensive chemotherapy than previously available.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Peak flow based asthma self-management: a randomised controlled study in general practice. British Thoracic Society Research Committee.

BACKGROUND: Peak flow based asthma self-management plans have been strongly advocated in consensus statements, but convincing evidence for the effectiveness of this approach has been largely lacking. METHODS: A randomised controlled trial was conducted in 25 general practices comparing an asthma self-management programme based on home peak flow monitoring and surgery review by a general practitioner or practice nurse with a programme of planned visits for surgery review only over a six month period. RESULTS: Seventy two subjects (33 in the self-management group and 39 in the planned visit group) completed the study protocol, but diary card data for at least three months were available on a total of 84 (39 in the self-management group and 45 in the planned visit group). Teaching self-management took longer than the planned visit review. In the self-management group home peak flow monitoring was felt to be useful by doctors and patients in 28 (85%) and 27 (82%) cases, respectively. There were no between group differences during the study period in terms of lung function, symptoms, quality of life, and prescribing costs. Only within the self-management group were improvements noted in disturbance of daily activities and quality of life. Possible explanations for these negative results include small numbers of subjects, the mild nature of their asthma, and inappropriate self-management strategies for such patients. CONCLUSIONS: Rigid adherence to long term daily peak flow measurement in the management of mild asthma in general practice does not appear to produce large changes in outcomes. Self-management and the use of prescribed peak flow meters need to be tailored to individual circumstances.

Adolescent↗
PubMed1992

Targeting asthma care in general practice using a morbidity index.

OBJECTIVES: To evaluate a morbidity index as a postal surveillance tool in defining previously diagnosed asthmatic patients needing extra education or management; to determine the accuracy of a computerised asthma register in general practice. DESIGN: Postal questionnaire survey of asthmatic patients identified from a computer register. Questionnaire comprised three morbidity questions, two questions about current asthma status, and one about treatments. SETTING: Urban general practice of 8400 patients linked to academic unit. SUBJECTS: 853 asthmatic patients of all ages. MAIN OUTCOME MEASURES: Numbers of patients with low, medium, and high morbidity; associations of these groups with age, asthma status, and drugs taken. RESULTS: Two mailings yielded 621 replies (73%); 28 patients (5%) had moved away, leaving 593 for analysis. Attempts were subsequently made to contact 20% sample of non-respondents. 234 respondents (40%) were in the "low morbidity" group, 149 (25%) in the "medium morbidity" group, and 210 (35%) in the "high morbidity" category. 53% of patients perceiving themselves as currently asthmatic (193/362) were in the high morbidity group, but 7% (11/153) who said they were no longer asthmatic and 8% (6/78) who did not believe they had ever been asthmatic were also in that group. High morbidity was also found in 10% (18/185) of those on no treatment, 38% (59/154) of those on bronchodilators alone, and 54% (119/220) of those on inhaled corticosteroids. 25 patients (4%) were wrongly identified as asthmatic; when combined with returns marked "gone away" this gave a disease register accuracy of 91%. CONCLUSIONS: This exercise identified subgroups of previously diagnosed asthmatic patients with high morbidity in general practice who might benefit from extra education and management and revealed some misclassification on the asthma disease register.

Asthma↗
PubMed1992

Correlates of asthma morbidity in primary care.

OBJECTIVES: To explore the morbidity of patients diagnosed as asthmatic in general practice, to examine the determinants of this morbidity, and to derive a simple morbidity screening tool for use in primary care. DESIGN: Patient interviews, lung function measurements, and data extraction from general practice case notes. SUBJECTS: 300 asthmatic patients aged 5 to 65 years randomly selected from the repeat prescribing registers of three general practices in the Southampton area. MAIN OUTCOME MEASURES: Reported morbidity using a calculated index based on three questions (Are you in a wheezy or asthmatic condition at least once per week; Have you had time off work or school in the past year because of your asthma; Do you suffer from attacks of wheezing during the night?); mean forced expiratory volume in one second and mean peak expiratory flow (over a seven day period); diurnal variation in peak flow; and the relation of the morbidity index to lung function. RESULTS: Mean forced expiratory volume in one second was 67% predicted (SD 18.4), mean peak expiratory flow was 80% predicted (SD 18.9), and mean diurnal variation was 10% (SD 7.7). 76 subjects were classified as having low morbidity, 95 medium, and 125 high. The morbidity index was significantly associated with forced expiratory volume in one second, mean peak expiratory flow rate, and diurnal variation (p less than 0.05); it was not significantly associated with inhaler technique or use of prophylaxis. CONCLUSIONS: There was a large burden of persisting morbidity across all ages of patients diagnosed as asthmatic in the three well resourced practices studied. The use of the morbidity index may help to target the asthmatic patients needing more attention by concentrating on those reporting medium to high morbidity.

Absenteeism↗
PubMed1992

MR imaging of the pituitary gland in infants and children: changes in size, shape, and MR signal with growth and development.

It has been reported that on MR images of the brain in neonates the entire pituitary gland is hyperintense. This is quite different from the well-established observation that portion is isointense. To better understand the development of the neonatal pituitary gland, we studied the timing and magnitude of changes in the size, shape, and MR signal of the pituitary gland in early childhood and infancy. The study included 76 infants and children ages 3 days to 4 years old. In each MR study, the signal intensity of the pituitary gland on T1-weighted coronal (n = 24) and sagittal (n = 76) images was compared with the signal intensity of the pons by using region-of-interest methods. The size and shape of the pituitary glands were recorded. Statistical comparisons were made for signal intensity and size of the pituitary gland between boys and girls and among age groups. The results showed that the MR signal of the posterior lobe remained hyperintense relative to the pons for all age groups represented in our study (through 4 years). However, the signal intensity of the anterior lobe gradually diminished and by approximately age 2 months was isointense with the pons. Thus, by approximately age 2 months the MR signal intensity of the infant's pituitary gland has changed from being entirely hyperintense (as seen in neonates) to isointense in the anterior lobe and hyperintense in the posterior lobe (as seen in adults). In the first 2 months of life the pituitary gland is bulbous in shape; later it has a flatter upper surface. We found no significant changes in the length or signal intensity of the pituitary gland; no differences among sexes in size, shape, or signal intensity were demonstrated. Findings of a bulbous pituitary gland and high MR signal of the entire pituitary are normal in neonates up to 2 months of age. After that, the gland gradually flattens and the MR signal of the anterior lobe decreases until it has characteristics similar to the adult pituitary. Lack of high signal or discovery of a small pituitary gland in a neonate should alert the radiologist to the possibility of pituitary malformation or dysfunction.

Child, Preschool↗