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Biomedical subjects

H Anderson

Publications and source records attributed to H Anderson.

At least 109 records · Page 6Linked to original sources
PubMed1996

Metaphase cytogenetics and DNA flow cytometry with analysis of S-phase fraction in prostate cancer: influence on prognosis.

OBJECTIVES: To compare the prognostic significance of chromosome aberrations, DNA ploidy, and S-phase fraction (SPF) in prostate adenocarcinomas and to compare the sensitivity of metaphase cytogenetics with flow cytometry (FCM) in detecting abnormal tumor clones. METHODS: Prostate adenocarcinomas from 57 men were previously successfully analyzed with metaphase cytogenetics. Archival material from these tumors were further analyzed with FCM for DNA content and SPF. RESULTS: The patients were followed for 4.5 to 7.7 years. DNA ploidy was analyzed in 51, and SPF in 45 of the 57 tumors. Clonal chromosomal aberrations, DNA aneuploidy, and high SPF were all significantly associated with poor survival. Of these three variables, SPF was the best predictor of survival, but compared with tumor stage and grade in multivariate analysis, SPF was not an independent prognostic factor. Patients with locally advanced tumors or metastatic disease with SPF less than 8% had a median survival of 5.9 years, compared with only 1.3 years for those with SPF more than 8%. Twenty-eight abnormal clones were detected with FCM and 20 with cytogenetic analysis, but only for two of these clones could the results from the two different methods be regarded as concordant. CONCLUSIONS: SPF was superior to karyotype and ploidy in predicting death in prostate cancer, but it remains to be shown whether SPF analysis adds prognostic information to tumor stage and grade. The cytogenetic analyses correlated poorly with results of FCM, indicating low sensitivity of both methods.

Adenocarcinoma↗
PubMed1996

Rising incidence of pancreatic carcinoma in middle-aged and older women-time trends 1961-90 in the city of Malmö, Sweden.

The city of Malmö (population 230 000), situated in the south of Sweden, is in an area which has the highest incidence of pancreatic cancer in the country. The present study was designed to assess time trends of the incidence of pancreatic cancer 1961-90. The 1314 incident cases, 651 men and 663 women, were retrieved from the Regional Tumour Register and the National Cause-of-Death Register. In 75% of cases diagnosis was based on autopsy. Twenty per cent of the these cases were first found at autopsy, being undiagnosed. The average age-standardised incidence was 20.4 per 10(5) person-years for men and 13.7 for women. The incidence was higher for men than for women in all age groups above 44 years. No change in incidence over time was observed for men. In older and middle-aged women there was however a statistically significant increase. The average relative change in women above age 64 was 1.7% per year after age adjustment and in women aged 55-64 years 2.6% per year. We have found no results indicating that this increasing incidence could be caused by detection bias as a result of changing autopsy rates during the study period and hence conclude that the observed increase is explained by a growing number of women being exposed to factors with a potential tumour-promoting or -initiating effect.

Adult↗
PubMed1996

Blood transfusion as a risk factor for non-Hodgkin lymphoma.

In a case-control study of 280 out of 426 consecutive patients with a recent diagnosis of non-Hodgkin lymphoma (NHL) and 1827 control subjects, 53 (19%) and 230 (13%) respectively had received blood transfusions 1 year or more before the interview. Using an age- and sex-stratified analysis the odds ratio (OR) for transfusion was 1.74 (95% CI 1.24-2.44). ORs were also determined for transfusions received in the intervals 1-5, 6-15, 16-25 and > or = 26 years before diagnosis. In the interval 6-15 years, the OR for transfusion was 2.83 (95% CI 1.60-4.99) whereas ORs for transfusions received in other intervals were lower and not significantly elevated. Histological diagnoses (Kiel classification) and results of staging procedures were known for 185 patients. For low-grade NHL of nodal B-cell chronic lymphocytic leukaemia (B-CLL) or immunocytoma type, the OR for transfusions was 4.15 (95% CI 1.92-9.01). For low-grade nodal lymphomas of follicle centre cell type and high-grade nodal lymphomas, no relation to transfusions could be demonstrated. For high-grade extranodal lymphoma as sole manifestation, OR for transfusions was 3.27 (95% CI 1.30-8.24). It is concluded that blood transfusion may be a risk factor for NHLs especially those of B-CLL or immunocytoma type and for high-grade extranodal lymphoma.

