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P J Fitzpatrick

Publications and source records attributed to P J Fitzpatrick.

At least 19 recordsLinked to original sources
PubMed1995

Characterization of a glutathione S-transferase and a related glutathione-binding protein from gill of the blue mussel, Mytilus edulis.

The major isoenzyme of glutathione S-transferase (GST 1) was purified to homogeneity from cytosolic extracts of Mytilus edulis gill tissue by GSH-agarose affinity chromatography followed by Mono Q ion-exchange f.p.l.c. This enzyme was particularly active with 1-chloro-2,4-dinitrobenzene, ethacrynic acid and cumene hydroperoxide as substrates. Immunoblotting and amino acid sequencing studies indicate that the enzyme belongs to the Pi class of GSTs. A related protein which binds to GSH-agarose was also purified. This GSH-binding protein did not immunoblot with GST antisera and showed no detectable catalytic activity with GST substrates although its N-terminal sequence was similar to Mu-class GSTs. Gel-filtration chromatography indicated that GST 1 is a dimer and the GSH-binding protein a monomer. Mass spectrometry and SDS/PAGE indicate subunit molecular masses of 24 kDa (GST 1) and 25 kDa (GSH-binding protein), respectively. Both proteins have amino acid compositions typical of GSTs.

Amino Acid Sequence↗
PubMed1995

Drug metabolizing enzymes of mussels as bioindicators of chemical pollution.

The GSTs of M. edulis provide an easily assayed activity which would be expected to respond to changes in pollution status. The main GST and a related GSH-binding protein have been purified and biochemically characterized. The former protein is most similar to the Pi class while the latter is a catalytically inactive monomer which appears to be related to the Mu class. This enzyme activity has been assessed as a potential indicator of exposure to chemical pollutants in both Cork Harbour and Venice Lagoon (using the closely related species, M. galloprovincialis). Controlled exposure studies with mussels in holding tanks have indicated that the herbicide aldicarb gives a slight but significant increase in GST activity consistent with the inducibility of these enzymes by xenobiotics in this bivalve. At present, we are studying samples which have been deliberately exposed to PAH and PCB compounds. Studies of this type are important in helping to understand the effects and fate of chemical pollutants released into estuarine environments.

Animals↗
PubMed1993

Separation of multiple forms of glutathione S-transferase from the blue mussel, Mytilus edulis.

1. Glutathione S-transferase isoenzymes from Mytilus edulis and M. galloprovincialis have been partially purified by glutathione-sepharose affinity chromatography followed by Mono Q anion exchange fast protein liquid chromatography (f.p.l.c.). 2. The tissue distribution of glutathione S-transferase in M. edulis has been studied. Using 1-chloro-2,4-dinitrobenzene as substrate, highest specific activity is observed in the gill, the main feeding organ. Affinity-purified extracts of this organ give a characteristic f.p.l.c. profile. A similar profile is obtained with affinity-purified extracts of the digestive gland of M. galloprovincialis. 3. The subunit structure of the purified isoenzymes has been studied by SDS polyacrylamide gel electrophoresis and reversed-phase h.p.l.c. The subunits have similar molecular weights and h.p.l.c. retention times to rat glutathione S-transferases.

Animals↗
PubMed1992

Analysis of supradiaphragmatic clinical stage I and II Hodgkin's disease treated with radiation alone.

Patients with clinical Stage I and II Hodgkin's disease have been managed at the Princess Margaret Hospital for over 20 years, without the use of routine staging laparotomy. Our experience identified as adverse prognostic factors presence of a large mediastinal mass, B symptoms, and advanced age in presence of unfavorable histology (20). We had suggested previously that the use of extended field radiation therapy (XRT) was associated with a lower risk of relapse than involved field XRT or mantle XRT. There has been a trend over the past decade to select those patients with favorable prognostic factors for treatment with XRT alone and to use mantle plus upper abdominal XRT (extended field XRT) to treat them. A retrospective study of patients with clinical Stage I and II Hodgkin's disease treated at the Princess Margaret Hospital between 1978 and 1986 was conducted to determine the impact of patient selection and extended field radiation on outcome. The study involved 250 patients with supradiaphragmatic disease selected for treatment with radiation alone on the absence of adverse prognostic factors. Radiation techniques included involved field radiation in selected patients (those with upper neck involvement), mantle radiation in the earlier years, and mantle plus upper abdominal radiation in the later years of the study. Actuarial survival was 83.3% at 8 years; cause-specific survival was 90.1% and the relapse-free rate 71.6%. Local tumor control was 94.6%; only two patients had true infield failure. Multivariate analysis showed that significant prognostic factors included age, histology, and erythrocyte sedimentation rate. Extent of the radiation treatment volume was significant and influenced the risk of relapse, particularly out-of-field relapse, independently of other factors. A dose of 35 Gy was found to be sufficient for control of clinical disease. This study validated a previously developed model for the selection of clinically staged patients with Stage I and II Hodgkin's disease for treatment with radiation alone. Careful selection of these patients can yield excellent results without requiring that staging laparotomy be routinely performed or the use of systemic chemotherapy as the initial treatment.

