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Biomedical subjects

J Purvis

Publications and source records attributed to J Purvis.

15 recordsLinked to original sources
PubMed1992

Phase I study of BCNU and intravenous 6-mercaptopurine in patients with anaplastic gliomas.

On the basis of response rates of up to 50%, BCNU [1,3-bis(2-chloroethyl)-1-nitrosourea] is the primary drug used in the chemotherapy of anaplastic gliomas. Preclinical data obtained in several experimental systems show that the cytotoxicity of chloroethylnitrosoureas can be increased by the concomitant use of thiopurines. In this phase I trial, patients with anaplastic gliomas received standard-dose BCNU (200 mg/m2 x 1) in combination with escalating doses of intravenous 6-mercaptopurine (200, 350, 500, and 750 mg/m2 daily x 3), with BCNU being given on day 3 to maximize the effect of the drugs on cellular DNA. No increase in hematologic toxicity was demonstrated as the dose of 6-mercaptopurine was increased. Responses and stabilization of disease were observed in several patients. Due to the safety of and the evidence of activity found for this regimen in the present trial, 750 mg/m2 6-mercaptopurine has been incorporated into subsequent studies.

Adolescent↗
PubMed1991

Clinically unsuspected inclusion body myositis.

We describe a patient with inclusion body myositis presenting as chronic, therapy resistant polymyositis. Our report highlights the slow evolution of inclusion body myositis in some patients, and emphasizes the diagnostic importance of examining one or more muscle biopsy specimens by both frozen section and electron microscopy.

Biopsy↗
PubMed1991

The initial electrocardiogram in patients seen by a mobile coronary care unit.

The advent of thrombolytic therapy for patients with suspected acute myocardial infarction has highlighted the importance of the initial electrocardiogram (ECG) in decision making. Thus we analysed the initial ECGs of 94 consecutive cases with suspected myocardial infarction who were seen within six hours after the onset of chest pain by a mobile coronary care unit. The study included 91 patients (three patients admitted twice) (61 male), aged 27-83 years (mean 60.5). Median time from onset of chest pain to arrival of the mobile coronary care unit was 75 minutes (range 15-345), and mean mobile coronary care unit response time was 12.3 +/- 7 (SD) minutes (range 5-45). The majority of cases (65 of 94, 69.1 per cent) were seen within two hours of the onset of symptoms. A final diagnosis of myocardial infarction was made in 48 of 94 (51.1 per cent) cases; 38 had unstable angina and eight other diagnoses. Of the 48 with myocardial infarction the initial ECG showed ST segment elevation in 37, ST depression and or T wave inversion in six, Q waves only in three and left bundle branch block in two. No patient with an initially normal ECG had a myocardial infarction. Thrombolytic therapy was given out of hospital to 33 of 38 patients with ST segment elevation. In seven patients with ST elevation (median delay time to intensive care 60 minutes), rapid resolution of ST segment elevation occurred following thrombolytic therapy and there was no significant elevation of cardiac enzymes, suggesting that the infarct had been aborted.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Phase I and clinical pharmacology trial of 502U83 using a monthly single dose schedule.

502U83 is an arylmethylaminopropanediol derivative exhibiting significant antineoplastic activity in a number of murine and human tumor models. In this Phase I trial, a 1-h or 4-h infusion of the agent was administered i.v. in 250 ml of 5% dextrose in water every 28 days. Fifty-three courses at doses of 25 to 2000 mg/m2 were administered to 36 patients with refractory solid tumors. Prolongation of the PR, QRS, and QT intervals on electrocardiograms was dose limiting at 2000 mg/m2. This prolongation appeared dose related and was reversible upon discontinuation of the infusion. No hematological toxicity was observed. Other toxicities included only sporadic and mild to moderate nausea and vomiting. No tumor responses were noted. 502U83 plasma concentrations were determined by high-pressure liquid chromatography. Complete pharmacokinetic profiles were obtained for 21 of the 36 patients. After infusion, plasma concentrations declined in a biexponential or in a triexponential manner with a harmonic mean terminal t 1/2 of 8.83 h. Using a three-compartment model, the mean apparent volume of distribution at steady state and total-body clearance were 195 liters/m2 and 42.5 liters/h/m2, respectively, indicative of extensive tissue distribution. No correlation could be found between the pharmacokinetic parameters and prolongation of the cardiac conduction intervals. Because of the cardiac effects with the drug, the schedule of administration of 502U83 used in this study cannot be recommended.

