A community based study of unmarried & married mothers.
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Employment↗
Biomedical subjects
T Kinsella
Publications and source records attributed to T Kinsella.
Adjuvant chemotherapy for patients with high-grade soft-tissue sarcomas of the extremity.
We have previously reported the results of a randomized trial that demonstrated the survival benefit of adjuvant chemotherapy in the treatment of patients with high-grade extremity sarcomas compared with no chemotherapy. This regimen included doxorubicin, cyclophosphamide, and methotrexate. This report updates and extends our experience. The median follow-up of this trial is now 7.1 years and reveals a 5-year disease-free survival of 75% and 54% for chemotherapy and no chemotherapy groups, respectively (two-sided P [P2] = .037). The 5-year overall survival for patients in this trial was 83% and 60% for the chemotherapy and no chemotherapy groups, respectively, with a trend towards improved survival in the chemotherapy arm (P2 = .124). Because of doxorubicin-induced cardiomyopathy we performed a subsequent randomized trial comparing this high-dose regimen to reduced cumulative doses of doxorubicin and cyclophosphamide without methotrexate. Eighty-eight patients were entered into this trial which has a median follow-up of 4.4 years. The 5-year disease-free and overall survival for patients treated with the reduced doses of chemotherapy was 72% and 75%, respectively, and was not significantly different from the high-dose regimen. No patients developed congestive heart failure on this study. We conclude that adjuvant chemotherapy improves disease-free survival in patients with extremity soft-tissue sarcomas. The overall survival advantage in patients receiving adjuvant chemotherapy in our initial randomized high-dose chemotherapy trial has diminished though it continues to favor the chemotherapy group. A reduced-dose chemotherapy regimen was found to be comparable to the high-dose regimen.
Antineoplastic Combined Chemotherapy Protocols↗
Halogenated pyrimidines as radiosensitizers in the treatment of glioblastoma multiforme.
Sixty patients with high-grade gliomas (including 50 patients with glioblastoma multiforme) were entered on four sequential Phase I trials combining continuous intravenous infusions of halogenated pyrimidines and high-dose brain irradiation. Patients received two 14-day infusions of bromodeoxyuridine (BUdR) or iododeoxyuridine (IUdR) during the initial wide field and later reduced field radiation treatment (total radiation dose 65-70 Gy). All patients were followed a minimum of 6 months or until death. The actuarial median survival was 13 months for the entire group, with an 18-month survival of 24%. No significant survival differences were observed based on BUdR versus IUdR, 12-h versus 24-h infusion schedule, degree of surgical resection, or sex. Good performance status and age under 50 years were significant favorable prognostic factors. Of interest, the 48 patients who completed planned treatment had a 14-month median survival, with a 30% 18-month survival. These survival observations are at least comparable to other combined modality trials in patients with glioblastoma multiforme. Ongoing and planned clinical trials using the halogenated pyrimidine analogs as radiosensitizers in patients with glioblastoma multiforme are discussed.
Astrocytoma↗
High-grade soft tissue sarcomas of the extremities.
From July 1975 to December 1982, 358 patients were referred to the Surgery Branch of the National Cancer Institute (NCI) with the diagnosis of soft tissue sarcoma of the extremities. Two hundred eleven of these patients presented with resectable, localized high-grade soft-tissue sarcomas and have been included in the present analysis of the management and outcome of patients with high-grade soft tissue sarcomas of the extremity treated at the NCI. One hundred forty-seven of these 211 patients have been included in randomized prospective trials. The remaining 64 patients in this analysis have been followed at the NCI, but were not included in randomized trials because of patient refusal or ineligibility. Tumor size was identified as a highly significant prognostic variable for disease-free and overall survival (P2 = 0.00001 and 0.0081, respectively). Tumor site, histologic type, and microscopic margins of resection were not significant prognostic variables. There was no difference between patients undergoing amputation compared to those undergoing limb-sparing procedures plus postoperative radiotherapy in disease-free or overall survival for all 211 patients in this study (P2 = 0.068 and 0.131, respectively). A significantly greater frequency of local failure among patients treated by local excision was noted compared to patients undergoing amputation (12/128 versus 0/83, P2 = 0.004), but this did not result in decreased overall survival in patients undergoing combined modality limb-sparing procedures. Adjuvant chemotherapy significantly prolonged disease-free survival (P2 = 0.005) for the 124/211 patients treated with adjuvant chemotherapy, although analysis of overall survival did not reveal a significant increase (P2 = 0.10). In a subset of 65 patients included in a prospective randomized trial evaluating the efficacy of adjuvant chemotherapy, a significant improvement in both disease-free (P2 = 0.033) and overall (P2 = 0.055) survival was seen in patients receiving chemotherapy. Sixty-five patients developed recurrent disease (65/211, 31%) and 42 of these patients were rendered disease-free surgically. Survival from the time of first recurrence was significantly prolonged among the 42 patients who were rendered disease-free (median survival, 31 months) compared to those who were not (median survival, 9 months, P2 less than 0.001).
