Biomedical subjects

R Henriksson

Publications and source records attributed to R Henriksson.

At least 127 records · Page 7Linked to original sources

PubMed1992

Bilateral irradiation of head and neck induces an enhanced expression of substance P in the parasympathetic innervation of the submandibular gland.

Substance P and calcitonin gene-related peptide (CGRP) are present in nerve fibers innervating the submandibular gland. Radiotherapy of tumors in the head and neck region usually embraces the salivary glands in the irradiated field and consequently a dramatic decrease in salivary function is seen. In this study, the submandibular glands and ganglia of rats subjected to fractionated irradiation were examined by use of immunohistochemical techniques for demonstration of substance P and CGRP. Irradiation was given on five consecutive days (daily doses of 6-9 Gray) with unilateral or bilateral irradiation techniques. Specimens of control and experimental animals were processed in parallel. A marked increase in the expression of substance P in the ganglionic cells--presumably parasympathetic--and in the number of fibers showing substance P-like immunoreactivity in association with acini and small ducts was seen in response to bilateral irradiation. (Surprisingly, unilateral irradiation of the parotid area had no effect on peptide distribution in the irradiated gland and ganglion). No changes in the pattern of CGRP immunoreactivity occurred. In the trigeminal ganglion, which supplies the submandibular gland with the majority of the sensory substance P- and CGRP-containing nerve fibers, no changes in the expression of substance P or CGRP immunoreactivity were seen. The results suggest that bilateral irradiation leads to an increase in the synthesis of substance P-like substance in the parasympathetic ganglionic cells supplying the submandibular gland with secretory nerves, and can thus be an additional factor in explaining the altered secretory capacity of salivary glands.

Animals↗

PubMed1992

Parotid gland function during and following radiotherapy of malignancies in the head and neck. A consecutive study of salivary flow and patient discomfort.

Radiotherapy of tumours in the head and neck region usually involves the salivary glands in the treatment volume with ensuing dryness and discomfort. In the present study, a prospective evaluation of the same patients were performed before, during radiotherapy and 6, 12 and 18 months after the end of treatment. Three different groups were outlined, one receiving doses not exceeding 45 Gy, another 47-52 Gy and a third group treated with doses over 64 Gy. All but one of the patients receiving doses less than 52 Gy showed a recovery of secretion beginning after 2 months with a continuous improvement of the salivary flow up to 18 months. Doses exceeding 64 Gy caused irreversibly depressed parotid function in the vast majority of glands. The subjective experience of discomfort with dry mouth was not at all correlated to the initial flow rate. Treatment with unilateral technique and doses below 52 Gy caused just no or slight dryness and 3 out of 4 patients with bilateral involvement of the glands displayed problem with subjective dryness even after 18 months. Doses over 64 Gy with one gland involved had only slight dryness, however, patients with both glands affected showed severe problems with dryness. It has to be emphasised that there were relatively large interindividual differences with respect to salivary flow and discomfort of dryness. It is obvious that these patients need a careful dose planning and a close follow up with co-operation between radiotherapeutists and dentists.

Dose-Response Relationship, Radiation↗

PubMed1992

Effects of tobacco-smoke on radiation-induced pneumonitis in rats.