Adolescent↗
PubMed1992

A review of the oncology curriculum at Dalhousie medical school.

The teaching of oncology at Dalhousie medical school is currently left to the discretion of the 30 university departments. There is no central coordination. This organization leaves no monitoring of curriculum content to see that what should be covered is indeed covered, nor does it provide teaching from the perspective of oncology rather than the perspective of the other individual disciplines. Following an inventory of the oncology curriculum and a survey of interns graduating from Dalhousie in 1991, we recognize deficiencies in the clinical portion of the curriculum that could be rectified with a small number of hours designed to teach the various aspects of the management of cancer patients in case-scenario, student participation sessions.

Curriculum↗
PubMed1990

Outcome analysis of localized gastrointestinal lymphoma treated with surgery and postoperative irradiation.

One hundred thirteen patients with localized gastrointestinal lymphoma treated by surgery and postoperative irradiation between 1967 and 1985 were reviewed. At 15 years, actuarial survival of this group was 40.6%, with a cause-specific survival of 69.2% and a relapse-free rate of 64%. Two-thirds of relapses occurred at distant sites. In Stage IA and IIA patients with no residuum or with positive resection margins, (N = 90) only site of involvement and stage predicted for relapse. Age, histologic subtype group, and depth of bowel wall invasion did not affect relapse risk. In the very favorable group (Stage IA, IIA, no residuum or microscopic residuum), 8.4% of patients with stomach lymphoma relapsed compared to 25% of patients with small bowel lymphoma. The risk of early relapse was higher in those with Stage IIA small bowel lymphoma than those with Stage IA small bowel lymphoma. We continue to recommend adjuvant abdominal irradiation for patients with Stage IA, IIA completely resected stomach lymphoma and Stage IA completely resected small bowel lymphoma. We recommend combined modality therapy for patients with completely resected Stage IIA small bowel lymphoma and all other localized gastrointestinal lymphoma where visible residual disease is present.

Adolescent↗
PubMed1989

Ultrasound determination of the relationship of radioactive plaques to the base of choroidal melanomas.

There is an assumption that radioactive plaques placed at surgery are, and will remain, in proper relationship to the base of the tumor. The plaque dose is calculated based on this assumption. In fact, factors such as loose sutures, improper diameter estimations, pressure from adjacent rectus muscles, and intervening tissue (oblique muscles) can compromise this relationship. Ultrasound provides a practical method of imaging the tumor and plaque simultaneously. The authors have used postoperative ultrasound to monitor the accuracy of iodine-125 plaque placement in nine cases. Detection of eccentrically placed and malpositioned plaques provides valuable insight which can be used to refine surgical technique. Detection of plaque tilting by oblique muscles can serve as a basis for recalculating dosage. The relationship of plaque margins to vital ocular structures such as the optic nerve can also be determined by ultrasound.

Brachytherapy↗
PubMed1988

Malignant submandibular gland tumors. A review of 91 patients.

A retrospective review of 91 patients with submandibular gland carcinoma seen between 1958 and 1984, is reported. Among these were 37 (41%) adenoidcystic carcinomas, 14 (15%) adenocarcinomas, 14 (15%) mucoepidermoid carcinomas, and 10 (11%) malignant mixed tumors. The median patient age was 58 (26-93) [corrected] years and the male to female ratio was was 1.2:1. At diagnosis, 15 (16.5%) patients had regional metastases and six (7%) had distant metastases. The first planned treatment was surgery in 30 (33%) patients, radiotherapy in five (5%), and surgery and radiotherapy combined in 54 (59%) patients. The 5- and 10-year cause-specific survival rates were 60 and 48%, respectively, and the relapse-free rates 42 and 34%. The locoregional control at 5 years was 30% when surgery was the only treatment, and 69% when combined with radiation. These results suggest the advantages of combining surgery and radiotherapy as the first planned treatment for most tumors.

Adult↗
PubMed1987

Metastatic squamous cell carcinoma in linear porokeratosis of Mibelli.

We describe the clinical and pathologic observations of a 45-year-old woman with linear porokeratosis who developed squamous cell carcinoma in lesional sites. The squamous cell carcinoma metastasized to a regional lymph node. This is the second case of metastatic squamous cell carcinoma reported in porokeratosis and the first reported in the linear variety.

Carcinoma, Squamous Cell↗
PubMed1986

Cutaneous malignant lymphoma.

The skin as the first site of non-Hodgkin's lymphoma is uncommon. Between 1967-1982 only 61 evaluable patients were seen; lymphoma was confined to the skin in 43. Most histological subtypes of non-Hodgkin's lymphoma were represented with diffuse histiocytic tumors accounting for 28 (46%). Overall, there was a 5-year survival rate of 52% with a median of 75 months. For patients with disseminated lymphoma involving the skin, the median survival was 18 months and there were no 10 year survivors. Patients with disease confined to the skin had 5 and 10-year survival rates of 62 and 57%, and a median survival of 159 months. Significant prognostic indicators included the site and bulk of tumor, but not the histological subtype. For small bulk localized tumors radiotherapy achieved local control in all patients and an over 80% five-year relapse-free rate. We conclude that lymphomas confined to the skin can be adequately treated by radiotherapy, whereas disseminated tumors require systemic therapy in addition. The management of bulky cutaneous lymphoma remains controversial.