Age Factors↗
PubMed1996

A phase I study of a 24 hour infusion of gemcitabine in previously untreated patients with inoperable non-small-cell lung cancer.

A phase I study to determine the maximum tolerated dose and toxicity of gemcitabine when given as a 24 h infusion to patients with inoperable non-small-cell lung cancer (NSCLC). A total of 24 patients with unresectable stage IIIa-IV NSCLC were entered into the study. Gemcitabine was administered as a 24 h infusion on days 0, 7 and 14. Courses of therapy were repeated every 28 days. There were 16 males and 8 females with a median age of 51 years (range 40-73 years). The WHO performance score was 1 (21 patients) or 2 (3 patients). The TNM stage was IIIa (6), IIIb (10) and IV (8). Three patients were entered at each dose level with six at the maximum tolerated dose (MTD). Dose levels were 10, 20, 40, 80, 120, 180 and 210 mg m-2. The MTD was 180 mg m-2 and dose-limiting toxicity was neutropenia and lethargy. Partial response was observed in five (21%) patients (95% CI 7-42%) lasting 10, 14, 18, 47 and 51 + weeks. The maximum tolerated dose of gemcitabine given as a 24 h infusion was 180 mg m-2.

Adult↗
PubMed1996

A non-thrombocytopenic bleeding disorder due to an IgG4-kappa anti-GPIIb/IIIa autoantibody.

Autoantibodies in chronic immune thrombocytopenic purpura occasionally interfere with platelet function. We describe a patient with a normal platelet count who had clinically significant mucosal bleeding, a prolonged bleeding time and abnormal platelet aggregation. The patient had high titres of an IgG4 kappa autoantibody, directed to a cation-dependent epitope on platelet glycoprotein IIb/IIIa, which blocked the binding of fibrinogen and fibronectin to this complex. Corticosteroid treatment resulted in clinical improvement and a marked drop in autoantibody concentration. The lack of thrombocytopenia in this patient, despite high autoantibody levels, is best explained by the poor recognition of IgG4 antibodies by phagocytic cells.

Autoantibodies↗
PubMed1996

Reproducibility of a self-administered questionnaire for assessment of melanoma risk.

BACKGROUND: The reproducibility of a self-administered questionnaire on different epidemiological variables was examined in a random sample of a cohort of healthy women from the South Swedish Health Care Region. An identical questionnaire has previously been used for assessment of melanoma risk, in a population-based, matched, case-control study from the same region. METHODS: Repeat questionnaires were completed on two occasions, 1-3 years apart, by 670 randomly selected subjects. In addition, exposure data from a case-control study were used to estimate the effect of misclassification. RESULTS: Overall, there was a fair to good consistency between the answers on the two occasions for the various epidemiological variables. Exposure variables identified as risk factors for melanoma development were reasonably reproducible. The estimated proportion of agreement, A, ranged from 0.74 to 0.92, the average correct classification rate (assuming common sensitivity and specificity), pi, was > or = 0.85 and the kappa coefficient, kappa, ranged between 0.52 and 0.83. However, the question on number of raised naevi on the arm was an exception since it had a lower test-retest reliability (A = 0.62, pi = 0.77, kappa = 0.40). When using data from the case-control study, the effect of the estimated random misclassification was found to only slightly bias odds ratios toward one. CONCLUSION: Our questionnaire, used for assessment for melanoma risk, provided information with fair to good test-retest reliability, and corrected odds ratios were found to be only slightly higher than observed odds ratios.

Adolescent↗
PubMed1996

Teens teach skin cancer prevention.

