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Biomedical subjects

H Anderson

Publications and source records attributed to H Anderson.

At least 127 records · Page 7Linked to original sources
PubMed1995

Chemotherapy in non-small cell lung cancer.

BACKGROUND: Non-small cell lung cancer can no longer be regarded as resistant to chemotherapy, and there have recently been considerable improvements in the use of the older agents and advances in the identification of new drugs. Recent meta-analysis has also confirmed the view that chemotherapy can have small but modest survival benefits. Although in the treatment of stage IV disease the criteria of efficacy have concentrated on tumour response rates, more recently it has become obvious that these patients can also benefit in terms of improved symptom control. RECENT ADVANCES: For patients with locally advanced stage III disease there have been important developments indicating the benefit of combined modality treatment with chemotherapy and thoracic irradiation. Furthermore, the use of neoadjuvant chemotherapy indicates that resection is possible in about half the patients, and on pathological examination of 15%-20% of the resected specimens there is no evidence of residual tumour. These results justify an increase in the use of systemic chemotherapy in this disease.

Antineoplastic Agents↗
PubMed1995

Incidence and prognostic significance of t(14;18) translocation in follicle center cell lymphoma of low and high grade. A report from southern Sweden.

BACKGROUND: The t(14;18)(q21;q32) is the most common recurrent genetic defect in follicle center cell lymphoma (FCC). Conflicting reports exist in regard to a possible prognostic significance for the translocation. PATIENTS AND METHODS: In a single center, 102 patients with either low-grade (n = 50) or high-grade (n = 52) FCC (Kiel classification) and a median follow-up of 82 months were retrospectively studied to determine survival in relation to t(14;18) as shown by either PCR of the bcl-2 rearrangement in paraffinized tissue or karyotype analysis. RESULTS: t(14;18) was detected in 30 of 50 (60%) low-grade FCC and in 12 of 52 (23%) high-grade FCC. The presence of the t(14;18) was not related to morphologic bone marrow involvement or other clinical parameters, but it was related to age: in low-grade FCC, patients with t(14;18) were an average of 17 years younger (p = 0.002) than those without the translocation. In the group with high-grade histology, 30% survived beyond 60 months regardless of t(14;18) status (p = 0.92). Patients with low-grade histology and t(14;18) fared better than those without, irrespective of age (p = 0.01). No significant difference in disease-free survival related to t(14;18) was found in either low- or high-grade FCC. CONCLUSIONS: The incidence of t(14;18) is in accord with that of other European reports. T(14;18) does not define a prognostic subset of high-grade FCC, but is significantly correlated with a better survival in low-grade FCC. The association of t(14;18) with younger age and indolent lymphoma is perplexing in light of recent findings of an age-related increase in t(14;18) in normal subjects.

Adult↗
PubMed1995

Tropisetron alone or in combination with dexamethasone for the prevention and treatment of emesis induced by non-cisplatin chemotherapy: a randomized trial.

This study compared the efficacy and tolerability of tropisetron (Navoban, Novaban) alone or in combination with dexamethasone for the treatment of emesis induced by moderately emetogenic non-cisplatin chemotherapy. In total, 126 patients with cancer, who had never received chemotherapy and who required at least two courses of moderately emetogenic non-cisplatin chemotherapy each lasting for a minimum of 5 days, were recruited into the study. Patients were randomized to receive tropisetron, 5 mg o.d., plus either dexamethasone, 12 mg i.v. on day 1 followed by 4 mg orally b.i.d. on days 2-5, or placebo. Greater control of acute and delayed vomiting and nausea was achieved in patients given the tropisetron-dexamethasone combination than in those who received the tropisetron-placebo treatment. The majority of adverse events were mild and could be attributed to the chemotherapeutic regimen used or to the underlying disease. Patients and investigators both rated tropisetron alone or in combination with dexamethasone as a highly effective and well-tolerated antiemetic treatment. The results of this study show that tropisetron, 5 mg o.d., is an effective, well-tolerated and simple to use antiemetic treatment for patients receiving moderately emetogenic non-cisplatin chemotherapy. The addition of dexamethasone increases the efficacy of tropisetron without significantly decreasing its tolerability.

Antiemetics↗
PubMed1995

Symptomatic benefit from gemcitabine and other chemotherapy in advanced non-small cell lung cancer: changes in performance status and tumour-related symptoms.

