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Biomedical subjects

M Mason

Publications and source records attributed to M Mason.

At least 19 recordsLinked to original sources
PubMed1992

Risk of second brain tumour after conservative surgery and radiotherapy for pituitary adenoma.

OBJECTIVE: To assess the risk of second brain tumour in patients with pituitary adenoma treated with conservative surgery and external beam radiotherapy. DESIGN: Long term follow up of a cohort of patients with pituitary adenoma and comparison of tumour occurrence with population incidence rates. SETTING: The Royal Marsden Hospital. SUBJECTS: 334 patients with pituitary adenoma treated with conservative surgery and radiotherapy (median dose 45 Gy) and followed up for 3760 person years. MAIN OUTCOME MEASURES: Second intracranial tumour and systemic malignancy. RESULTS: Five patients developed a second brain tumour: two had astrocytoma, two meningioma, and one meningeal sarcoma. The cumulative risk of developing a second brain tumour over the first 10 years after treatment was 1.3% (95% confidence interval 0.4% to 3.9%) and over 20 years 1.9% (0.7% to 5.0%). The relative risk of a second brain tumour compared with the incidence in the normal population was 9.38 (3.05 to 21.89). There was no excess risk of any other type of second primary malignancy. CONCLUSIONS: There is an increased risk of second intracranial tumour in patients with pituitary adenoma treated with surgery and radiotherapy. Although radiation is likely to be the most important factor contributing to the excess risk, further study is required in a cohort of similar patients not receiving radiation.

Adenoma↗
PubMed1992

The activity of single-agent carboplatin in advanced seminoma.

Between 1982 and 1990, 70 patients with advanced metastatic seminoma were treated with 4-6 courses of single-agent carboplatin (SAC) administered at 400 mg/m2 every 3-4 weeks. Treatment was of low toxicity and no patients suffered neurotoxicity, ototoxicity or significant renal damage. There was only one episode of neutropenic sepsis and no thrombocytopenic bleeding. The median follow-up of surviving patients was 3 years. 16 patients have relapsed and 4 of these 16 have died, thus the actuarial 3-year relapse-free survival was 77% (95% CI 65-86%), cause-specific survival was 94% (95% CI 82-99%) and overall survival was 91% (95% CI 80-96%). The risk of relapse was reduced by post-chemotherapy irradiation (PCRT) to involved nodes, occurring in 1/20 patients treated with PCRT compared with 11/31 who could have been treated but were not (P = 0.04). Of the 16 patients who relapsed, 12(75%) have been salvaged with combination chemotherapy and remain free from further relapse with a median follow-up of 18 months. Though this level of survival is equivalent to that obtained with initial cisplatin-based combination chemotherapy, the recurrence rate indicates that SAC remains an investigative treatment, except for unfit patients.

Adult↗
PubMed1992

Distribution of follicle-stimulating hormone and luteinizing hormone isoforms in sera from women with primary ovarian failure compared with that of normal reproductive and postmenopausal women.

OBJECTIVE: To demonstrate if molecular heterogeneity of gonadotropins correlates with the type of primary gonadal failure. DESIGN AND METHODS: Aliquots of sera from women with hypogonadism were subjected to gel filtration chromatography to be assayed for follicle-stimulating hormone (FSH) and luteinizing hormone (LH) by the use of radioimmunoassay. Molecular weight (MW) of isoforms was calculated on a calibration curve obtained with molecular markers. The molecular variants were characterized on the basis of elution volume, MW, and partition coefficient. RESULTS: Chromatographic profile of sera from four women with natural menopause exhibited two FSH peaks of immunoreactivity and a heavier LH isoform. This pattern was different from that obtained in sera from women of reproductive age who presented a single peak that eluted after the corresponding standard. In six cases of idiopathic premature menopause and three more with gonadotropin-resistant ovary, the chromatographic profile showed a marked and remarkable molecular heterogeneity, particularly LH, and this was more apparent in women with resistant ovary. CONCLUSIONS: Our investigation confirms the relationship between the gonadotropin heterogeneity with the gonadal failure. The duration of the ovarian failure may influence the molecular proportion of gonadotropins and the predominance of heavier MW isohormones.

Adult↗
PubMed1992

Intra-arterial adriamycin, conventionally fractionated radiotherapy and conservative surgery for soft tissue sarcomas.

Thirteen patients with soft tissue sarcomas were treated with a combination of intra-arterial Adriamycin, conventionally fractionated radiotherapy (2 Gy per day), and conservative surgery (trimodal therapy). Severe acute complications occurred in 10 patients: 3 brachial artery thromboses, 6 delayed wound healing, 4 wound infections, and 3 cases of necrosis of the skin plus subcutaneous tissues. Three patients have developed local recurrence. Five patients are alive, 4 of whom are disease-free, and the median follow up time of surviving patients is 56 months. One has significant impairment of limb function due to joint ankylosis. An additional 2 patients were treated with intra-arterial Adriamycin and conservative surgery for local recurrence after previous surgery and radiotherapy; both died of subsequent metastatic disease, one having a further local recurrence. One patient with multifocal angiosarcoma was treated with intra-arterial Adriamycin and radiotherapy but no surgery, and is alive free of disease 49 months later. The combination of radiotherapy and intra-arterial Adriamycin with surgery resulted in significant acute toxicity. This small study has not demonstrated any improvement in local control compared with that expected with conservative surgery and radiotherapy alone.