To investigate the effect of exposure to tobacco smoke (TS) on the development of irradiation-induced pneumonitis in rats, five groups of animals were investigated including controls (C), tobacco smoke exposed (S), irradiated (RNS) and irradiated and tobacco smoke exposed (RS). An additional group (RS/NS) was exposed to tobacco before irradiation but not afterwards. Rats were exposed to diluted mainstream cigarette smoke at a concentration of about 0.4 mg/l in a nose-only exposure system for 1/day, 5 days/week for 10 weeks. Exposure to TS started 3 weeks before irradiation in which the basal one-third of both lungs was exposed to a single dose of 28 Gy. In previous studies this dose had been shown to cause significant pneumonitis. All the animals were killed at 7 weeks after irradiation. Examination of the morphology of lung sections showed less pulmonary inflammation in the RS group than in the RNS group. This was also reflected in the results of bronchoalveolar lavage (BAL) which showed a decline in cell recovery and a marked decrease in the numbers of mast cells and neutrophils in the RS rats compared with the RNS animals. The concentration of hyaluronan in lavage fluid was increased in the RNS and RS/NS group while no increase was found in the RS group. A marked increase in BAL protein was also seen in the RNS and RS/NS groups as compared with the RS group but all were significantly higher than in unirradiated controls. This indicates that smoking suppresses the radiation-induced inflammation but to a lesser degree affects the radiation-induced increase in membrane permeability as reflected by increased protein levels in BAL. Moreover, the marked effects on the numbers of mast cells and neutrophils in the RS group may indicate that these cells play an important role in the mechanism by which tobacco smoke modulates the effects of irradiation. When exposure to tobacco smoke was terminated immediately after irradiation (RS/NS), the inflammatory response was unaffected.

Animals↗

PubMed1992

Effects of sucralfate on acute and late bowel discomfort following radiotherapy of pelvic cancer.

PURPOSE: Radiotherapy, a cornerstone in the management of pelvic cancer, is accompanied by intestinal reactions. Therefore, we investigated the possible effects of sucralfate, an aluminium hydroxide complex of sulfated sucrose used in the treatment of gastric ulcer, in preventing radiation-induced diarrhea and bowel discomfort in patients treated with curative intention for pelvic cancer with external radiotherapy. PATIENTS AND METHODS: The study was double-blind and placebo-controlled and included 70 patients with carcinoma in the prostate or urinary bladder without distant metastases (T1-4No1xMo) and a performance status of greater than or equal to 90% on the Karnofsky scale. Radiotherapy was conventionally delivered with high-energy photons (four-field technique, the total dose 64 Gy, 2 Gy daily, total treatment time 5 to 6 weeks). Dose granules of sucralfate or placebo were dispensed to each patient 2 weeks after radiation started and continued for 6 weeks. All analyses were performed blindly. RESULTS: The frequency of defecation and stool consistency were significantly improved by sucralfate. Fourteen patients in the placebo group and three in the sucralfate group required symptomatic therapy with loperamide. One year later, the patients in the sucralfate group displayed significantly less problems with frequency of defecation, mucus, and blood in the stools compared with the placebo group. There was also a lower intake of loperamide and the weight decrease was less pronounced in the sucralfate group. There was no evidence of adverse effects associated with the use of sucralfate. CONCLUSION: It is suggested that sucralfate can be of beneficial value in diminishing bowel discomfort during treatment and, most importantly, sucralfate also reduces the late bowel disturbances that follow radiotherapeutic treatment of pelvic malignancies. The earlier proposed mechanisms of action (eg, protection of denuded mucosa, cytoprotective properties, binding bile acids) seem adequate to explain the present effects of sucralfate.

Diarrhea↗

PubMed1992

Chlorpromazine enhancement of epirubicin cytotoxicity in vitro: effects on plasma membrane and DNA damage.

The frequently used antiemetic drug chlorpromazine has previously been shown to augment anthracycline-induced toxicity to cultured Chinese hamster fibroblasts measured by cloning /1/. We therefore tested the ability of chlorpromazine to affect the induction of plasma membrane and DNA damage by the anthracycline epirubicin. Plasma membrane damage was determined by the cells' ability to accumulate 86Rb after incubation with 10 mg/l epirubicin, and DNA damage was determined by measuring the amount of DNA precipitation after incubation with 25 mg/l epirubicin. The epirubicin-induced inhibition of 86Rb-accumulation as well as the enhancement of epirubicin-induced DNA damage were markedly enhanced in the presence of chlorpromazine. Chlorpromazine augmentation of epirubicin cytotoxicity, including plasma membrane and DNA damage, may be due to its calmodulin antagonistic action and related to the maintenance integrity. Further studies are justified to evaluate the effects of chlorpromazine influence on antineoplastic drug action in vitro and in vivo.

