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Biomedical subjects

M H Tattersall

Publications and source records attributed to M H Tattersall.

At least 145 records · Page 8Linked to original sources
PubMed1987

Chemotherapy of advanced colorectal cancer. A randomized trial of sequential methotrexate and 5-fluorouracil.

Fifty-five patients with advanced colorectal cancer were entered into a randomized controlled clinical trial to evaluate order of administration and sequential methotrexate (MTX) and 5-fluorouracil (5-FU) therapy. Patients were randomized to receive either MTX, 250 mg/m2, followed 1 h later by 5-FU, 600 mg/m2, or 5-FU followed 1 h later by MTX in the same doses. Fifty-four patients were evaluable for response, of whom 15 (28%) achieved objective partial tumor response. There were no significant differences between the two sequences in response rate, time to treatment failure, or survival duration. The results of this study do not indicate a clinically significant difference between the two sequences tested, in which MTX preceded or followed 5-FU by 1 h. Determination of the value of these drugs given sequentially at longer intervals must await appropriate controlled trials.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Phase II study of mitoxantrone in advanced or metastatic endometrial carcinoma.

Mitoxantrone was administered to 12 patients with advanced or recurrent endometrial carcinoma of whom only 1 had received prior chemotherapy (chlorambucil). The drug was given every 21 days, the initial dose of either 12 mg/m1 or 14 mg/m1 being decided by the patient's age, timing of prior radiotherapy, tolerance of prior chemotherapy and baseline haematological parameters. One partial response was observed in the 11 patients evaluable for assessment of response. Mitoxantrone was well tolerated with the major toxicity being myelosuppression, particularly granulocytopenia. With the observed response rate of 9%, we conclude that mitoxantrone does not have significant activity in endometrial carcinoma.

Adenocarcinoma↗
PubMed1987

Immunohistochemical detection of proliferating cells in vivo.

Incorporation of the thymidine analogue 5-bromo-2'-deoxyuridine (BrUdR) into newly synthesized DNA provides the basis of a simple technique for identifying proliferating cells. BrUdR was administered to C57BL/6 mice by continuous infusion for 1-7 days, or by intraperitoneal injection for shorter intervals. Various tissue types, including gut, kidney, and liver, were excised, fixed in neutral buffered formalin, and paraffin-embedded for sectioning. De-paraffinized 4-micron tissue sections and bone marrow samples were incubated with an anti-BrUdR antibody and cells that had traversed S-phase during the BrUdR exposure period were identified immunohistochemically. Proliferation and migration of intestinal epithelial cells were identified by antibody staining after continuous in vivo exposure to BrUdR for 1-4 days, and BrUdR incorporation into proliferating marrow cells was detected within 30 min. Tissues such as normal liver, known to have low levels of proliferation, remained unstained after 3 days' exposure to BrUdR. After we established that normal proliferating cells could be identified using this technique, BrUdR was administered to mice bearing B16 melanomas. Again, proliferating tumor cells were clearly identified in histological sections. The nuclei from these paraffin-embedded tumors were also collected for flow cytometric analysis after de-waxing, rehydration, and pepsin treatment. This combination of techniques made possible the comparison in adjacent tissue sections of labeling index, obtained from stained sections, with percentage S-phase, measured using DNA flow cytometry. The % S-phase was consistently higher than the labeling index obtained with immunocytochemistry, and two-parameter DNA vs BrUdR flow cytometry showed that this difference could be accounted for by a population of unlabeled cells with an S-phase DNA content.

Animals↗
PubMed1987

Proton magnetic resonance spectroscopy and tumour detection.

High resolution proton magnetic resonance spectroscopy is a powerful technology in the study of tumour cell membranes. Lipid domains in the plasma membrane are the origin of high resolution spectra seen in tumour cells, and changes in those domains can be correlated not only with changes in lipid and carbohydrate components of the membrane, but also with changed tumour behaviour, ie metastatic capacity, and sensitivity to cytotoxic drug treatment. An understanding of the biological importance of lipid changes in the cell membrane paves the way to high resolution spectroscopy being useful in classifying tumours, and perhaps in tumour imaging.

Breast Neoplasms↗
PubMed1987

Biochemical modulation of fluorouracil therapy in advanced colorectal cancer.

Fluorouracil has been the mainstay of chemotherapy in colorectal cancer for many years. We report our experience using fluorouracil in combination with other drugs which may modulate the spectrum of activity. Patients have been treated with allopurinol and fluorouracil and with two schedules of methotrexate and fluorouracil. We discuss other possible approaches to modulate fluorouracil action.

Allopurinol↗
PubMed1987

Metastatic adeno or undifferentiated carcinoma from an unknown primary site--natural history and guidelines for identification of treatable subsets.

