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Biomedical subjects

M E O'Brien

Publications and source records attributed to M E O'Brien.

At least 37 records · Page 2Linked to original sources
PubMed1996

Relief of suffering: where the art and science of medicine meet.

The physical, emotional, and spiritual components of suffering are myriad. Fortunately, physicians have available an ever-increasing array of scientific advances to provide relief and comfort from physical pain and distress. Relief of the emotional and spiritual suffering that is part of the human condition requires more--it requires physicians to look beyond the bounds of clinical treatment and draw upon the time-honored wisdom of the art of medicine.

Analgesics↗
PubMed1996

The prognostic implications of chemotherapy in the treatment of breast cancer.

Randomized trials with long follow-up confirm the beneficial effect of adjuvant chemotherapy in most groups of patients with operable breast cancer. The use of chemotherapy in large tumours before surgery does not appear to jeopardize survival. High-dose chemotherapy and the use of taxoids may change the natural history of metastatic disease.

Breast Neoplasms↗
PubMed1995

Hutchinson-Gilford progeria fibroblasts exhibit metabolically normal uridine uptake and RNA synthetic rates.

The accelerated aging disease Hutchinson-Gilford progeria syndrome displays altered messenger RNA levels in cultured fibroblasts, yet little is known of effects on transcription by RNA polymerases other than RNA polymerase II. Total RNA metabolism was examined by incubation of Hutchinson-Gilford progeria fibroblasts with [5-3H]uridine in asynchronous culture. Uptake of radiolabel was quantitative and was incorporated preferentially (99 +/- 0.3%) into newly synthesized RNA. Progeria and control cultures showed comparable rates of uptake of radiolabel, time courses of RNA synthesis, and relative intensity profiles of newly synthesized ribosomal RNA. These characteristics held over a greater than ten-fold range of cell densities (5 x 10(3) to 8 x 10(4) cells/cm2). Progeria and control fibroblasts thus have comparable metabolic capacities for uridine uptake and net RNA production, emphasizing the relative specificity of transcriptional changes previously identified in progeria cells.

Biological Transport↗
PubMed1995

Epirubicin, cisplatin and infusional 5-fluorouracil (5-FU) (ECF) in hepatobiliary tumours.

Hepatobiliary tumours are rare, often present late and have a poor prognosis, with no current effective systemic therapy available. This study aimed to evaluate the activity and toxicity of epirubicin, cisplatin and continuous infusional 5-fluorouracil (5-FU) (ECF) in patients with these tumours. From March 1991 to November 1993, 25 patients with advanced biliary tumours and 7 with hepatoma were treated with epirubicin 50 mg/m2 and cisplatin 60 mg/m2 intravenously (i.v.) day 1, each given every 21 days and 5-FU 200 mg/m2/day given as a continuous 24 h i.v. infusion throughout the treatment course. 8 of the 20 (40%) evaluable patients with biliary tumours responded. Median duration of response was 10 months. 2 of the 7 (29%) patients with hepatoma responded. The regimen was well tolerated with minimal haematological and non-haematological toxicity. This novel regimen is active in advanced hepatobiliary tumours.

Adult↗
PubMed1995

Randomized trial of chemoendocrine therapy started before or after surgery for treatment of primary breast cancer.

