Risk factors for lung cancer: a pilot study in five counties.
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Adult↗
Biomedical subjects
H Anderson
Publications and source records attributed to H Anderson.
Adhesion molecules and animal development.
In recent years considerable progress has been made in the identification and characterization of molecules that mediate cell adhesion during animal development. This review attempts to pick out from the vast amount of information in this rapidly expanding field some of the key features of adhesion molecules, to present ideas about their role in development, and to indicate the directions in which the field is now moving.
Amino Acid Sequence↗
Functions and complications of shunts in different etiologies of childhood hydrocephalus.
Shunt function and complications in different etiologies of childhood hydrocephalus were studied in a series of 306 patients involving 1102 shunt operations. Shunts in patients with hydrocephalus caused by neoplasms proved to be most prone to shunt complications. The patency time for shunts in these patients was significantly shorter than for shunts in other patient categories [Standard number of deviations (SND) 5.9; P less than 0.001, Meyer-Kaplan life table analysis]. When the two main groups of infantile hydrocephalus-congenital obstructive hydrocephalus and hydrocephalus caused by perinatal intracerebral hemorrhage-were compared, the latter group proved to be significantly more prone to shunt infections (P less than 0.01), with an infection rate of 17.8% compared with 8.9% for the former group. The importance of this fact is stressed by the observation that these patients appear to constitute an increasing percentage of hydrocephalic patients. According to the present study, patients with congenital intracranial cysts and hydrocephalus are less prone to shunt complications, i.e., the infection rate is 6.8%, which is significantly less than that of patients with other types of hydrocephalus (P less than 0.01; chi-square test).
Brain Diseases↗
Therapy for poor-risk patients with small-cell lung cancer using bolus ifosfamide and oral etoposide.
A total of 47 poor-risk small-cell lung cancer patients (elderly, poor performance status, recent myocardial infarction, or extensive-stage disease with biochemical abnormalities) were treated with a regimen of bolus ifosfamide at 1.5 g/m2 with equidose mesna as a 30-min infusion, followed by 100 mg oral etoposide daily for 8 days. Therapy was repeated every 3 weeks. The overall response rate was 60% (75% for limited-stage and 48% for extensive-stage disease), and the overall median survival was 7 months. Patients' performance status significantly improved with therapy (P less than 0.0001). Despite the poor-risk factors, the Manchester prognostic score was applied and verified. The median survival was 8 months for patients with a good prognosis, 6 months for those with an intermediate prognosis and 2.5 months for poor-prognosis patients (P = 0.0002). Therapy was well tolerated. The median WHO grade of haematological toxicity was 2 (range, 0-4). Only 10/226 (4%) courses were delayed due to leukopenia. Blood transfusions followed 18/226 (8%) courses. Intravenous antibiotics were given following 15/226 (7%) courses. No patient required platelet support. Poor-risk patients who have a good or intermediate Manchester prognostic score may benefit from this low-toxicity regimen.
Aged↗
New endocrine approaches to breast cancer.
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Androgen Antagonists↗
Autoimmune cytopenias in Castleman's disease.
The authors report a case of Castleman's disease in which the major clinical problems have been caused by severe thrombocytopenia and neutropenia. The cytopenias were caused by autoimmune destruction of mature cells as demonstrated by bone marrow findings and cell-specific antibody assays. There also was evidence of red cell autoantibody production but no overt hemolysis. The thrombocytopenia currently is controlled by intermittent vincristine, having proved refractory to steroids, splenectomy, and danazol and only partially responsive to high dose intravenous immunoglobulin. The neutropenia showed temporary improvement with immunoglobulin but has been resistant to all other therapy. This case provides further evidence for disordered immune regulation in Castleman's disease.
Adolescent↗
CFOs see physician relations as key to hospital survival.
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Financial Management, Hospital↗
Trends in equipment acquisition.
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Capital Expenditures↗
Five year follow-up and dose delivery analysis of cisplatin, iproplatin or carboplatin in combination with cyclophosphamide in advanced ovarian carcinoma.