Actuarial Analysis↗
A randomized, prospective trial of adjuvant chemotherapy in adults with soft tissue sarcomas of the head and neck, breast, and trunk.
Since 1977, 31 patients were entered in a randomized, prospective study testing the efficacy of adjuvant chemotherapy after aggressive local treatment of high-grade sarcomas of the head, neck, breast, and trunk (excluding retroperitoneal sarcomas). All patients had complete resection of gross tumor and underwent postoperative radiotherapy (6000-6300 rads over 7-8 weeks). Seventeen patients received adjuvant chemotherapy consisting of doxorubicin (less than or equal to 550 mg/m2), cyclophosphamide (less than or equal to 5500 mg/m2), and methotrexate (less than or equal to 1000 mg/kg). Three-year actuarial disease-free survival in the chemotherapy arm was 77%, compared to 49% in the no-chemotherapy arm (P = 0.075). Three-year overall actuarial survivals in the two treatment arms, however, were 68% and 58%, respectively (P = 0.38). Considering only patients with tumors of the trunk (22 patients), 3-year actuarial disease-free survival in the chemotherapy arm was 92%, compared to 47% in the no-chemotherapy arm (P = 0.006). Actuarial 3-year overall survival in the chemotherapy arm was 82%, compared to 61% in the no-chemotherapy arm (P = 0.18). An additional 26 patients were treated in an identical fashion, but were not part of the randomized trial because of contraindications to chemotherapy, refusal to enter the randomized trial, or because they were treated before 1977 in a trial in which all patients received chemotherapy. Considering the entire group of 57 patients, follow-up ranged from 10 to 86 months (median, 35 months). Local control was achieved in 46 patients (81%); 3-year actuarial disease-free and overall survivals were 67% and 77%, respectively. A tendency toward improved disease-free survival was apparent among patients treated with chemotherapy (P = 0.018), but there was no statistically significant improvement in overall actuarial survival (P = 0.46). The subgroup of patients with sarcomas of the trunk (39 patients) demonstrated the greatest benefit from chemotherapy, with regard to disease-free survival (P less than or equal to 0.001). The most significant toxicity associated with chemotherapy was doxorubicin-induced cardiomyopathy, which resulted in clinically apparent congestive heart failure in five patients. Thus, the use of chemotherapy when combined with aggressive local measures appears to improve disease-free survival, but additional patients and longer follow-up are necessary to determine if improved overall survival will result.
Actuarial Analysis↗
Patterns of recurrence in patients with high-grade soft-tissue sarcomas.
