Search PubMed⌕ Search

Biomedical subjects

G Gill

Publications and source records attributed to G Gill.

At least 109 records · Page 6Linked to original sources
PubMed1989

Dose intensity and outcome with combination chemotherapy for germ cell carcinoma. Australasian Germ Cell Trial Group.

Two hundred and fifty-three patients with advanced stage germ cell carcinoma received induction chemotherapy with vinblastine, bleomycin and cisplatin, sometimes with subsequent surgical resection of residual masses. Overall, 191 patients (76%) achieved complete remission or no evidence of disease after surgery (CR + NED). With 64 months median follow-up only 24 patients have relapsed (13%) and 68% of all patients treated are long-term survivors and 84% of patients entering CR + NED are alive. Toxicity with this chemotherapy was considerable, including seven deaths from leukopenia and septicaemia and eight deaths from bleomycin lung toxicity. Dose reductions or omissions of the drug from the treatment programme was necessary with cisplatin in 8% of patients, with vinblastine in 37% and with bleomycin in 35% of patients. Analysis of these alterations in dose intensity for each drug revealed that initial treatment response and subsequent survival were not compromised by reductions in intended doses of drug administered for either vinblastine or bleomycin. Too few patients had dose reductions of cisplatin for meaningful analysis. This apparent lack of major dose-response effect for either vinblastine or bleomycin in the present treatment programme for germ cell carcinoma has prompted the initiation of a randomized study to determine whether deletion of bleomycin from treatment for patients with good prognostic pretreatment characteristics improves the therapeutic index of this very successful therapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Hypoglycaemic brittle diabetes successfully managed by social worker intervention.

The case is presented of a 39-year-old Type 1 diabetic patient of 22 years duration with recurrent hypoglycaemic comas. He was of unusual personality and had bizarre ideas on self-regulation of his diabetes, resulting in wide variations of insulin dosage. In one 12-month period he had 88 separate admissions to an emergency department with severe hypoglycaemic coma requiring intravenous glucose administration. The cycle of admissions was eventually broken by the intervention of a social worker, who provided structured non-medical support. The patient's diabetic misconceptions remained, but he appeared to gain sufficient insight to prevent recurrent hypoglycaemia.

Adult↗
PubMed1988

Negative effect of the transcriptional activator GAL4.

The yeast transcriptional activator GAL4 binds specific sites on DNA to activate transcription of adjacent genes. The distinct activating regions of GAL4 are rich in acidic residues and it has been suggested that these regions interact with another protein component of the transcriptional machinery (such as the TATA-binding protein or RNA polymerase II) while the DNA-binding region serves to position the activating region near the gene. Here we show that various GAL4 derivatives, when expressed at high levels in yeast, inhibit transcription of certain genes lacking GAL4 binding sites, that more efficient activators inhibit more strongly and that inhibition does not depend on the DNA-binding domain. We suggest that this inhibition, which we call squelching, reflects titration of a transcription factor by the activating region of GAL4.

Binding Sites↗
PubMed1988

A prospective study of cisplatin-based combination chemotherapy in advanced germ cell malignancy: role of maintenance and long-term follow-up.

Two hundred fifty-three patients with advanced germ cell malignancy received initial chemotherapy with cisplatin, vinblastine, and bleomycin followed by surgical resection of residual masses if possible. Patients achieving complete remission (CR) were prospectively randomized to receive 6 months maintenance therapy with vinblastine or no further treatment. CR was achieved in 183 patients (72%) and a further eight patients (4%) had complete resection of residual viable malignancy (no evidence of disease [NED]). Pretreatment factors having a significant adverse influence on response by univariate analysis included extragonadal origin of the tumor, poor performance status, advanced lung or lung and abdominal disease, and elevated serum levels of human chorionic gonadotropin (HCG) and alpha-fetoprotein (AFP) greater than 1,000 ng/mL. Multivariate regression analysis indicated the independent prognostic factors of significance were advanced lung or advanced lung and abdominal disease, total tumor diameter greater than 10 cm, and a serum level of HCG greater than 1,000 ng/mL. Of the toxicities encountered, myelosuppression was significant, being exacerbated by radiotherapy, and seven deaths occurred from septicemia. Bleomycin pulmonary toxicity occurred in 46% of patients and was severe in 4%, resulting in eight deaths. With a median follow-up of 64 months, relapses have occurred in 25 patients with no significant difference between those patients receiving or not receiving maintenance vinblastine. Eight of these relapses occurred beyond 1 year and four beyond 2 years of follow-up. Presently, 68% of the total patient population is alive and disease-free, with 84% of the CR and NED patients alive and 81% alive and disease-free. It is concluded that with prolonged follow-up, vinblastine maintenance therapy does not improve treatment outcome. Moreover, late relapses occur, cautioning against premature pronouncements of cure.

Adolescent↗
PubMed1988

Phagocytosis of autologous lymphocytes by cervical preneoplastic and neoplastic cells.

