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Biomedical subjects

C Svensson

Publications and source records attributed to C Svensson.

At least 127 records · Page 7Linked to original sources
PubMed1994

Histamine-induced airway mucosal exudation of bulk plasma and plasma-derived mediators is not inhibited by intravenous bronchodilators.

Experimental data suggest the possibility that common bronchodilators, such as the xanthines and beta 2-adrenoceptor agonists, may produce microvascular anti-permeability effects in the subepithelial microcirculation of the airways. In this study, we have examined the effect of bronchodilators given intravenously on exudation of different-sized plasma proteins (albumin and fibrinogen) and the generation of plasma-derived peptides (bradykinins) in human nasal airways challenged with histamine. In a double-blind, crossover, placebo-controlled and randomised trial, 12 normal volunteers were given i.v.infusions of terbutaline sulphate, theophylline and enprofylline to produce therapeutic drug levels. The effect of topical nasal provocation with histamine was closely followed by frequently nasal lavage with saline. The lavage fluid levels of albumin, fibrinogen and bradykinins increased significantly after each histamine provocation. The ratio of albumin-to-fibrinogen in plasma and the lavage fluid was 24 and 56, respectively, indicating that topical histamine provocation induced a largely non-sieved flux of macromolecules across the endothelial-epithelial barriers. The systemically administered drugs did not affect the nasal symptoms (sneezing, secretion and blockage), nor did they significantly reduce the levels of plasma proteins and plasma-derived mediators in the nasal lavage fluids. The present data suggest that systemic xanthines and beta 2-adrenoceptor agonists, at clinically employed plasma levels, may not affect the microvascular (and epithelial) exudative permeability and the bradykinin forming capacity of human airways.

Adolescent↗
PubMed1994

Changes in the blood composition of calves during experimental and natural infections with Eimeria alabamensis.

Two trials were carried out to assess the changes in blood composition of calves infected either experimentally or naturally with Eimeria alabamensis. In the first, 12 calves were dosed orally with 10 to 400 million sporulated oocysts and compared with three control calves. The second trial used eight calves turned out to graze a permanent pasture known to induce E alabamensis coccidiosis in calves and eight calves turned out on to a previously ungrazed pasture. In both trials the serum activities of glutamate dehydrogenase (GLDH) and alkaline phosphatase (AP) and the serum concentration of total bile acids decreased in the infected animals while total bilirubin increased. The changes in GLDH, bile acids and bilirubin were most pronounced just before the calves began to excrete oocysts. In the first trial the lowest AP activity was observed 10 days after infection, but in the second its activity continued to decrease throughout the trial. In the first trial haematology, serum fibrinogen, total protein and protein fractions were also investigated. All the significant changes were small and the potential of the investigated blood components as diagnostic markers is therefore minimal.

Animals↗
PubMed1994

Experimental Eimeria alabamensis infection in calves.

Four groups of three conventionally reared 2-month-old bull calves were inoculated with 10 million to 400 million sporulated oocysts of Eimeria alabamensis isolated from Swedish calves which had diarrhoea while at pasture. Their appetite, clinical condition, growth rate and the dry matter content of their faeces were compared with those of three similar but uninoculated calves. The prepatent period was 6-8 days, and the period during which large numbers of oocysts were excreted was 2-7 days. In two of the inoculated calves only a slight softening of the faeces was observed. The other ten calves developed watery diarrhoea, had a poor appetite and appeared depressed. The clinical signs were most severe in the calves which received the highest doses and included signs of abdominal pain and a reluctance to rise. The growth rates of the infected calves were significantly reduced for 18 days after inoculation, and 71 days after inoculation they had not compensated for this period of reduced growth rate.

Animals↗
PubMed1994

Eimeria alabamensis infection as a cause of diarrhoea in calves at pasture.