Cumulative sun exposure has been linked to about 95 percent of all skin cancers. Farmers and their families, by nature of their occupations, are exposed to an abundance of sun over a long period of time and, therefore, are at an increased risk for skin cancer. Because education is known to be a primary means of health, Future Farmers of America (FFA) peer facilitators (teen educators) provided third graders in rural communities sun protection education with the hope that the message would reach the entire family. The FFA facilitators (n = 217) from 39 FFA organizations throughout Wisconsin were trained with skin cancer and sun protection information. The FFA facilitators then gave presentations on sun protection to third graders (n = 2,007) in their school districts. Control schools included 57 facilitators and 669 third graders. Evaluation involved pre-, post-, and six-month follow-up surveys testing knowledge gained by the third graders. Students who correctly responded to a question on the post-survey after incorrectly answering it on the pre-survey were said to have had a knowledge gain for that question. By using chi-square tests, the intervention group demonstrated a statistically significant (P < 0.001) higher proportion of students experiencing knowledge gain than did the control group from pre- to post-surveys for nine of the 10 questions. Summary statistics were used to describe the study population. In addition to skin cancer knowledge questions, the survey of facilitators included sun protection behavior and attitude questions. This intervention was able to use peer educators as instructors to demonstrate knowledge gain in the youths of the target population. The pilot project materials costs were +0.55 per third grade student and +3.50 per facilitator. Using a school-based organization such as FFA provided a cost-effective means of reaching the rural population.

Adolescent↗
PubMed1996

Aggressive vs nonaggressive therapy for metastatic NSCLC.

Clinicians tend to underestimate potential modest benefits of chemotherapy. They are often reluctant to refer patients for chemotherapy, perhaps because they expect the side effects to outweigh any perceived benefits. However, patients are much more ready to accept chemotherapy, even when the likely benefits are small. Quality of life, change in performance status, and relief of tumor-related symptoms are important additional parameters of treatment assessment. Taking account of these other factors will help clinicians balance quality and quantity of life in patients with metastatic non-small cell lung cancer.

Carcinoma, Non-Small-Cell Lung↗
PubMed1996

Methodological aspects of flow cytometry DNA analysis in endometrial carcinoma, with special reference to sampling and reproducibility.

Two adjacent paraffin-embedded sections manifested concordance in ploidy status in 96% of cases (45/47), and the standard deviation (SD) for SPF was 2.7%. Analysis of 'micro-heterogeneity', within a distance of < or = 700 microm, yielded results for concordant ploidy status in 94% of cases, and the SD for SPF was 1.9% (n = 17). Frozen and paraffin-embedded material yielded concordant results for ploidy status in 87% (39/45) of cases, and SPF values were significantly lower (mean difference 1.5%) in the frozen samples. Diagnostic and repeat curettage material yielded concordant results for DNA ploidy status in 85% (40/47) of cases, and no significant difference in mean SPF (12% vs. 11%) was found. Discordant DNA ploidy results were attributable to small differences in the DNA histograms influencing the interpretation of near-diploid, near-tetraploid and small non-diploid cell populations, and the influence of debris on SPF estimation. On the basis of our findings and the practical advantage we recommend paraffin-embedded material from diagnostic curettage for FCM DNA analysis; the results are available sooner and the handling and transportation of tumor samples is more convenient.

Cryopreservation↗
PubMed1996

Topoisomerase II inhibitors affect entry into mitosis and chromosome condensation in BHK cells.