Two hundred and eighty-six patients presenting with metastatic adenocarcinoma or undifferentiated carcinoma whose primary site was not identified by clinical history, physical examination and chest radiograph have been studied. Median survival from presentation was 22 weeks. Factors independently predicting improved survival were lymph node presentations, good performance status and body weight loss of less than 10 per cent. In 88 (31 per cent) patients the primary tumour site was subsequently identified, in 58 (20 per cent) during life. Lung cancer was the most frequently identified primary tumour, and in only 32 (11 per cent) of the patients was a 'treatable' primary tumour (i.e. germ cell, breast, ovarian, prostate, thyroid cancer or lymphoma) identified. Among the treatable primary tumours were those in eight out of 16 female patients presenting with axillary metastases who were subsequently shown to have primary breast cancer and four of 13 females presenting with ascites who were found to have primary ovarian cancer. Prostatic cancer was confirmed in five out of 13 men with raised serum acid phosphatase. Of 22 patients with elevated serum alphafoetoprotein (AFP) or beta-human chorionic gonadotrophin levels (beta HCG) 18 had some features of the 'atypical teratoma syndrome'. Of the total of 32 patients with treatable tumour types, 29 (90 per cent) were identified during life. Median survival for patients with treatable tumour types identified during life was 104 weeks, compared with 22 weeks for the group as a whole. Retrospective immunocytochemical staining of the original biopsy showed that prostatic specific antigen and antibodies to beta HCG and AFP were diagnostically useful, but a series of organ site non-specific markers of histogenesis or cellular differentiation (carcinoembryonic antigen, secretory component for IgA, peanut lectin binding, epithelial membrane antigen and keratin) showed no significant correlations with identified primary sites, responsiveness to empirical chemotherapy or survival. Metastatic undifferentiated carcinoma or adenocarcinoma from an unknown primary site represents 6.5 per cent of all referrals to the medical oncology unit, Royal Prince Alfred Hospital, Sydney. We offer guidelines for the rapid identification of the limited number of primary sites for which effective and specific forms of systemic treatment are available.

Adenocarcinoma↗
PubMed1987

Chemotherapy of adult soft tissue sarcoma with combination of doxorubicin and methotrexate.

Thirty-six adult patients with measurable advanced soft tissue sarcoma were treated with a combination of doxorubicin (70 mg/m2) and methotrexate (50 mg/m2) iv every 21 days. Partial remission was seen in ten of 33 evaluable patients (30%). Median duration of remission was 23 weeks, and median survival was 42 weeks. Bone marrow toxicity was the main toxic effect; 23% of the patients had a nadir leukocyte count less than 2.0 X 10(9)/L during therapy. These results do not suggest any therapeutic advantage in adding methotrexate to doxorubicin in this context.

Adult↗
PubMed1986

Informed consent.

Explore the source record for details and available documents.

Attitude↗
PubMed1986

Randomised comparison of procedures for obtaining informed consent in clinical trials of treatment for cancer.

Methods of obtaining informed consent have evolved differently in Western countries without substantive information on the impact of these different practices on the patients. A randomised study was performed to compare two commonly adopted methods of seeking consent to randomised treatment: an individual approach at the discretion of each doctor and a uniform policy of total disclosure of all relevant information. The impact of both consent procedures on the patient's understanding and anxiety levels and on the doctor-patient relationship was assessed by means of a questionnaire given soon after the consent interview. Fifty seven patients were assigned at random to two groups: to 29 patients an individual approach to seeking consent was adopted and to 28 patients all relevant information was given. Seven patients refused consent to randomised treatment, with slightly more refusals by patients in the total disclosure group (5 v 2, p = 0.25). The main effects of total disclosure of all information compared with an individual approach to seeking consent were: a better understanding of treatment and side effects and of research aspects of the treatments; less willingness to agree to randomised treatment; and increased anxiety. No significant differences were found in patients' perceptions of the doctor-patient relationship. A repeat questionnaire given three to four weeks later no longer showed significant differences between the two groups.

Anxiety↗
PubMed1986

Classification of human tumours by high-resolution magnetic resonance spectroscopy.

Malignant tumours yield a high-resolution proton magnetic resonance (MR) spectrum. Fifty-one tumour biopsy specimens from patients with cancer of the ovary or colon were examined by magnetic resonance spectroscopy (MRS) to determine whether it was possible to identify tumour subtypes with metastatic potential. Relaxation parameters (T2) for visible lipid methylene protons were within the range of those measured for three animal metastasis models. Primary carcinomas with metastases gave T2 values greater than 350 ms, whereas carcinomas not associated with known metastases at the time of tumour excision gave a range of values from 150 to 1500 ms. All but two carcinomas gave a long T2 (greater than 350 ms) indicating metastatic potential. The MRS method designated five of six histologically borderline epithelial ovarian tumours as malignant with metastatic potential. MRS may be sensitive enough to detect malignant cells in a tumour which is of intermediate or borderline malignancy by light microscopy. Malignancy without a potential for metastasis is uncommon.