Large numbers of oocysts of Eimeria alabamensis have been found in the faeces of calves suffering from diarrhoea shortly after being turned out to pasture. To investigate the source and clinical significance of this coccidial infection, the numbers of oocysts excreted, the consistency of the faeces and the growth rates of four groups of 12 calves were compared. Group I calves were kept indoors and their diet was unchanged, Group II calves were turned out onto a previously ungrazed pasture, Group III calves were turned out onto a permanent pasture and Group IV calves were kept indoors and fed cut grass from a previously ungrazed field. Eight days after the animals were turned out there was an almost 1000-fold increase in the numbers of oocysts in the faeces of Group III calves, the dominant species being E. alabamensis, but there were only minor fluctuations in the numbers of oocysts excreted by the other groups. It was therefore concluded that the source of the infection was oocysts that had overwintered on the permanent pasture. Most of the calves in Group III developed watery diarrhoea 5 days after turnout, but there was only a slight softening of the faeces of the calves in Groups II and IV at about the same time. The faeces of the calves in Group I was of firm consistency throughout the trial. The calves in Group III lost 18 kg during the 24 day period following turnout, whereas the calves in the other groups gained between 6 and 18 kg.

Animal Husbandry↗
PubMed1994

Glucocorticoid-induced attenuation of mucosal exudation of fibrinogen and bradykinins in seasonal allergic rhinitis.

The mucosal plasma exudate with its proteins, enzymes, derived peptides, and matrix molecules is an important factor in inflammatory airway diseases. This study investigated whether topical glucocorticosteroid treatment influences mucosal exudation of bulk plasma (fibrinogen) and the generation of plasma-derived mediators (bradykinins) in seasonal allergic rhinitis. Twenty-two patients with birch-pollen-induced allergic rhinitis participated in a double-blind, randomized, placebo-controlled study during the birch pollen season in 1989. After a 2-week run-in period, the participants received treatment with budesonide (200 micrograms per nasal cavity and day) or placebo. The patients kept a diary to record their daily nasal symptoms (itching, sneezing, nasal blockage, and secretion). The amount of birch pollen in the air was determined with the aid of a Burkhard pollen trap. A nasal lavage was performed once a week, and the levels of bradykinins and fibrinogen were determined in the lavage fluid samples. The birch pollen season was very mild, resulting in only minor nasal symptoms. In spite of the low pollen exposure, treatment with budesonide reduced the lavage fluid levels of both bradykinins and fibrinogen. The present results show that topical glucocorticosteroid treatment attenuates plasma exudation and the generation of plasma-derived mediators in seasonal allergic rhinitis. This action may not result from simple vascular antipermeability effects of the drug but may rather reflect the anti-inflammatory efficacy of topical glucocorticoids in the airway mucosa.

Administration, Topical↗
PubMed1994

Microvascular exudative hyperresponsiveness in human coronavirus-induced common cold.

BACKGROUND: The inflammatory response of the airway microcirculation in rhinitis and asthma may be recorded as luminal entry of plasma macromolecules (mucosal exudation). This study examines the exudative responsiveness of the subepithelial microvessels in subjects with and without common cold after inoculation with coronavirus. METHODS: The airway mucosa was exposed to exudative concentrations of histamine (40 and 400 micrograms/ml) before and six days after inoculation. To assess whether mucosal penetration of a topically applied agent was altered, nasal absorption of chromium-51 labelled ethylene diamine tetraacetic acid (51Cr-EDTA, MW 372) was also examined. A nasal pool technique kept the challenge and tracer solutes in contact with the same ipsilateral mucosal surface. Concentrations of albumin in lavage fluids were measured as an index of mucosal exudation of plasma. Nasal absorption of 51Cr-EDTA was determined by the cumulated 24 hour urinary excretion of radioactivity. RESULTS: Nine subjects developed common cold after coronavirus inoculation and 10 remained healthy. Histamine produced concentration dependent mucosal exudation of plasma in all subjects before and after coronavirus inoculation. In subjects with common cold, however, the histamine-induced mucosal exudation was significantly augmented compared with the group without common cold. This exudative hyperresponsiveness is not explained by an increased baseline exudation because the lavage regimen used produced comparably low baseline exudation in both groups of subjects, nor is it explained by an increased penetration of topical histamine because the ability of the nasal mucosa to absorb 51Cr-EDTA was not significantly increased in the subjects with common cold. CONCLUSIONS: An increased proclivity of the airway subepithelial microcirculation to respond with plasma exudation develops during coronavirus-induced common cold. This specific exudative hyperresponsiveness may be a feature of inflammatory airway diseases.