Adolescent↗
PubMed1986

Malignant salivary gland tumors.

A retrospective review of 403 patients with salivary gland tumors seen between 1958 and 1980 and a mean follow-up of 10 years is reported. The median age was 58 (7-94) years and the male to female ratio 1.3:1. There were 293 (72%) parotid, 83 (21%) submaxillary and 27 (7%) tumors developed at other sites. Among these were 84 (22%) mucoepidermoid (all degrees of differentiation), 87 (22%) adenocystic carcinomas, 70 (17%) adenocarcinomas, 25 (6%) acinic, 26 (6%) squamous cell, 44 (11%) undifferentiated, 52 (13%) mixed and 12 (3%) nonspecified carcinomas. A painless lump was the first symptom in 338 (84%) patients. The first planned treatment was surgery in 110 (27%), radiotherapy in 50 (12%), and surgery and radiotherapy combined in 239 (59%) patients. Following the first treatment, the primary parotid tumor was controlled by surgery in 17/70 (24%), by irradiation in 6/39 (15%) and surgery and radiation combined in 134/182 (74%) patients. Altogether, regional metastases developed in 36 (12%) and distant metastases in 36 (12%) of 293 patients with parotid tumors. For the submandibular tumors the primary tumor was controlled by surgery in 9/31 (29%), 0/4 (0%) by irradiation, and in 32/46 (70%) by surgery and irradiation. Here, regional and distant metastases developed in 16/84 (19%) and 19/84 (23%) patients. Among the other sites the primary tumor was controlled by surgery in 4/9 (44%), 0/7 (0%) by irradiation, and in 8/11 (73%) by surgery and radiotherapy combined. In this group 4/27 (15%) and 5/27 (18%) patients developed regional and distant metastases. The 5- and 10-year cause specific survival rates were 65 and 59% for the parotid tumors, 61 and 48% for the submaxillary tumors and 62 and 52% for the other sites. These results clearly demonstrate the advantages of combining surgery and radiotherapy as the first planned treatment for most tumors.

Adolescent↗
PubMed1986

Malignant parotid tumors. Prognostic factors and optimum treatment.

A retrospective study of 271 patients with parotid carcinoma seen between 1958 and 1980 is reported. Among these were 64 (24%) mucoepidermoid tumors (all degrees of differentiation), 50 (18%) adenocarcinomas, 40 (15%) malignant mixed tumors, 39 (14%) adenoid cystic carcinomas, 37 (14%) undifferentiated, 21 (8%) acinic, and 20 (7%) squamous cell carcinomas. The proportion of advanced (T3T4) to early (T1T2) tumors was 1.7:1. At diagnosis, 42 (15%) patients had regional metastases. An analysis for prognostic factors showed that the histology, tumor stage, regional metastases (No vs. N+), age, and damage to the facial nerve all influence cause-specific survival. After multivariate analysis the tumor size and the presence of regional metastases were the two most significant factors (p less than 0.0001 and 0.004). The prognostic characteristics were similar for the 67 (25%) patients treated by surgery and for the 169 (62%) patients treated with surgery and postoperative radiotherapy. Patients treated with combined therapy had a 10-year relapse-free rate of 62% compared to 22% for those treated by surgery alone (p = 0.0005).

Adolescent↗
PubMed1985

Role of radiation therapy in localized non-Hodgkin's lymphoma.

Relapse occurs in 50% of patients receiving radiation for clinical stage (C.S.) I and II nodal and extranodal non-Hodgkin's lymphoma (N.H.L.). Prior to the introduction of intensive chemotherapy those failing primary control with irradiation and most of those who relapsed died of their disease with a resultant overall mortality of 50%. An analysis of Princess Margaret Hospital results with radiation for C.S. I and II N.H.L. between January 1967 and December 1978 revealed that tumour bulk, age, stage and histology were of independent prognostic significance. It was possible to group patients using combinations of these attributes so that each group encompassed only patients with similar outcomes. Such prognostic groups were identified separately within the low grade and the intermediate plus high grade categories of the Working Formulation. Patients with a high probability of cure with radiation were so defined. Also those patients in whom chemotherapy would be optimal initial therapy were also defined. Such patients were in the intermediate plus high grade histology groups. Thirty percent of all patients with low grade histology lymphoma had an actuarial survival of 83%, and relapse-free rate of 63% at 10 years. By implication, approximately 20% of all patients with these histologies seen at the Princess Margaret Hospital for the same time period achieved prolonged relapse-free survival by localized therapy. This is at variance with the implications of staging from studies where laparotomy and multiple bone marrow biopsies have been used. Such aggressive staging procedures suggest truly localised disease in only 5-6% of patients with low grade lymphoma. A significant relationship between radiation dose and disease control was demonstrated only for patients with intermediate and high grade lymphoma of medium or large bulk. A minimum tumour dose of 30 Gy was required for optimal local control with radiation.

Adult↗