Biomedical subjects

B Karlsson

Publications and source records attributed to B Karlsson.

At least 37 records · Page 2Linked to original sources

PubMed1999

Characterization of antibodies to prostate-specific antigen.

Antibodies submitted to the ISOBM TD-3 PSA Workshop were tested for reactivity with free prostate-specific antigen (PSA) and the PSA alpha1-antichymotrypsin (ACT) complex, inhibition of proteolytic activity, recognition of continuous epitopes, and epitope specificity based on complete cross-inhibition studies. The antibodies could be separated into two categories: those recognizing hidden epitopes specific for free PSA, and those recognizing epitopes in both free PSA and the PSA-ACT complex. A large number of distinct antigenic domains were identified both in free PSA and the PSA-ACT complex.

Antibodies, Monoclonal↗

PubMed1999

Imaging changes after radiosurgery for vascular malformations, functional targets, and tumors.

Normal brain tissue is probably the most important tissue compartment in the brain involved in adverse radiation effects (AREs). The capabilities of computerized tomography, magnetic resonance imaging, and positron emission tomography in repeat examinations of a treatment outcome provide a baseline by which to monitor the AREs in vivo and to follow their sequential changes. This article relates the AREs seen after radiosurgery to the dose/volume and specific tissue effects established from 30 years of collected experience with radiosurgery at the Karolinska Hospital.

Brain↗

PubMed1998

Enzyme-based microassay for accurate determination of soman in blood samples.

Successful medical therapy for nerve agent intoxication requires early diagnosis and treatment. Current clinical diagnostic methods do not permit early or definitive confirmation of intoxication. To improve the chances of successful medical therapy against nerve agent intoxication, a sensitive enzyme-based microassay for rapid and accurate quantification of residual soman levels in blood was developed. The new analytical technique is based on the linear correlation between residual eel acetylcholinesterase activities and the inhibitor concentration. Blood samples were deproteinized with perchloric acid, followed by immediate neutralization after deproteinization. The mixtures were centrifuged at 3000g and the supernatant was directly assayed for soman. The sensitivity of the technique (18-1820 pg/ml blood) is comparable to that attained by GC-FID analysis (250 pg/ml blood). To facilitate routine analysis, the linear range of the assay was optimized to span over a factor of 100 (0.1-10 nM), with a typical correlation factor of at least 0.999 (six standards). The assay accuracy, checked with four different concentrations of soman, was within +/- 10%. The assay capability in monitoring the pharmacokinetic of soman was validated using both in vitro and in vivo rat models.

Acetylcholinesterase↗

PubMed1998

An in vivo method for measuring the mechanical properties of the skin using ultrasound.

In this study, we report a new and original device called the "echorheometer," comprising a suction system with an ultrasound scanner (A-mode, TM-mode and B-mode) that enables the simultaneous visualization and measurement of the deformation of skin structures in vivo. With the scanner described here, high resolution is obtained using a strongly focused, wide-band 20-MHz center frequency transducer, with an axial resolution of 0.07 mm. This device can determine, noninvasively, not only those skin structures that are involved in the deformation, but also their morphological variation and their extent of involvement with the degree of stress applied. Using this device, the behavior of the dermis and subcutaneous fat, while under suction, was investigated on the volar forearm of 10 volunteers. The results showed that the resistance to the applied vertical stress is essentially due to the dermis rather than the subcutaneous fat, and that there is a certain amount of infiltration of fluid into the tissues under suction. In addition, it was shown that the dermal response to an applied suction is initially due to its own natural tension and that, with increasing deformation, the intrinsic dermal elasticity has a greater contribution to the resistance of stress. With this information, we hope to develop a mechanical model to define appropriate mechanical parameters for skin. This will allow the evaluation of changes in the dermis and also enable therapeutic intervention to be assessed. Furthermore, it could also be applied to studies of skin ageing and the assessment of cosmetic product efficacy (emolliency, hydratation, etc.).

Adult↗

PubMed1998

Spermine affects intestinal in vitro permeability to different-sized molecules in rats.