Adult↗
PubMed1994

Identified and unidentified mental illness in primary health care--social characteristics, medical measures and total care utilization during one year.

OBJECTIVE: To screen patients in general practice with regard to identified and unidentified mental illness, and to describe social and demographic profiles of the two groups and their medical measures and total care utilization. DESIGN: Cross sectional study of 333 consecutive patients with one year follow-up. SETTING: Two primary health care units in a Stockholm suburb area. PARTICIPANTS: Patients 18 years and older. MAIN OUTCOME MEASURES: Mental illness according to either ICD-9 diagnosed by GPs (identified cases) or when not identified by GPs according to a self-assessment questionnaire HSCL-25 with cut-off point 1.75 (unidentified cases). RESULTS: In comparing identified (15.3%) and unidentified patients (11.7%) with other patients (No mental illness) no differences were found in demographic antecedents. Social problems existed in 31% of identified, 49% in unidentified, and 14% in patients with no mental illness. Sick-listing and issuing of prescriptions were more frequent in patients with identified mental illness. The one year follow-up study also showed over-utilization of care in these patients. The psychiatric services were sought by about one fifth of both the patient groups with mental illness, which is to a significantly greater extent than for patients without mental illness (2%). CONCLUSION: Patients with self-assessed mental illness not identified by GPs are not deemed to be "over-medicalized" nor to overload care-services, while patients identified by GPs with a diagnosis of mental illness receive a lot of medical input and require much care. Psychosocial inputs for the latter group within primary care can presumably reduce unnecessary utilization of resources.

Adolescent↗
PubMed1994

Glucocorticoids may not inhibit plasma exudation by direct vascular antipermeability effects in human airways.

In animal airways, single topical treatment with glucocorticoids produces a prompt vascular anti-permeability effect that may last for several hours. This has been considered a potentially important anti-inflammatory action in human airways. The present study, involving nine healthy subjects, examines whether nasal budesonide application affects histamine-induced mucosal exudation of plasma and plasma-derived mediators in human airways. A selected low concentration (40 micrograms.ml-1) of the vascular permeability-inducing agent histamine was kept in one of the nasal cavities for 10 min, and this challenge was repeated at 50 min intervals over 4 h. Ten minutes after the first histamine-challenge, a clinical dose of budesonide (100 micrograms) was sprayed into the same nasal cavity. Nasal lavage fluid levels of albumin and fibrinogen were measured as indices of mucosal exudation of bulk plasma, and bradykinins were analysed to indicate generation of plasma-derived mediators. The baseline levels of albumin and fibrinogen were evaluated in 24 healthy control subjects by means of a 10 min saline lavage. Histamine produced significant mucosal exudation of albumin and fibrinogen, compared to control subjects. Topical budesonide treatment did not affect the histamine-induced mucosal exudation of albumin or fibrinogen, nor did budesonide affect the mucosal output of bradykinins. The present human airway data do not support the view, based on animal findings, that airway glucocorticoids reduce mucosal exudation of plasma by direct vascular effects. We suggest that anti-exudative effects of topical glucocorticoids in airway diseases indirectly reflect the inhibition of cellular inflammatory processes by these drugs, rather than any direct effects on the airway microcirculation.

Administration, Intranasal↗
PubMed1994

Tumorigenic and metastatic properties of two ras-oncogene transfected rat fibrosarcoma cell lines defective in c-jun.

