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R Hultborn

Publications and source records attributed to R Hultborn.

At least 19 recordsLinked to original sources
PubMed2005

Early disturbance of microvascular function precedes chemotherapy-induced intestinal injury.

Intestinal injury 4-48 hr after cytotoxic therapy (etoposide phosphate, 100 mg/kg body weight [bw], intravenously [i.v.]) was studied in rats using ligated intestinal loops. Chromium-51 ethylenediaminetetraacetic acid ((51)Cr-EDTA) and rubidium-86 chloride ((86)RbCl) were deposited intraluminally to determine the extent of the increase in intestinal permeability and ion channel disruption. Evans Blue (EB) was used for detection of endothelial leakage. Intestinal morphology was documented. Endothelial dysfunction, as observed by an increased extravasation of EB, was evident already 4 hr after cytotoxic therapy. Intestinal epithelial injury, as observed by an increase in (51)Cr-EDTA permeation and a decrease in (86)Rb absorption, occurred after 48 hr. Finally, histology disclosed a reduced crypt cell proliferation, displayed as a decrease in Ki67-positive cells. The findings suggest that, in the development of intestinal injury after cytotoxic therapy, endothelial disruption is an early event, whereafter epithelial dysfunction and crypt stem cell arrest occur. This knowledge could be of importance in the design of future intervention trials.

Animals↗
PubMed2003

Chromatin- and temperature-dependent modulation of radiation-induced double-strand breaks.

PURPOSE: To investigate the influence of chromatin organization and scavenging capacity in relation to irradiation temperature on the induction of double-strand breaks (DSB) in structures derived from human diploid fibroblasts. MATERIALS AND METHODS: Agarose plugs with different chromatin structures (intact cells+/-wortmannin, permeabilized cells with condensed chromatin, nucleoids and DNA) were prepared and irradiated with X-rays at 2 or 37 degrees C and lysed using two different lysis protocols (new ice-cold lysis or standard lysis at 37 degrees C). Induction of DSB was determined by constant-field gel electrophoresis. RESULTS: The dose-modifying factor (DMF(temp)) for irradiation at 37 compared with 2 degrees C was 0.92 in intact cells (i.e. more DSB induced at 2 degrees C), but gradually increased to 1.5 in permeabilized cells, 2.2 in nucleoids and 2.6 in naked DNA, suggesting a role of chromatin organization for temperature modulation of DNA damage. In addition, DMF(temp) was influenced by the presence of 0.1 M DMSO or 30 mM glutathione, but not by post-irradiation temperature. CONCLUSION: The protective effect of low temperature was correlated to the indirect effects of ionizing radiation and was not dependent on post-irradiation temperature. Reasons for a dose modifying factor <1 in intact cells are discussed.

Androstadienes↗
PubMed2001

Bone marrow micrometastases in patients with stage I-II localised prostate cancer.

Prostate cancer commonly metastasises to the bones. Detection of bone marrow micrometastases (BMM) may give important information that helps define treatment strategies. This study was undertaken to analyse BMM in early prostate cancer patients and to determine the accuracy of immunohistochemical (IHC) and morphological methods in detecting cancerous cells. Preoperative core bone marrow biopsy (BMB) was performed in 103 patients with T1-2, N0, M0 prostate cancer after neoadjuvant androgen blockade. BMB were examined by IHC using monoclonal antibodies for cytokeratins (CK) (18, 19, PAN) and by cytomorphology of IHC-positive cells. In 103 patients, BMM were detected in 2 cases (2%) and an additional 3 cases (3%) were classified as suspicious. IHC alone revealed positive cells in 19 patients (18%). Cytomorphology disclosed IHC false-positive staining of some apparently normal bone marrow elements such as plasmocytes. The study shows a rather low rate of BMM in early prostate cancer. It also stresses the importance of cytomorphology as an adjunct to IHC as IHC alone may not be sufficient and appropriate for BMM detection.

Adult↗
PubMed2001

The diagnosis of cancer in the "roar" of potential cancer symptoms of patients in primary health care. Research by means of the computerised journal.

