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Biomedical subjects

T A McPherson

Publications and source records attributed to T A McPherson.

At least 19 recordsLinked to original sources
PubMed1991

Improved survival in patients with poor-prognosis malignant melanoma treated with adjuvant levamisole: a phase III study by the National Cancer Institute of Canada Clinical Trials Group.

Five hundred forty-three patients with completely resected malignant melanoma who were considered to have a significant risk of developing recurrent disease were randomized to one of four study groups. One group received levamisole 2.5 mg/kg on 2 consecutive days weekly for 3 years, a second group received bacillus Calmette-Guérin (BCG) for 3 years. A third group alternated 8-week courses of BCG and levamisole for 3 years and a fourth group underwent clinical assessment at the same frequency as the three treatment groups. The median duration of follow-up is 8.5 years. The percentage of reduction in the death rate and the recurrence rate in the treatment groups compared with the control group was calculated using the Cox proportional hazards model and adjusted for age, sex, and stage as covariants. The patients treated with levamisole were estimated to have a 29% reduction in both the death rate (P = .08) and the recurrence rate (P = .09) compared with patients receiving no further treatment. Fifty-five patients discontinued levamisole early because of gastrointestinal intolerance or arthralgia, myalgia, fever, and immune leukopenia. The patients treated with BCG alternating with levamisole experienced a 10% reduction in the death rate and a 6% reduction in the recurrence rate, and the patients treated with BCG alone experienced a 4% reduction in the death rate and a 3% increase in the recurrence rate compared with the control group. The degree of improvement experienced by the patients that were treated by levamisole is of sufficient magnitude to warrant further investigation of this dose of levamisole as adjuvant treatment in patients with melanoma.

Adolescent↗
PubMed1989

Adjuvant chemoimmuno- and immunotherapy in Dukes' stage B2 and C colorectal carcinoma: a 7-year follow-up analysis.

A prospectively randomised controlled clinical trial of adjuvant therapy was undertaken, at a single-centre, population-based cancer institute, in patients with Dukes' stages B2 and C colorectal carcinoma after curative surgery. Between 1976 and 1983, 253 patients were randomised to either control (no further therapy after surgery), immunotherapy (oral bacille Calmette-Guérin [BCG] 120 mg once a month) for 5 years or chemoimmunotherapy (oral BCG as above with methyl-cyclohexyl-chloroethyl nitrosourea [meCCNU] 130 mg/m2 on day 1 and 5-fluorouracil [5-FU] 325 mg/m2/day on days 1-5 and 375 mg/m2/day on days 36-40) repeated every 10 weeks for 8 cycles. The median follow-up of patients is now 6.95 years. Of the control, immunotherapy, and chemoimmunotherapy groups 22.35%, 39.28%, and 28.57%, respectively, have relapsed. The log-rank analysis of results shows no disease-free or overall survival advantage for patients receiving adjuvant therapy compared with the control group. Patients receiving adjuvant immunotherapy for stage B2 appear to have a significantly inferior disease-free survival compared with other groups, but their overall survival is similar. There are no significant differences in disease-free or overall survival in the three groups of patients with stage C tumour. Of 82 patients dying, 78.05% died of progressive colorectal carcinoma, 13 patients developed a second malignancy; the remainder died of seemingly unrelated causes.

Adenocarcinoma↗
PubMed1988

Natural human interferon-beta in metastatic malignant melanoma. A phase II study.

A phase II trial of natural human fibroblast interferon (HuIFN-beta) in 15 previously untreated patients with advanced metastatic malignant melanoma is reported. It was given as out-patient treatment by 30 min i.v. infusion of 60 x 10(6) U/m2/day on 4 consecutive days each week. Systemic toxicity was acceptable to all patients except one who declined further treatment. Performance status of treated patients was good. Three patients had a partial response and 3 patients had stable disease. The median time to response was 13.3 weeks and the duration of response was 22.6 weeks. Responses were seen in lungs and soft tissues only and relapses were seen particularly in the central nervous system and the liver. Overall survival of the patients was only 20.7 weeks. Those who achieved a partial remission had a median survival of 34.7 weeks and those with disease stabilisation a survival of 22.0 weeks. HuIFN-beta is shown to have anti-tumour activity in advanced metastatic melanoma, although the unit dose of HuIFN-beta is much larger than that required to achieve similar anti-tumour activity with interferon-alpha.

