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Biomedical subjects

J Andersen

Publications and source records attributed to J Andersen.

At least 127 records · Page 7Linked to original sources

High-dose carboplatin and etoposide with autologous bone marrow transplantation in refractory germ cell cancer: an Eastern Cooperative Oncology Group protocol.

PURPOSE: A phase II trial was undertaken to assess the feasibility, toxicity, and efficacy of high-dose carboplatin and etoposide with autologous bone marrow transplantation in patients with relapsed or refractory germ cell tumors. PATIENTS AND METHODS: Forty patients with recurrent germ cell cancer received carboplatin 500 mg/m2 and etoposide 400 mg/m2 given at 7, 5, and 3 days before marrow infusion. Autologous marrow infusion (day 0) was accomplished using one half of the bone marrow harvested before chemotherapy. Patients who achieved a complete or partial response with the first cycle of treatment received a second identical cycle of chemotherapy followed by infusion of the remaining cryopreserved bone marrow. RESULTS: Objective responses were obtained in 17 of the 38 patients (45%) assessable for response, including eight partial and nine complete remissions. Five of these patients remain in continuous complete remission with minimal follow-up of 1 year. Toxicity encountered was primarily hematologic, and five patients (13%) died of treatment-related complications. Significant toxicities often seen with high-dose cisplatin (ototoxicity, neurotoxicity, and renal toxicity) were manageable in this regimen of high-dose carboplatin. CONCLUSIONS: This trial confirms the curative potential of high-dose carboplatin and etoposide in highly refractory germ cell cancer.

Adolescent

Variation in hepatic estrogen receptor concentrations in patients with liver disease. A multivariate analysis.

Hepatic estrogen receptor concentrations were measured in liver biopsy specimens from 102 patients (58 women and 44 men) with liver disease and correlated to several clinical, biochemical, and histologic background variables by means of multiple regression analysis. Half of the tissue was processed for histologic evaluation with a semiquantitative registration of histologic characteristics, whereas the other part was used for receptor analysis by enzyme immunoassay. Fifteen patients with no or minimal histologic changes served as controls. The analysis shows that the reduced estrogen receptor concentrations observed in patients with chronic liver diseases reflect the degree of liver dysfunction and not the specific type of liver disease. Serum albumin, log serum bilirubin, log serum alkaline phosphatases, and the degree of parenchymal fibrosis were significantly related to hepatic estrogen receptor level in the final regression model, but only part of the variation can be explained by these variables, and other factors must be of importance.

Adult

Determination of estrogen receptors in paraffin-embedded tissue. Techniques and the value in breast cancer treatment.

Estrogen receptor (ER) analysis in breast cancer has been used in three clinical situations: to select patients with advanced breast cancer for hormonal therapy, as a prognostic parameter, and for selection of women with early breast cancer to adjuvant hormonal treatment. ER has traditionally been measured using labelled hormone in binding assays--often in dextran-coated charcoal assays (DCC). Monoclonal antibodies to ER has permitted development of a solid phase enzyme immunoassay (ER-EIA) used for quantitative determination of ER in tissue homogenates, and have also been used for determination of ER using an immunohistochemical assay in frozen sections (ER-ICA) or in formalin-fixed, paraffin-embedded tissue (ER-PAR). A large number of studies has compared ER-EIA with ER-DCC assays. There is a good linear correlation between the two types of assay but ER-EIA measure more ER and classify a larger fraction of tumors ER-positive than conventional ER assays. Lack of clinical data makes the significance of this uncertain. Numerous studies have reported on the correlation between ER-ICA and ER-DCC or ER-EIA. There is a good correlation among the assays on classification of ER status with a median 86% concordance, but a somewhat poorer correlation between semiquantified ER of immunohistochemical assays and ER determined by the quantitative methods (median coefficient of correlation 0.67). There is a large variation in the cut-off level for definition of ER-positive in immunohistochemical assays emphasizing the need for quality control studies. The major problem involved in ER analysis in paraffin-embedded tissue is a considerable loss of immunoreactivity compared to sections from frozen tissue. This can partly be overcome by modifications of the immunohistochemical technique using enzyme pretreatment and other amplification systems, but the sensitivity of ER-PAR remains lower than ER-ICA despite these modifications, and the ER status is less reliably determined in tumors with low ER contents (< 100 fmol). The prognostic value of ER-PAR was evaluated with a multivariate analysis. The endpoint was disease-free interval in systemically untreated patients with early breast cancer, and the variables used were: ER-DCC, ER-PAR, age, tumor size, tumor grade, and nodal status. A total of 133 patients from the Danish Breast Cancer Cooperative Group's (DBCG) 77c protocols had a complete set of variables. The analysis showed that only nodal status, ER-DCC, and tumor grade were significant and independent prognostic variables. An overview of larger multivariate studies on mainly node-negative patients failed to show independent prognostic significance of ER-DCC.(ABSTRACT TRUNCATED AT 400 WORDS)

Antibodies, Monoclonal

Classical prognostic factors in node-negative breast cancer: the DBCG experience.