Results from recent trials challenge the traditional view that chemotherapy offers no survival or quality of life benefits over best supportive care. Meta-analyses of recent trials reveal a modest survival benefit for combination chemotherapy over best supportive care, although there is no strong evidence from randomized trials for superiority of combination over single-agent therapy. In chemotherapy trials where data on performance status change were collected, performance status improved in one-third of patients and remained constant in a further third. Fewer studies have measured changes in specific disease-related symptoms, but there are data from studies with gemcitabine which show improvements in a range of symptoms, including cough, haemoptysis, pain, dyspnoea and anorexia. Thus more patients benefit from chemotherapy than may be suggested by objective response. Surveys have shown that patients are more likely to accept intensive chemotherapy for what are perceived by health care professionals as potentially small benefits. Studies have shown evidence of cost savings associated with chemotherapy over best supportive care.

Antimetabolites, Antineoplastic↗
PubMed1995

Survival and risk of leukaemia in polycythaemia vera and essential thrombocythaemia treated with oral radiophosphorus: are safer drugs available?

For 366 patients with polycythaemia vera (PV) or essential thrombocythaemia (ET) diagnosed 1971-1990, oral administration of 32-P was used as myelosuppressive treatment. Retreatment was not restricted to any defined interval and the number of treatments or the total dose were not limited. For 107 patients, follow-up was > 10 years. 15 of these presented with life-threatening occlusive vascular symptoms and their survival was short. For the remaining 92 patients 5-yr survival was not significantly worse than for a Swedish population matched for age and sex. Survival at 10 yr was lower, 51% versus 66% expected. Acute myeloid leukaemia (AML) was diagnosed in 11 of the 107 patients (10.3%). In the whole material of 366 patients, 17 have developed AML with a median time of 8.5 yr from start of treatment. There was a maximum incidence of 4% per yr after 8-12 yr. Later, the incidence decreased. The median annual dose of 32-P for the AML patients was 100 MBq and was not significantly larger than for a matched control group surviving without AML, 96 MBq. The results are compared with reports on PV or ET patients treated with busulphan (Bu) or hydroxyurea (HU). With comparable periods of follow-up there are no indications that an adequate myelosuppression with oral 32-P will be associated with shorter survival or higher incidence of AML than treatment with Bu or HU. It is concluded that, for the time being, oral administration of 32-P is an acceptable standard treatment in PV and ET.

Administration, Oral↗
PubMed1995

Mortality after remote surgery for benign gastroduodenal disease.

Mortality was studied after partial gastrectomy in a cohort of 1575 patients operated on because of benign gastroduodenal disease 29 to 59 years ago. The final status was confirmed in all but 8.4% of the cohort. At the close of the study 78% of the traced population were dead. Overall mortality was significantly higher than in the general population of southern Sweden (standardised mortality ratio = 1.10; 95% confidence intervals 1.03 to 1.17). Excess deaths resulted from neoplasms in the stomach, pancreas, male genital organs, and respiratory organs, as well as from respiratory diseases and suicide. Patients operated on before the age of 45 had a 60% increase in overall mortality during the first 19 years after surgery, mainly because of cardiovascular disease and suicide, whereas among those operated on after this age mortality was comparable to that in the reference population. The 75% increased death rate in cardiovascular disease during the first 19 years after surgery in patients operated on at young age, dramatically decreased during the years thereafter. An increased risk of death caused by malignancy was apparent more than 20 years postoperatively, irrespective of age at surgery. Excess deaths resulting from gastrointestinal malignancies, mainly gastric and pancreatic carcinoma, outnumbered the increased number of deaths resulting from cancer in the respiratory organs.

Adult↗
PubMed1995

The prognostic information of DNA ploidy and S-phase fraction may vary with histologic grade in endometrial carcinoma.