OBJECTIVE: To describe the diagnostic work-up pattern in primary health care, aiming, with as few diagnostic activities as possible, to identify a number of malignancies among patients presenting with various symptoms, where a malignancy may be a differential diagnosis. DESIGN: Survey of computerised journals. Diagnostic codes (ICD-9 system in primary health care) relating to signs, symptoms or diagnosis were selected where colorectal, pulmonary, breast and prostate malignancies might be differential diagnoses. All diagnostic actions were analysed. SUBJECTS: 6812 patients over 30 years of age from four health centres who were recorded for a total of 14455 selected diagnostic codes. RESULTS: The diagnostic actions resulted in 1426 X-ray or sonographic investigations, 340 endoscopies, 16203 haematology, clinical chemistry or microbiology tests and 667 referrals to specialists. Forty-nine malignancies were diagnosed at the primary health care centres, while 10 malignancies were classified as "missed". The frequency of faecal-occult blood tests performed was low while that of ESR and pulmonary X-ray examinations was high. CONCLUSION: The task for a GP identifying one or two undiagnosed malignancies per year of the four most common types among all the non-neoplastic ailments, and with as little diagnostic activity as possible, is a professional challenge to be scrutinised continuously.

Abstracting and Indexing↗
PubMed2000

Radiation-induced double-strand breaks in mammalian DNA: influence of temperature and DMSO.

PURPOSE: To investigate the effects of subphysiological irradiation temperature (2 28 degrees C) and the influence of the radical scavenger DMSO on the induction of double-strand breaks (DSB) in chromosomal DNA from a human breast cancer cell line (MCF-7) as well as in intact cells. The rejoining of DSB in cells irradiated at 2 degrees C or 37 degrees C was also investigated. MATERIALS AND METHODS: Agarose plugs with [14C]thymidine labelled MCF-7 cells were lysed in EDTA-NLS-proteinase-K buffer. The plugs containing chromosomal DNA were irradiated with X-rays under different temperatures and scavenging conditions. Intact MCF-7 cells were irradiated in Petri dishes and plugs were made. The cells were then lysed in EDTA-NLS-proteinase-K buffer. The induction of DSB was studied by constant field gel electrophoresis and expressed as DSB/100/Mbp, calculated from the fraction of activity released into the gel. RESULTS: The induction of DSB in chromosomal DNA was reduced by a decrease in temperature. This protective effect of low temperature was inhibited when the DNA was irradiated in the presence of DMSO. No difference was found when intact cells were irradiated at different temperatures. However, the rapid phase of rejoining was slower in cells irradiated at 37 degrees C than at 2 degrees C. CONCLUSIONS: The induction of DSB in naked DNA was reduced by hypothermic irradiation. The temperature had no influence on the induction of DSB in the presence of a high concentration of DMSO, indicating that the temperature effect is mediated via the indirect effects of ionizing radiation. Results are difficult to interpret in intact cells. Rejoining during irradiation at the higher temperature may counteract an increased induction. The difference in rejoining may be interpreted in terms of qualitative differences between breaks induced at the two temperatures.

DNA Damage↗
PubMed1999

Influence of temperature on radiation-induced inhibition of DNA supercoiling.

The influence of subnormal temperatures (2, 15 and 28 degrees C) on the effects of radiation in MCF-7 cell cultures was studied using the fluorescent (halo) nucleoid assay. Increasing the propidium iodide (PI) concentration (0.5-7.5 microgram/ml PI) resulted in relaxation, i.e. in increasing nucleoid area; higher concentrations up to 50 microgram/ml caused rewinding that resulted in nucleoid contraction. Rewinding was inhibited by X irradiation (2, 4 and 8 Gy) in a dose-dependent way. Incubation at subnormal temperature did not influence the nucleoid area but did reduce radiation-induced inhibition of rewinding after 4 Gy. The low temperature (2 degrees C) during rather than prior to irradiation appeared to protect from radiation-induced inhibition of nucleoid rewinding. Decreased temperature during irradiation may change the conditions so as to reduce DNA- matrix damage induced by radiation.

DNA Damage↗
PubMed1999

Symptom pattern and diagnostic work-up of malignancy at first symptom presentation as related to level of care. A retrospective study from the primary health care centre area of Kungsbacka, Sweden.

