Search PubMed⌕ Search

Biomedical subjects

N Thatcher

Publications and source records attributed to N Thatcher.

At least 235 records · Page 13Linked to original sources
PubMed1982

The "hot spleen" phenomenon in metastatic malignant melanoma: its incidence and relationship with the immune system.

Of patients with Stage II and III malignant melanoma, 34.7% display reversal of the liver-spleen ratio on technetium-99m-sulphur colloid isotope scans. Such an occurrence does not suggest a greater likelihood of relapse or a worse survival. The phenomenom is more common in female patients and there is a significant relationship between the presence of a "hot spleen" and a high IgM level. Patients with Stage II disease and high IgM levels have relapses more quickly than do those with normal IgM levels. Lymphopenia is common in patients with Stage II and III disease and the survival of these patients is worse than that of those with normal lymphocyte counts. In this report, the data are discussed together with results from other investigations, and a unifying hypothesis is presented which explains the phenomenon and relates it to increased activity of macrophages as a result of the presence of the tumor. The usefulness of isotope liver scanning in stage III malignant melanoma is also discussed.

Bacterial Vaccines↗
PubMed1982

Blood clearance of three radioactively labelled platinum complexes: cis-dichlorodiammine platinum II, cis, trans-dichlorodihydroxy-bis-(isopropylamine) platinum IV, and cis-dichloro-bis-cyclopropylamine platinum II, in patients with malignant disease.

The blood clearances of three platinum compounds, cis-dichlorodiammine platinum II (DDP), cis, trans-dichloro-dihydroxy-bis-(isopropylamine) platinum IV (CHIP), and cis-dichloro-bis-cyclopropylamine platinum II (CP), were determined in nine patients with malignant disease. The complexes were prepared using radioactive platinum (191Pt and 193Pt). A 10-mu Ci dose of each complex, containing the equivalent of 1-2 mg elemental platinum, was injected IV into groups of three patients. Serial blood and urine samples were collected over 72 h. No obvious difference was found between the three complexes for blood clearance, median t1/2a being 16.8 (range 11.2-23.5) min and median t1/2 beta 89 (range 63.7-127) h. The urinary excretion was greatest for CHIP, 60% of injected dose as against 42.6% for CP and 38.8% for DDP. Differences in renal excretion of DDP analogues could indicate potentially less nephrotoxic agents. The use of radioactive Pt will allow in vivo dynamic imaging of the distribution of platinum compounds in areas of interest.

Aged↗
PubMed1982

Effects of diphenylhydantoin on killer cell activity and other immunological functions. A sequential study including the interaction of Corynebacterium parvum in melanoma patients.

The effects of a single Phenytoin dose, given to patients with malignant melanoma, upon peripheral blood counts, serum immunoglobulins, lymphocyte subpopulations and lymphocytotoxicity (using Chang target cells) were recorded. Sequential blood samples were taken before and 10, 14, 34, 38 and 58 h after the Phenytoin. Early reductions (P less than 0.05) in lymphocyte count, NK, K and PHA induced cytotoxicity, when compared with initial, pre-Phenytoin values were noted. Immunisation with i.v. C. parvum prevented the reductions occurring after a second dose of Phenytoin. Indeed, significant increases above the values of samples taken immediately before the second dose, were observed in T cells, PHA blastogenesis, NK and K cell Cytotoxicity. The second dose did however cause some immunosuppression; the increase in T cells, NK and PHA induced cytotoxicity above initial values expected from previous investigations were not observed. The immunosuppression, particularly of killer cell function, occurring after phenytoin could have implications for the pathogenesis of malignancy and transplacental carcinogenesis, reported as following Phenytoin exposure.

Bacterial Vaccines↗
PubMed1981

Effects of Corynebacterium parvum on cellular immunity of cancer patients, assayed sequentially over 63 days.