Colonic Neoplasms↗
PubMed1986

Extraskeletal Ewing's sarcoma: a clinical, morphological and ultrastructural analysis of five cases with a review of the literature.

In 1969 it was recognised that tumors with light microscopic appearances indistinguishable from Ewing's sarcoma of bone may arise in extraskeletal sites (extraskeletal Ewing's sarcoma). Here, we review the available literature and report five new cases. All five received combined modality therapy with combination chemotherapy and radiotherapy to the primary site followed by surgical excision in two. All attained complete remission; after a median follow-up of 26 months, three remain disease-free but two have relapsed and died. Our experience, in accord with previous series, suggests that extraskeletal Ewing's sarcoma compared with its bony counterpart tends to occur in older subjects, has a similar incidence in males and females, usually presents with a painless mass and readily responds to combined modality therapy. We detected no light or electron microscopic features to denote a histogenetic origin. However, we suspect extraskeletal Ewing's sarcoma may occur more frequently than previously supposed.

Adult↗
PubMed1986

Drug resistance in clinical practice: patterns of treatment failure in advanced breast and ovarian cancer.

We have analyzed the patterns of disease progression in patients with advanced breast and ovarian cancer receiving systemic therapy. Approximately 50% of patients developed progressive disease in a new, rather than a previously documented, disease site. Even when disease progressed in a previously involved disease site, in only half the cases was this identified as the bulk disease site before commencing treatment. The CNS was rarely a new site of disease progression in our patients, a finding that contrasts with a report that identified the CNS as the predominant new disease site in advanced breast cancer patients relapsing following a complete response. Progression of disease on second line treatment commonly occurred at sites of known disease. A number of factors influencing the pattern of disease progression have been examined. Disease progression on endocrine therapy tended to be more common in a previously involved disease site than in patients receiving cytotoxic therapy. There was a trend for patients who progressed within 6 months of chemotherapy to do so in an old site, whereas new disease sites predominated among those progressing later. Strategies for overcoming the causes of treatment failure should take account of the patterns of disease progression. Our results question the wisdom of always ceasing existing therapy when progressive disease is first documented.

Adult↗
PubMed1986

Analysis of a prospectively randomized comparison of doxorubicin versus 5-fluorouracil, doxorubicin, and BCNU in advanced gastric cancer: implications for future studies.

A multi-institutional cooperative study of patients with locally advanced, recurrent, or metastatic gastric adenocarcinoma who had not previously received chemotherapy was conducted, prospectively randomizing patients to receive either doxorubicin or the three-drug combination, 5-fluorouracil (5-FU), doxorubicin (Adriamycin; Adria Laboratories, Columbus, Ohio), and BCNU (FAB). The 187 evaluable patients were initially stratified according to the presence of measurable or evaluable disease and performance status. There was a significantly higher response rate observed for FAB (40%) compared with doxorubicin (13%) among the 145 measurable-disease patients. Duration of response and survival were significantly longer for FAB in the measurable-disease group, but for the total patient population an early advantage for FAB in time to disease progression and survival was lost with continued follow-up. Median survival was 33 weeks for patients receiving FAB and 19 weeks for those receiving doxorubicin. Significant pretreatment factors adversely affecting survival included poor performance status, weight loss of greater than 10%, and more than two sites of metastases. Toxicity was not severe in either treatment arm, and only thrombocytopenia occurred significantly more often with FAB. It is contended that in the treatment of advanced gastric cancer, chemotherapy only exerts a relatively short-term and modest beneficial effect, most apparent in patients with intermediate tumor bulk. 5-FU remains the most active single agent, and combination chemotherapy has not yet proven its overall worth. Further studies are indicated comparing the most active combinations with 5-FU using optimal doses and schedules, and consideration must be given to the incorporation of no-treatment controls.

Adenocarcinoma↗
PubMed1986

Malignant effusions.

Recurrent malignant effusions present a difficult management problem and are a major cause of morbidity. This article reviews the pathophysiology of serosal effusions, with particular reference to those occurring in malignant diseases. A detailed review of the investigations available and the characteristic findings in malignant effusions is presented. The influence of serosal cavity fluid dynamics on the pharmacology of intracavitary chemotherapy is discussed, and a rational approach to intracavitary treatment is presented. The treatment options for patients with malignant effusions are described and the present status of medical treatment is discussed.

Ascites↗