We here report the spontaneous loss of both homologues of the c-jun gene in two cell lines, isolated after transfection of rat embryo fibroblasts with single ras-oncogenes. These cells lines (designated A14 and B25) grow rapidly in vitro, have transformed morphologies and are invasive through reconstituted basal membranes. Both c-jun defective cell lines were found to be tumorigenic and metastatic in athymic mice. Loss of c-jun was paralleled by a dramatic decrease in interstitial collagenase expression, whereas stromelysin mRNA expression in c-jun- A14 and B25 cells was similar to that observed in c-jun+ transformed cell lines. Transient transfection experiments using reporter plasmids showed that stromelysin promoter activity in A14 cells was severely impaired by a point mutation in the -71 to -65 AP-1 motif, and was inhibited by a Jun dominant negative mutant. Gel mobility shift studies demonstrated the presence of a factor in A14 nuclear extracts capable of binding the stromelysin TRE. This factor bound JunB, JunD and Fos antibodies. Our findings suggest that c-Jun is not required for the tumorigenic and metastatic potential of ras-transformed fibrosarcoma cells, and that AP-1 protein(s) lacking c-Jun are capable of activating the stromelysin gene promoter.

Animals↗
PubMed1993

Radiation treatment of epidermoid cancer of the anus.

PURPOSE: The purpose of this study was to evaluate our treatment results of anal cancer. METHODS AND MATERIALS: During the years 1985-1990, 82 patients with invasive epidermoid and cancer were referred to the Department of Oncology at Södersjukhuset. In 76 cases irradiation was used in the primary therapy, and in 43 cases bleomycin was administered concurrently. Fifteen of these tumors were situated in the perianus and 61 in the anal canal. Probability of survival, recurrence, and preservation of anal sphincter was analyzed according to Kaplan-Meier. Cox multivariate analysis was used in studying potential determinants of risk for treatment failure. RESULTS: Tumor-specific survival at 5 years was 71% for both anal canal and perianal cancer. Analyses with regard to cancer of the anal canal indicated that T4 tumors had significantly worse prognosis than those in stages T1-3. Overall survival was 73% and 79% at 5 years for T1 and T2 tumors and 73% and 18% at 4 years for T3 and T4 tumors. Corresponding figures for tumor specific survival were 79%, 79%, 82%, and 31%. Eighty-five percent of patients with T1 tumors, had a preserved anal sphincter after 4 years. For T2 and T3 tumors the corresponding figures were 62% and 60%. Also the multivariate analyses showed stage T4 to be a strong negative prognostic determinant. There was no firm evidence of a positive effect of bleomycin on the treatment results, but it increased the acute radiation toxicity. CONCLUSION: Primary radiotherapy of anal cancer yielded a high probability of survival, but in many cases sphincter amputation have been necessary. The role of bleomycin appears questionable.

Aged↗
PubMed1993

Changes of gamma/delta T cells in blood after radiation therapy for prostatic cancer.

The changes of the size of gamma/delta T (gamma delta T) and alpha/beta T (alpha beta T) cell subsets in the blood were examined after radiation therapy (66 Gy) for prostatic carcinoma in 17 men. Following radiation both subpopulations of T cells were reduced to 52% and 36% of starting values, respectively. gamma delta T cells were not replaced four months after radiation therapy, in contrast to alpha beta T cells, which were increased to 47% of initial values. The T alpha beta/T gamma delta ratio was significantly reduced immediately after radiation therapy but was normalised after four months. Blood gamma delta T cells may be reduced for a long time after radiation therapy and this may be true also for gamma delta T cells in irradiated epithelial organs and tumours.

Aged↗
PubMed1993

Prognostic significance of serum concentration of squamous cell carcinoma antigen in anal epidermoid carcinoma.

