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Biomedical subjects

M E O'Brien

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

At least 73 records · Page 4Linked to original sources

Fludarabine in lymphoproliferative disorders: the Royal Marsden Hospital experience.

Fludarabine 25 mg/m2 was given on five consecutive days every four weeks to 85 patients with B- and T-cell malignancies. The median number of courses given was five. All patients except one had received previous chemotherapy. The overall response rate in non-Hodgkin's lymphoma (NHL) was 50% (five complete responses (CR) and 19 partial responses (PR)). The response rate in chronic lymphocytic leukemia (CLL) was 43% (four CR and 12 PR). Responses were seen in all groups of B-cell malignancies, but no T-cell malignancies (n = 4) responded. The median duration of CR has not been reached and the median duration of PR was 14 months for NHL and 16 months for CLL. The median survival from starting fludarabine for patients who achieved a CR or PR in NHL has not been reached and the median duration of PR in CLL was 23 months. The median duration of survival in non-responders was five months. Fludarabine was well tolerated and the main toxicity was myelosuppression. Our results suggest that even in patients who have never responded to any chemotherapy, regardless of the number of treatment regimens previously given, there is a 36% chance of response. In addition, this is the first report of fludarabine activity in Franklin's disease.

Adult↗

Evaluation of a hemodialysis patient education and support program.

This study examined the effects of a hemodialysis educational and support program (HESP) on patients' physical and psychosocial adaptations to end stage renal disease. The study employed a pretest/posttest modified Solomon experimental design with control group. Data were collected at 3-month intervals following the educational intervention. Results of the study indicated that nurses can have an impact on the patient learning experience by providing support and one-to-one teaching sessions, and actively involving patients in their own care. Additionally, nurses can facilitate active patient learning through enhanced teaching methods.

Adult↗

The dementia syndromes. Distinguishing their clinical differences.

Dementia is one of the most devastating illnesses that affect the elderly. The progressive decline in memory, judgment, intellectual function, and adaptive ability places an immense burden on families, healthcare providers, and communities. Because advancing age is the leading risk factor for most types of dementia, the prevalence of this tragic disorder will increase as the population ages. How can primary care physicians help?

Aged↗

Clear cell epithelial ovarian cancer (mesonephroid): bad prognosis only in early stages.

Clear cell ovarian carcinoma accounts for 4.5% of all cases of ovarian cancer at this center; 43% of patients presented with stage I disease. Stage for stage patients with advanced disease (II-IV) did no worse than other subtypes of epithelial tumors but patients with stage I disease did significantly worse at both 5 (P < 0.05) and 10 years (P < 0.02). Young age (< 60 years), advanced stage, and the presence of vascular invasion are independently poor prognostic factors, while the presence of a predominantly (> 75%) papillary or tubulocystic morphological pattern independently predicts a better prognosis.

Adenocarcinoma↗

Primary medical (neo-adjuvant) chemotherapy for operable breast cancer.

84 patients with large operable breast cancer have been treated with primary medical chemotherapy rather than mastectomy in three sequential studies. 86% had tumours greater than 4 cm in diameter; median diameter was 6 cm (range 1-12). Median age was 46 years (range 23-66). In the first two studies 64 patients were treated with either CMF [cyclophosphamide 100 mg orally days 1-14, methotrexate 50 mg intravenously (i.v.) days 1 and 8, and 5-fluorouracil 1 g i.v. days 1 and 8, repeating at 28-day intervals for six courses] or MMM (mitozantrone 8 mg/m2 i.v. once every 3 weeks, methotrexate 50 mg i.v. once every 3 weeks, mitomycin C 8 mg/m2 once every 6 weeks, for 8 courses). 69% achieved an overall response including 17% complete remissions. 27% have had local relapse but only 3% uncontrolled local relapse. Only 14% have required mastectomy. In the third study which is ongoing, 19 patients have been treated with infusional FEC (5-fluorouracil 200 mg/m2 i.v. 24 hourly by continuous infusion via a Hickman line for 6 months, epirubicin 50 mg/m2 i.v. bolus once every 3 weeks for 6 months, cisplatin 60 mg/m2 i.v. once every 3 weeks for 6 months with appropriate intravenous hydration). Overall response rate so far is 84% with 58% complete remissions. There have been no local relapses and no patient has required mastectomy. This study demonstrates that primary medical chemotherapy can be used to avoid mastectomy in the great majority of patients presenting with large operable primary breast cancer. Infusional FEC may be more active than conventional chemotherapy in terms of overall response and complete remission rate, and infusional FEC chemotherapy now needs to be compared with conventional chemotherapy. The concept of primary medical therapy should also be compared with conventional mastectomy followed by adjuvant chemotherapy.

Adult↗

A toxic interaction between mitomycin C and tamoxifen causing the haemolytic uraemic syndrome.