PURPOSE: To evaluate in a randomized clinical trial systemic chemoendocrine therapy used as primary (neo-adjuvant) treatment before surgery in women with primary operable breast cancer. PATIENTS AND METHODS: Patients aged less than 70 years with clinically palpable, primary operable breast cancer diagnostically confirmed by fine-needle aspiration cytology (FNAC) and suitable for treatment with surgery, radiotherapy, cytotoxic chemotherapy, and tamoxifen were considered eligible. Patients randomized to neoadjuvant treatment received four cycles of chemo-therapy for 3 months before surgery followed by another four cycles after surgery, and were compared with patients randomized to adjuvant therapy who received eight cycles of chemotherapy over 6 months after surgery. RESULTS: Of 212 patients who were randomized to receive either adjuvant (n = 107) or neoadjuvant (n = 105) chemoendocrine therapy, 200 are now assessable for response. The two groups are comparable for age, menopausal status, disease stage, and surgical requirements. The overall clinical response rate was 85%, with a complete histologic response rate of 10%. There was a significant reduction in the requirement for mastectomy in patients who received neoadjuvant treatment (13%) as compared with those who received adjuvant therapy (28%) (P < .005). Symptomatic and hematologic acute toxicity was low and similar for adjuvant and neoadjuvant therapy. The median follow-up period for patients in this trial is 28 months, during which time four patients have relapsed locally and 20, including one of the local relapses, have developed metastatic disease, 19 of whom have died. The follow-up period is too brief to evaluate relapse rate or survival duration. CONCLUSION: This trial confirms previous reports of a high rate of response to neoadjuvant therapy, but is the first to include small primary cancers and to show, in the context of a randomized trial, a reduction in the requirement for mastectomy. Until disease-free and overall survival data are available from the larger National Surgical Adjuvant Breast and Bowel Project (NSABP)-18 trial, such neoadjuvant treatment cannot be recommended outside of a clinical trial.

Adult↗
PubMed1995

Undercarboxylated osteocalcin and development of a method to determine vitamin K status.

We developed a RIA involving a polyclonal antibody against bovine osteocalcin, which has a carboxy-terminal epitope. Although the antibody recognizes both native and descarboxy osteocalcin, the two forms of osteocalcin were differentiated by adsorption to barium sulfate, taking advantage of the calcium-binding properties of the vitamin K-dependent gla domain. To test the clinical application of undercarboxylated osteocalcin, we examined the effect of minidose warfarin on this measure in nine healthy subjects, ages 60 to 80 years. The percentage of undercarboxylated osteocalcin increased by 170% +/- 36% (mean +/- SE) after 7 days of treatment with warfarin, 1 mg/day. The effectiveness of undercarboxylated osteocalcin as a sensitive measure of vitamin K nutritional status was further established when concentrations dropped to 17% +/- 14% below baseline with 2 days of repletion with vitamin K1, 5 mg/day, during which prothrombin times did not leave the normal range.

Adsorption↗
PubMed1995

The role of chemotherapy for metastatic gastric cancer.

Gastric cancer is one of the most chemosensitve tumors of the gastrointestinal tract. Chemotherapy treatment in patients with metastatic disease has been shown to improve quality of life and prolong survival. There are a number of second-generation active regimens that give high response rates and are currently being assessed in phase III studies. Ultimately these regimens will find their role in the preoperative and adjuvant setting. At present, in patients with metastatic disease, there is a need to compare these regimens to single-agent schedules with less toxicity. Continued optimism is necessary in gastric cancer with new types of drugs, high-dose treatment and revisiting old drugs--all potential ways of increasing the cure rate in this disease.

Antineoplastic Agents↗
PubMed1995

Assessment of dietary phylloquinone intake and vitamin K status in postmenopausal women.

OBJECTIVE: To examine the relationship between dietary phylloquinone intake and vitamin K status of postmenopausal Caucasian women. DESIGN: Cross-sectional study, in which dietary intake was estimated using weighed record techniques and vitamin K status was measured by a single plasma phylloquinone concentration and 24-h urinary gamma-carboxyglutamic acid (Gla) excretion. SETTING: The metabolic research unit at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA. SUBJECTS: 402 healthy postmenopausal Caucasian women who were participating in a randomized trial to determine the effect of calcium supplementation on bone loss. Of the original group, 362 had complete weighed diet records, 358 had corresponding plasma phylloquinone concentrations, and 346 had corresponding urinary Gla measurements. RESULTS: There was a significant correlation (r = 0.13, P = 0.01) between total dietary intake of phylloquinone (geometric mean = 89 micrograms/day) and plasma phylloquinone levels (mean = 1.12 nmol/l). Dietary intake was neither correlated with urinary Gla excretion (mean = 4.0 mumol/mmol creatinine) nor did it vary by season. The ratio of intra- to interindividual variance in phylloquinone intake was 2.6, from which it was estimated that 5 days of independent recording is necessary to estimate true usual dietary intake, assuming a correlation of 0.8. CONCLUSIONS: A weighed record has the potential to be a reliable method for estimating dietary intakes of vitamin K which relate to plasma phylloquinone levels used as an indicator of vitamin K status in postmenopausal Caucasian women.