Adult↗
PubMed1987

Adjuvant chemoimmunotherapy after regional lymphadenectomy for malignant melanoma.

Thirty patients with malignant melanoma metastatic to regional lymph nodes who underwent either a full or partial node dissection were treated with adjuvant chemoimmunotherapy (CIT). In this pilot study, 11 patients were given intravenous (i.v.) DTIC plus intradermal (i.d.) BCG (D/BCG), 19 patients received i.v. DTIC, BCNU, and hydroxyurea plus oral BCG (DBH/BCG). Their overall survival (OS) and disease-free interval (DFI) following node dissection and CIT were compared with 33 historical control (HC) patients from the preceding 4 years, matched for the known prognostic factors in melanoma. The D/BCG group received a median of five courses, the DBG/BCG group six courses. Minimum follow-up of all patients is in excess of 7 years. No significant differences were observed in either DFI or OS from diagnosis between the two treatment groups or between CIT patients and HC patients. A highly significant difference was observed in DFI and OS in favor of the partial node dissection (PND) group when compared with full node dissection (FND) group. No other known variables in the PND group accounting for their improved survival are noted. Five patients in DBH/BCG and three in D/BCG group are still alive 84-114 months after completing therapy.

Adjuvants, Immunologic↗
PubMed1986

Radioiodinated peanut lectin: clinical use as a tumour-imaging agent and potential use in assessing renal-tubular function.

Peanut lectin (PNA) has been shown to have a high affinity for Thomsen-Friedenreich (T) antigen, which is associated with the membrane of many solid tumour cells. PNA labelled with 131I was used as a tumour-imaging substance in patients with known metastatic cancer. Serial gamma scintiscans were obtained in 17 patients following a single injection of 131I-labelled PNA. Only in 1 patient was this technique able to reveal a known metastasis at analogue imaging. In the remaining patients, no visible uptake of 131I-PNA could be demonstrated at sites of known metastases. PNA is rapidly excreted through the kidneys and localizes in the renal tubules. As a tumour-imaging agent, 131I-PNA appears to be without value, but its renal-excretory characteristics make it a potentially useful agent for the in vivo assessment of renal-tubular disorders.

Humans↗
PubMed1986

Combination of fibroblast interferon (HuIFN beta), carboxamide (DTIC), and cimetidine for advanced malignant melanoma.

In vitro synergism between interferons (IFNs) and chemotherapeutic drugs has been demonstrated, and an enhancement of IFN's antiproliferative effects when combined with cimetidine has been suggested in melanoma patients. In this pilot study, 12 patients with advanced malignant melanoma received HuIFN beta by 30 min i.v. infusion at 30 X 10(6) u/m2 day for 4 days, followed by i.v. decarbazine (DTIC) 1.0 g/m2 on day 5, repeated every 4 weeks. Oral cimetidine, 300 mg q.i.d., was given continuously. All the patients had visceral (bulky) metastases. No objective responses were observed; however, two patients had stable diseases for 16 and 20 weeks, respectively. Mild chills and fever with IFN, and mild to moderate emesis with DTIC, were noted. No additive haemopoietic or hepatic toxicity was observed. Combination of HuIFN beta, DTIC, and cimetidine is relatively nontoxic, but does not appear to have a significant antitumor activity in patients with advanced malignant melanoma.

Adult↗
PubMed1986

Extended phase I study of human beta-interferon in human cancer.

Ten patients with advanced cancer were treated with weekly intravenous escalating doses of human beta-interferon (HuIFN beta) 4 days each week. The starting dose of HuIFN beta was 3.0 X 10(6) units/m2 and the dose was doubled each week until dose-limiting toxicity was observed. Subjective toxicity included mild fevers and chills, malaise and flu-like symptoms. The lowest dose which caused suppression of the platelet and/or white cell count was 64 X 10(6) units daily, and the maximum dose given was 320 X 10(6) units daily. Both subjective and objective toxicity were not dose-related, easily managed and reversible. Serum interferon levels and the duration of measurable interferon activity on natural killer cells was in general dose-dependent. Two patients had an objective partial response, and two others showed stable disease while receiving HuIFN beta.

