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M Pedersen

Publications and source records attributed to M Pedersen.

At least 19 recordsLinked to original sources

Adjuvant radiotherapy and risk of contralateral breast cancer.

BACKGROUND: The risk of contralateral breast cancer is increased twofold to fivefold for breast cancer patients. A registry-based cohort study in Denmark suggested that radiation treatment of the first breast cancer might increase the risk for contralateral breast cancer among 10-year survivors. PURPOSE: Our goal was to assess the role of radiation in the development of contralateral breast cancer. METHODS: A nested case-control study was conducted in a cohort of 56,540 women in Denmark diagnosed with invasive breast cancer from 1943 through 1978. Case patients were 529 women who developed contralateral breast cancer 8 or more years after first diagnosis. Controls were women with breast cancer who did not develop contralateral breast cancer. One control was matched to each case patient on the basis of age, calendar year of initial breast cancer diagnosis, and survival time. Radiation dose to the contralateral breast was estimated for each patient on the basis of radiation measurements and abstracted treatment information. The anatomical position of each breast cancer was also abstracted from medical records. RESULTS: Radiotherapy had been administered to 82.4% of case patients and controls, and the mean radiation dose to the contralateral breast was estimated to be 2.51 Gy. Radiotherapy did not increase the overall risk of contralateral breast cancer (relative risk = 1.04; 95% confidence interval = 0.74-1.46), and there was no evidence that risk varied with radiation dose, time since exposure, or age at exposure. The second tumors in case patients were evenly distributed in the medial, lateral, and central portions of the breast, a finding that argues against a causal role of radiotherapy in tumorigenesis. CONCLUSIONS: The majority of women in our series were perimenopausal or postmenopausal (53% total versus 38% premenopausal and 9% of unknown status) and received radiotherapy at an age when the breast tissue appears least susceptible to the carcinogenic effects of radiation. Based on a dose of 2.51 Gy and estimates of radiation risk from other studies, a relative risk of only 1.18 would have been expected for a population of women exposed at an average age of 51 years. Thus, our data provide additional evidence that there is little if any risk of radiation-induced breast cancer associated with exposure of breast tissue to low-dose radiation (e.g., from mammographic x rays or adjuvant radiotherapy) in later life.

Adult

Time to loco-regional recurrence after resection of Dukes' B and C colorectal cancer with or without adjuvant postoperative radiotherapy. A multivariate regression analysis.

Factors influencing time to loco-regional recurrence were identified in a multivariate regression analysis of data from a series of 468 radically operated patients (260 Dukes' B and 208 Dukes' C) with carcinoma of the rectum and the rectosigmoid. A number of clinical and pathological characteristics were prospectively collected and recorded. In addition, carcinoembryonic antigen (CEA) was measured within 1 week before surgery. The endpoint used was recurrence below the level of the umbilicus. All patients were followed for at least 5 years or until time of death. The two Dukes' stages B and C were analysed in two separate analyses using the Cox proportional hazards model. In patients with Dukes' B tumours, an increased risk of loco-regional recurrence was associated with perineural invasion, tumour located less than 10 cm from the anal verge, patient aged above 70 years, and small tumour size. In patients with Dukes' C tumours, the necessity to resect neighbour organs, perineural and venous invasion, tumour located less than 10 cm from the anal verge, and large tumour size were all associated with a poor loco-regional outcome. Postoperative radiotherapy was not a significant prognosticator for loco-regional control. An update of the 5-year results of the randomised study of post-operative radiotherapy (50 Gy with 2 Gy per fraction in an overall treatment time of 7 weeks) showed no survival benefit from adjuvant radiotherapy in either Dukes' category and no statistically significant improvement in the 5-year loco-regional control rate. However, when the comparison was restricted to a group of high-risk patients there was a statistically significant benefit from radiotherapy with respect to loco-regional control (P = 0.03) but not with respect to survival (P = 0.23). The potential advantage, in terms of the required number of patients, of restricting clinical trials of intensified loco-regional therapies to the high-risk patients, is illustrated.