Eighty-nine random Pap smears of the uterine cervix were examined to evaluate the phagocytic abnormal cells (PACs) of atypical, dysplastic and neoplastic tissues against infiltrated blood cells. The results revealed that none of the PACs have been identified in atypical (II) and mild dysplastic cells (IIIa). Low levels (1.2%) of PACs were initially demonstrated in patients with moderate dysplasia (IIIb) that increased 1.7-fold in subsequent severe dysplasia (IIIc) and further increased 2.8-fold in invasive carcinomas of the cervix (V). In addition, the data showed age-related responsiveness toward the development of PACs, where 82% of old patients have developed phagocytic activity in moderate dysplastic cells compared with 27% of young patients. However, the difference became less significant at the subsequent classes of the disease. These data further demonstrated that PACs are class-dependent and it may explain one mechanism by which precancerous cells escape immunosurveillance.

Adolescent↗
PubMed1987

Improving the quality of life during chemotherapy for advanced breast cancer. A comparison of intermittent and continuous treatment strategies.

Since chemotherapy for metastatic breast cancer is not curative, consideration of the quality of life is important in selecting a treatment regimen. We conducted a randomized trial comparing continuous chemotherapy, administered until disease progression was evident, with intermittent therapy, whereby treatment was stopped after three cycles and then repeated for three more cycles only when there was evidence of disease progression. Each approach was tested with doxorubicin combined with cyclophosphamide or with cyclophosphamide combined with methotrexate, fluorouracil, and prednisone. Intermittent therapy resulted in a significantly worse response (P = 0.02 by Mann-Whitney test), a significantly shorter time to disease progression (relative risk based on proportional-hazards model, 1.8; 95 percent confidence interval, 1.4 to 2.4), and a trend toward shorter survival (relative risk, 1.3; confidence interval, 0.99 to 1.6). The quality of life was expressed as linear-analogue self-assessment scores for physical well-being, mood, pain, and appetite and as a quality-of-life index. It improved significantly during the first three cycles, when all patients received treatment. Thereafter, intermittent therapy was associated with worse scores for physical well-being (by 23 percent of scale; 95 percent confidence interval, 11 to 35 percent), mood (25 percent; 13 to 37 percent), and appetite (12 percent; 0 to 24 percent) and for the quality-of-life index as indicated by the patient (14 percent; 5 to 23 percent) and the physician (16 percent; 7 to 26 percent). Changes in the quality of life were independent prognostic factors in proportional-hazards models of subsequent survival. We conclude that, as tested, continuous chemotherapy is better than intermittent chemotherapy for advanced breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Mutants of GAL4 protein altered in an activation function.

Activating region I of GAL4 has been defined as a region 48 amino acids long which, when attached to GAL4's DNA-binding domain, activates transcription in yeast. Here we describe mutants bearing changes in and around this highly acidic activating region. We find mutations that increase the activation function invariably increase the acidity of the region and some but not all of the mutations that decrease the activation function decrease the acidity of the region.

Amino Acid Sequence↗
PubMed1987

Suppression of basal and Corynebacterium parvum-augmented NK activity during chemically induced tumor development.

C3H mice were injected subcutaneously (s.c.) with a tumorigenic dose (150 micrograms/mouse) of 3-methylcholanthrene (MC), followed by a 24-h injection and subsequent weekly injections of Corynebacterium parvum (CP) i.p. for a total of 100 days. Basal and CP-augmented NK cell activities were measured in controls and treatment groups during pre-tumor and tumor development stages. Basal NK activity in spleen, peripheral blood and lung tissue was enhanced by CP, but was suppressed by MC. A resulting transient MC induced suppression of splenic NK activity at 10 days was partially restored and sustained by CP treatment and immunosuppression was again observed in tumor-bearing compared to control mice. Mice treated with MC alone showed a higher tumor incidence than animals treated with MC + CP at 45-60 days, while there was no difference in tumor incidence in these two treatment groups at 100 days post injection. The mechanism of the observed transient immunosuppression induced by MC appears to be related to an early toxic effect on large granular lymphocytes (LGL) which was decreased at 10 days and again at 100 days in tumor-bearing mice. Although MC did not appear to exert an effect on effector:target cell conjugate formation, an early suppression in the lytic activity of LGL, may have predisposed the animal to malignant transformation of susceptible cells at the site of MC injection.

Animals↗
PubMed1987

Natural cell-mediated cytotoxicity in vitiligo.

Natural cell-mediated cytotoxicity was studied in 18 patients with vitiligo and 13 healthy age-, race-, and sex-matched control subjects. The 4-hour chromium51 (51Cr) release assay was used to determine the activity of natural killer (NK) cells in the peripheral blood against K562 and Molt-4 target cells. Patients with vitiligo had a 50%, 67%, and 60% decrease in the cytotoxic response with Molt-4 cells at effector-target ratios of 25:1, 50:1, and 100:1, respectively, in comparison with control subjects (p less than 0.001). This inhibition was consistent with an 80% decrease in the binding capacity of NK cells to Molt-4 target cells (p less than 0.005). In contrast, cytotoxic responses did not differ in patients and control subjects with K562 target cells. These results suggest that patients with vitiligo have a decreased capacity for effector cell recognition of Molt-4 target cells but not K562 target cells. Hence patients with vitiligo may have defective clones of NK cells that are incapable of initial recognition of Molt-4 target cells, a necessary prerequisite for target cell lysis. Perhaps this phenomenon occurs with other tumor cells, which would explain the association of vitiligo with certain internal malignancies.