Adult↗
PubMed1985

A double antibody radioimmunoassay for myelin basic protein in cerebrospinal fluid.

Levels of myelin basic protein (MBP) in cerebrospinal fluid (CSF) are useful in assessing the extent of demyelination which has occurred, or is occurring, in a variety of human problems associated with demyelination. Thus, an accurate, specific, simple, and consistent test for detecting MBP in CSF is needed. We describe such a test herein. The radioimmunoassay (RIA) described is a double antibody RIA using human MBP, and rabbit anti-MBP as reagents. The test can be done using only 200 microL of unconcentrated CSF. The test was sensitive to 0.1 microgram MBP/L. Recovery of known amounts of MBP was 97-105%, the within-assay and between-assay reproducibility were excellent. The "normal range" for our MBP-RIA was less than 2 micrograms/L, with a "grey area" between 2.0 and 3.0 micrograms/L.

Animals↗
PubMed1985

Retinol and postoperative colorectal cancer patients.

In order to determine whether low plasma levels of retinol and its carrier (retinol binding protein) are related to increased risk of cancer recurrence, these were measured in 103 patients who had had colorectal cancer surgically removed. According to the modification of the Dukes' classification, 66 had B2 tumours (with no nodal involvement' and 37 had C tumours (with lymph-node metastases). These patients were part of the Cross Cancer Institute Adjuvant GI Cohorts who were on the control arms receiving no further treatment. At the time of blood sample collection, they were believed to be free of neoplastic disease. The post-operative patients were found to be associated with subnormal circulatory levels of retinol (43.3 micrograms dl-1 vs 65.3 micrograms dl-1) and its carrier protein (4.6 mg dl-1 vs 5.7 mg dl-1), when compared with apparently healthy subjects. The latter being more markedly depressed in patients with "C" type tumour (3.8 mg dl-1) than that in those with "B2" type tumour (5.0 mg dl-1). These findings appeared to be persistent during the follow-up study when a second blood sample was collected, one to four months later from 40 patients. Furthermore, the initial plasma retinol level in conjunction with RBP was found to be even lower in 12 patients (35.1 micrograms dl-1, 3.7 mg dl-1) who subsequently had cancer recurrence than in those who remained free of apparent cancer (44.5 micrograms dl-1, 4.6 mg dl-1). The lowest initial values of retinol (19.3 micrograms; 18.8 micrograms dl-1) and RBP (2.4; 1.6 mg dl-1) recorded in the study were seen in the only two patients who died of the disease at the time of follow-up.

Adult↗
PubMed1985

Cerebrospinal fluid myelin basic protein as a prognostic marker in patients with head injury.

Despite increasing interest in identifying biochemical and serologic markers to judge the severity of closed head injury in comatose patients, clinical variables remain the most readily available methods for assessing prognosis. In a series of 35 severely head-injured comatose patients, the cerebrospinal fluid (CSF) level of myelin basic protein (MBP) was analyzed by radioimmunoassay. MBP levels during the first week after injury were significantly correlated with the Glasgow outcome score at 7 days (p less than .005), 3 months (p less than .005), and 6 months (p less than .05) postinjury. Measurement of CSF MBP appears to be a useful laboratory adjunct to clinical assessment, for judging the outcome of severely head-injured patients.

Adolescent↗
PubMed1984

Adjuvant BCG immunotherapy for malignant melanoma.

