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Biomedical subjects

R Hultborn

Publications and source records attributed to R Hultborn.

At least 19 recordsLinked to original sources

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

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

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

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

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

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

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

Vascular reactivity to norepinephrine of 7,12-dimethylbenz(a)anthracene-induced rat mammary tumors and normal tissue as studied in vitro.

Vascular reactivity to norepinephrine has been studied in dimethyl-benz(a)anthracene-induced rat mammary neoplasia and compared with that of skeletal muscle, salivary gland, kidney, and uterus by means of an artificial perfusion technique. Perfusion of tissues and organs was measured with the microsphere tracer technique during smooth muscle relaxation and infusion of norepinephrine at two different dose levels. This procedure makes possible a dose-response analysis of several tissues under controlled conditions without confounding endogenous vasoregulation. The tumor vascular bed has a low perfusion capacity during smooth muscle relaxation and responds rapidly with an increased resistance to norepinephrine infusion. The results indicate a hypersensitivity, although the relative maximal constrictor response is equal to or less than that of other vascular beds studied.

9,10-Dimethyl-1,2-benzanthracene

Effects of noradrenaline on interstitial fluid pressure in induced rat mammary tumours.

Interstitial fluid pressure was measured by the wick-in-needle technique in DMBA-induced rat mammary tumours during resting conditions and during noradrenaline infusion. The rate of infusion was chosen to increase the systemic blood pressure by 30-40 mmHg, known to result in a markedly increased vascular resistance of these tumours. During resting conditions tumour interstitial fluid pressure was 10.3 +/- 1.3 mmHg (n = 13) but fell to 7.0 +/- 1.1 mmHg (n = 13) during noradrenaline infusion. The results suggests that noradrenaline is likely to affect the pre-capillary resistance vessels of the tumour vascular bed. This result, together with earlier perfusion studies, indicates that noradrenaline is unsuitable for increasing tumour cell perfusion as an adjunctive in radiation and cytotoxic drug therapy.

Animals

A spectrophotometric method for measuring oxygen consumption in monolayers of cultured endothelial cells.

A new method for measuring oxygen consumption in monolayer cell cultures is described. Cells are cultured in shallow microchambers etched in glass chips. A haemoglobin solution is added and the microchambers are sealed airtight, the oxygenated haemoglobin solution serving as an indicator of oxygen tension within the microchamber as well as a source of oxygen. With cellular extraction of oxygen, an increasing amount of reduced haemoglobin is formed within the microchamber resulting in an increased absorbance of the haemoglobin solution at 435 nm. With a specially prepared device, it is possible to record this absorbance change with an ordinary laboratory spectrophotometer and, from this recording, it is possible to calculate the respiratory rate, provided the number of cells (or any other quantity of biological material), microchamber volume and haemoglobin concentration are known. Repeated measurements on the same undisturbed culture is possible. The system was tested on monolayer cultures of endothelial cells from the rat pulmonary artery.

Animals

Vascular resistance characteristics of 7,12-dimethylbenz(a)anthracene-induced rat mammary tumors and normal tissues as studied in vitro.

Vascular perfusion characteristics have been studied in dimethylbenz(a)anthracene-induced rat mammary neoplasia and compared with those of skin, skeletal muscle, salivary gland, kidney, spleen, uterus, and brain by means of an artificial perfusion technique. Perfusion of tissues and organs was measured by the microsphere tracer technique. This procedure makes possible a detailed hemodynamic analysis of several tissues under controlled conditions, in this study maximum vascular relaxation, without confounding endogenous vasoregulation. The maximal perfusion capacity, i.e., during smooth muscle relaxation, of tumors and various tissues was related to perfusion pressure at three levels by means of three differently labeled microspheres. Tumors, especially large ones, have a low maximum perfusion capacity, i.e., high vascular resistance, compared to most other tissues. For the tumors, a relatively high perfusion pressure is required to open up the otherwise collapsed vascular network.

9,10-Dimethyl-1,2-benzanthracene

Blood flow and reactivity to noradrenaline in induced and autotransplanted DMBA rat mammary neoplasia.

Blood flow during the 'resting condition' and during noradrenaline infusion was compared by means of a microsphere tracer technique in induced DMBA-tumours along the mammary ridge and in autotransplanted tumours, as well as in abdominal skin, skeletal muscle, liver and kidneys. During 'resting conditions' the blood flow of tumours transplanted into skeletal muscle of the hindlimb, liver and kidney was similar to that of the non-transplanted tumours present along the mammary ridges. A pronounced decrease of blood flow upon moderate noradrenaline infusion was characteristic of autotransplanted as well as non-transplanted tumours, which contrasted to the insignificant reaction of skeletal muscle. The striking similarities in blood flow and reactivity of non-transplanted DMBA tumours and autotransplanted ones, and the dissimilarities of the transplanted tumours and the hosting tissues, favour the idea that these tumours regulate their blood supply irrespective of host tissue.

9,10-Dimethyl-1,2-benzanthracene

Transcapillary passage of albumin in mammary tumours and in normal lactating mammary glands of the rat.

A triple-isotope technique was used to obtain albumin clearances and blood flow in DMBA induced mammary tumours, normal lactating mammary glands and various other tissues of the rat. Albumin clearance was high both in tumours (0.0337 ml/min/100 g) and in lactating mammary glands (0.0414 ml/min/100 g). Albumin extraction (defined as the ratio of clearance over plasma flow) was exceptionally high in tumours (23 X 10(-4)) and lactating glands (18 X 10(-4)) as compared to all other tissues (1-7 X 10(-4)). This probably reflects an increased capillary permeability to macromolecules and/or a change in the relation between blood flow and available capillary surface area, both in the physiological, hormonally induced gland and in the abnormal neoplasia derived from the same tissue. Increased extravasation of albumin, together with other changes (e.g. impaired lymph formation) may be important factors behind the production of increased tumour interstitial pressure, which tend to reduce nutritional blood flow in tumours.