Classical prognostic factors were analyzed in patients with low-risk primary breast cancer, defined as absence of tumor-positive axillary lymph nodes, tumor size less than or equal to 5 cm in diameter, and no invasion into skin or deep fascia. The primary surgical treatment was total mastectomy and lower axillary dissection. None of the patients received adjuvant therapy. Between 1977 and 1990, 7315 patients entered the study, and at the time of this analysis (January 1, 1990), the median follow-up time is 5 years. In univariate analyses, the following variables were significantly related to recurrence-free survival: age in premenopausal patients; tumor size; number of negative nodes removed; histological grade; and in premenopausal patients, estrogen receptor and progesterone (PgR) status. In multivariate analyses, age in premenopausal patients was the most important factor, followed by tumor size and histological grade, whereas PgR status in premenopausal patients was just of borderline significance. These variables should be included in multivariate analyses testing the value of more recently introduced prognostic factors.

Breast Neoplasms

[Emergency treatment of alcoholics. Review of the admissions and readmissions to a psychiatric department with regard to the features of the group].

A retrospective investigation revealed 107 patients (29 women and 78 men) with the diagnosis of alcoholism who were admitted to the County Hospital in Vordingborg during a period of six months. Readmissions of these patients during the subsequent two years were registered. The object of the investigation was to characterize these patients as regards the mental and social conditions, as it was our impression that these conditions were of significance in the referral for treatment in the psychiatric department. In addition, we have investigated whether it is possible to point out prognostic factors for the frequency of readmission. 78% of the patients were between 30 and 50 years. Patients in social class 8 were overrepresented. This supports the presumption that admission to a psychiatric department is not based on the abuse per se but rather on the problem complex of abuse, mental and social problems. 2/3 of the patients had previously been treated for alcohol abuse. The frequency of readmission during the subsequent two years was highest for patient aged 30-50 years. In the age group 30-39 years, changes in the social and mental circumstances had occurred and, in the age group 40-49 years, somatic complications on account of the abuse had more frequently developed. No connection could be found between the duration of the first admission in the period of investigation and the frequency of readmission during the subsequent two years. It is concluded that the group of patients aged 30-39 years appears to require social initiative whereas the group of patients aged 40-49 years has a greater need for somatic treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Recombinant granulocyte-macrophage colony-stimulating factor after autologous bone marrow transplantation for relapsed non-Hodgkin's lymphoma: blood and bone marrow progenitor growth studies. A phase II Eastern Cooperative Oncology Group Trial.

Sixteen patients with relapsed non-Hodgkin's lymphoma underwent autologous bone marrow transplantation and infusion of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF). Treatment consisted of involved-field radiotherapy, cyclophosphamide 60 mg/kg/d intravenously (IV) for 2 days, and fractionated total body irradiation (1,200 cGy). Autologous bone marrow was thawed and infused IV, followed 3 hours later by the first infusion of IV rhGM-CSF 11 micrograms/kg/d over 4 hours. Infusions of rhGM-CSF were continued daily until either both neutrophil count exceeded 1,500/microL and platelet count exceeded 50,000/microL, or until 30 days after marrow re-infusion. Toxicities encountered were mild and included fever, chills, hypertension, alopecia, rash, diarrhea, stomatitis, myalgias, and synovial (knee) effusions. Neutrophil recovery greater than 500/microL occurred a median of 14 days (range, 9 to 30 days) after marrow infusion, significantly earlier than in a comparable group of historic controls who recovered counts at a median time of 20 days (range, 12 to 51 days) (P = .00002). Median time to self-sustaining platelet counts greater than 20,000/microL was 23.5 days (range, 12 to 100 days), comparable with the historic group (P = .38). One bacteremia (central venous catheter exit site infection with Staphylococcus epidermidis) and one local infection (Giardia lamblia in stool) occurred. Patients received a median of 11.4 (range, 4.4 to 20.2) x 10(4) colony-forming unit granulocyte-macrophage (CFU-GM) progenitors per kg. Stem cell progenitors CFU-GM, CFU-granulocyte, erythroid, monocyte, megakaryocyte (CFU-GEMM), and burst-forming unit-erythroid (BFU-E) were detected in the bone marrow as early as 7 days after marrow re-infusion, and increased in proportion to peripheral blood counts, but by 30 to 60 days still remained much lower than before transplant. Neutrophils transiently decreased in 13 of 16 patients (median decrease, 42%) within 24 to 72 hours of discontinuing rhGM-CSF infusions. These data suggest that rhGM-CSF therapy enhances neutrophil recovery by forcing stem cells to produce mature elements at an enhanced rate but may not affect marrow stem cell and early progenitor population sizes.