Eighty eight patients with FIGO stage IIb/c (postoperative residual) or III/IV epithelial ovarian cancer were randomised to receive cycles of cyclophosphamide (600 mg/m2) with either iproplatin (240 mg/m2), cisplatin (100 mg/m2) or carboplatin (300 mg/m2). A total of six cycles were given at monthly intervals. Patients were well-balanced for major prognostic factors. There was no significant difference in overall response rate (iproplatin arm, 64.3%, cisplatin arm 72.7% and carboplatin arm 66.7%). There were more complete remissions on the carboplatin arm, 45.8% compared with 21.4% on iproplatin and 22.7% on cisplatin but the difference was not statistically significant (p = 0.11). With a median follow up of 50 months the median survival for the iproplatin arm is 18 months, for the cisplatin arm 19 months and for the carboplatin arm 24 months (p = 0.15). Toxicity was greatest with cisplatin and least with carboplatin. Myelotoxicity limited the dose delivery of iproplatin as measured by total dose, dose intensity and dose intensity product. Carboplatin is at least as effective and less toxic than cisplatin when used in conjunction with cyclophosphamide for the treatment of ovarian carcinoma, and this analogue has been selected for dose intensification studies in this tumour at the Christie Hospital.
Adult↗
The PRECEDES Project: background and methods.
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Chronic Disease↗
Liver cancer in Wisconsin: the potential for prevention.
In this study liver cancer deaths that could be attributed to certain risk factors were calculated. Applying population attributable risk methodology, the attributable risk of liver cancer was estimated for alcohol use, hepatitis B viral exposure, and occupational and industrial exposures. We found that these three risk factors accounted for 38% of liver cancer mortality in Wisconsin; 29% was attributable to alcohol consumption, 7% to occupational exposures, and 2% to hepatitis B viral infection. More than half of liver cancer mortality, however, was not accounted for by the three risk factors studied.
Alcohol Drinking↗
Epidermal and transforming growth factor alpha in patients with breast tumours.
Measurements of transforming growth factor alpha (TGF-alpha) in cancer patients have produced variable results. We have now used a specific radioimmunoassay (RIA) and a mitogenic assay to evaluate TGF-alpha content of tumour and urine samples separated by an analytical HPLC system. Urine samples from patients with breast tumours and from age matched controls gave TGF-alpha amounts ranging from 0 to 61.5 ng 24 h-1 compared to urogastrone epidermal growth factor figures of 3.0-26.2 micrograms 24 h-1. The quantities of TGF-alpha in patient and control groups were not significantly different. The majority of breast tumour extracts contained mitogenic material eluting from the HPLC system at the TGF-alpha calibration point. Measurement by RIA of combined samples from each group showed that steroid receptor positive tumours had a mean figure of 14.8 ng g-1 tissue and steroid receptor negative 7.4 ng g-1. Receptor positive tumours from patients treated with an antioestrogen, tamoxifen citrate (Nolvadex), had 0.16 ng g-1. Thus TGF-alpha is found in tumours as a biologically active entity and in quantities sufficient to promote cell division. In addition the observation that tamoxifen causes a significant reduction in the content of TGF-alpha may be an additional beneficial action.
Breast Neoplasms↗
The role of postoperative alkylating agent therapy in early-stage epithelial ovarian cancer.
Forty-six patients with early (Stage I and II) ovarian cancer referred as free of residual disease after primary surgery, selected for high-risk features, were treated with adjuvant single-agent alkylating therapy comprising either intravenous cyclophosphamide (1 g/m2) in 36 patients, or oral melphalan (0.2 mg/kg daily for 5 days) in eight. Cyclophosphamide was repeated every 3 weeks for 10 cycles and melphalan every 6 weeks for 12 cycles. With a median follow-up of 36+ months, 18 patients have relapsed. The actuarial 5-year relapse-free survival was 48% and the overall 5-year survival was 54%; median survival was 84 months. Pretreatment FIGO stage was the single most important predictor of relapse-free and overall survival duration. For patients with Stage IA and IB tumours the 5-year actuarial relapse-free survival was 89%; for patients with stage IC and II (all substages), the 5-year relapse-free survival was 24% (P = 0.001). For this latter group adjuvant single alkylating agent therapy was not adequate and alternative therapeutic regimens are required. The problem of suboptimal primary surgical staging is also addressed.
Administration, Oral↗
Randomized trial comparing ciprofloxacin plus netilmicin versus piperacillin plus netilmicin for empiric treatment of fever in neutropenic patients.
To assess the efficacy of ciprofloxacin in neutropenic patients, we conducted a randomized prospective trial comparing the combination of ciprofloxacin and netilmicin against piperacillin plus netilmicin as an empiric treatment of fever in cancer patients with neutropenia. Of 214 evaluable episodes, 115 and 99 were randomly assigned to the ciprofloxacin and the piperacillin arms, respectively. The overall response rates were very similar (59 and 62% for the ciprofloxacin and piperacillin arms, respectively). The response for the gram-positive bacteremias was almost identical (around 40%); this low response was due in part to an outbreak of infection by a multiply resistant strain of Staphylococcus epidermidis (for which the ciprofloxacin MIC was greater than or equal to 128 micrograms/ml) which occurred during the second half of the trial. Among gram-negative bacteremias, 9 of 11 infections (82%) responded to the ciprofloxacin combination compared with 3 of 7 (43%) that responded to the piperacillin combination (P = 0.23). The incidences of persistent, profound neutropenia were comparable in both treatments, but the susceptibility of the gram-negative organism to ciprofloxacin and netilmicin was significantly higher than was susceptibility to the other combination. Ciprofloxacin was well tolerated, and patients were able to convert from intravenous to oral therapy in 64 of 115 episodes.