Animals↗

PubMed1992

Different effects of fractionated irradiation on potassium efflux and exocytotic amylase release.

Irradiation of head-neck cancer influences the salivary glands with dryness and discomfort for the patients as a consequence. In the present study we used in vitro secretory models and morphological characterization of rat parotid gland. Irradiation was given as a 5-day schedule with total doses from 20 Gy to 45 Gy. Electrolyte secretion (86Rb as indicator for potassium) caused by noradrenaline was decreased in correlation to irradiation dose delivered compared to controlateral control glands 10 days following irradiation. Noradrenaline stimulated exocytotic amylase release was not at all affected, and there were no signs of quantitative morphological alterations following irradiation compared to control glands. The results indicate that there are differences in radiation sensitivity for the two different secretory processes in the salivary glands; the structures regulating electrolyte and fluid secretion seem to be more vulnerable to irradiation than those regulating exocytosis.

Amylases↗

PubMed1992

Prevention and therapy of radiation-induced bowel discomfort.

In a double-blind randomized placebo-controlled study, including 70 patients treated with radiotherapy of localized malignancies in the pelvis, the effects of prophylactic sucralfate in preventing bowel discomfort were evaluated. Radiotherapy was delivered in a conventional manner with high-energy photons in a total dose of 62-66 Gy (target dose, 1.8-2.2 Gy) during 6.5 weeks. Dose granules of sucralfate or placebo were given 2 weeks after irradiation started and continued for 6 weeks. All analyses were performed blindly. The patients in the sucralfate group had significantly less problems with acute (5 weeks) and chronic (66 weeks) bowel discomfort. The consumption of loperamide was also reduced in the sucralfate group, and the weight decrease was less pronounced. No adverse effects were seen. Thus, sucralfate seems to be beneficial in minimizing the problems of bowel discomfort during and after irradiation of malignancies in the pelvis. These results are discussed in relation to other related observations.

Diarrhea↗

PubMed1992

The effect of ondansetron on radiation-induced emesis and diarrhoea.

Fractionated radiotherapy of malignancies in the abdomen induces nausea and vomiting in approximately 50% of the patients. During abdominal irradiation the damaged gastrointestinal mucosa releases 5-HT with ensuing activation of 5-HT3 receptors which may explain the nausea and vomiting. Ondansetron is a new 5-HT3-antagonist with antiemetic properties. In this consecutive study, 33 patients receiving fractionated upper abdominal irradiation (> or = 100 cm2, 1,8-4 Gy daily dose for a mean of 13 days) were treated with ondansetron (8 mg t.d.s. p.o.). Emesis was completely controlled in 26/33 (79%) patients throughout their radiation course, which embraced 628 (94%) treatment days. Ondansetron was well tolerated. Eleven patients developed mild constipation. No patients experienced diarrhoea (a common distressing side-effect of abdominal irradiation). It is suggested that ondansetron can be of value in preventing emesis in patients receiving fractionated radiotherapy. The possible beneficial effect in preventing diarrhoea must be further evaluated.

Abdominal Neoplasms↗

PubMed1992

Fractionated irradiation and early changes in noradrenaline induced potassium efflux (86Rb+) in rat parotid gland.

The effects of fractionated irradiation on the electrolyte fluid secretion from rat parotid gland were studied. Secretion was measured as noradrenaline stimulated potassium efflux in vitro with 86Rb+ as tracer for potassium. The irradiation was delivered either as a five-day schedule (total dose 20, 25, 30, 35, 40, 45 Gy) or a two-day schedule (total dose 24, 32 Gy). The noradrenaline stimulated efflux was decreased in comparison with contralateral controls 10 days after the last irradiation. The effect was dose-dependent. Based on the data available, alpha/beta ratio of the used system was calculated to about 20 Gy, which corresponds to other results regarding early radiation effects.