DNA ploidy and S-phase fraction (SPF) were determined by flow cytometry on paraffin-embedded tumor material from 243 patients treated during 1980-1985. Patients with well differentiated and moderately differentiated tumors without solid areas (n = 351) formed a low-risk group (corrected 5-year survival 90%). Twenty-four patients, dead of disease within 5 years, were compared with 52 survivors. The estimated death risk was higher for those with SPF > or = 8.0% compared with those with SPF < 8.0% (odds ratio = 18.2; p < 0.001). SPF was the only independent prognostic factor in a multivariate analysis also including age, clinical stage and grade of differentiation. Patients with moderately differentiated tumors with solid areas or poorly differentiated tumors (n = 208) were regarded as a high-risk group. There was a difference in survival according to ploidy; the corrected 5-year survival was 75% for 106 patients with diploid tumors compared with 44% for those with non-diploid tumors (p < 0.0001). In a multivariate analysis DNA ploidy, age and clinical stage were independent prognostic factors, whereas SPF was no longer significant. Thus, DNA ploidy and SPF have different prognostic values depending on histological grade of endometrial carcinoma.

Adult↗
PubMed1994

Antitumor drug fostriecin inhibits the mitotic entry checkpoint and protein phosphatases 1 and 2A.

In most eukaryotic cells, entry into mitosis is tightly controlled and requires completely replicated and undamaged DNA. We show that the antitumor drug, fostricin, interferes with this control; it induces cycling cells to enter mitosis prematurely, and it can overcome the mitotic entry checkpoint, forcing into mitosis cells that were arrested in the division cycle by treatment with the DNA replication inhibitor aphidicolin or with the DNA-damaging agents camptothecin and teniposide. This effect was observed in all rodent, simian, and human cell lines tested. Fostriecin also hampers progression through the later stages of mitosis as determined by the absence of normal half-spindles, anaphase figures, and telophase figures. The only previously known target for fostriecin is topoisomerase II, which is inhibited in vitro with a 50% inhibitory concentration of 40 microM (T. J. Boritzki, T. S. Wolfard, J. A. Besserer, R. C. Jackson, and D. W. Fry. Inhibition of type II topoisomerase by fostriecin. Biochem. Pharmacol., 37: 4063-4068, 1988). We show that fostriecin is a more potent inhibitor of protein phosphatase 1, with a 50% inhibitory concentration of 4 microM and protein phosphatase 2A, with a 50% inhibitory concentration of 40 nM. Inhibition of the mitotic entry checkpoint and inhibition of protein phosphatases are novel properties for antitumor drugs with potential or proven therapeutic value.

Alkenes↗
PubMed1994

Evaluation of a method for quantitative immunohistochemical analysis of cisplatin-DNA adducts in tissues from nude mice.

The reproducibility of an immunohistochemical method for visualization and quantitation of the cytotoxic drug cisplatin (CDDP) in its active position, bound to nuclear DNA, was investigated in tissues from CDDP-treated nude mice. Kidney, liver, and tumor sections were stained with a PAP technique using an antiserum elicited against CDDP-DNA adducts. The resulting brown nuclear precipitate was quantitated using a CAS 200 image analyzer. The variance components of the errors in the staining procedure and in the image analysis were estimated. The method was found to be feasible for comparisons between slides of the same type of tissue, stained in the same batch, and measured by one observer on one occasion. The method should be a valuable tool for studies of CDDP pharmacodynamics, sensitivity prediction, and the effects of interactions between CDDP and other drugs and chemomodulators.

Animals↗
PubMed1994

Deep venous thrombosis and occult malignancy: an epidemiological study.

OBJECTIVE: To determine the risk of subsequent cancer in patients with deep venous thrombosis confirmed by venography. DESIGN: Follow up of all patients who had venography for suspected deep venous thrombosis during 1984-88. Patients were traced through a cancer registry up to 1 January 1991. SUBJECTS: 4399 patients who had phlebography in one hospital. SETTING: General hospital in Malmö, Sweden, serving a population of 230,000. MAIN OUTCOME MEASURE: Number of cancers recorded. RESULTS: 4399 patients had venography for suspected deep venous thrombosis; 604 were known to have a malignancy at the time of venography and were excluded from further analysis. 1383 had deep venous thrombosis, 150 of whom subsequently developed cancer. 182 of the 2412 patients without thrombosis developed cancer. During the first six months after venography 66 patients with thrombosis developed malignancy compared with 37 patients without thrombosis (P < 0.0001). 38 of the cancers in the deep venous thrombosis group were detected by history, physical examination, and laboratory tests. Three patients had postoperative or post-traumatic deep venous thromboses. Only two of the remaining patients would have benefited from early detection by extensive screening. After six months the incidence of cancer was identical in patients with and without thrombosis. CONCLUSION: Deep venous thrombosis is associated with a significantly higher frequency of malignancy during the first six months after diagnosis. Malignancies can be found with simple clinical and diagnostic methods and extensive screening is not required.