This retrospective study was aimed to characterize the diagnostic process of cancer with respect to level of care, initial symptoms, and diagnostic procedures. It was based on analysis of medical records of all subjects with colorectal, pulmonary, breast or prostate cancer, reported to the Swedish Cancer Registry during defined periods of time in the community of Kungsbacka with about 46,500 inhabitants. Initial symptoms, diagnostic procedures, outcome of diagnostic procedures, level of care, and doctor's delay were analyzed. Most patients (62-73% for the different cancers studied) first visited a general practitioner for the symptoms which lead to the diagnosis of cancer. The most common initial symptom for colorectal cancer was defecation abnormality, for breast cancer a palpable mass in the breast, for pulmonary cancer cough, and for prostate cancer symptoms of prostatism. There was no difference in doctor's delay between general practitioners and other physicians. Nonspecific blood laboratory tests made little contribution to the diagnosis of cancer. The results indicate that most cancers of the types studied are diagnosed in primary health care and that it is possible to improve the identification of the few malignant cases among the "noise" of benign diseases, both with respect to accuracy and cost-effectiveness. It seems that focused investigations such as fecal occult blood tests and rectoscopy should be more frequently used in patients with gastrointestinal symptoms.

Adult↗
PubMed1998

Prognostic value of bone marrow biopsy in operable breast cancer patients at the time of initial diagnosis: Results of a 20-year median follow-up.

From May 1975 until May 1980,128 operable breast cancer patients, clinical stage I-II, had a core bone marrow biopsy (BMB) from the posterior iliac crest as a part of the routine diagnostic work-up at the time of initial diagnosis. The mean age of the patients was 56 years, range 26-93. In a previous study on this material, 10 patients (7.8 per cent) were positive for tumor cells and 118 negative by conventional histopathology of BMB [1]. In 1996 we reexamined all BMB separately at two laboratories, using monoclonal antibodies against cytokeratins AE1-AE3, KL1, CAM 5-2 (DOP), and DC10, BA17 (MCI). The number of extrinsic cells in the bone marrow was graded positive for micrometastases when > or = 5 cells or suspicious when 1-4 cells per approximately 2 x 10(6) bone marrow cells were found, using high power field magnification. Micrometastases were detected in 17 patients (13.3 per cent) and another 8 patients were classified as suspicious. The presence of micrometastases was correlated to the axillary lymph node stage and primary tumor location. Median follow-up was 20 years. All 17 micrometastatic patients relapsed and died within 6 years of disease progression with evident osseous metastases. There was one disease-free survivor of the 8 patients with suspicious BMB after 17 years of follow-up. The median overall survival was significantly shorter in tumor-cell positive patients, being 1.9 years compared to 11.7 years in the BMB negative and BMB suspicious groups (p < 0.0001). Immunohistochemical analysis of core BMB taken postoperatively may be useful in predicting the prognosis in patients with breast cancer clinical stage I-II.

Adult↗
PubMed1997

Pharmacokinetics of doxorubicin and epirubicin in mice during chlorpromazine-induced hypothermia.

Blood concentrations of doxo- and epirubicin were studied in mice after i.v. or i.p. administration under normal and hypothermic conditions. The animals either were pretreated i.p. with chlorpromazine at 15 mg/kg and allowed to cool to a rectal temperature of 28 degrees C or were given saline i.p. with their rectal temperature remaining at 37 degrees C. The anthracyclines were 14-14C-labeled and were given at a dose of 0.85 mg/kg. Blood samples were taken at 5, 15, and 25 min and 2, 6, 24, and 48 hours after injection and were analyzed by liquid scintillation counting. The blood concentration related to time was similar for the two anthracyclines. The peak concentration was highest for i.v. administration and was higher for the hypothermic groups. The peak concentration and the area under the curve were highest under hypothermic conditions. The terminal half-life was longer after i.p. administration. The ratio calculated for the blood concentration under hypothermic/normothermic conditions over time was substantially increased after i.p. administration, the increase being most pronounced for epirubicin. The pharmacokinetic characteristics found might be related to the anthracycline toxicity encountered in tumor-inoculated mice treated at different body temperatures.