The gut epithelial lining is normally an effective barrier to entry of luminal bacteria and macromolecules into the body and dietary polyamines may influence its function. Therefore, the effects of spermine on regional intestinal permeability to different-sized marker molecules in rats were investigated in Ussing diffusion chambers. Mucosal exposure to 1 mM spermine reduced the permeation of the marker Na-fluorescein in jejunum, expressed as the apparent permeability coefficient (Papp). In contrast, Papp for Na-fluorescein was increased by 10 mM spermine in ileum and by 50 mM spermine in both jejunum and ileum. No effects were observed on [51Cr]-EDTA permeability in any of the intestinal regions. For the larger marker molecules, bovine serum albumin (BSA) and FITC-dextran 71200 (FITC-D), mucosal exposure to 0.5 mM spermine reduced Papp in colon. Spermine (10 mM), increased Papp for FITC-D in all regions and for BSA only in ileum, while Papp for BSA was increased by 50 mM spermine in both jejunum and ileum. The effects of spermine on the intestinal permeability to different-sized molecules generally seemed to depend on the intestinal region and on the polyamine concentration; higher spermine concentrations (10-50 mM) enhanced, while lower (0.5-1 mM) decreased the permeability. These findings may be important when trying to modulate epithelial barrier functions, especially during barrier dysfunction.

Animals↗

PubMed1998

Chloramine-T in high-specific-activity radioiodination of antibodies using N-succinimidyl-3-(trimethylstannyl)benzoate as an intermediate.

Monoclonal antibodies C215 and MOv18 have been radiohalogenated, using a single-batch method employing N-succinimidyl-3-(trimethylstannyl)benzoate, m-MeATE. Labelling to the stannyl ester was optimized using chloramine-T as oxidizing agent. The results show that the stannyl ester is effectively labelled with short reaction times giving reproducible yields from 85% to 95%. Subsequent antibody conjugation, 10 to 80 microg MAb, resulted in biologically active, labelled antibodies with overall radiochemical yields of 50% to 80%, with corresponding specific activities of 490-50 kBq(125I)/microg.

Antibodies↗

PubMed1998

Distance of foetal movement measured using the analytical signal derived from non-directional Doppler sound.

Foetal heart rate (FHR) monitoring using the Doppler shift resulting from the movements of the foetal heart is a standard examination in most obstetrical wards. Other movements also give rise to a low frequency Doppler shift. These signals are incompletely understood. Their characteristics may offer a way for diagnostic exploitation through complementing or replacing time consuming ultrasound observation of foetal movements. It is shown that a wealth of information is contained in these signals which can easily be extracted on line by a standard PC computer using straightforward methods of signal processing. In its amplitude an ultrasonic Doppler signal contains information concerning the size of the reflector in movement and speed as frequency. The displacement of the reflector can also be derived from the phase evolution of a complex Doppler signal. Examples of signals generated by various types of foetal activity are shown and analyzed.

Female↗

PubMed1998

Increased colonic permeability in patients with ulcerative colitis: an in vitro study.

BACKGROUND: Colonic permeability was studied in vitro in patients subjected to colectomy because of ulcerative colitis and in control patients undergoing colonic resections for cancer. METHODS: The mucosal layer from fresh colonic segments was stripped and mounted in Ussing diffusion chambers containing modified Krebs buffer solution. The mucosa to serosa passage of the marker molecules 14C-mannitol and ovalbumin was measured for 120 min. RESULTS: Marker passage was significantly increased in colitis patients compared with control patients, irrespective of age, sex, duration of disease, and treatment. Marker passage was further increased in patients with acute colitis. The increased colonic permeability may be explained by inflammation and the resultant loss of mucosal integrity. The increased permeability to ovalbumin implies that permeability to luminal macromolecules, such as bacterial products and other antigenic substances, might be increased in colitis. CONCLUSIONS: The results suggest a derangement of the colonic barrier, as evidenced by an increased mucosal permeability in both chronic and acute colitis.

Adolescent↗

PubMed1998

Serosal but not mucosal endotoxin exposure increases intestinal permeability in vitro in the rat.

BACKGROUND: Microbial endotoxins are normally present in the gut, usually without apparent harmful effects, whereas systemically administered endotoxin impairs the mucosal barrier function. Our aim was to investigate whether in vitro exposure to bacterial lipopolysaccharide (LPS) could affect the intestinal barrier properties of the rat small intestine. METHODS: Small-intestinal segments from rats were mounted in Ussing diffusion chambers, and the mucosal to serosal permeation of the marker molecules bovine serum albumin (BSA) and 51Cr-ethylenediaminetetraacetic acid (EDTA) was measured after addition of LPS to the mucosal or serosal side. RESULTS: Mucosal exposure to LPS (0.01, 0.05, 0.25 mg/ml) had no effects on the permeation of BSA and 51Cr-EDTA, whereas when added to the serosal side at 0.05 or 0.25 mg/ml, LPS increased the marker permeation. CONCLUSION: Serosal LPS exposure in vitro increased the intestinal permeability to the different-sized markers, whereas mucosal LPS did not, indicating that the mechanisms leading to intestinal barrier impairment can be initiated in the intestinal wall itself.