From July 1975 to December 1982, 563 patients were referred to the Surgery Branch of the National Cancer Institute with the diagnosis of soft-tissue sarcoma. Three hundred and seven of these patients had fully resectable, localized high-grade soft-tissue sarcomas and were treated at the National Cancer Institute using standard protocols with surgery alone, or in combination with chemotherapy and/or radiotherapy. An aggressive surgical approach was undertaken in the management of patients who subsequently developed recurrent disease. These 307 cases have been reviewed, with a median duration of follow-up of 30 months, to determine the frequency of recurrent disease, the patterns of recurrence, and the impact of surgery on the survival of patients who developed recurrent disease. Disease recurred in one hundred seven patients (107/307, 35%), with a median disease-free interval of 18 months (range, 0.5 to 72.0 months). The frequency of recurrence by site of primary sarcoma was extremity, 31% (65/211); head and neck, 33% (4/12); trunk, 40% (17/42); retroperitoneum, 47% (17/36); and breast, 67% (4/6). Isolated pulmonary metastatic disease was the most common pattern of initial recurrence (56/107, 52%) followed by isolated local recurrence (21/107, 20%). Single other sites of recurrence and multiple concurrent sites of recurrence each accounted for 14% (15/107) of all initial recurrences. The relative frequency of each of these four patterns of recurrence varied with the site of the primary sarcoma. The outcome for patients with recurrent disease depended on the site of recurrence, rather than on the site of the primary sarcoma. Sixty-six patients (66/107, 62%) with recurrent disease were rendered surgically disease-free with the first recurrence, including 40 (40/56, 72%) patients with isolated pulmonary metastases, 20 patients (20/21, 96%) with isolated local recurrences, five patients (5/15, 33%), with isolated other sites of recurrence and one patient (1/15, 7%) with multiple sites of initial recurrence. Following surgical resection, the actuarial three-year survival for the 66 patients rendered disease-free was 51%. The median survival for the 41 patients not rendered surgically disease-free with the first recurrence was only 7.4 months. Thirty of the sixty-six patients (30/66, 45%) rendered disease-free with the first recurrence remained disease-free at follow-up, with a median follow-up of 28 months from the time of resection of the first recurrence. The remaining 36 patients (36/66, 55%) subsequently recurred, with a median disease-free interval of 7.3 months.(ABSTRACT TRUNCATED AT 400 WORDS)
Adolescent↗
Determinants of radiosensitivity.
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Cell Cycle↗
Results of multimodality therapy of resectable soft-tissue sarcomas of the retroperitoneum.
Thirty-seven patients with resectable retroperitoneal sarcomas were studied prospectively to determine the efficacy of aggressive multimodality treatments. No patients was lost to follow-up, which ranged from 11 to 85 months (median 29 months). All patients received radiotherapy and some received postoperative chemotherapy (doxorubicin, cyclophosphamide, and high-dose methotrexate). A subset of 15 patients were entered into a prospective, randomized study testing the efficacy of adjuvant chemotherapy (eight received chemotherapy; seven did not). Two-year actuarial survival rates were inferior in the chemotherapy arm (100% versus 47%; p = 0.06), but the small number of patients precluded drawing definitive conclusions from this randomized study alone. Among the entire 37 patients (21 received chemotherapy; 16 did not) the actuarial 3-year survival rate was 43% and appeared unaffected by chemotherapy. Two patients suffered doxorubicin infiltration, three sustained cardiac toxicity, two developed cyclophosphamide-induced cystitis, and three withstood transient, severe bone marrow suppression. Eight patients suffered severe radiation enteritis, and one patient died after bowel resection for this problem. Thus the chemotherapy regimen we administered did not appear to improve survival but was associated with major morbidity. Radiotherapy was also associated with major complications, and since all patients received radiotherapy, it remains to be established if this modality is beneficial in improving survival.
Actuarial Analysis↗
In vivo incorporation of bromodeoxyuridine into proliferating cells in the marrow and its effects on granulocyte-macrophage progenitor cells.
Bromodeoxyuridine (BUdR), a potential radiosensitizing drug, was given by intravenous infusion at 650-1000 mg/m2/day for up to 12 days. In vivo incorporation into human bone marrow was assayed by differential chromatid staining as well as by comparison of in vitro radiation survival curves of granulocyte-macrophage progenitor cells scored at both day 7 and day 14. Although a difference was found in the radiation survival of control (untreated) day-7 progenitor cells (Do = 1.39 Gy) and day-14 progenitor cells (Do = 0.89 Gy), a similar degree of in vitro radiosensitization was found for BUdR-treated bone marrow progenitor cells scored at day 7 and day 14. The culture technique provided a bioassay for the in vivo action of BUdR. BUdR treatment produced transient moderate myelosuppression that probably resulted from BUdR incorporation into normal marrow cells.
Bone Marrow↗
Identification of bromodeoxyuridine in malignant and normal cells following therapy: relationship to complications.