The immunologic effects of Corynebacterium parvum (2 mg/M2) infused at three-week intervals were determined by 19 sequential assays in each of nine patients with metastatic malignancy. Peripheral blood immunologic profiles were followed for 63 days. No statistical significant changes (P greater than 0.05) occurred in total white cell, lymphocyte, or monocyte counts. Subpopulation assays demonstrated significant increases in E rosetting cells but not in sIg-bearing cells; there was a corresponding significant decrease in null-cell proportions. Killer cell lymphocytotoxicity was measured by 51Cr release from Chang target cells. Significant increases were observed one week after immunization and were maintained on subsequent immunizations. NK- and K-cell cytotoxicity were particularly augmented; T-cell cytotoxicity expressed as lytic units/ml was significantly increased on fewer assay occasions. Killer cell function has a possible in vivo antitumor role and methods of boosting and maintaining the activity deserve consideration. A three-week immunization schedule with C. parvum is supported by the current work and is the basis of a randomized adjuvant immunotherapy study of patients with malignant melanoma.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1981

Malignant melanoma in children and adolescents.

Thirty-one children and adolescents with malignant melanoma were treated at the Christie Hospital and Holt Radium Institute between 1945 and 1977. Locations of primary lesions included head-neck 14, trunk nine, and extremity eight. Twenty-five patients had clinically localized tumor at diagnosis, four had regional disease, and two had generalized tumor. Surgery was the primary modality of therapy. Fifteen patients survive without active disease from two years to more than 18 years, and 16 patients died of disease.

Adolescent↗
PubMed1981

The migratory properties of indium-111 oxine labelled lymphocytes in patients with chronic lymphocytic leukaemia.

These studies describe the application of a new method for following the migration of autologous lymphocytes in normal subjects and patients with chronic lymphocytic leukaemia (CLL). There is evidence that Indium 111 oxine is a reliable radioactive cell label for in vivo studies of lymphocyte traffic in man. In normal subjects, where 60-70% of the lymphocytes labelled are T cells, the results are different from those of previous workers. The lymphocytes leave the blood initially but later return to it. It is believed that this is due to the reappearance of cells which at first entered the spleen. It is suggested that the difference between these data and those of Hersey (1971) is due to the failure of lymphocytes in the latter studies to return to the blood after primary migration. In CLL no such reappearance in the blood is seen and the lymphocytes do not leave the spleen in significant numbers over 48 h. This suggests that CLL B cells either do not recirculate through spleen or that their transit time is greater than 48 h. Bone marrow localization in CLL patients is greater than in the normal subjects, suggesting that either a larger proportion of the neoplastic B lymphocytes enter this compartment or their transit time through it is longer than the transit time of a normal T cell predominant population. Localization in normal-sized lymph nodes in patients with CLL is less than that in the lymph nodes of normal subjects. This may possibly be explained by the greater propensity of T lymphocytes to enter lymph nodes than B lymphocytes, or by the altered migratory properties of CLL B lymphocytes as compared with normal B cells.

Adult↗
PubMed1981

A method for following human lymphocyte traffic using indium-111 oxine labelling.

A method is described whereby large numbers of human lymphocytes are separated from peripheral blood and labelled in vitro with indium-111 oxine. Following autologous reinjection, the distribution within the body is followed by means of serial blood samples, surface-probe counting and gamma camera imaging. The distribution of radioactivity following reinjection of heat-damaged labelled lymphocytes and free indium-111 oxine is different from that of 'normal' lymphocytes. The results suggest that the separation and labelling procedure does not cause significant physical damage to the lymphocytes The importance of restricting the specific lymphocyte activity to 20-40 microCi per 10(8) cells in order to minimize radiation damage to the lymphocytes is emphasized. Good resolution of lymphoid structures is obtained using gamma camera imaging and the changes recorded in organ distribution correlate well with data from animal models of lymphocyte migration. Thus, indium-111 oxine labelling of human lymphocytes provides a non-invasive method whereby the migratory properties of human lymphocytes can be followed.

Cell Movement↗
PubMed1981

Human lymphocyte traffic assessed by indium-111 oxine labelling: clinical observations.

Clinical studies using indium-111 oxine labelling of human peripheral blood lymphocytes are presented. Data from animal models of lymphocyte migration are compared with results found in healthy subjects and patients with malignant neoplasms. The physiological significance of bone marrow and liver localization on gamma camera imaging is discussed and the importance of considering the surface marker characteristics of the lymphocytes under study, when interpreting results, is emphasized. The possibility that the redistribution of lymphocytes within the body is a cause of the peripheral blood lymphopenia in patients with Hodgkin's disease and other malignancies is suggested, and the usefulness of indium-111 oxine labelling in clarifying this problem is proposed.