Albumins

Hypothermic perfusion of human kidney carcinoma: effects on viability and perfusate distribution.

A more deteriorating effect on tumour tissue than on normal renal parenchyma by hypothermic perfusion has previously been observed. The purpose of this study was to further evaluate changes in the perfusate distribution and the viability of normal cortical tissue and of kidney carcinoma during hypothermic perfusion. Tumour-involved kidneys obtained by nephrectomy from 12 patients were studied either with regard to viability, as measured with the Na+-K+ pump function in incubated tissue slices, or with regard to perfusate flow, as analysed with an isotope labelled microsphere technique. Six days of hypothermic perfusion decreased the potassium content in the tumour tissue, while it was mainly unchanged in the cortical tissue. The steady-state level of potassium in incubated slices reflected that the transmembrane K+ influx was unchanged after 6 days of perfusion in normal cortical tissue, whereas a significant reduction was observed in the tumour tissue. The relative perfusate flow in the tumour, when compared to the normal kidney cortex flow, was reduced from 60% after 1 hr of perfusion to 30% after 6 days of perfusion.

Adult

Vascular reactivity and perfusion characteristics in 7,12-dimethylbenz(a)anthracene-induced rat mammary neoplasia.

Blood flow during "resting conditions" and during noradrenaline infusion were studied by the labeled microsphere technique in dimethylbenz(a)anthracene-induced mammary tumors, skin, muscle, and lung in the rat. Intratumoral distribution of flow was studied by autoradiography of spheres trapped in the vascular beds of the tumors. Histological examination was performed and correlated to the blood flow data. Mean blood flow to the tumors during "resting conditions" was relatively high (49 ml/min/100 g tissue) but was substantially decreased (5 ml/min/100 g tissue) during noradrenaline infusion which produced a pressure elevation of 35 mm Hg. Thus, vascular resistance of the tumor tissue increased dramatically. Cardiac output increased, but total systemic resistance was unchanged. Vascular resistance in muscle was unchanged in contrast to an increase seen in skin. Shunted systemic blood flow to the lungs and bronchial arterial flow decreased indicating reactivity of abnormally large arteriovenous passages in the tumors. Poorly differentiated tumors had a higher vascular resistance than did well-differentiated tumors. Autoradiography revealed a nodular flow distribution with a slight tendency of higher perfusion in the periphery of these tumors.

9,10-Dimethyl-1,2-benzanthracene

Respiration rate in human pituitary tumor explants.

Studies on the respiration rate of human pituitary tumor tissue have so far been lacking in the literature. This study presents the results from four adenomas causing acromegaly, all with different clinical degrees of the disease. Determination of oxygen uptake was performed in vitro with a spectrophotorespirometric system. Pieces of the tumors were explanted to an organ culture system with a high degree of stability. The secretion rate of growth hormone (GH) and prolactin (PRL) was determined. After 4-8 days in vitro, specimens were analyzed for respiration rate. This was approximately 1-1.5 microliters O2/h/micrograms dry weight. The activity of the pituitary tumor tissue was characterized by both the hormone secretion rate and the respiration rate. Particularly active foci were found to occur in the adenoma tissue. Depending on the individual tumor, the GH secretion rate was approximately 0.1-100 pmol/micrograms dry weight/h and PRL secretion rate approximately 0.4-18 micrograms/micrograms dry weight/h. The respiration rate--as is also the hormone secretion rate--is dependent on the time in vitro prior to analysis. The respiration rate in individual tumors is a parameter which does not reflect GH or PRL serum levels or clinical activity of the disease.

Acromegaly

Interstitial fluid pressure in DMBA-induced rat mammary tumours.

Interstitial fluid pressure (IFP) in DMBA-induced rat mammary tumours was measured by micropuncture with sharpened glass capillaries (diameter 1-3 micron) and by the 'wick-in-needle' technique (WIN). IFP in the superficial layers of the tumours (depth less than 800 micron) was measured with micropuncture, while WIN was used for measurements in deeper areas. IFP in the superficial layers of the tumours was 2.4 mmHg (SD 2.4, n=19), while IFP in deeper layers increased with increasing tumour weight. Thus central IFP in tumours weighing more than 5.5 g was 16.0 mmHg (SD 4.8, n=10), with a maximum value of 23.3 mmHg. When related to tumour histopathology a significant correlation was found between high cellular differentiation (i.e. low degree of malignancy) and high interstitial fluid pressure only. The high IFP may be secondary to a high capillary protein premeability and/or a relatively insufficient lymphatic drainage. A further rise in IFP might result from ischaemic cell swelling and/or a continuous cell proliferation within a tissue of rather low compliance. Together or alone one or more of these factors could facilitate the development of a compartment syndrome with concomitant cell death and tissue necrosis.

9,10-Dimethyl-1,2-benzanthracene

[Metabolic and circulatory aspects of hypothermic perfusion of human kidney cancers].

In this study a report is made on the hypothermal perfusion of 15 renal tumours. Protein synthesis by incorporation of 14C leucine, lipide synthesis by conversion of 14C mevalonic acid and the activity of the sodium-potassium pump by incubation of sections of tissue were used as parameters of the vitality of the tissue. Circulation was studied before and after perfusion by means of angiography and the microsphere technique. After 6 days of perfusion the tumour tissue is found to be less vital in comparison with the renal cortex.

Cold Temperature