Adult

13-cis-retinoic acid in the treatment of elderly patients with acute myeloid leukemia. A phase II pilot study of the Eastern Cooperative Oncology Group.

The management of acute myeloid leukemia in the elderly (65 years and older) is unsatisfactory because of poor patient tolerance of standard myeloablative chemotherapy. The authors conducted a Phase II study to evaluate the effectiveness and toxicity of 13-cis-retinoic acid (CRA) in the therapy of elderly patients with acute myeloid leukemia (AML). Patients presenting with leukocyte counts less than 20,000/microliters were treated with CRA alone. Those with leukocyte counts of 20,000/microliters or greater were pretreated with hydroxyurea, followed by CRA. Twelve of 18 patients received at least 4 weeks of CRA and were thus considered evaluable for toxicity and response. No objective responses were observed. Cis-retinoic acid administration was well tolerated; only modest dermatologic, musculoskeletal, and gastrointestinal toxicity was observed. Alternative therapeutic strategies should be investigated in this subpopulation of AML patients.

Aged

Assembly and intracellular transport of snRNP particles.

The assembly of the major small nuclear ribonucleoprotein (snRNP) particles begins in the cytoplasm where large pools of common core proteins are preassembled in several RNA-free intermediate particles. Newly synthesized snRNAs transiently enter the cytoplasm and complex with core particles to form pre-snRNP particles. Subsequently, the cap structure at the 5' end of the snRNA is hypermethylated. The resulting trimethylguanosine (TMG) cap is an integral part of the nuclear localization signal for snRNP particles and the pre-snRNP particles are rapidly transported into the nucleus. SnRNP particles mature when snRNA-specific proteins complex with the particles, in some cases, just before or during nuclear transport, but in most instances after the particles are in the nucleus. In addition, U6 snRNA hybridizes with U4 snRNA to form a U4/U6 snRNP in the nucleus. The transport signals are retained on the snRNP particles and proteins since existing particles and proteins enter the reformed nucleus after mitosis.

Amino Acid Sequence

Perioperative blood transfusion does not promote recurrence and death after mastectomy for breast cancer. The Danish Breast Cancer Cooperative Group.

Several reports suggest that perioperative blood transfusion promotes recurrence and death after cancer surgery. We studied the effect of transfusion in 1599 patients who had mastectomy for carcinoma of the breast. In 228 transfused patients the disease recurred in 110 (48 per cent), compared with 647 (47 per cent) of 1371 non-transfused patients (P = 0.85). The 5-year recurrence-free survival rate was 0.54 in the transfused patients and 0.60 in the non-transfused group (P = 0.44). The transfused patients had a higher prevalence of risk factors than the non-transfused patients. Cox's multiple regression analysis confirmed that perioperative blood transfusion was of no importance. The study does not support the hypothesis that perioperative blood transfusion promotes recurrence after operation for breast cancer.

Adult

Investigation of a family with von Hippel-Lindau syndrome.

A family with Von Hippel-Lindau syndrome has been investigated with Ultrasound, CT and MRI. The major lesions found were posterior fossa haemangioblastomas, retinal haemangioblastomas and renal cell carcinoma. Screening of family members has been undertaken due to the known autosomal dominant inheritance of this condition.

Adolescent

Prolactin responses to thyrotropin-releasing hormone in multi-infarct dementia and senile dementia of the Alzheimer type.