Animals↗
PubMed1994

DNA content and S-phase fraction in male breast carcinomas.

Eighty-five male breast carcinomas limited to the breast, diagnosed between 1958 and 1967 in Sweden, were investigated by flow cytometry using paraffin-embedded tissue. DNA ploidy and S-phase fraction (SPF) were studied in relation to lymph node status, tumour size and malignancy grade, and with respect to clinical outcome. Median age at diagnosis was 65.5 years. Median survival time related to breast cancer was 78.7 months, and 37 patients died from the disease. Forty-nine (57.6%) carcinomas were aneuploid or had multiple stemlines. Median SPF was 8.9% for all tumours, for diploid and tetraploid (euploid) together 6.6%, and for aneuploid tumours 14.3% (p < 0.001). Ploidy was significantly related to the tumour size (p = 0.03), but no significant correlations with node status or malignancy grade were observed. In univariate survival analysis, node status, tumour size and malignancy grade predicted breast cancer mortality significantly. In a multivariate Cox's model, only node status and tumour size were independent prognostic factors. In contrast to females with breast cancer, ploidy and SPF had no significant relation to prognosis in males. This lack of predictive value of DNA analysis needs further evaluation. Studies based on extended materials are necessary to further investigated the role of DNA analysis as a predictor of outcome in male breast cancer patients.

Analysis of Variance↗
PubMed1992

Bleomycin/cis-platin as neoadjuvant chemotherapy before radical radiotherapy in localized, inoperable carcinoma of the esophagus. A prospective randomized multicentre study: the second Scandinavian trial in esophageal cancer.

Survival and swallowing function were studied in a randomized trial of 97 patients with inoperable, localized esophageal carcinoma. Radical radiotherapy was given to 51 patients, while 46 patients had two courses of bleomycin/cisplatin before radiotherapy. The survival was 29% after one year, and 6% after 3 years in the radiotherapy group. The survival in the combined treatment group was 18 and 0%, respectively; p = 0.1895. The number of patients who could swallow any food increased from 6% before treatment to 38% after 3 months in the radiotherapy group, and from 0% to 23% in the combined group. No benefit was found by combining bleomycin/cisplatin with radiotherapy.

Aged↗
PubMed1990

Chlorpromazine-induced hypothermia in tumour-bearing mice, acute cytotoxic drug lethality and long-term survival.

The acute lethality of various cytotoxic drugs (doxorubicin, vinblastine and nitrogen mustard) and long-term survival in a syngenic mouse-tumour system were studied at normal body temperature and at 28 degrees C induced by chlorpromazine. Chlorpromazine-induced hypothermia itself neither caused acute toxicity nor influenced long-term survival. Doxorubicin (15 mg/kg) and nitrogen mustard (6 mg/kg) lethality was reduced at decreased temperature. The median survival time increased significantly from 35 days in normothermic to 52 days in hypothermic doxorubicin-treated mice. With nitrogen mustard, no increase in long-term survival was seen in the hypothermic group. The acute lethality of vinblastine was enhanced by hypothermia and the long-term tumour survival was unaffected. Hypothermia or possibly chlorpromazine considerably modulates drug toxicity and possibly anti-tumoural activity.

Animals↗
PubMed1987

Perfusion characteristics and norepinephrine reactivity of human renal carcinoma.

Kidneys, surgically removed due to carcinoma, were subjected to perfusion in vitro. The perfusion distribution was studied by means of labeled microspheres injected during maximal vascular dilation and during two different norepinephrine concentrations. The perfusion concluded with injection of barium sulfate. Two-mm-thick slices of tissue were autoradiographed and microangiographed for visualization of perfusion and distribution of vascular density, respectively. Multiple specimens from tumor and cortical tissues were subjected to quantitative perfusate flow analysis. In spite of regionally high vascular density, perfusion through "normal-sized" capillaries was very low in tumor tissue as compared to cortex (during maximal dilation, one-tenth of the cortical flow). During moderate norepinephrine infusion, the perfusate flow decreased, and the resistance of the cortex increased. The flow to tumor tissue increased while the vascular resistance remained constant. During higher norepinephrine concentrations, the flow was redistributed; i.e., the cortical flow increased while that of the tumor decreased, due to a marked increase in tumor vascular resistance while the cortical tissue showed a very moderate rise in resistance. The thin-walled tumor vessels might be collapsed under a high tissue pressure at low perfusion pressures. At higher perfusion pressure, the vessels might open up, and contractile activity may not be expressed until then. The tumor vascular resistance increased 3 to 4 times, while that of cortex showed a 7-fold increase. Indications that a considerable fraction of the perfusate passes arteriovenous passages larger than 15 micron were obtained in individual experiments, this fraction increasing upon norepinephrine infusion.