Animals↗

PubMed1992

Radiation-induced increase in hyaluronan and fibronectin in bronchoalveolar lavage fluid from breast cancer patients is suppressed by smoking.

Bronchoalveolar lavage (BAL) fluid was analysed from 21 patients with breast cancer, stage T1N0M0, who had undergone tumour resection and post-operative local irradiation (accumulated dose 56 Gy). The lavage was performed two months after radiotherapy, in the anterior part of the lingula (left side) or of the right middle lobe (right side), depending on which side had been exposed to radiation. The patients had significantly increased concentrations of fibronectin (FN) (p less than 0.001), hyaluronan (HA) (p less than 0.01) and albumin (p less than 0.05) in BAL fluid compared with the healthy controls (n = 19). However, when the patients were separated, according to smoking history, it was obvious that the inflammatory reaction occurred entirely in the nonsmoking patient group (n = 10), whilst no difference could be found between the smoking patients (n = 11) and the controls. In the nonsmoking patient group, there was a sevenfold increase in BAL concentrations of FN and a threefold increase in HA. Moreover, four patients had detectable levels of procollagen III peptide in BAL, all were nonsmokers. The smoking habits of the controls had no influence on the BAL measurements. These findings indicate that smoking interferes with the radiation-induced early inflammatory connective tissue reaction of the lung. Finally, the results justify further investigation of interaction of smoking with cancer treatment, both from the view of therapy effectiveness and reduction of adverse effects.

Albumins↗

PubMed1991

Prevention of irradiation-induced bowel discomfort by sucralfate: a double-blind, placebo-controlled study when treating localized pelvic cancer.

Sucralfate, an aluminum hydroxide complex of sulfated sucrose used in the treatment of gastric ulcer, was shown to prevent irradiation-induced diarrhea and bowel discomfort significantly in patients treated for pelvic cancer with external radiotherapy with intent to cure. The double-blind placebo-controlled study included 70 patients with carcinoma of the prostate and urinary bladder without distant metastasis (T1-4NO1xMO) and performance status of greater than or equal to 90% Karnofsky scale. Radiotherapy was administered in a conventional manner with MeV photons and a four-field technique. The total dose was 62-66 Gy and total treatment time of 6.5 weeks. Dose granules of sucralfate or placebo were dispensed to each patient 2 weeks after radiation started and continued for 6 weeks. All analyses were performed blindly. Seven of 34 evaluable patients in the placebo group and 18 of 32 evaluable patients in the sucralfate group did not present with diarrhea during the observation period. The frequency of defecation and stool consistency were significantly improved by sucralfate. Fourteen patients in the placebo group and only three in the sucralfate group required symptomatic therapy with loperamide. There was no evidence of adverse effects associated with the use of sucralfate. Sucralfate can be of beneficial value in diminishing the bowel discomfort during radiotherapy of pelvic malignancies, and the earlier proposed mechanisms of action (e.g., protection of denuded mucosa, cytoprotective properties, binding bile acids) can also be valid for the current effects of sucralfate.

Diarrhea↗

PubMed1991

Interaction between cytostatics and nutrients.

Cancer patients have the highest prevalence of malnutrition of any group of hospitalized patients. The presence of the tumor alone may lead to reduced intake of different nutrients and treatment modalities such as surgery, chemotherapy and radiation therapy may further exacerbate nutritional disturbances. Dietary manipulation in experimental systems has shown improvement of tumor response to cancer therapy. Drug pharmacokinetics has been shown to be altered by changes in nutritional delivery. This article reviews the present knowledge, from experimental and clinical standpoints, of the potential role of different nutritional factors on the specific cancer treatment. It is obvious that alteration of at least some dietary factors affect the outcome of different forms of cancer treatment. Indeed, although interest in the clinical significance of optimal dietary intake and supplementation during cancer therapy so far remain marginal, accumulating data indicate that this area deserves further research attention.