During a clinical Phase I study of bromodeoxyuridine (BUdR) as a radiation sensitizer we identified the normal and malignant cells that incorporated the BUdR. BUdR was infused for up to 14 days and the in vivo incorporation of BUdR into DNA was assessed using an immunohistochemical technique and a monoclonal antibody directed against BUdR. BUdR was identified in 50% of breast cancer cells and 10% of cells in a malignant melanoma. BUdR was also found in the basal layer of the normal epidermis and in 50% of cells in the marrow. The incorporation of BUdR into cells in the epidermis and marrow may produce the phototoxicity and myelosuppression observed in patients treated with BUdR. Sequential biopsies from a breast cancer taken prior to and following radiotherapy suggested that cells that incorporated BUdR may have been selectively killed by the radiation. The immunohistochemical technique used to identify BUdR appeared to be useful for studies of in vivo and in vitro cell proliferation.
Bone Marrow↗
Bromodeoxyuridine in tumors and chromosomes detected with a monoclonal antibody.
Using a monoclonal antibody to bromodeoxyuridine (BUdR) and immunohistochemistry, we measured the incorporation of this thymidine analogue into the DNA of human normal and malignant cells exposed in vivo. BUdR given as a constant intravenous infusion for 12 or 24 h daily for up to 13 d resulted in a steady-state plasma level of 10(-6) M during the infusion. We demonstrated extensive incorporation of BUdR into both normal skin, normal bone marrow, and malignant melanoma cells. In addition, this infusion of BUdR was adequate to identify sister chromatid exchanges from human marrow chromosomes exposed in vivo. Using this constant infusion, significant but reversible (acute) toxicity was observed with myelosuppression and skin photosensitivity. These techniques, which are considerably less cumbersome and time-consuming than the use of radioactive isotopes of thymidine, can be used for further human studies of cell kinetics and chromosomal replication in both normal and malignant cells.
Animals↗
Experimental and clinical studies with intraoperative radiotherapy.
Studies of normal tissue tolerance to intraoperative radiotherapy were done upon 65 dogs subjected to laparotomy and 11 million electron volt electron irradiation in doses ranging from zero to 5,000 rads. Results of studies indicated that intact aorta and vena cava tolerate up to 5,000 rads without loss of structural integrity. Ureteral fibrosis and stenosis develop at doses of 3,000 rads or more. Arterial anastomoses heal after doses of 4,500 rads, but fibrosis can lead to occlusion. Intestinal suture lines heal after doses of 4,500 rads. Bile duct fibrosis and stenosis develop at doses of 2,000 rads or more. Biliary-enteric anastomoses fail to heal at any dose level. A clinical trial of intraoperative radiotherapy combined with radical surgery was performed upon 20 patients with advanced malignant tumors which were considered unlikely to be cured by conventional therapies and which included carcinomas of the stomach, carcinomas of the pancreas, carcinomas involving the hilus of the liver, retroperitoneal sarcomas and osteosarcomas of the pelvis. All patients underwent resection of gross tumor, followed by intraoperative irradiation of the tumor bed and regional nodal basins. Some patients received additional postoperative external beam radiotherapy. Treatment mortality for combined operation and radiotherapy occurred in four of 20 patients. Postoperative complications occurred in four of the 16 surviving patients. Local tumor control was achieved in 11 of the 16 surviving patients, with an over-all median follow-up period of 18 months. The clinical trial suggested that intraoperative radiotherapy is a feasible adjunct to resection in locally advanced tumors, that the resulting mortality and morbidity is similar to that expected from operation alone and that local tumor control may be improved.
Abdominal Neoplasms↗
Concomitant hepatic radiation and intraarterial fluorinated pyrimidine therapy: correlation of liver scan, liver function tests, and plasma CEA with tumor response.
Sixteen patients with metastatic disease to the liver (12 colorectal and four unknown primary tumors) were treated in a pilot study of hepatic irradiation (2500-3000 rads in 10-12 fractions) delivered concomitantly with continuous short-term intraarterial infusion of 5-fluorouracil (1 g/d) or FUDR (0.5 mg/kg/d) via a percutaneously placed hepatic artery catheter. Abnormal liver function tests, including SGOT, LDH, and alkaline phosphatase, decreased in all patients by day 7-10 of treatment, and other metabolic factors, including serum cholesterol, calcium, albumin, phosphorous, and uric acid, also decreased, often to subnormal levels by termination of treatment (day 15-20). These chemical alterations did not correlate with tumor response in that the identical pattern was observed in responders (ten patients) as well as nonresponders (six patients). Objective determinants of response were assessed by serial monitoring of the plasma carcinoembryonic antigen (CEA) and liver scan. In 14 patients with elevated CEA levels, tumor response (nine patients), nonresponse (four patients), and relapse (five patients) was predicted and confirmed by sequential monitoring of CEA. In one patient, a paradoxical decrease in plasma CEA was associated with progressive disease. The liver scan identified all responding patients but was difficult to quantitate and was delayed for months following subjective clinical response and changes in plasma CEA levels.