The prognostic significance of pre-treatment serum concentration of squamous cell carcinoma antigen (SCCAg) was investigated in a population of 60 patients with anal epidermoid cancer. Serum concentration was determined during the period 1985-90. The patients were followed until December 1991. An antigen level above 2.0 ng/ml was classified as elevated. Thirty-eight patients had T1-2 tumours, while 22 had T3-4 tumours. Sixteen of the 20 patients (80%) with an elevated SCCAg concentration relapsed or had residual tumour after conclusion of primary therapy, compared to 8 of 40 (20%) with a normal concentration (P = 0.00001). Six patients of 40 (15%) with a normal SCCAg had died at the end of follow-up compared to 10 of 20 (50%) with an elevated value (P = 0.006). For patients with T1-2 tumours 2 of 29 (7%) with a normal SCCAg had died with or from their cancer compared to 3 of 9 (33%) with an elevated value (P = 0.14); for T3-4 tumours these figures were 3 of 11 (P = 0.14); for T3-4 tumours these figures were 3 of 11 (27%) and 7 of 11 (64%) respectively (P = 0.009). Actuarial survival analyses for patients with normal vs elevated SCCAg concentration showed that the projected five year overall survival was 81% for those with a normal level and 43% for those with an elevated level (P = 0.004). For tumour specific survival the figures were 83% vs 45% (P = 0.004).(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗
PubMed1993

Dry powder inhalation of budesonide in allergic rhinitis.

Topical steroids are known to be effective in allergic inflammatory airway diseases. However, progress in the treatment of these diseases has also called for the use of unadulterated drugs, without lubricants and preservatives. Rhinocort Turbuhaler, a multi-dose inhaler containing budesonide as a pure powder, is a newly developed device without any carrier gas, preservatives or lubricants. The efficacy and tolerance of this product were evaluated in 60 patients with birch pollen rhinitis. After a run-in period of 1 week the patients received once daily for 4 weeks either budesonide pure powder (400 micrograms) or placebo in a double-blind randomized fashion. Assessment of efficacy was made by comparing scores for different nasal and eye symptoms. The additional use of antihistamine tablets was assessed. In 22 of the patients nasal peak inspiratory flow rate was measured before and after 1 week of treatment. Budesonide was significantly more effective than placebo in controlling the nasal symptoms (P-values ranging from 0.011-0.045). The use of antihistamine tablets was significantly lower in the budesonide group (P = 0.012). The nasal inspiratory flow rate was increased after 1 week of treatment in the budesonide treated group of patients as compared with placebo (P = 0.007). No differences were observed between the groups with regard to eye symptoms or adverse effects. The results show that budesonide delivered from a dry powder inhaler is an effective and well tolerated treatment of seasonal allergic rhinitis.

Administration, Inhalation↗
PubMed1993

Plasma exudation and solute absorption across the airway mucosa.

The airway mucosa responds to inflammatory provocations with bulk exudation of plasma into the airway tissue (vascular exudation) and lumen (mucosal exudation). The intensity and time course of the exudative response can be relevantly examined by sampling and analysing airway surface liquids, because the luminal entry of plasma proteins/tracers promptly and quantitatively reflects the exudative response of the airways. The process of mucosal exudation of plasma is a prominent feature of airway inflammation and has been demonstrated in rhinitis, asthma, and bronchitis. Inflammatory mediators and allergen produce mucosal exudation of plasma into the airway lumen (outward permeability) whereas the solute absorption across the mucosa (inward permeability) is unaffected. Hence, in contrast to current views, we have demonstrated that in airway inflammation the solute absorption across the airway mucosa is not increased. The findings suggest the plasma exudation response also as a first line respiratory mucosal defence, allowing potent plasma protein systems to appear on an airway mucosa functionally intact as a barrier toward undue luminal material. Our data on plasma exudation and solute absorption across the mucosa of upper and lower airways further suggest the human nasal airways as a model relevant also for the tracheobronchial airways.

Animals↗
PubMed1993

Repression of RNA polymerase III transcription by adenovirus E1A.