Administration, Oral↗
Spatial and temporal variation in the structure of the basal lamina in embryonic grasshopper limbs during pioneer neurone outgrowth.
The pioneer neurones of the embryonic grasshopper limb use the basal lamina underlying the limb ectoderm as a substratum over which to grow from the periphery to the CNS (Anderson & Tucker, 1988). In this paper we use transmission electron microscopy to describe the structure of this substratum before, during, and after the time of axon navigation. The organization of the basal lamina varies considerably in different regions and at different times of development of the embryonic limbs, and is unlike that of the fully developed limb at the time of hatching. We suggest that this spatial and temporal variation could play a role in regulating the direction of outgrowth of pioneer neurones.
Animals↗
Effects of formaldehyde on the mucous membranes and lungs. A study of an industrial population.
One hundred nine workers and 254 control subjects were studied to evaluate the effects of formaldehyde on the mucous membranes and lungs. A modified, respiratory symptom questionnaire and spirometry were administered to all study participants before and after their work shift, and formaldehyde levels were determined for each test subject. Over the course of the monitored work shift, test subjects demonstrated a dose-dependent excess of irritant symptoms and a statistically significant decline in certain lung function parameters. Analysis of test and control subject data combined revealed a correlation between formaldehyde exposure and these pulmonary changes. Baseline spirometry values were not significantly different between test and control groups, and formaldehyde-exposed workers did not report an excess of respiratory symptoms. Formaldehyde is a dose-dependent irritant of the eyes and mucous membranes at low-level exposures. It can exert a small, across-shift effect on airways but after a mean exposure of ten years does not appear to cause permanent respiratory impairment.
Adult↗
Double alkylating agent therapy with ifosfamide and cyclophosphamide for advanced non-small cell lung cancer. From the Manchester Lung Tumour Group.
Forty-five patients with advanced non-small cell lung cancer (NSCLC), with progressive inoperable tumors were treated. Twenty-three patients were of "limited" stage. Six patients had received previous thoracic radiotherapy. Patients with central nervous system (CNS) metastases, Karnofsky scores of less than 30 or more than 70, and patients over 70 years of age were excluded from the study. Cyclophosphamide (2.5 g/m2) was infused intravenously over 3 hours with the same Mesna dose. At the midpoint of the infusion, 3.5 g/m2 infosfamide was delivered as a bolus. Additional Mesna was administered over the next 8 hours. A maximum of four courses were given at three weekly intervals. One-hundred-thirty-eight courses were administered and 53% of patients completed all four treatments. The response rate was 38%, with three (7%) complete responses. Seven additional patients (15%) with stable disease symptomatically improved by two steps or more on the Karnofsky scale at the end of treatment. Median survival for all 45 patients was 7 months, range less than 1 to 25 months. Sixteen courses were complicated by Grade 3 thrombocytopaenia and/or leukopenia (Grade 4 on six occasions, Grade 3 on seven occasions) on the blood count taken immediately before chemotherapy. Intravenous antibiotics were required on 14% of the total number of courses; and three patients died of probable treatment related causes. Two episodes of severe ifosfamide encephalopathy occurred but recovery was complete, and four episodes of frank hematuria also occurred. The Karnofsky score was more than 70 in 33% of patients one month after the end of chemotherapy compared with 0% before treatment. Unlike many chemotherapeutic regimens for NSCLC, double alkylating agent treatment with ifosfamide and cyclophosphamide improved the performance status without major toxicity in a selected patient population. The overall survival, however, remains short and further alkylating agent combinations need to be considered in the future.
Aged↗
24-hour cyclophosphamide infusion therapy for malignant mesothelioma of the pleura.
Thirteen patients with malignant mesothelioma of the pleura have been treated with 24-hour cyclophosphamide infusion (2.5 g/m2) therapy. There were no complete responders. Three patients (23%) had a partial response, and a further three patients who did not fulfil the criteria for objective response, had subjective benefit from therapy with increase in performance status. The overall median survival from the onset of therapy was 6 months (range 2-19 months). High dose cyclophosphamide offers no advantage over standard dose therapy.
Adult↗