DNA topoisomerase II (topo II) is required at mitosis in yeast for high chromosome condensation and for chromosome segregation. Recent studies on intact mammalian cells using topo II inhibitors that do not stabilize cleavable complexes also suggest a requirement for topo II for complete chromosome condensation and perhaps also for entry into mitosis. We have investigated the effects of merbarone, ICRF-187, and aclarubicin, three topo II inhibitors that do not stabilize the cleavable complex, on entry into mitosis and on chromosome condensation in BHK and in tsBN2 cells. We have compared their effects with those of etoposide, a topo II inhibitor that stabilizes the cleavable complex. All inhibitors induced a concentration-dependent G2 delay or arrest that could be overcome with fostriecin or okadaic acid or by inactivation of RCC1 in tsBN2 cells. Mitotic chromosomes from cells treated with etoposide were extensively fragmented, whereas mitotic chromosomes from cells treated with merbarone, ICRF-187, or aclarubicin were intact but elongated and tangled. These results provide strong evidence that topo II activity is required in chromosome condensation for final coiling of the chromatids. Our results also indicate that protein phosphatases and RCC1 play a role in G2 delay induced by all inhibitors, whether they do or do not stabilize the cleavable complex.

Aclarubicin↗
PubMed1996

Gemcitabine: once-weekly schedule active and better tolerated than twice-weekly schedule.

This paper reviews the toxicity profile of gemcitabine, a novel anticancer drug. Gemcitabine has been administered using two different treatment schedules: once weekly or twice weekly for 3 weeks followed by a week of rest (one cycle). It was well tolerated and alopecia was not a problem. Toxicity was greater in the twice-weekly schedule. Comparing the once-weekly with the twice-weekly schedule, WHO grade 3 or 4 thrombocytopenia was reported in 4.7 and 25.6% of patients, respectively. Other hematological toxicity was minimal. Transient WHO grade 3 or 4 elevations of ALT and AST occurred in 9.2 and 7.2% of patients, respectively, in the once-weekly schedule. For the twice-weekly schedule the corresponding percentages were 12.2 and 13.8%. Symptomatic toxicity was greater in patients who received twice-weekly gemcitabine. Nausea and vomiting was mild and generally well controlled without 5HT3 antagonists. However, there was a greater incidence of nausea and vomiting on the twice-weekly schedule. Flu-like symptoms were documented in 19.8% of patients receiving once-weekly and 63.3% of patients receiving twice-weekly gemcitabine. Peripheral edema, not related to cardiac, hepatic or renal failure, was seen more often in patients on twice-weekly treatment. As the efficacy of gemcitabine in non-small cell lung cancer was equivalent when using both regimens, the better tolerated and more easily administered once-weekly schedule is recommended.

Antimetabolites, Antineoplastic↗
PubMed1995

Incidence of colorectal cancer and all cause mortality in non-selected patients with ulcerative colitis and indeterminate colitis in Malmö, Sweden.

Cancer morbidity and all cause mortality were studied prospectively in all patients with definite and probable ulcerative colitis and indeterminate colitis diagnosed from 1958 to 1982, in the city of Malmö, Sweden. The follow-up to Jan. 1, 1990 was complete for all but ten patients. Nine of the 471 patients with ulcerative colitis and three of the 100 patients with indeterminate colitis developed colo-rectal cancer. The incidence of colorectal cancer in ulcerative colitis was 1.4 per 1000 person-years. The observed number of cases was 2.1 times higher than expected; (95% C.I. 1.0-4.1), based on the age- and sex-specific cancer incidence in the city during the study period. Indeterminate colitis was associated with a higher colorectal cancer risk than ulcerative colitis; 2.4 per 1000 person-years; (SMR 8.6, 95% C.I. 1.8-25.1). Both conditions were associated with a slight increased mortality rate, for ulcerative colitis 12.6 per 1000 person-years; (SMR 1.3, 95% C.I. 1.0-1.5), and for indeterminate colitis 11.7 per 1000 person-years; (SMR 2.7, 95% C.I. 1.6-4.4). Complications of colitis were the main cause of death in both groups. The cancer risk was related to extent of disease, duration of disease and female gender. Ten out of the 12 cases with cancer had or developed total colitis. However, only seven of the 134 cases with total ulcerative colitis and two of 87 cases with total indeterminate colitis developed cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

The feasibility of using glycosylated recombinant human granulocyte colony-stimulating factor (G-CSF) to increase the planned dose intensity of doxorubicin, cyclophosphamide and etoposide (ACE) in the treatment of small cell lung cancer. Medical Research Council Lung Cancer Working Party.