Animals↗

PubMed1998

Gamma knife surgery for previously irradiated arteriovenous malformations.

OBJECTIVE: The goal was to report the treatment results after a second gamma knife treatment and to compare them with the results obtained after a first gamma knife treatment, as well as to investigate whether the models to predict the results after a first treatment are also applicable after gamma knife treatment of previously irradiated arteriovenous malformations. METHODS: The number of complications and the posttreatment hemorrhage rate were recorded for 112 patients in the study, and the number of obliterations was recorded for the 101 patients for whom conclusive angiograms were obtained. The results were compared with the expected results after a first gamma knife treatment. RESULTS: The observed number of obliterations was 62, which is not significantly different from the predicted number of 65. There were 14 observed and 5 predicted complications. When the risk from the preceding radiation treatment was added, the observed number of complications was similar to the predicted number. Six hemorrhages were observed after the second treatment. Of the 5 patients with unchanged arteriovenous malformation size after both the first and second treatments, 2 experienced hemorrhages after the second treatment, compared with none among the 81 patients for whom the malformation was obliterated or significantly decreased in size after the second treatment. CONCLUSIONS: The obliteration rate after gamma knife surgery for previously irradiated arteriovenous malformations is similar to that after primary gamma knife treatment. The complication rate increases with the amount of radiation previously given. The incidence of posttreatment hemorrhages is lower in the latency period if the malformation is affected by the radiation.

Adolescent↗

PubMed1998

Thyroid dysfunction in Down's syndrome: relation to age and thyroid autoimmunity.

BACKGROUND: The prevalence of thyroid disease is increased in Down's syndrome. Most available data come from cross sectional studies. AIMS: To study longitudinally thyroid function in patients with Down's syndrome in Uppsala county (85 patients) up to the age of 25 years. METHODS: Observational study based on yearly follow up in a children's clinic. Thyroid function tests were performed at each visit to the clinic. RESULTS: Hypothyroidism was found in 30 and hyperthyroidism was found in two of the 85 patients. No sex difference was seen. Half of the patients with hypothyroidism acquired the condition before the age of 8 years, but only one of them displayed thyroid autoantibodies at diagnosis. Most patients who developed hypothyroidism after this age had thyroid autoantibodies. In the prepubertal patients with hypothyroidism, growth velocity was lower during the year before the start of thyroxine treatment than during the year after treatment began; it was also lower than that of sex and age matched euthyroidic children with Down's syndrome. CONCLUSION: Thyroid dysfunction in patients with Down's syndrome is common in childhood. Consequently, annual screening is important. Autoimmune thyroid disease is uncommon in young children with Down's syndrome but is common after 8 years of age.

Adolescent↗

PubMed1998

Radiosurgery for cavernous malformations.

OBJECT: The authors examined 22 patients with cavernous malformations (CMs) who had undergone gamma knife radiosurgery (GKRS) to assess the value of this procedure in treating these lesions. METHODS: At the Karolinska Hospital, GKRS was used to treat 23 patients with CMs during the period of 1985 through 1996. One of the patients was lost to follow up and the treatment results of the 22 remaining patients were analyzed. In the first half of the series, the CMs were treated with high doses of radiation (> 15-Gy dose to the periphery); in the second half of the series, lower doses were used. Nine of the 22 patients suffered a post-GKRS hemorrhage and six developed a radiation-induced complication (two of these patients experienced both). Some time after GKRS was performed, surgical removal of the CM had to be undertaken in four patients because of hemorrhage and in two patients because of radiation-induced complications. Four of the nine patients who experienced no post-GKRS hemorrhage or radiation-induced complication were treated before 1990; recent magnetic resonance imaging revealed a decrease in the size of the CM in three of these individuals and no size change in the other. The annual post-GKRS hemorrhage rate was 8% in this group. There was a trend in the hemorrhage rate to decrease 4 years postsurgery. There was also a trend for higher radiation doses administered to the periphery of the lesion to result in a lower risk of posttreatment hemorrhage. However, it could not be concluded whether GKRS affects the natural course of a CM. The incidence of radiation-induced complications was approximately seven times higher than that expected if the same number of patients had been treated by GKRS with the same radiation dose distributions for arteriovenous malformations instead of CMs. CONCLUSIONS: The high incidence of radiation-induced complications does not seem to justify the limited protection the treatment may afford in only exceptional cases. A prospective randomized study is needed before the role of radiosurgery in the management of these lesions can be defined. Until such a study has proved differently, a caveat must be raised for the treatment of CM with GKRS.