Adult

Non-Hodgkin's lymphoma in the elderly. A study of 602 patients aged 70 or older from a Danish population-based registry. The Danish LYEO-Study Group.

Within a 7-year period 1,597 newly diagnosed cases of non-Hodgkin's lymphoma (NHL) were included in a Danish population-based NHL registry. Of these, 602 (38%) were aged 70 years or older (age range 70-94, median: 76.8). They represent the population defined as 'elderly' patients in the present study. The average annual incidence rate for this elderly patient population was 35.7/10(5), as compared with 6.6/10(5) for patients aged less than 70 (overall annual incidence: 9.5/10(5)). Localised cases (stage I and II) and extranodal manifestations were found more frequently among elderly patients. The most common sites of extranodal involvement were the stomach (21% of all extranodal cases) and the bone marrow (16%). Histologically, follicular centroblastic/centrocytic cases were found to be less frequent (p less than 0.01) in elderly patients as compared to their younger counterparts (less than 70 years), who in contrast had a lower occurrence of diffuse centroblastic cases (p less than 0.01). Overall 7-year survival for the elderly patient population was 35% (median 1.7 years), and for patients aged less than 70 it was 57%. This difference persisted after correction for apparently NHL-unrelated deaths (52% vs. 66%, respectively, p less than 0.0001). Elderly patients with poor prognosis were characterised by the following features identified in a Cox-regression model: hepatic involvement, presence of B-symptoms, high-grade histology and elevated s-LDH. The corresponding relative risk values were in the order 2.4, 2.2, 1.9 and 1.6.

Aged

IgE-mediated reaction to vancomycin and teicoplanin after treatment with vancomycin.

A 38-year-old male patient developed severe signs of type 1 allergy after treatment with vancomycin. By the basophil histamine release test, the patient's isolated basophil leucocytes were shown to react IgE dependent after challenge with vancomycin and teicoplanin. This indicates that the patient is type 1 allergic towards vancomycin and teicoplanin.

Adult

Amplification and sequencing of the control regions of BK and JC virus from human urine by polymerase chain reaction.

The various strains of BKV and JCV exhibit a remarkable degree of heterogeneity in the noncoding region near the origin of DNA replication. It is of great interest, therefore, to characterize the naturally occurring variants as a first step towards the attainment of an understanding of the origin and the biological significance of this hypervariability. In this paper we report the use of polymerase chain reaction for amplification and sequencing of the control regions of BKV and JCV DNAs from urines of AIDS patients, bone marrow transplantation recipients, and other patient groups. Our results support the conclusion that BK(WW) and its variants constitute the most prevalent strain in the human population tested so far. A new strain, designated BK(TU), was isolated from some patients from Norway. Urine inocula containing BK(WW) gave BK(TU) after propagation in cell culture, while BK(TU) did not change the sequence of its control region during the same procedure. The JCV isolates were almost identical with several strains molecularly cloned from the urine reported by Y. Yogo, T. Kitamura, C. Sugimoto, T. Ueki, Y. Aso, K. Hara, and F. Taguchi (J. Virol., 1990, 64, 3139-3143). This archetypal strain may represent the JCV circulating in the human population, from which various regulatory sequences of JCV isolates could have evolved by deletions and amplifications.

BK Virus

Paternity in patients with testicular germ cell cancer: pretreatment and post-treatment findings.

Paternity before and after treatment was investigated in 177 patients with unilateral germ cell tumours of the testis. Before the cancer was diagnosed, 51% had fathered at least 1 child, 9% had a history of infertility and 40% had not wanted to have children. It was estimated that 72% of the patients would have fathered at least 1 child at the age of 40 years. After treatment 41 patients had wished to have children. Infertility was still a problem 5 years after the end of treatment in 53% of these men. No significant differences was observed between patients treated with orchiectomy alone and patients treated with cisplatin-based chemotherapy or subdiaphragmatic irradiation. In 8 patients, infertility was present in spite of an evident recovery of spermatogenesis. Congenital malformations were recorded in 3.8% of the live-born children conceived before the orchiectomy. This incidence did not exceed the Danish national rate, the relative risk being 2.5 (95% confidence limits, 0.9-5.5). No malformations were observed in the 22 children conceived after ending treatment.