1-Carboxyglutamic Acid↗
PubMed1994

The Royal Marsden Hospital pilot tamoxifen chemoprevention trial.

A pilot randomised placebo controlled trial using tamoxifen in healthy women at increased risk of developing breast cancer, has been undertaken in order to evaluate the problems of accrual, acute symptomatic toxicity, compliance, and safety as a basis for subsequent large national multicentre trials designed to test whether tamoxifen can chemoprevent breast cancer. From October 1986 until June 1993, 2012 healthy women with an increased risk of developing breast cancer, usually because of a strong family history, were randomly allocated to receive tamoxifen 20 mgs/day or placebo for up to 8 years if possible. Accrual remained high in spite of extensive informed consent regarding potential risk. Acute symptomatic toxicity was low for participants on tamoxifen or placebo and compliance remained correspondingly high with a predicted 77% of women on tamoxifen and 82% of women on placebo continuing medication at 5 years. There was a significant increase in hot flushes (34% versus 20%) mostly in premenopausal women (p < 0.005), vaginal discharge (16% versus 4%, p < 0.005), and menstrual irregularities (14% versus 9%, p < 0.005). The requirements for hormone replacement therapy for women on tamoxifen or placebo were the same. Safety monitoring indicates no adverse anti oestrogenic effects of tamoxifen. There was no obvious effect of tamoxifen on bone mineral densities (single photon radial absorption). The fibrinogen and antithrombin III were both lowered, resulting in no observed detrimental effect on the ratio of these clotting factors. There was a significant reduction in the serum cholesterol maintained out to 5 years. Annual pelvic assessment using transvaginal ultrasound indicates an increased incidence of uterine fibromata and benign ovarian cysts.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Steroid hormone profile in postmenopausal women with ovarian cancer.

Raised levels of steroid hormones are not expected in postmenopausal women. Therefore, if detected in postmenopausal women with ovarian cancer, they must be assumed to be related to the presence of the tumour and, therefore, may be of use as tumour markers. Serum levels of CA125, progesterone, 17-hydroxyprogesterone, sex hormone binding globulin and oestradiol were measured in 44 postmenopausal women with ovarian cancer, postsurgery and prior to chemotherapy. The relationship between the four hormone levels, CA125, patient age, stage, residual disease after surgery and differentiation were tested using the Spearman and Kendall rank coefficients. A significant inverse association was found between CA125 and progesterone levels, and CA125 and 17-hydroxyprogesterone. A positive association between 17-hydroxyprogesterone and progesterone was also found, and positive correlations between stage and CA125, and residual disease and CA125 were confirmed.

17-alpha-Hydroxyprogesterone↗
PubMed1994

Phase I study of mitozantrone, methotrexate and mitomycin with granulocyte colony-stimulating factor (filgrastim) in patients with advanced breast cancer.

The combination of mitozantrone, methotrexate and mitomycin (3M) gives a response rate of around 50% in patients with advanced breast cancer. The predominant toxicity is haematological. In this study, previously untreated patients were given 3M with increasing doses of mitozantrone (7-14 mg m-2) with recombinant human granulocyte colony-stimulating factor (metHuG-CSF) (filgrastim) to prevent marrow toxicity. Doses administered were 7 mg m-2 mitomycin i.v. 6 weekly, methotrexate i.v. 35 mg m-2 (maximum 50 mg) 3 weekly and mitozantrone i.v. 3 weekly as follows: 7 mg m-2, six patients (group 1); 10 mg m-2, six patients (group 2); 12 mg m-2, six patients (group 3); 14 mg m-2, six patients (group 4); all on day 1 for six cycles at the assigned dose. All patients received filgrastim (Amgen 0.3 mg ml-1) at a dose of 5 micrograms kg-1 subcutaneously daily on days 4-17 of each cycle. All treatment was given on an out-patient basis. A total of 24 patients were entered into the study. The median age was 63 years (range 48-75). ECOG performance status was 0 in ten, 1 in 11 patients and 2 in three patients. Locoregional disease alone was present in seven patients. The remainder had one or more sites of metastases. The actual dose administered to the 24 patients was as follows. The six patients in group 1 all completed six courses of treatment as per protocol. In group 2, three patients completed six courses, two stopped because of toxicity after one and four courses and one had progressive disease after one course. In group 3, three patients completed and three stopped early because of progressive disease. In group 4, two patients completed, one progressed after four courses and three responding patients stopped treatment because of toxicity. The maximum tolerated dose of mitozantrone in the 3M combination was 12 mg m-2. The use of filgrastim with increasing doses of chemotherapy prevents neutropenia, but other toxicities, namely thrombocytopenia and lethargy, then become dose limiting.