Cavernous Sinus↗

PubMed1998

Factors influencing the presence of uterine cavity fluid in a random sample of asymptomatic postmenopausal women.

AIMS: To assess possible endometrial pathology and other factors influencing the presence of uterine cavity fluid in postmenopausal women. STUDY DESIGN: A random sample of 559 asymptomatic postmenopausal women, recruited from the total population, were examined by transvaginal sonography (TVS) for the presence of uterine cavity fluid. Women with uterine cavity fluid who had an endometrial thickness of > or = 8 mm (including fluid) were admitted for hysteroscopy and a dilatation and curettage (D & C), and those with <8 mm underwent a new TVS examination one year later. A medical history, including details regarding previous minor gynecological surgery, was taken from the women and from an age-matched control-group of women from the same population. RESULTS: Uterine cavity fluid was found in 8.9% (50/559) of the women. In four women with an endometrium measuring > or = 8 mm, curettage revealed polyps in three women and atrophy with a pyometra in one woman. At the one-year follow-up, 22 women who originally had an endometrial thickness<8 mm had an endometrial thickness of<5 mm; 11 women had no cavity fluid and in the remaining 11 the cavity fluid had decreased. In 17 women, endometrial thickness measured > or = 5 mm and subsequent histology showed 11 endometrial biopsies with atrophy, four endometrial polyps and two cervical polyps. The prevalence of uterine cavity fluid increased with increasing age (p<0.0001) and was increased in smokers (p<0.013) but was unaltered by the presence or absence of hormone replacement therapy (HRT). CONCLUSION: There were no indications that uterine cavity fluid was associated with malignancy. The prevalence of uterine cavity fluid increased with increasing age and was higher in smokers. We could not demonstrate an increased prevalence of fluid in HRT-users.

Age Factors↗

PubMed1997

[Multidisciplinary treatment of cerebral arteriovenous malformations: preliminary results in 115 consecutive patients].

OBJECTIVE: Preliminary evaluation of the combined treatment (surgery, embolization and stereotactic gamma radiosurgery) of 115 consecutive patients with a cerebral arteriovenous malformation (AVM). DESIGN: Retrospective. SETTING: St. Elisabeth Hospital, Tilburg, the Netherlands. PATIENTS AND METHODS: In a 35-month period 115 consecutive patients presented with an AVM. The mean age was 41.8 years (range: 6-72). The main clinical presentation was haemorrhage in 65 patients (56.5%), seizures in 31 patients (27.0%), neurological deficit in 7 patients (6.1%) and hydrocephalus in 2 patients (1.7%); in 10 patients (8.7%) the AVM was an incidental finding. Treatment consisted of surgery, radiosurgery with the gamma knife and embolization. Embolization was mostly used to reduce the size of an AVM before surgery or radiosurgery. RESULTS: Out of 115 patients 5 were referred for a treatment advice only and treatment was performed elsewhere. Of the remaining 110 patients 84 (76.4%) were treated and 26 (23.6%) were not treated for various reasons. Of the 84 treated patients 17 (20.2%) had surgery only, 17 (20.2%) had radiosurgery only, and 12 (14.3%) were treated with embolization only. Surgery after embolization was performed in 8 patients (9.5%) and radiosurgery after embolization in 26 patients (31.0%). In 4 patients an unusual combination of these treatment methods was used for a variety of reasons. At the time of writing 35 of 84 treated AVMs (41.7%) were completely cured, 39 patients were awaiting the definitive result of radiosurgery. Deliberate partial embolization was performed in 5 patients. In 5 patients (6.0%), the pretreatment objective was not achieved with embolization. Total permanent morbidity was 4.8% (4 patients) and mortality was 1.2% (1 patient). CONCLUSIONS: Given a multidisciplinary combination of treatment methods a treatment is indicated and possible in the majority (76.4%) of patients with an AVM. There is a reasonable chance of a complete cure with an acceptable complication rate.