Antineoplastic Agents↗

PubMed1991

Early morphological detection of estramustine cytotoxicity measured as alteration in cell size and shape by a new technique of microperifusion.

The present study describes a new microscopic perifusion technique for detecting momentary alterations in cell volume and shape. The method has been applied for evaluating early signs of cytotoxicity following chemotherapeutic treatments. The effects of estramustine phosphate (EMP) have been evaluated. EMP is a complex between oestradiol-17 beta and the alkylating agent nor-nitrogen mustard and has recently demonstrated a marked cytotoxicity against malignant glioma cells. The results showed a concentration-dependent increase in cell size and a concomitant decrease in shape factor following EMP-treatment of glioma cells. These changes correlated with cytotoxicity evaluated as cell proliferation and cell membrane alterations shown by 86Rb fluxes and ultrastructural visible membrane damage. The colon cancer line HT-29 displayed no reactions at all following EMP treatment. It is suggested that acute alterations in cell morphology and shape display a strong correlation to the cytotoxicity of EMP encountered by traditional cell culture systems. The findings are discussed with respect to cell membrane disturbances caused by EMP and its potential role as an early test of cytotoxicity.

Cell Line↗

PubMed1991

Planning of radiotherapy for patients with hip prosthesis.

The effects of a hip prosthesis on the dose distribution when treating pelvic cancer have been evaluated. A prosthesis of titanium alloy in a water phantom was used as a model. Photon radiation beams with energies of 6, 20, and 50 MV and with a focus phantom distance of 100 cm were directed against the prosthesis. The dose profiles at different depths were measured with the RFA-7 system. The sphere of the prosthesis was inhomogeneous. The dose in a beam behind the prosthesis was reduced with the order of 10-40% and the largest distortion was behind the shaft. Using an opposed four-field technique with the same weight on all the fields, the dose reduction was as large as 7-12% in a string across the target behind the end of the shaft. With 50% weight on the lateral fields, the dose reduction was 4-8% of the average dose. Such an uneven dose distribution may decrease the curability, and a treatment technique not including the prosthesis should be preferred. Finally, a local increase of the dose close to the prosthesis seems to be of limited practical concern even at the highest energies.

Hip Prosthesis↗

PubMed1991

Effects of estramustine on DNA and cell membrane in malignant glioma cells.

Estramustine phosphate (EMP), a complex between estradiol-17 beta and nor-nitrogen mustard, commonly used in treatment of prostatic cancer, also exerts marked antiproliferative effects on cultured human malignant glioma cells. The mechanism of action is unknown but has previously been considered to be mediated through non-DNA targets, specifically via the mitotic spindle, and related to the intact estramustine complex. EMP cytotoxicity was studied on the malignant glioma cell line U-251 MG. A dose-dependent increase in DNA strand breaks was demonstrated at EMP-concentrations ranging 10-40 mg/l. The uptake of 86Rb, used as a tracer for potassium to study ion transport and membrane permeability, was reduced after incubation with EMP. The mean decline in 86Rb accumulation by U-251 MG cells was 12, 20 and 32% at EMP concentrations 10, 20 and 40 mg/l respectively. Scanning electron microscopy gave further evidence for cell membrane damage. In conclusion, EMP seems to affect malignant glioma cells on several vital functions and the results indicate the the cytotoxic potential may at least partially be related to effects on DNA and cell membrane.

Cell Membrane↗

PubMed1991

Estramustine binding protein in human brain-tumor tissue.