Aged↗
PubMed1994

The endodermal sinus tumour and clear cell ovarian cancer.

There are similarities between clear cell epithelial ovarian carcinoma and endodermal sinus tumours. Apart from the morphological and clinical characteristics there are immunohistochemical markers of value in differentiating these 2 tumours and the detection of a raised serum AFP is characteristic of endodermal sinus tumours. These 3 cases we describe show the fallibility of the classical differentiating criteria between these two tumours.

Adenocarcinoma, Clear Cell↗
PubMed1994

Aggressive management of doxorubicin-induced cardiomyopathy associated with 'low' doses of doxorubicin.

There is a dose-effect relationship between doxorubicin and the incidence of symptomatic cardiac failure. It is generally thought that doses below 500-550 mg/m2 are safe but, when objective measures of cardiac function are used, it becomes apparent that degrees of cardiac failure occur at doses below this. We present here the case histories of two patients who developed very severe cardiac failure at cumulative doses well below 500 mg/m2 but who survived their initial cardiac illness due to aggressive intervention. In one case, the patient was successfully treated by orthotopic cardiac transplantation.

Adolescent↗
PubMed1994

Information needs prior to breast biopsy.

Biopsy is the definitive diagnostic procedure for breast cancer. The fear of cancer may make the breast biopsy itself a distressing experience for women and their significant others. Information seeking is believed to be a primary mode of coping with distressful events. The purpose of this study was to describe the information needs of women and their significant others prior to a breast biopsy and to explore the influence of information on the breast biopsy experience. Semi-structured, audiotape-recorded interviews with 11 women and 8 significant others were conducted prior to breast biopsy, and categories arising from the data were developed. The primary information need identified by the participants was to know "Is it cancer?" Participants' uncertainty regarding the outcome of the biopsy led to feelings of distress. The major strategy used to reduce distress was information management, in which the amount and type of incoming information was controlled. Nursing interventions based on the study findings are presented.

Adult↗
PubMed1994

Phase II study of continuous infusion fluorouracil with epirubicin and cisplatin in patients with metastatic and locally advanced breast cancer: an active new regimen.

PURPOSE: To investigate the efficacy and toxicity of continuous infusion fluorouracil (5-FU) with every-3-weeks epirubicin and cisplatin (ECF) in advanced breast cancer in a phase II study. PATIENTS AND METHODS: Forty-three patients with metastatic (n = 29) or locally advanced/inflammatory (n = 14) breast cancer were treated with 5-FU 200 mg/m2/d via a Hickman line using an ambulatory pump for 6 months with epirubicin 50 mg/m2 intravenously (IV) and cisplatin 60 mg/m2 IV every 3 weeks, for eight courses. RESULTS: The overall response rate (complete plus partial) was 84% (95% confidence interval [Cl], 76% to 96%), with a complete response rate of 24% (95% Cl, 9% to 40%) in patients with metastatic disease and 36% (95% Cl, 11% to 61%) in patients with locally advanced disease. The main World Health Organization [WHO] grade 3 or 4 toxicities included leukopenia, emesis, and alopecia. CONCLUSION: Infusional ECF is a highly active regimen in advanced breast cancer and warrants evaluation in high-risk early breast cancer.

Adult↗