Carcinoma↗
PubMed1987

Blood-to-tissue transport of albumin in rat fibrosarcomas at two different implantation sites.

Albumin clearance and blood flow were measured in normal tissues and in fibrosarcomas by means of a multiple tracer method in intact male rats. Sarcomas implanted in testes had higher albumin clearances than the same tumours implanted in skeletal muscle, 59 and 26 microliters min-1 per 100 g, respectively. Albumin extraction (defined as the ratio of albumin clearance to plasma flow) was found to be 1 x 10(-4) - 14 x 10(-4) in normal tissues. Fibrosarcomas in muscle showed high extractions (24 x 10(-4)), especially in the central portions (96 x 10(-4)), where the extraction was similar to that in tumours implanted in the testes (111 x 10(-4)). The high albumin extraction in poorly perfused central parts of the muscle-implanted tumours and in the similarly insufficiently perfused testicular sarcomas is probably due to an increased endothelial permeability of the exchange vessels and not to an increased capillary exchange surface area compared with the better-perfused peripheral parts of the muscle-implanted tumours. The latter tissue also had a high albumin clearance, however, in the range of that of maximally dilated skeletal muscle vasculature, possibly reflecting a large functional capillary surface area.

Albumins↗
PubMed1987

Male breast carcinoma. I. A study of the total material reported to the Swedish Cancer Registry 1958-1967 with respect to clinical and histopathologic parameters.

During the time period 1958-1967 190 cases of male breast cancer were reported to the Swedish Cancer Registry. The reported cases were thoroughly re-evaluated from the evidence of the clinical records and histopathologic specimens. The material contained 166 cases of histologically verified invasive breast carcinoma which were analyzed with respect to different clinical and histopathologic parameters. In contrast to the rate in females, the breast cancer incidence rate in males did not increase significantly during the period under review, and the age-specific incidence rate did not show a Clemmesen's hook but increased relatively more rapidly at high ages than for female breast carcinoma. The mean age at diagnosis was 4 to 5 years higher in male breast cancer patients than in females. Larger tumours were more frequent among older patients and there was a 5-year shift between the age-distribution curves for small (less than 2 cm) and larger (2-5 cm) tumours. A similar difference was found between pN0 and pN1 tumours. This difference might reflect the progression rate of male breast cancer. The histopathology pattern and distribution of histologic malignancy grades were similar to those in female breast carcinoma with the exception that lobular carcinoma and medullary carcinoma with lymphoid infiltration were lacking in the male material.

Adult↗
PubMed1987

Male breast carcinoma. II. A study of the total material reported to the Swedish Cancer Registry 1958-1967 with respect to treatment, prognostic factors and survival.

The complete material of male breast cancer, 166 cases, reported to the Swedish Cancer Registry in 1958-1967 is described and analyzed concerning different prognostic parameters, treatment methods and survival. Age at diagnosis, axillary lymph node status and tumour size all had significant prognostic importance in a multivariate analysis with axillary lymph node status as the strongest factor. Histologic malignancy grade was strongly correlated to axillary lymph node status and tumour size and thus to prognosis, but did not seem to be an independent prognostic factor. The primary treatment methods were quite heterogeneous and were obviously influenced by both age of the patient and clinical tumour status. No significant correlation was found between type of primary treatment and survival, but due to the retrospective nature of the study no definite conclusion could be drawn. Radical mastectomy seemed, however, to give fewer loco-regional recurrences than both modified radical mastectomy and simple mastectomy. Very few patients in the present series had received radiation therapy in adequate doses. The material gave some indications that orchiectomy might prolong survival in patients with recurrent or generalized disease.

Age Factors↗