Adult↗
PubMed1994

Tropisetron compared with a metoclopramide-based regimen in the prevention of chemotherapy-induced nausea and vomiting.

This randomised, open, parallel group study compared the antiemetic efficacy and tolerability of tropisetron with metoclopramide plus lorazepam in 102 patients receiving a first course of non-cisplatin-containing chemotherapy. Control of acute vomiting by tropisetron was significantly superior to that of the metoclopramide regimen, with total control (no vomiting) in 45% of 51 patients in the tropisetron group compared with 22% of 51 patients in the metoclopramide group (P = 0.013); total and partial control (< 5 vomits) occurred in 67 and 47% of patients, respectively (P = 0.044). The incidences of acute nausea and of delayed nausea and emesis were similar in the two treatment groups. Both tropisetron and metoclopramide were well tolerated; no adverse effects were attributed to tropisetron administration with the exception of headache. One patient in the metoclopramide group reported confusion and tremor thought to be related to the antiemetic therapy. Tropisetron is an effective and well-tolerated agent in the prevention of chemotherapy-induced vomiting. The control of acute nausea was similar in the two treatment groups, but tropisetron was superior to a metoclopramide-based regimen in the control of acute vomiting.

Acute Disease↗
PubMed1994

Single-agent activity of weekly gemcitabine in advanced non-small-cell lung cancer: a phase II study.

PURPOSE: To evaluate the efficacy and safety of gemcitabine, a pyrimidine antimetabolite with activity against solid tumours. PATIENTS AND METHODS: Eighty-two patients with unresectable stage IIIa to IV non-small-cell lung cancer (NSCLC) were entered. The first 54 patients received gemcitabine 800 mg/m2, and subsequent patients 1,000 mg/m2, as a 30-minute intravenous infusion on days 0, 7, and 14. Courses of therapy were repeated every 28 days. Twenty percent dosage escalation was permitted after course no.1 if World Health Organization (WHO) toxicity was < or = 1. RESULTS: Sixteen (20%; 95% confidence interval [CI], 12% to 31%) of 79 patients assessable for response had independently validated partial responses, with a median duration of 7 months. The overall median survival duration was 7 months. Gemcitabine improved disease-related symptoms (70% patients) and increased WHO performance status (44%). Toxicity was generally mild and reversible. Patients experienced little WHO grade 3 and 4 toxicity, with anemia in four (5%), thrombocytopenia in one (1%), leukopenia in six (7%), and neutropenia in 18 (22%). Infection occurred in nine patients (12%) during the study (four were neutropenic), but there were no episodes of WHO grade 3 or 4 infection. WHO grade 3 and 4 biochemical toxicity occurred with transient elevations of transaminases in 10 patients (12%). Two patients had transient WHO grade 3 elevation of serum creatinine levels, and two developed acute renal failure 4 and 6 weeks after the last dose of gemcitabine. There was no WHO grade 4 symptomatic toxicity. WHO grade 3 vomiting occurred in 31 patients (38%) and grade 3 alopecia in one (1%). Flu-like symptoms were associated with gemcitabine administration in 36 patients (44%). Twenty-six patients (32%) experienced fever (1% WHO grade 3), 33 (40%) ankle edema not associated with cardiac failure, 31 (38%) lethargy, and 11 (13%) dyspnea. CONCLUSION: Gemcitabine is an active new agent in the treatment of NSCLC. This schedule was associated with little alopecia or myelosuppression. Gemcitabine warrants further investigation in other malignancies and in combination with other agents.

Adult↗
PubMed1994

Gastrointestinal upsets associated with ingestion of copper-contaminated water.

During 1992 and 1993 the Wisconsin Division of Health investigated five cases in which copper-contaminated drinking water was suspected of causing gastrointestinal upsets. Each of these case studies was conducted after our office was notified of high copper levels in drinking water or notified of unexplained illnesses. Our findings suggest that drinking water that contains copper at levels above the federal action limit of 1.3 mg/l may be a relatively common cause of diarrhea, abdominal cramps, and nausea. These symptoms occurred most frequently in infants and young children and among resident of newly constructed or renovated homes.

Adult↗