Cell Movement↗
PubMed1980

Advanced recurrent squamous cell carcinoma of the head and neck. Results of a chemotherapeutic regimen with adriamycin, bleomycin, 5-fluorouracil, methotrextate, and vitamin A.

Twenty-five patients with advanced squamous cell carcinoma of the head and neck were entered into this study. All patients had previously been irradiated and the majority had also undergone surgery for recurrent tumor. A low-dose regimen consisting of adriamycin, bleomycin, 5-fluorouracil, methotrexate, and vitamin A was prescribed, the median number of courses was four and a total of 95 were administered. Ten patients (40%) achieved objective responses (7 partial, 3 complete). The median duration of response was 14 weeks (range, nine to 60 weeks) with a median survival time of 38.5 weeks (range, eight to 72 weeks). The nonresponding patient group's survival time was significantly reduced (P = 0.002; median, 12 weeks; range, three to 40 weeks). The treatment was given on an outpatient basis and no serious hematologic toxic reactions were encountered. Mucositis was uncommon. This regimen produced an acceptable response rate without serious side-effects. The use of Vitamin A may have helped to prevent further impairment of the patient's nutritional status by ameliorating drug-induced mucositis.

Adult↗
PubMed1980

Anti-T antibody in malignant melanoma patients. Influence of response and survival following chemotherapy--changes in serum levels following C parvum, BCG immunization.

The level of anti-T antibodies directed towards the precursor T antigen of the MN blood group system was measured in the sera of 55 patients with disseminated melanoma, before and during chemoimmunotherapy. The anti-T titer was subnormal in patients before therapy; patients who responded to therapy had significantly higher titers than did nonresponders in sera taken before therapy, at regression/progression of disease, and during the last pulse of treatment. Higher pretreatment titers were associated with a significntly longer survival time. A single infusion of Corynebacterium parvum was given to 14 other melanoma patients and significant elevation of preimmunization titers was observed on days 14, 21, and 28 after infusion; Bacillus Calmette-Guerin, vaccination of 9 patients did not significantly alter the anti-T titer. The expression of the normally cryptic T antigen on melanoma cells would absorb naturally circulating anti-T antibodies. Less dense expression of T antigen on melanoma cells that were responsive to therapy, i.e., less "malignant," would explain the better prognosis for patients with higher titers. The increase in anti-T antibodies following administration of C parvum but not of BCG is of possible clinical relevance when C parvum is used as an immunotherapeutic agent.

Adult↗
PubMed1979

Chemotherapy in the management of invasive bladder cancer. A review.

In this review of the management of invasive carcinoma of the bladder the results of primary and systemic therapies are evaluated in the light of the natural history of the disease. The clinical and pathological causes of treatment failure are assessed in an attempt to identify new approaches that may be used in the future management of patients with bladder cancer. To improve survival in this disease requires different approaches to both the control of local disease and the early control of metastatic disease.

Adult↗
PubMed1979

Lack of effect of immunotherapy with BCG and Corynebacterium parvum on hepatic drug hydroxylation in man.

Serial serum diphenylhydantoin and urinary 5-(p-hydroxphenyl)-5-phenylhydantoin concentrations were determined in 8 patients with malignant disease and 4 healthy volunteers on 2 separate occasions after an oral dose of diphenylhydantoin (500 mg). No significant difference was observed between metabolism before and 10 days after immunization with BCG or Corynebacterium parvum. Volunteers without intervening immunization similarly showed no difference.

Adenocarcinoma↗
PubMed1979

Effects of Corynebacterium parvum and BCG therapy on immune parameters in patients with disseminated melanoma. A sequential study over 28 days. II. Changes in non-specific (NK, K and T cell) lymphocytoxicity and delayed hypersensitivity skin reactions.

C. parvum and BCG produced significant changes in NK, K and T cell lymphocytotoxicity using a Chang liver target cell. A consistent temporal pattern over 28 days of early depression, recovery, overshoot and then decline was described. This was particularly marked for C. parvum and 'K' cell activity. Skin test reactivity to recall antigens at 28 days was not appreciably different from the pre-immunization reactivity. The importance of using lymphocyte concentration-cytotoxicity titration curves and the linearization of such curves is discussed. An immunotherapy schedule with 3 weekly immunization intervals is proposed as the optimum schedule in patients receiving C. parvum at a dose of 2.0 mg/m2 i.v.

Antibody-Dependent Cell Cytotoxicity↗