Adult↗
PubMed1992

Use of carboplatin in germ cell tumors of the testis.

The high cure rate among young men with metastatic testicular germ cell tumors heightens the issue of late treatment toxicity. Conventional combination chemotherapy based on cisplatin can be expected to cure 85% to 90% of patients with metastatic disease; however the cost of this success includes severe treatment side effects, including irreversible renal damage and the risk of neurotoxicity and ototoxicity. Carboplatin was investigated as a replacement for cisplatin in the treatment of these tumors because of its reduced toxicity. The Royal Marsden Hospital pilot studies have included 76 patients treated for metastatic nonseminoma with the combination carboplatin/etoposide/bleomycin between 1984 and 1988. The median follow-up at time of analysis was 24 months. The complete remission rate was 95% and the overall cause-specific survival was 98.5%. Also, 33 patients treated with single-agent carboplatin for advanced metastatic seminoma were followed for a median of 36 months. The actuarial progression-free survival was 79%, and 91% of patients were alive and disease-free. The results of these studies indicate that carboplatin has activity equivalent to cisplatin in germ cell tumors of the testis and is less toxic.

Adolescent↗
PubMed1992

[Effect of primary ovarian insufficiency on the molecular heterogeneity of pituitary gonadotropins].

It is known that hypophysial gonadotropins circulate in different molecular forms which are provided with different biological activity and that the proportion of such varieties keep a relation with the concentrations of estrogens in circulation. In physiological menopause predominate the great molecular forms which have a lesser biological activity and when estrogens are administrated a change is produced to smaller molecular forms. The present study tries to determine if in cases of ovarian insufficiency of long duration as in precocious menopause and the syndrome of refractory ovary the chromatographic conduct of gonadotropin is similar. Six patients with precocious menopause, and three with the syndrome of refractory ovary, were studied, in order to make a comparison of chromatographic pattern of FSF and LH in serum, with the one found in women with normal ovarian function and with physiologic menopause. The chromatographic analysis was done by filtration in gel of the serum and the subsequent determination of LH and FSH by RIA of double antibody. It was found that the chromatographic pattern of patients with ovarian insufficiency of long duration, characteristically presents larger molecular forms, specially in the refractory ovary syndrome with a greater alteration in the profile of LH. With base on these results it is concluded that the duration of ovarian insufficiency determine the type of molecular form, predominant, of gonadotropins. Also it is suggested that for the syndrome of refractory ovary, the greater heterogenicity of gonadotropins may explain part of physiopathogeny.

Adult↗
PubMed1992

On the use of historical control data to estimate dose response trends in quantal bioassay.

New tests for trend in proportions, in the presence of historical control data, are proposed. One such test is a simple score statistic based on a binomial likelihood for the "current" study and beta-binomial likelihoods for each historical control series. A closely related trend statistic based on estimating equations is also proposed. Trend statistics that allow overdispersed proportions in the current study are also developed, including a version of Tarone's (1982, Biometrics 38, 215-220) test that acknowledges sampling variation in the beta distribution parameters, and a trend statistic based on estimating equations. Each such trend test is evaluated with respect to size and power under both binomial and beta-binomial sampling conditions for the current study, and illustrations are provided.

Analysis of Variance↗
PubMed1991

Microdissection of chromosome band 11p15.5: characterization of probes mapping distal to the HBBC locus.

Both cytogenetic and molecular genetic analyses of the 11p15.5 subband suggest it may contain loci important in the genesis of a wide variety of tumors such as rhabdomyosarcomas and Wilms' tumors as well as the congenital tumors associated with the Beckwith-Wiedemann syndrome. As a first step in further defining the involvement of this chromosomal region in these various maladies, a library was constructed from the specific microdissection of chromosomal fragments representing 11p15.5-pter. Of 98 microclones analyzed, 31 identified single copy human DNA sequences, 21 of which mapped to 11p15.5 while 10 mapped proximal to the HBBC locus. Five of the 11p15.5-positioned microprobes detected restriction fragment length polymorphisms at their homologous genomic loci for various enzymes. These microprobes are now being utilized in several ways in order to address the underlying basis of the Beckwith-Wiedemann syndrome and its associated tumors.

Animals↗
PubMed1991

Effectiveness of carboplatin, etoposide, and bleomycin combination chemotherapy in good-prognosis metastatic testicular nonseminomatous germ cell tumors.