Alkaline Phosphatase↗
A correction method for high-count-rate quantitative radionuclide angiography.
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Angiography↗
The Oral Care Link Nurse: a facilitator and educator for maintaining oral health for patients at the Royal Hospital for neuro-disability.
This paper describes an ongoing oral health education project developed and implemented at the Royal Hospital for Neuro-disability (RHN) by the Dental Team. The Oral Care Link Nurse (OCLN) project was developed to assist the dental team in the promotion of oral care within the hospital. The Dental Team identified that, in addition to providing knowledge and skills to perform effective oral care, it is important that nursing staff retain positive attitudes and behavior toward providing that care. In conjunction with the Quality Assurance department, oral care guidelines were introduced throughout the hospital, with further input being focused on the training of at least one unqualified nursing auxiliary from each ward. These became the OCLN who were trained by the Dental Team to assist with the promotion of good oral care practices on the wards and to aid communication regarding patient oral health within the multidisciplinary team. Formal evaluation, by clinical audit, indicated that the project continued to improve the overall standard of oral care throughout the hospital. To ensure that this high standard continues, it is essential that continued support, commitment, and enthusiasm be given from the dental team and that support is constant.
Adolescent↗
Tomotherapy: a new concept for the delivery of dynamic conformal radiotherapy.
Tomotherapy, literally "slice therapy," is a proposal for the delivery of radiation therapy with intensity-modulated strips of radiation. The proposed method employs a linear accelerator, or another radiation-emitting device, which would be mounted on a ring gantry like a CT scanner. The patient would move through the bore of the gantry simultaneously with gantry rotation. The intensity modulation would be performed by temporally modulated multiple independent leaves that open and close across the slit opening. At any given time, any leaf would be (1) closed, covering a portion of the slit, (2) open, allowing radiation through, or (3) changing between these states. This method would result in the delivery of highly conformal radiation. Overall treatment times should be comparable with contemporary treatment delivery times. The ring gantry would make it convenient to mount a narrow multisegmented megavoltage detector system for beam verification and a CT scanner on the treatment unit. Such a treatment unit could become a powerful tool for treatment planning, conformal treatment, and verification using tomographic images. The physical properties of this treatment delivery are evaluated and the fundamental design specifications are justified.
Humans↗
Bronchitis symptoms in young teenagers who actively or passively smoke cigarettes.
This study was undertaken to examine the prevalence of bronchitis (cough with phlegm) symptoms in teenagers who either smoked cigarettes on a regular basis (active smokers) or were non-smokers but who are exposed to passive smoking (passive smokers) in the home. The study was undertaken in 1995 and repeated in 1998. The 1995 study was a cross sectional questionnaire survey of smoking habits in secondary school children aged 13-14 years and was undertaken as part of the ISAAC questionnaire survey. Thirty representative and randomly selected schools from throughout the Republic of Ireland took part in the study. In the 1995 study, 3066 students completed a questionnaire on their current smoking habits and symptoms of cough and phlegm. We found that 634 (20.7%) of these young teenagers actively smoked cigarettes with significantly more females smoking than males with 23.3% of girls compared to 17.6% boys (p = 0.0001). We found that 46.3% of non-smoking children were exposed to smoking in the home (passive smokers) with parental smoking accounting for most of the passive smoking. Bronchitis symptoms were more commonly reported in active smokers compared to non-smokers with an odds ratio of 3.02 (95% CI 2.34-3.88) (p < 0.0001) or in passive smokers compared to those not exposed to smoking with odds ratio of 1.82 (95% CI 1.32-2.52) (p < 0.0001). The 1998 study showed similar results for smoking habits, passive smoking and prevalence of bronchitis symptoms as with the 1995 study. These results document that increased bronchitis symptoms occur in teenagers exposed to active or passive smoking.
Adolescent↗