Adolescent

Clinicopathological features and prognostic factors in extranodal non-Hodgkin lymphomas. Danish LYFO Study Group.

In a Danish population-based non-Hodgkin lymphoma (NHL) registry, 1257 newly diagnosed NHL cases were registered over a 5-year period. Of these, 463 (37%) were extranodal. The gastrointestinal tract was the most common site of extranodal involvement (30% of the cases). Histologically, 44% of all extranodal NHL cases had high-grade, 17% intermediate and 27% low-grade features, while 12% were unclassified. The most common histological subtype (Kiel) was the centroblastic diffuse (23% of cases). 50% of all extranodal NHL were localised (stage IE or IIE) and 27% had B symptoms. Site-specific features included a strong age-correlation for thyroid and testes lymphoma (greater than 50 years) and a high prevalence of female cases in thyroid and salivary glands lymphomas (M/F 0.14 and 0.30, respectively). Overall 7-year survival for extranodal NHL was 46% (median 4.9 years). Poor prognosis patients could be identified by the presence of one or more of the following presentation characteristics: age greater than 65 years, B symptoms, high-grade histology, disseminated disease, elevated s-IgA and hyperuricaemia. Relative risk values ranged from 2.1 for age and B symptoms to 1.7 for hyperuricaemia.

Adolescent

Bacteria-induced histamine release from human bronchoalveolar cells and blood leukocytes.

Histamine release induced by Staphylococcus aureus was examined in cells obtained by bronchoalveolar lavage (BAL) in non-atopic individuals. Approximately half of the individuals responded with mediator release to the bacterium, and the release was found to be time- and concentration dependent. No difference was found between the patients who responded and those who did not respond in regard to age, sex, smoker/non-smoker, % recovery of BAL-fluid, total cell count, differential cell counts, histamine content per mast cell, or diagnoses. Also stimulation of the BAL-cells with the calcium-ionophore A23187 resulted in histamine release. S. aureus-induced histamine release from basophils was examined in leukocyte suspensions obtained from the same individuals, and in all experiments release was found. The dose-response curves were similar to those obtained with BAL cells. The bacteria-induced mediator release from superficially lying cells in the airways epithelium might be of importance for the precipitation or exacerbation of bronchial asthma in respiratory tract infections.

Adult

Cytokine-induced histamine release from basophils of AIDS patients. Interaction between cytokines and specific IgE antibodies.

Basophil leukocytes obtained from AIDS patients, allergic patients and healthy controls were stimulated in vitro with interleukin 4, lymphotoxin, tumour necrosis factor alpha and interferon gamma to examine the histamine releasing effect. The cytokines caused histamine release from the basophils of approximately half the AIDS patients and from 8-17% of the allergic patients. No response was obtained in the control group. Removal of cell surface immunoglobulins abolished the response to cytokines, indicating an Ig-dependent mechanism. Passive sensitization with cell-derived Ig, with Ig deprived of IgE, or with IgG, indicated that cell-bound IgE was responsible for the cytokine-induced histamine release in AIDS patients. This response may be mediated by cytokine-selective IgE antibodies.

Acquired Immunodeficiency Syndrome

HIV antigen-induced release of histamine from basophils from HIV infected patients. Mechanism and relation to disease progression and immunodeficiency.

Basophil leukocytes from 39 HIV-infected patients with various degrees of immunodeficiency and disease progression were stimulated with an HIV antigen preparation. Cells from 19 of 22 patients with AIDS and all of six patients with milder degrees of HIV-related disease showed significant histamine release. In contrast, cells from 11 asymptomatic HIV-infected patients and 11 healthy control persons released no histamine. The histamine release induced by HIV antigen was found to be inversely correlated to the number of CD4 positive T lymphocytes. These results indicate that the histamine release was related to both the clinical stage of disease and the degree of immunodeficiency. Passive sensitization experiments showed that IgE, but not IgG, was responsible for the induction of histamine release, indicating the reaction to be type 1 allergic. The histamine release caused by HIV might be involved in the development of disease because of the immunomodulating properties of this mediator.