The combination of carboplatin, etoposide, and bleomycin (CEB) was evaluated as initial chemotherapy in 76 patients with good-prognosis metastatic nonseminomatous germ cell tumors (NSGCT) between 1984 and 1988. The classification of eligible patients included Royal Marsden Hospital (RMH) stages IM, IIA, IIB, IIC, IIIA, IIIB, IV0ABCL1, and IV0ABL2. Four courses of combination chemotherapy were administered in a 21-day cycle, and surgical excision of residual mass was performed in 27 cases (23 laparotomies and four thoracotomies). At the time of analysis, median follow-up was 24 months from start of chemotherapy (range, 6 to 54 months). The 2-year cause-specific survival probability was 98.5%, the single cause-related mortality being caused by bleomycin pneumonitis. Five patients failed CEB chemotherapy, but all have been successfully salvaged with a combination of surgery and intensive chemotherapy, follow-up from completion of all treatment being 35 to 44 months. The toxicity of CEB included bone marrow suppression and alopecia in all patients but no significant neurotoxicity or ototoxicity, and minimal renal toxicity. Only four (5%) patients had a decrease in the glomerular filtration rate greater than 15%. In 51% of patients, the hemoglobin fell below 10 g/dL. The WBC count nadir was less than 1,500/microL in 11% of treatment cycles and in 16% the platelet nadir fell below 50,000/microL. Decreases in the WBC and platelet counts were of very brief duration. Only one of 310 CEB cycles was complicated by neutropenic sepsis, and there were no episodes of thrombocytopenic purpura or bleeding. We conclude that the CEB combination represents an effective alternative to cisplatin-based chemotherapy in good-prognosis NSGCT and that the replacement of cisplatin by carboplatin leads to reduced toxicity.

Adolescent↗
PubMed1991

Impact of chemical dependency on family health status.

Previous discussions of the relationship between chemical dependency and family health have been based primarily on clinical observations and on the perceptions of family members rather than on research evidence. In order to systematically document the relationship, this study compared family medical insurance claims 2 years prior to and 2 years following the year in which a family member completed a chemical dependency treatment program. Results indicate a significant decrease in claims following the family member's completion of treatment, thus suggesting a relationship between the chemical dependency of one family member and the health status of other family members.

Adult↗
PubMed1979

Purification and comparison of several catalytic parameters of the gamma-glutamyltranspeptidase of rat mammary adenocarcinoma (13762) and of normal rat mammary gland.

A method for the purification of a membrane-bound glycoprotein, gamma-glutamyltranspeptidase ((gamma-glutamyl)-peptide:amino-acid gamma-glutamyltransferase, EC 2.3.2.2), from a transplantable rat mammary tumor (13762 MT) is described. The properties of the tumor enzyme were compared with those of gamma-glutamyltranspeptidase similarly isolated from mammary tissue of nonpregnant multiparous rats. Evidence has been presented elsewhere that the mammary and tumor enzymes exist as groups of species differing in isoelectric point and that the tumor enzyme contains more of the those species with lower isoelectric points. In this study the normal and tumor enzyme preparations are found to be identical or very similar in regards to the effect of papain on molecular size, the ratios of the enzymatic activities as measured with various amino acids, the Km for gamma-glutamyl-p-nitroanilide, and the Ki for inhibition by glutathione. Neuraminidase treatment had no effect on these catalytic properties. The properties observed were generally similar to those previously reported for highly purified rat kidney preparations.

Adenocarcinoma↗
PubMed1979

Tumor inhibitory and non-tumor inhibitory L-asparaginases from Pseudomonas geniculata.

Two enzymes that catalyze the hydrolysis of l-asparagine have been isolated from extracts of Pseudomonas geniculata. After initial salt fractionation, the enzymes were separated by chromatography on diethylaminoethyl-Sephadex and purified to homogeneity by gel filtration, ion-exchange chromatography, and preparative polyacrylamide electrophoresis. The enzymes differ markedly in physicochemical properties. One enzyme, termed asparaginase A, has a molecular weight of approximately 96,000 whereas the other, termed asparaginase AG, has a molecular weight of approximately 135,000. Both enzymes are tetrameric. The asparaginase A shows activity only with l-asparagine as substrate, whereas the asparaginase AG hydrolyzes l-asparagine and l-glutamine at approximately equal rates and it is also active with d-asparagine and d-glutamine as substrates. The asparaginase A was found to be devoid of antitumor activity in mice, whereas the asparaginase AG was effective in increasing the mean survival times of both C3H mice carrying the asparagine-requiring Gardner 6C3HED tumor line and Swiss mice bearing the glutamine-requiring Ehrlich ascites tumor line. These differences in antitumor activity were related to differences in the K(m) values for l-asparagine for the two enzymes. The asparaginase A has a K(m) value of 1 x 10(-3) M for this substrate whereas the corresponding value for the AG enzyme is 1.5 x 10(-5) M. Thus the concentration of asparagine necessary for maximal activity of the asparaginase A is very high compared with that of the normal plasma level of asparagine, which is approximately 50 muM.

Animals↗