Adolescent↗
PubMed1987

Pain during angiography: a randomized double-blind trial comparing ioxaglate and diatrizoate.

We performed a randomized, double-blind prospective study comparing pain experienced during peripheral and aortic angiography with two different contrast agents. Sixty patients, receiving a total of 107 injections, were randomized to receive either ioxaglate (Hexabrix) or sodium-meglumine diatrizoate (Renografin-76). Subjects scored the pain they experienced on a 10-point visual analog scale, and the physician also scored their discomfort on a five point scale. Hemodynamic parameters were monitored during the procedure in all patients, and subsequent hematology, serum chemistry, and urinalysis were performed in 19 of the 60 patients. There was a significant reduction in the degree of pain experienced by the Ioxaglate group compared to the reference group (p less than 0.001). The patients in the Hexabrix group had a mean pain score of 1.3 compared to the patients in the Renografin-76 group who had a mean pain score of 6.1. The two groups did not differ in their hemodynamic responses to the contrast agents, and no significant differences were noted in the subsequent laboratory measures.

Adult↗
PubMed1987

Susceptibility of natural killer cell activity of old rats to stress.

We determined an in vivo response of NK cells in young and old rats towards the suppressive effect of stress. Stress was developed by isolating rats in separate cages, but control littermates were kept together. Animals were subjected to stress for 7 days, and alterations of NK cell activities were examined in the spleen, peripheral blood (PB) and bone marrow (BM). The results showed that old rats subjected to stress had a remarkable decrease in splenic and PB-NK activity compared to old control rats, concomitant with a highly increased level of NK cell activity in BM. Suppression of the lytic activity in the spleen of stressed old rats was correlated with a decrease in the percentage of conjugate formation between splenic NK cells and target tumour cells. In contrast, stressed young rats demonstrated relatively unchanged activity of NK cells examined in different tissues compared to age-matched controls. We concluded that old animals are more sensitive to the suppressive effect of stress compared to young ones, and the mechanism of this suppression is probably due to the migration of large granular lymphocytes (LGL) from spleen and PB to other sites such as BM.

Aging↗
PubMed1987

In situ lymphophagocytosis by nonlymphoreticular neoplasms.

Lymphophagocytosis by nonlymphoreticular neoplasms has been observed. Twenty cancer patients having either adenocarcinoma or epidermoid carcinoma were the subjects of our study. Malignant cells were found to phagocytize autologous lymphocytes, polymorphonuclear cells (PMNs) and red blood cells (RBCs). Papanicolaou smears from cancer patients revealed that 30% (6/20) of the patients had phagocytic malignant cells in situ, the mean phagocytosis for this group was 3.7%. Different cellular elements showed differences in their susceptibility towards phagocytic activity of tumor cells: 2.6% for lymphocytes, 0.7% for PMNs and 0.4% for RBCs. The patients having phagocytic malignant cells showed complete absence of monocytes in their peripheral blood. In contrast, other patients had peripheral blood monocyte percentages within the limits of control values (7.2). However, there was no correlation between development of phagocytic activity of malignant cells and age and sex of patients or type of tumor. This study further confirms that phagocytic activity of nonlymphoreticular neoplasms is a general phenomenon which can be directed against erythroid elements. In addition, we have demonstrated that these tumor cells also phagocytize autologous leukocytes.

Adenocarcinoma↗
PubMed1986

Value of the lateral radiologic view of the chest in children with acute pulmonary illness.

Although expert committees have questioned the usefulness of lateral radiologic views of the chest without specific indications, many physicians commonly order both posteroanterior and lateral views in assessing pediatric patients who have signs and symptoms of acute chest disease. To investigate the usefulness of lateral view in children, three experienced physicians independently reviewed and interpreted the posteroanterior view alone and the posteroanterior and lateral views for 179 children 1 to 10 years of age. The films were made between 1980 and 1982 at McMaster University Medical Centre, Hamilton, Ont. A high level of agreement was found between the interpretations based on the posteroanterior view alone and those based on both views. Addition of the lateral view did not improve agreement between the interpretations and the final hospital chart radiologic diagnosis in a clinically significant manner, nor did the lateral view improve the accuracy of localization of radiologic abnormalities. Obtaining a lateral view whenever radiologic examination of the chest is indicated but when specific indications are lacking is unlikely to prove useful to experienced physicians in diagnosing and managing acute pulmonary illness in children.

Acute Disease↗
PubMed1986

Separation of DNA binding from the transcription-activating function of a eukaryotic regulatory protein.

The yeast GAL4 protein (881 amino acids) binds to specific DNA sites upstream of target genes and activates transcription. Derivatives of this protein bearing as few as 74 amino terminal residues bind to these sites but fail to activate transcription. When appropriately positioned in front of a gene these derivatives act as repressors. These and related findings support the idea that GAL4 activates transcription by touching other DNA-bound proteins.

Amino Acid Sequence↗