The serum prolactin (PRL) responses to stimulation with thyrotropin-releasing hormone (TRH) (500 micrograms Protirelin) were compared in 14 patients with multi-infarct dementia (MID) and 10 patients with senile dementia of the Alzheimer type (SDAT). Between the MID and the SDAT patients, there were no statistically significant differences in the median serum PRL concentrations, median changes in serum PRL concentrations or median proportional changes in serum PRL concentrations. Further, the serum PRL responses did not correlate with the GBS scale scores (degrees of dementia) or the GBS subscale scores (clinical profiles, including motor functioning, emotional functioning and intellectual functioning). In conclusion, the study does not support the hypothesis that serum PRL responses to TRH stimulation are of diagnostic value in differentiating between MID and SDAT.

Aged

Enzyme immunoassay of oestrogen receptors in needle biopsies from human liver.

For quantitative assessments of sex hormone receptors in liver tissue, ligand binding assays are inconvenient, as they require large biopsies (0.5-1.0 g). The present study shows that it is possible to measure oestrogen receptors (ER) quantitatively in needle biopsy specimens as small as 10 mg by modifications of a commercial enzyme immunoassay employing monoclonal antibodies. Sucrose gradient centrifugation and the dextran charcoal method served as reference methods. A consecutive series of needle biopsies from patients suspected of liver disease were investigated. The biopsies (n = 37) had a median weight of 14 mg and cytosolic protein concentrations greater than 1 mg/ml (median 1.28 mg/ml). The median ER concentration was 20 fmol/mg cytosolic protein (range 5 to 57 fmol/mg). The intra-assay coefficient of variation was 8.9%, the inter-assay 13.2%, and the detection limit 2.7 fmol/ml cytosol. Women had significantly higher ER concentrations (median 22 fmol/mg) compared to male patients (median 16 fmol/mg) (P = 0.007). The enzyme immunoassay measures ER in liver specimens as small as 10 mg, compared to the large tissue specimens necessary for the conventional DCC assay, and the method is a convenient tool for further studies of ER in routine needle biopsies from the liver.

Biopsy, Needle

Contrast sensitivity in radial keratotomy.

In a prospective study, contrast sensitivity function was determined before and one month postsurgery in 15 consecutive cases of radial keratotomy. The results obtained pre-operatively were compared to those of an age-matched, emmetropic reference group also comprising 15 persons. Three different test conditions were employed. High luminance background levels of 130 cd/m2, low luminance levels of 3.5 cd/m2 and low luminance levels completed with a central glare source of 7.5 lux. Using an eight-incisional radial keratotomy technique with a 3 mm optical zone, a median reduction in myopia of 3.5 diopters was observed. Corrected visual acuity was not affected by the surgery. The contrast sensitivity functions of the myopic group pre-operatively compared to the post-operative values showed no significant difference for any of the three test conditions. Compared to the reference group, the myopic group pre-operatively demonstrated a statistically significant reduced contrast sensitivity for all test conditions.

Adult

Progressive noninfectious anterior vertebral fusion.

We reviewed 26 patients with progressive spinal kyphosis due to anterior fusion between the vertebrae. No patient had back pain or any neurological defect. The kyphosis appeared to be progressive until the fusion had included all of the disc. Progression was faster during the adolescent growth-spurt. Kyphosis increased with the number of discs involved, from one to six, and the extent of fusion within each disc. In six of the nine cases treated by spinal bracing, progression of the kyphosis was arrested.

Adolescent

Pattern of spread and progression in relation to the characteristics of the primary tumour in human breast cancer.

Characteristics of primary breast tumours were related to the extent of dissemination, the anatomical location of metastases, and the rate of progression in 863 patients with recurrent breast cancer. The following features were examined: tumour laterality, location within the breast, size, invasion of skin or fascia, presence of residual cancer tissue (RCT) in the mastectomy specimen, and number of positive lymph nodes. Increasing tumour size, increasing number of nodes, and the presence of local invasion and RCT were all associated with a short duration of survival both from initial diagnosis and from first recurrence. None of the factors were related to either the extent of dissemination or the rate of progression. Patients who had their primary tumours located in the medial or central part of the breast had an increased incidence of mediastinal and pleural recurrences respectively. Primary tumours greater than 5 cm, invasion of skin or fascia, and presence of RCT were all associated with an increased incidence of local recurrences. In addition, both RCT and fascial invasion were associated with increased occurrence of brain metastases. Most differences were explainable on the basis of local and regional lymphodynamics. Since the status of the features examined here all vary with time from tumour inception, it is suggested that the impact on prognosis is related to variations in tumour age from inception to primary diagnosis rather than to qualitative biological differences.

Bone Neoplasms