This study was conducted to test the feasibility of reducing the interval between cycles of doxorubicin, cyclophosphamide, etoposide (ACE) chemotherapy to 2 weeks, thereby increasing dose intensity, by adding granulocyte colony-stimulating factor (G-CSF) to reduce the duration of neutropenia following a cycle. 20 patients with small cell lung cancer (SCLC) were prescribed six cycles of 2-weekly ACE, with G-CSF on the intermediate days. 3 patients died during the treatment period and a further 5 had ACE terminated, 3 for toxicity and 2 for progressive disease. Of the 71 intervals between cycles, 42 (59%) were of the prescribed 14 days, 9 (13%) of 15-20 days, 15 (21%) of 21 days and five (7%) longer, but during the first four cycles, 36 (77%) of 47 intervals were of 14 days. The main reason for delay was haematological toxicity. All 20 patients experienced WHO grade 3 or 4 neutropenia, but at 2 weeks after a cycle only 3 had grade 4 and 1 grade 3. 17 patients required blood transfusion and 12 platelet transfusion. The only potentially serious adverse reaction to G-CSF was an episode of rash with facial oedema. Adding G-CSF allows ACE chemotherapy to be intensified by reducing the interval between cycles.

Aged↗
PubMed1995

Increasing and planned dose intensity of doxorubicin, cyclophosphamide and etoposide (ACE) by adding recombinant human methionyl granulocyte colony-stimulating factor (G-CSF; filgrastim) in the treatment of small cell lung cancer (SCLC). Medical Research Council Lung Cancer Working Party.

The aim of this Phase II study was to test the feasibility of intensifying standard chemotherapy in the treatment of small cell lung cancer (SCLC) by reducing the interval between cycles from 3 to 2 weeks by adding recombinant human methionyl granulocyte colony-stimulating factor (G-CSF; filgrastim) to shorten the duration of neutropenia following each cycle. Thirty-two patients with SCLC were prescribed six cycles of 2-weekly doxorubicin 50 mg/m2 and cyclophosphamide 1 g/m2 on day 1, and etoposide 120 mg/m2 i.v. on days 1, 2 and 3 (ACE), plus filgrastim in a fixed dose of 300 micrograms s.c. on days 4-14 of each cycle. Three patients died during the treatment period and a further nine had chemotherapy terminated before the sixth cycle, all nine because of toxicity. All 32 patients have been followed up for at least 21 months; 14 (44%) were alive at 12 months and the median survival period was 356 days. Of the 127 intervals between cycles of chemotherapy, 74 (58%) were of the prescribed 14 days, 18 (14%) of 15-20 days, 25 (20%) of 21 days, and 10 (8%) were longer. The results were best during the first four cycles, during which 71% of the 83 intervals were of 14 days and a further 10% were less than 21 days. The main reason for delay was haematological toxicity in 37 of the 53 instances. Symptoms of myelosuppression occurred in 23 patients, but at 14 days after a cycle of chemotherapy, all 127 available neutrophil granulocyte counts were normal. Twenty-one patients received blood transfusion and five platelet transfusion. The only adverse effects attributed to filgastrim were episodes of rash, throat swelling, anorexia and shivering, affecting one patient. We conclude that the policy of adding filgrastim allows the dose intensity of ACE chemotherapy to be increased by reducing the intervals between cycles. The findings reinforce those of a parallel study involving lenograstim.

Aged↗
PubMed1995

Carboplatin combined with amifostine, a bone marrow protectant, in the treatment of non-small-cell lung cancer: a randomised phase II study.