Adenovirus E1A encodes two major proteins of 289 and 243 amino acids (289R and 243R), which both have transcription regulatory properties. E1A-289R is a transactivator whereas E1A-243R primarily functions as a repressor of transcription. Here we show that E1A repression is not restricted to RNA polymerase II genes but also includes the adenovirus virus-associated (VA) RNA genes. These genes are transcribed by RNA polymerase III and have previously been suggested to be the target of an E1A-289R-mediated transactivation. Surprisingly, we found that during transient transfection both E1A proteins repressed VA RNA transcription. E1A repression of VA RNA transcription required both conserved regions 1 and 2 and therefore differed from the E1A-mediated inhibition of simian virus 40 enhancer activity which primarily required conserved region 1. The repression was counteracted by the E1B-19K protein, which also, in the absence of E1A, enhanced the accumulation of VA RNA. Importantly, we show that efficient VA RNA transcription requires expression of both E1A and the E1B-19K protein during virus infection.

Adenovirus E1A Proteins↗
PubMed1993

Effect of seasonal allergic rhinitis on airway mucosal absorption of chromium-51 labelled EDTA.

BACKGROUND: Hyperpermeability of the airway mucosa is thought to be characteristic of allergic rhinitis and asthma. Nine subjects with seasonal rhinitis caused by birch pollen were studied and the nasal mucosal absorption of chromium-51 labelled EDTA was examined both in an asymptomatic period before the season and late into the season when significant allergic rhinitis symptoms were present. METHODS: A nasal pool device was used to keep a concentration of the absorption tracer in contact with a larger part of the mucosa of the ipsilateral nasal cavity. Absorption was allowed for 15 minutes and measured as the radioactivity appearing in the 24 hour urine sample. RESULTS: The nasal absorption of 51Cr-EDTA in subjects with seasonal allergic rhinitis was less during active disease than before the season. CONCLUSIONS: An airway epithelial barrier that is subject to prolonged eosinophilic inflammation may not be disrupted but may rather increase its functional tightness.

Absorption↗
PubMed1993

Lack of long-term beta-cell glucotoxicity in vitro in pancreatic islets isolated from two mouse strains (C57BL/6J; C57BL/KsJ) with different sensitivities of the beta-cells to hyperglycaemia in vivo.

Previous studies have shown that 4 weeks after syngeneic transplantation of a suboptimal number of islets into either C57BL/6J (BL/6J) or C57BL/KsJ (BL/KsJ) diabetic mice there is an impaired insulin secretion by the perfused grafts. After normalization of the blood glucose level with a second islet graft, the BL/6J strain showed restored insulin secretion whilst that of the BL/KsJ strain remained impaired. The aim of the present work was to study the effects of glucose on the in-vitro function of islet beta-cells from these two mouse strains, with different sensitivities of their beta-cells to glucose in vivo. Isolated pancreatic islets from each strain were kept for 1 week in tissue culture at 5.6, 11, 28 or 56 mmol glucose/l and were subsequently analysed with regard to insulin release, (pro)-insulin and total protein biosynthesis, insulin, DNA and insulin mRNA contents and glucose metabolism. Islets from both strains cultured at 28 or 56 mmol glucose/l showed an increased accumulation of insulin in the culture medium and an enhanced glucose-stimulated insulin release compared with corresponding control islets cultured at 11 mmol glucose/l. After culture at either 5.6 or 56 mmol/l, rates of (pro)insulin biosynthesis were decreased in BL/KsJ islets in short-term incubations at 17 mmol glucose/l, whereas islets cultured at 56 mmol glucose/l showed a marked increase at 1.7 mmol glucose/l. In BL/6J islets, the (pro)insulin biosynthesis rates were similar to those of the BL/KsJ islets with one exception, namely that no decrease was observed at 56 mmol glucose/l. Islets of both strains showed a decreased insulin content after culture with 56 mmol glucose/l.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