A comparison of patients receiving combination chemotherapy with mitomycin C, mitozantrone and methotrexate (3M) with and without tamoxifen for treatment of primary breast cancer indicates an increased risk of anaemia (P < 0.0001) and thrombocytopenia (P < 0.001), but not leucopenia for patients receiving tamoxifen with their chemotherapy compared to those receiving the chemotherapy alone. Furthermore, 9 out of 94 patients receiving tamoxifen with 3M developed progressive anaemia, thrombocytopenia and abnormal renal function as early features of microangiopathic haemolytic anaemia, progressing on to various degrees of the haemolytic uraemic syndrome (HUS). This is only rarely seen with patients receiving mitomycin C alone at higher doses than used in the 3M combination and in the presence of active metastatic disease. This syndrome can be fatal and 1 of our 9 patients died. These observations indicate that there may be an interaction between tamoxifen and mitomycin C, causing an increased incidence of anaemia, thrombocytopenia and an increased risk of HUS. The combination of these two drugs should be avoided or carefully monitored.

Adult↗

Dietary induced subclinical vitamin K deficiency in normal human subjects.

A subclinical vitamin K deficiency was induced in 32 healthy subjects (four groups of eight males and females) aged 20-40 and 60-80 yr residing in the Metabolic Research Unit of the Human Nutrition Research Center on Aging at Tufts University. Volunteers were initially fed (4 d) a baseline-period diet containing the recommended daily allowance for vitamin K which is equivalent to 80 micrograms/d of phylloquinone (vitamin K1). During the baseline period various parameters of vitamin K nutritional status were monitored. The baseline period was followed by a 13-d depletion period during which the subjects were fed a very low vitamin K1 diet (approximately 10 micrograms/d). After depletion, the subjects entered a 16-d repletion period (four stages lasting 4 d each) during which time they were repleted with 5, 15, 25, and 45 micrograms of vitamin K1 per day. Vitamin K1 depletion dramatically and significantly decreased plasma vitamin K1 levels (P < 0.0001) in both elderly and young groups to values 13-18% of day 1 (elderly 0.22 nM, young 0.14 nM). Repleting the subjects with up to 45 micrograms of vitamin K1 per day failed, in the case of the young subjects, to bring plasma vitamin K1 levels back into the normal range. Dietary vitamin K1 restriction induced different responses in the urinary excretion of gamma-carboxyglutamic acid between the young and the elderly subjects with values decreasing significantly (P < 0.03) in the young while remaining unchanged in the elderly. The vitamin K1 depletion period had no significant effect on either prothrombin and activated partial thromboplastin times, or Factor VII and protein C (as determined by antigenic and functional assays). By using a monoclonal antibody, decarboxy prothrombin was found to increase slightly but significantly in both groups (P < 0.05) as a consequence of the low vitamin K1 diet. This study clearly shows that a diet low in vitamin K1 can result in a functional subclinical deficiency of vitamin K (decreased urinary gamma-carboxyglutamic acid excretion) without affecting blood coagulation.

1-Carboxyglutamic Acid↗

Carboplatin in the treatment of advanced breast cancer: a phase II study using a pharmacokinetically guided dose schedule.

PURPOSE: We performed a phase II study of single-agent carboplatin against metastatic/locally advanced breast cancer using a pharmacokinetically guided dose schedule, to define further the potential role for this agent in combination and high-dose therapy. PATIENTS AND METHODS: Forty patients with metastatic/locally advanced breast cancer were treated with carboplatin based on glomerular filtration rate (GFR) to achieve an area under the concentration-versus-time curve (AUC) of 7 mg/mL.min, with each course repeated at 4-week intervals. The median age was 57 years (range, 37 to 71). RESULTS: Ten patients achieved a partial response (PR), for an overall response rate of 25% (95% confidence interval, 13% to 41%). One of 13 (8%) previously treated patients responded compared with nine of 27 (33%) patients who had not received previous chemotherapy. Median response duration was 18 weeks (range, 10 to 68). World Health Organization (WHO) grade 2 or greater toxicity was as follows: anemia, 42%; leukopenia, 20%; thrombocytopenia, 35%; nausea/vomiting, 39%; and infection, 9%. CONCLUSION: This study confirms other reports indicating that carboplatin has moderate activity in previously untreated patients, but not in previously treated patients. In our view, carboplatin is a more appropriate agent than cisplatin for inclusion in high-dose chemotherapy schedules with autologous bone marrow rescue, and our results support the concept of calculating dose escalation on the basis of the area under the dose-response curve using the Calvert formula, rather than on surface area.

Adult↗

Physical and psychosocial nursing care for patients with HIV infection.