Adult↗
PubMed1988

Cytokeratins in cervical dysplasia and neoplasia: a comparative study of immunohistochemical staining using monoclonal antibodies NCL-5D3, CAM 5.2, and PKK1.

The expression of low molecular weight cytokeratins (normally expressed only in simple epithelia) in intraepithelial neoplasia of grade CIN III or greater in cervical biopsies has recently been described by Bobrow et al. Our study of 127 cases confirms this finding and in addition we compare the use of three monoclonal antibodies, namely NCL-5D3, CAM 5.2, and PKK1, in demonstrating the phenomenon. Both NCL-5D3 and CAM 5.2 give consistently negative results for non-neoplastic stratified squamous epithelium, as well as CIN I and CIN II lesions, whilst staining about 30 per cent of CIN III biopsies and most carcinomas. PKK1, on the other hand, stained 50 per cent of non-neoplastic epithelia and thus did not serve as a marker of severe dysplasia. The possible implications of these observations are discussed.

Antibodies, Monoclonal↗
PubMed1988

Alternating non-cross-resistant chemotherapy for metastatic hormone-independent breast cancer.

A phase II clinical trial was designed to apply the treatment strategy of alternating non-cross-resistant chemotherapy regimens to patients with metastatic estrogen-receptor negative or hormone-refractory breast cancer. Twenty-six patients received Adriamycin and cyclophosphamide alternating at 3-week intervals with the combination of vinblastine, mitomycin-C, and 5-fluorouracil (5-FU). Toxicity was moderately severe. Two patients developed grade 2 and three developed grade 1 stomatitis. A single patient developed a WBC count of less than 1000/mm3, whereas five had a lowest recorded WBC count of 1,000-1,999/mm3. Two patients displayed thrombocytopenia of less than 50,000/mm3, one in conjunction with a fatal hemolytic-uremic syndrome. There were six complete and eight partial responses (PRs) for an objective response rate of 54% (64% of fully evaluable patients). The median survival after onset of protocol therapy was 13.3 months. These results are no better than those reported for other Adriamycin-containing regimens.

Adult↗
PubMed1988

Clinical modulation of doxorubicin resistance by the calmodulin-inhibitor, trifluoperazine: a phase I/II trial.

Drug resistance to chemotherapy agents such as doxorubicin appears to be an important cause of therapeutic failure in cancer treatment. Based on preclinical information demonstrating that the phenothiazine calmodulin-inhibitor trifluoperazine can enhance retention and cytotoxicity of doxorubicin in resistant cells, a phase I/II trial of the combination was performed to determine the maximally tolerated dose (MTD) of trifluoperazine that could be administered with doxorubicin. Patients with intrinsic (no previous response) and acquired (previous response with relapse) doxorubicin resistance were eligible. Doxorubicin was administered as a 96-hour continuous infusion (60 mg/m2) on days 2 through 5. Trifluoperazine was administered in divided doses orally on days 1 through 6, with dose escalation from 20 to 100 mg/d. Thirty-six patients were evaluable. The MTD of trifluoperazine was 60 mg/d, with dose-limiting toxicity being extrapyramidal side effects. No alteration of doxorubicin toxicity was observed. Seven of the 36 patients responded (one complete response [CR], six partial responses [PR]), with seven of 21 patients having acquired resistance, and zero of 15 with intrinsic resistance demonstrating responses. Doxorubicin plasma levels were not affected by trifluoperazine, and the maximal trifluoperazine plasma levels achieved were 129.83 ng/mL. This trial demonstrates the combination of trifluoperazine and doxorubicin is well tolerated, and the schedule recommended for phase II trials is doxorubicin, 60 mg/m2 (continuous infusion) days 2 through 5, and trifluoperazine, 15 mg four times per day orally days 1 through 6. Continued investigation of this combination is indicated for patients with acquired doxorubicin resistance.

Adult↗
PubMed1987

NCL-5D3: a new monoclonal antibody recognizing low molecular weight cytokeratins effective for immunohistochemistry using fixed paraffin-embedded tissue.

Production of a new monoclonal antibody designated NCL-5D3 is described. The antibody recognizes several low molecular weight cytokeratins, in particular cytokeratin Moll number 8 as determined by immunoblotting studies, and is highly effective for immunocytochemistry using routinely processed paraffin-embedded material. Staining is enhanced by prior treatment of the sections with trypsin. Assessment using a wide variety of normal and neoplastic tissue indicates reactivity with all tissues of simple or glandular epithelial origin, and in addition with many squamous carcinomas. Thus the antibody should prove of value in diagnostic histopathology.