Estramustine, an estradiol-17 beta and nornitrogen mustard complex, is used in the treatment of advanced prostatic carcinoma. A specific estramustine binding protein (EMBP) is important for its cytotoxic action, and the presence of EMBP has previously been demonstrated in rat and human prostatic cancer tissue. Significant levels of EMBP were detected by radioimmunoassay in human brain-tumor tissue. The EMBP concentrations (expressed as ng/mg protein) in 16 astrocytomas (mean 2.6 ng/mg, range 0.5 to 6.2 ng/mg) and seven meningiomas (mean 5.1 ng/mg, range 0.3 to 9.3 ng/mg) were significantly higher than that found in four samples of epileptic brain (mean 0.7 ng/mg, range 0.5 to 1 ng/mg) and 18 samples of normal brain (mean 0.5 ng/mg, range 0.2 to 1.0 ng/mg). The uptake, metabolism, and antiproliferative effects of the prostatic anticancer agent estramustine have been previously demonstrated in cultured glioma cells. The presence of EMBP may suggest a selective binding and effectiveness in human brain-tumor tissue.

Astrocytoma↗

PubMed1991

Fractionated irradiation and early changes in salivary glands. Different effects on potassium efflux, exocytotic amylase release and gland morphology.

Irradiation is a potent treatment modality of head and neck cancer. However, the irradiation is usually associated with an influence on salivary glands with ensuing dryness and discomfort for the patients. In the present study we used different in vitro secretory models and morphologic characterization of rat parotid gland. Radiation was given to one gland on a 5-day schedule with 6 MV photons (total dose 20, 30, 35, 40, 45 Gy). The contralateral gland served as control, and the analysis of glands were performed 10 days after the last irradiation treatment. The noradrenaline stimulated electrolyte secretion (86rubidium tracer for potassium) was decreased in relation to the irradiation dose and in comparison to contralateral control glands. Noradrenaline stimulated exocytotic amylase release was not affected by irradiation and, there were no signs of obvious quantitative morphologic alterations after irradiation compared with controls. The results suggest that there are differences in the sensitivity to radiation for the two different secretory processes in salivary glands, and, thus, the structures regulating electrolyte and fluid secretion seem to be more vulnerable to irradiation than the process of exocytosis. The results, however, do not allow discrimination between temporary cellular impairment and irreversible damage leading to cell death.

Amylases↗

PubMed1990

Effects of smoking and irradiated volume on inflammatory response in the lung of irradiated breast cancer patients evaluated with bronchoalveolar lavage.

Quantitative measurements of the effects of irradiation on normal tissues in humans have been hard to obtain because most tissues are inaccessible and/or direct responses are difficult to quantify in a nondestructive manner. Pneumonitis and fibrotic lung disease are adverse effects seen in varying intensity in patients treated with radiotherapy for carcinomas of the thorax, e.g., breast cancer. In the present study the aim was to evaluate the inflammatory reaction in the underlying parenchyma following postoperative irradiation with bronchoalveolar lavage technique. Twenty-one patients (11 smokers, 10 nonsmokers) with breast cancer stage T1N0M0 received radiotherapy with photons to a target dose of 56 Gy following breast conservative surgery. Nineteen healthy controls were also included. The results showed a clear elevation of neutrophils, mast cells, eosinophils, and lymphocytes in the total irradiated groups, compared to controls. When subclassifying the material according to smoking habit, it was obvious that the smokers displayed a significantly decreased inflammatory reaction, i.e., reduced levels of mast cells and lymphocytes, compared to both nonsmoking controls and patients. Eosinophils were seen in an elevated number in all irradiated patients. Radiological signs of pneumonitis were observed in three patients, all in the nonsmoking group. No correlation was found between the volume of lung irradiated and the inflammatory response. It is concluded that bronchoalveolar lavage is a suitable and sensitive method for investigating radiotherapy-induced reactions in the human lung. Furthermore, ongoing smoking during the treatment depressed the inflammatory response in the lung parenchyma induced by irradiation. The present study as well as earlier observations justify further studies concerning the possibility of interaction of smoking with cancer treatment, both from the view of therapeutic failures and reduced adverse effects.

Breast Neoplasms↗