As suggested earlier we have chosen in this article to discuss only a small group of key physical and psychosocial concerns and needs associated with HIV and AIDS. These were the issues most frequently discussed by a study group of people living with HIV. We recognize, however, that holistic nursing intervention considers the totality of the individual living with HIV: body, mind, and spirit. It is to that end that the discussed nursing diagnoses and interventions are directed. Ultimately, the successful identification of and intervention in HIV related problems rests in the unique relationship between nurse and patient sharing as collaborators in the healing experience. The body of contemporary nursing and behavioral science research in the area of HIV/AIDS continues to grow. Presently the National Center for Nursing Research is supporting studies focusing on such areas as the use of designated versus general care settings for HIV patient care, quality of nursing care in HIV/AIDS, the effects of nurse-managed home care for AIDS patients, stress and coping in caregivers of AIDS children, the testing of interventions for black women with AIDS, and prevention studies (National Center for Nursing Research, personal communication, 1992). Nevertheless, as the HIV pandemic continues to grow and expand its demographic parameters, more research, particularly with such populations as women and children, is urgently needed. Studies exploring prevention issues and symptom management also are most important. Some suggestions for future study include examination of cultural variables associated with coping with HIV and AIDS; longitudinal research on surviving HIV over time; intervention studies to test specific nursing therapeutics in various settings such as hospital, home, and clinic; and finally, research describing the impact of HIV and AIDS on family functioning and adaptation. It is only through continued study of the impact of HIV, on both the individual living with HIV, and his or her significant others, that we will expand nursing knowledge and strengthen nursing care for those impacted with this fearsome and life-threatening condition.

Acquired Immunodeficiency Syndrome↗

A phase II study of sulofenur, a novel sulfonylurea, in recurrent epithelial ovarian cancer.

A total of 16 patients with recurrent epithelial ovarian cancer were treated with sulofenur (LY 186641), a novel oral sulfonylurea. All subjects had received previous chemotherapy. Anaemia occurred in all 16 patients, 14 of whom required a blood transfusion, and 2/16 patients received methylene blue for breathlessness due to methaemaglobinaemia. Treatment was discontinued in 2/16 cases due to rising liver enzyme values, which reverted to normal on cessation of the drug. There was no nausea or alopecia. Only two minor responses were seen. Plasma drug levels were insufficient to result in antitumour activity as extrapolated from animal data. Further studies that attempt to increase the bioavailability and improve the therapeutic index are warranted.

Adolescent↗

A randomised phase II study of carmustine alone or in combination with tumour necrosis factor in patients with advanced melanoma.

Laboratory data suggest a synergistic interaction between carmustine (BCNU) and tumour necrosis factor (TNF) in melanoma. We therefore studied the activity of 200 mg/m2 BCNU given alone or in combination with 88 micrograms/m2 recombinant human TNF-alpha (rhTNF alpha) as a daily i.v. infusion for 5 days at 48-day intervals to patients with metastatic melanoma. In this randomised phase II trial, the rate of response to BCNU alone was 20% [95% confidence interval (CI), 2%-38%], and this was not improved by the addition of TNF (response rate, 10.5%; 95% CI, 1.3%-33%). Toxicity was higher in the combination arm, and there was no difference in survival.

Adolescent↗

'VEEP' in children with Hodgkin's disease--a regimen to decrease late sequelae.

In an attempt to decrease the risk of second malignancies and future infertility in children with Hodgkin's disease (HD) while retaining acceptable remission rates, an anthracycline based regimen containing no alkylating agent has been devised. VEEP contains vincristine, epirubicin, etoposide and prednisolone given at 3 weekly intervals. Forty-four patients, aged 2-15 years, have been treated: ten relapsed patients and 34 previously untreated with chemotherapy (including three relapsed stage I treated initially with radiotherapy). The median follow up for all patients is 25 months (range 6-52 months). The response rate in previously treated patients was 80% (95% CI 44-97%) and five remain alive in remission. The response rate in untreated patients was 88% (95% CI 72-97%) with 62% CR + CR(u) (uncertain/unconfirmed) (95% CI 44-77%). Of four patients who had a final response of CR(u) three have relapsed at 9, 16 and 38 months. Two of the children in CR have relapsed at 6 and 16 months. The relapse free rate at 3 years is 67% (95% CI 17-82%). In this pilot study the event free survival appears somewhat poorer than conventional combinations and further follow up is required to confirm the salvagability of relapsed patients.

Adolescent↗

Dealing with delirium. A common problem in hospitalized elderly patients.

Delirium is a common problem, particularly in hospitalized elderly patients. It may be the first indication of serious illness, such as infection, cardiopulmonary disease, or a metabolic disturbance. The condition is precipitated by medications, toxins, and abrupt changes in environment. Delirium is often a frightening experience for patients and families and a challenge to treat. As the elderly population increases, physicians may expect to encounter this condition more often. Maintaining a high index of suspicion may prevent many cases and arrest others at onset. Proper management includes prompt diagnosis and treatment of the underlying illness, as well as use of commonsense measures to calm and reassure the patient.

Aged↗