Acquired Immunodeficiency Syndrome

Surveillance alone versus radiotherapy after orchiectomy for clinical stage I nonseminomatous testicular cancer. Danish Testicular Cancer Study Group.

From December 1980 to January 1984, all patients with stage I nonseminomatous testicular cancer in Denmark entered a randomized trial comparing surveillance only with radiotherapy after orchiectomy. One hundred fifty patients were assessable for the final analysis. Relapse occurred in 23 patients in the surveillance group and in 11 patients in the radiotherapy group. Radiotherapy completely prevented retroperitoneal relapse; 14 retroperitoneal relapses occurred in the surveillance-only group. All relapsing patients in the surveillance-only group are without evidence of disease with a median observation time after chemotherapy of 67 months. Two of the patients with relapse in the radiotherapy group died with disease; the others are alive without evidence of disease, with a median observation time after relapse treatment of 72 months. In the surveillance group, four relapses occurred later than 2 years after orchiectomy; only one such late relapse occurred in the radiotherapy group. Four of the retroperitoneal relapses occurred without concomitant increase in the serum marker levels (alpha-fetoprotein [AFP] and human chorionic gonadotropin [HCG]). It is concluded that surveillance only should replace radiotherapy after orchiectomy as standard treatment for clinical stage I nonseminomatous testicular cancer. Improved methods for control of retroperitoneal relapses, especially of embryonal carcinomas, are needed.

Adolescent

Virus enhances IgE- and non-IgE-dependent histamine release induced by bacteria and other stimulators.

Histamine release from human basophil leukocytes was triggered by Staph. aureus, Salmonella enteritidis, non-haemolytic streptococci, or E. coli. Influenza A virus was found to enhance the mediator release and the effect was caused by synergism, since the virus did not induce release of histamine per se. This potentiating effect of the virus was seen both when the bacteria-induced histamine release was IgE-dependent (i.e. patient sensitized to the bacterium) and when the bacterium caused mediator release by a non-immunological mechanism independent of IgE (putative sugar-lectin mediated). Histamine release induced by anti-IgE and calcium ionophore or agarose-beads was also enhanced in the presence of the virus. These findings indicate that influenza A virus potentiates both IgE- and non-IgE-mediated histamine release induced by bacteria and other stimulators.

Bacterial Infections

Cytokine-induced release of histamine from basophil leukocytes from AIDS patients.

Cytokine-induced histamine release from basophil leukocytes was examined in cell suspension from AIDS patients and compared with healthy controls. Cells from approximately half of the AIDS patients, in contrast to none from the control group, showed histamine release after stimulation with interleukin-4 (IL-4), tumor necrosis factor alpha (TNF alpha), lymphotoxin (LT) and interferon gamma (IFN gamma). These cytokines seem to induce histamine release from cells from AIDS patients by interaction with the cell surface immunoglobulins, since removal of the immunoglobulins prior to the exposure of the cytokines completely abolished the response to the cytokines. IL-1 alpha, IL-1 beta, IL-3, colony stimulating factor (CSF) and granulocyte-macrophage-CSF (GM-CSF) caused significant histamine release from cells from a similar number of AIDS patients and controls.

Acquired Immunodeficiency Syndrome

Ciliary activity and pollution.

The mucociliary clearance is an important part of the nonspecific defense mechanism of the human airways. Coordinated beats of cilia in the nose, trachea, and bronchi propel the mucous layer toward the pharynx, and with it inhaled microorganisms and other particles captured in the mucus. Normal function of this system depends on the efficacy of the ciliary beating and the properties of mucus. Primary ciliary dyskinesia--a congenital respiratory disease characterized by ultrastructural defects and motility disturbances of cilia--has provided us with valuable information about the role the mucociliary function plays in the protection against harmful agents in the inhaled air. Secondary ciliary dyskinesia is described in inflammatory disorders of the respiratory tract, but also some components in air pollution results in malfunction of cilia, damage of ciliated epithelium, or alteration in the mucus. This review will focus on investigations found in the literature concerning the influence of pollutants on ciliary activity. The methods applied will be evaluated.

Air Pollution