Antibodies, Monoclonal↗
PubMed1986

Survival in breast cancer related to tumour oestrogen receptor status and immunohistochemical staining for NCRC 11.

NCRC 11 is a monoclonal antibody raised against dissociated breast cancer cells. Using this antibody, it has been shown in an earlier study that staining of a high proportion of tumour cells is strongly associated with superior survival. Many investigators have found that positive tumour oestrogen receptor (OER) status is associated with better survival in breast cancer. In the present study of 136 breast cancer patients followed up for a minimum of 30 months, tumour oestrogen receptor assays were carried out, and using the indirect immunoperoxidase technique, histological sections of paraffin embedded material were stained for NCRC 11; for the purpose of this study, tumours showing 25 per cent or less cells staining were regarded as 'negative'. Patients whose tumours were OER positive had a significantly better prognosis (logrank test P less than 0.05). Patients whose tumours were graded as negative for NCRC 11 had a poorer prognosis compared with the positive group but this did not attain significance. Our failure to demonstrate convincingly a better prognosis for the NCRC 11 positive patients may relate to the shorter duration of our study, or to different tissue fixation techniques. In this study staining for NCRC 11 was positively correlated with oestrogen receptor status (P less than 0.02).

Antibodies, Monoclonal↗
PubMed1984

5-Fluorouracil and folinic acid: a Phase I-II trial in gastrointestinal malignancy.

Fifty-one patients with metastatic adenocarcinoma received Folinic Acid (FA) combined with 5-Fluorouracil (5FU) in a Phase I-II clinical trial. Two different schedules were used: (a) bolus infusion--5FU 7-12 mg/kg/d I.V. d1-5, FA 1.6 mg/kg/d I.V. d1-5; (b) continuous infusion--5FU 600-1200 mg/m2/d I.V. d1-4, FA 60 mg/m2/d I.V. d1-4. Mucositis and myelosuppression were dose-limiting, with recommended dose levels of 5FU for further trials being 10 mg/kg/d I.V. d1-5 and 1000 mg/m2/d I.V. d1-4 on the bolus and continuous infusion schedules, respectively. Forty-one evaluable patients with measurable disease were treated. Thirty-six had metastatic colorectal carcinoma, and 14/36 patients responded (CR-1, PR-13), including responses in three patients who had previously failed 5FU treatment alone. In the two patients with unknown primary sites and three with gastric cancer, no response were seen. 5FU and FA have activity equivalent to 5FU alone, and the responses in patients receiving prior 5FU suggest it may be superior. The possibility that toxicity may be enhanced does exist. Further trials of these two agents are warranted.

Adenocarcinoma↗
PubMed1983

Combination chemotherapy of metastatic thyroid cancer. Phase II study.

Eleven patients with metastatic thyroid cancer received combination chemotherapy with doxorubicin, bleomycin, vincristine, and melphalan. Six of 11 patients responded, two with a minor response, three a partial, and one with a complete response. Most responses were brief (2-3 months), but the patient with a complete response is alive and free of disease at 60+ months. Toxicity was moderate and predominantly hematologic. Thyroid carcinoma is a moderately sensitive neoplasm with occasional prolonged responses to chemotherapy.

Adult↗
PubMed1979

Infantile jejunal mucosa in infection and malnutrition.

Sixteen children with refractory diarrhea and three malnourished children who had frequent episodes of acute gastroenteritis but little diarrhea at the time of hospital admission, were studied by peroral upper small intestinal biopsy. Six children were adequately nourished; five children weighed 62 to 79% of expected weight and eight weighed less than 60% of expected weight. Two of the malnourished children had giardiasis. Pathogenic bacteria were found in only one case. Varying degrees of mucosal atrophy with reduction of mean villous height were seen in 18 cases. The concentration of mononuclear inflammatory cells and plasma cells was about half that seen in well-nourished children with severe nongastrointestinal infections. The concentration of mononuclear cells in the lamina propria was about twice that seen in normal adults. The proportions of IgA-producing cells and cells that stained for secretory component were significantly reduced, as compared with normal adult control values. This reduction was most striking in children with malnutrition complicated by giardiasis. Enzyme histochemical studies were performed for leucine aminopeptidase, alkaline phosphatase and acid phosphatase. There was a tendency for considerably reduced acid phosphatase activity in all clinical groups (kwashiorkor, marasmic kwashiorkor and marasmus) of growth-retarded infants.

Child, Preschool↗