A total of 199 patients with stage I malignant melanoma at Clark's level 3 to 5 of invasion were entered into a prospectively controlled randomized clinical trial that attempted to assess the value of local and systemic immunotherapy with BCG (bacille Calmette-Guérin) after surgery. The patients were randomly assigned, with stratification by Clark's level, to receive either routine follow-up or immunotherapy with BCG, administered intradermally with a Heaf gun around the site of wide excision and then given orally for 2 years. Intradermal administration of BCG was repeated after 1 year's oral therapy with BCG. Of the 99 patients in the treatment group 66 had Clark's level 3, 28 had level 4, and 5 had level 5 invasion. Of the 100 patients in the control group, 61 had level 3, 36 had level 4, and 3 had level 5 invasion. Other prognostic factors, such as sex, depth of invasion, histologic features, site of disease and type of surgery, were evenly distributed. There were 57 recurrences of the melanoma, 24 in the treatment group and 33 in the control group. However, this trend was not statistically significant (p = 0.194). The suggestion that BCG may reduce the likelihood of local/regional recurrence has not been confirmed with longer follow-up. There were 13 such recurrences in the BCG group, compared with 21 in the control group; the proportions of patients in each group who had such a recurrence were not significantly different. Of the 199 patients 41 died, 24 in the control group and 17 in the treatment group; again, this difference was not significant. While there may be minor activity in selected patients, there appeared to be no benefit from this form of adjuvant BCG therapy in patients with malignant melanoma.

Administration, Oral↗
PubMed1983

Cutaneous malignant melanoma in Alberta: 1967-1976.

The records of 519 patients with cutaneous malignant melanoma (CMM) were analyzed for the period 1967 to 1976 from the population-based cancer registry of the Province of Alberta in Canada. During this period, the incidence of CMM rose more rapidly in men (especially those older than age 50 years) than in women. Five-year survival rates were 59% and 74% for men and women, respectively. Women survived longer mainly because of a longer disease-free interval. Once the disease recurred, however, the mean time to death was similar for both men and women. Primary lesions were most frequent on the trunk, and head and neck in men, and on the lower limbs in women. The proportion of trunk lesions is increasing in both sexes, especially in persons younger than age 50 years. The lack of a consistent upward trend for lesions on the lower limbs in women was unexpected. The data predict a growing contribution of trunk lesions is young men to the increasing incidence and mortality of CMM in Alberta.

Adult↗
PubMed1983

Effect of indomethacin on human neutrophil chemiluminescence and microbicidal activity.

The action of indomethacin on the bactericidal processes and chemiluminescent activity of human neutrophils was examined. Indomethacin substantially reduced the ability of neutrophils to kill Staphylococcus aureus and Escherichia coli and impaired their ability to generate both native and luminol-dependent chemiluminescence (CL). In contrast to these effects, indomethacin exerted an amplifying effect on lucigenin-sensitized phagocytically induced CL. The data suggests that indomethacin interferes with neutrophil myeloperoxidase-mediated CL and microbial killing, while substantially augmenting PMN superoxide-forming activity.

Blood Bactericidal Activity↗
PubMed1983

CSF myelin basic protein levels in acute optic neuritis and multiple sclerosis.

Normal CSF-MBP levels as determined by a RIA were less than 6.2 ng/ml CSF (mean 3.9). Eighty percent of patients with acute optic neuritis have CSF-MBP levels greater than 6.2 ng/ml (mean 7.6 ng/ml CSF). Five of 7 patients with acute internuclear ophthalmoplegia due to an initial exacerbation of demyelination have CSF-MBP levels above 6.2 ng/ml (mean 6.8 ng/ml). Fifty percent of MS patients with chronic progressive disease have CSF-MBP levels above 6.2 ng/ml (mean 6.7 ng/ml). MS patients experiencing monosymptomatic exacerbations show elevated CSF-MBP levels in 75% in 75% of cases (mean 8.2 ng/ml). MS patients experiencing polysymptomatic exacerbations show significantly higher levels of CSF-MBP (mean 22.3 ng/ml) than the patients with monosymptomatic exacerbations. Ninety-five percent of MS patients experiencing polysymptomatic exacerbations have elevated levels of CSF-MBP.

Acute Disease↗
PubMed1983

Myelin basic protein: a component of circulating immune complexes in multiple sclerosis.

Myelin basic protein (MBP) is an antigenic component of circulating immune complexes (CIC) in patients with multiple sclerosis (MS). Immune complexes were isolated from the sera by adsorption to Raji cells and then acid eluted. Final identification of MBP from Raji eluates was done by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) followed by MBP radioimmunoassay (RIA) of gel eluates and by an immunoblot technique.

Antigen-Antibody Complex↗