Amifostine (WR-2721), a thiol compound, has been shown to protect normal tissue from alkylating agents and cisplatin-induced toxicity without loss of anti-tumour effects. To confirm this result, we conducted a phase II randomised trial to determine if the addition of amifostine reduces the toxicity of carboplatin without loss of anti-tumour activity in patients with inoperable non-small-cell lung cancer (NSCLC). After the first course of carboplatin (600 mg m-2 i.v. infusion), 21 patients were randomised to receive three cycles of carboplatin alone (C arm) or three infusions of amifostine at 910 mg m-2 (CA arm) at 28 day intervals. The amifostine was given 20 min before and at 2 and 4 h after carboplatin. Since the 910 mg m-2 amifostine infusion led to hypotension in six patients, the dosage was reduced by 25%, to 683 mg m-2 t.i.d., in the other four patients. Amifostine was well tolerated at this dose level. Five patients in the CA arm and three in the C arm had their planned treatment discontinued owing to progressive disease (n = 3), amifostine side-effects (hypotension, sneezing and sickness, n = 4), and carboplatin-induced thrombocytopenia (n = 1). Bone marrow and renal function at study entry and after the first course of carboplatin before randomisation were similar in both treatment arms. Twenty courses of carboplatin+amifostine have been compared with 25 courses of carboplatin alone. Although there was no statistically significant difference with respect to haematological values comparing both arms, the median time to platelet recovery (> 100 x 10(9) l-1) (13.5 days vs 21 days; P = 0.04) and the need for hospitalisation for i.v. antibiotic and other supportive treatment tended to be reduced in the CA arm (0/20 vs 6/25 patient courses; P = 0.06). Response rates and median survival (14 vs 9 months) were no different, excluding tumour protection activity by amifostine. These results with a small number of patients suggest that amifostine given with carboplatin may reduce the duration of thrombocytopenia and hospitalisation.

Adult↗
PubMed1995

VAD chemotherapy as remission induction for multiple myeloma.

A total of 142 patients with multiple myeloma received VAD as remission induction therapy. Seventy-five were previously untreated and 67 had relapsed (31) or refractory disease (36). Vincristine (total dose 1.6 mg) was infused with doxorubicin 36 mg m-2 by continuous ambulatory pump over 4 days. In addition, oral dexamethasone 40 mg day-1 was given for 4 days. Intermittent dexamethasone was only given to 19 patients. Courses were repeated every 21 days. The overall response rate was 84% [27% complete response (CR)] in previously untreated patients and 61% (3% CR) in patients with relapsed and refractory disease. The median survival was 36 months for untreated patients and 10 months for those who had received prior therapy. VAD was well tolerated; however, despite prophylaxis, 54% patients received antibiotics at some time during therapy and 37% had dyspepsia. Twenty-three patients subsequently received a transplant (eight allografts, eight marrow autografts and seven peripheral blood stem cell transplants). Eight have died-four in the allogeneic group and four in the autologous group. The overall median survival of transplanted patients has not yet been reached. VAD is an effective, out-patient therapy for inducing remission in multiple myeloma. Post-remission therapy needs to be optimised, but it is likely that the needs of previously untreated patients may be different from those with relapsed and refractory disease.

Adult↗
PubMed1995

The Value of Anatomic Staging and Other Prognostic Factors in Small Cell Lung Cancer Management: A View of European Studies.

The need to include simple laboratory indices and performance status evaluation in treatment decision making has been shown by multivariate analyses. The conventional limited-stage extensive-stage division of prognostic groups no longer provides sufficient information. Indeed, some patients in the limited-stage group have a poor prognosis and about one quarter of patients in the extensive-stage group have a better prognosis when information from performance status and pretreatment biochemistry is taken into account. There is no rational clinical need for elaborate staging procedures, eg, computed tomography scanning or bone marrow examination, in the majority of patients with small cell lung cancer. Adequate information for defining prognostic groups can be obtained by using performance status, lactate dehydrogenase, and other biochemical tests such as sodium, alkaline phosphatase, and albumin. Thereby the cost to the patient of unnecessary burdensome investigations and to health care could both be reduced.

Journal Article↗