Adolescent↗

PubMed1997

Factors influencing the risk for complications following Gamma Knife radiosurgery of cerebral arteriovenous malformations.

BACKGROUND AND PURPOSE: We reported previously a model predicting the risk for radiation-induced complications following Gamma Knife radiosurgery for AVM. No factor other than the dose distribution was related to the risk. The aim of this study was to define if other parameters are of importance for the risk of complications. MATERIAL AND METHODS: The model above was used to calculate the risk for complications in all 1128 AVM patients Gamma Knife-treated at the Karolinska Hospital 1970-1993. The number of predicted complications was compared to the number of observed ones for a number of different parameters. RESULTS: The model underestimated the risk of complications for patients previously given radiation with multiple or single fractions. Neither age nor gender influenced the risk of complications. Centrally located AVM had a higher, and peripheral a lower incidence of complications as compared to the calculated risk, and a previous hemorrhage reduced the risk of complications. From the observed number of complications, parameters in the model were determined by a fitting procedure separately for three groups of AVM: central and peripheral with and without a previous hemorrhage. It is also shown that the assumption of a serial functional architecture is valid in the model. This was investigated by the use of a relative seriality model with a combined serial-parallel functional architecture. CONCLUSIONS: The risk of complications following radiosurgical treatment of AVM is dependent on the clinical history, AVM location and whether the patient has received radiation earlier.

Adolescent↗

PubMed1997

Endometrial sonographic and histologic findings in women with and without hormonal replacement therapy suffering from postmenopausal bleeding.

OBJECTIVES: To evaluate, in women with postmenopausal bleeding, the effect of hormonal replacement (HRT) therapy on the endometrial thickness as measured by transvaginal sonography in relation to endometrial histology. METHODS: 1110 women with sequential/progestin treatment (E + P) (n = 202), with Estriol treatment (n = 149) or without HRT (n = 759) and postmenopausal bleeding were examined by transvaginal sonography (TVS) prior to curettage, with special reference to the relation of endometrial thickness to its histopathology. RESULTS: The distribution of endometrial pathology was different in those women with E + P and Estriol compared with those without HRT. Endometrial pathology was found most frequently in women with an endometrium exceeding 8 mm in thickness. Furthermore, the incidence was found to increase with increasing endometrial thickness in all treatment groups. Atrophy was found significantly more often in women without HRT. Hormonal effects on the endometrium were found significantly more often in women with E + P and Estriol. Endometrial hyperplasia was found most commonly in women with Estriol in the thickness group 5 8 mm (P < 0.001) as compared to those with HRT and without HRT. Endometrial cancer occurs most in women without HRT, in those women with an endometrium exceeding 8 mm in thickness as compared both to the E + P (P < 0.001) group and to the Estriol (P < 0.001) group. Endometrial cancer did not occur in any woman (with E + P, Estriol or without HRT) with an endometrial thickness of < or = 4 mm. CONCLUSIONS: TVS is of value for excluding endometrial pathology in women with HRT and postmenopausal bleeding. The distribution of endometrial findings and histopathological diagnosis in women with abnormal postmenopausal bleeding was different in women with E + P than in women without HRT. Furthermore, the cut-off for excluding endometrial abnormalities is the same in both groups i.e. < or = 4 mm.

Endometrium↗

PubMed1997

Antigenic determinants of prostate-specific antigen (PSA) and development of assays specific for different forms of PSA.

Monoclonal antibodies were raised against prostate-specific antigen (PSA) by immunization with purified free PSA, i.e. not in complex with any protease inhibitor (F-PSA) and PSA in complex with alpha1-anti-chymotrypsin (PSA-ACT). Epitope mapping of PSA using the established monoclonal antibody revealed a complex pattern of independent and partly overlapping antigenic domains in the PSA molecule. Four independent antigenic domains and at least three partly overlapping domains were exposed both in F-PSA and in the PSA-ACT complex, while one antigenic domain was specific for F-PSA. The different domains contained both continuous and discontinuous epitopes. The combination of antibodies recognizing antigenic domains exposed both in F-PSA and PSA-ACT made it possible to develop several highly sensitive sandwich immunoassays for determination of total PSA, i.e. F-PSA + PSA-ACT, with the same molar response for F-PSA and PSA-ACT. Assays specific for F-PSA (cross-reactivity between F-PSA and PSA-ACT < 1%) were developed by the combination of antibodies recognizing epitopes exposed only in F-PSA and antibodies recognizing epitopes exposed both in F-PSA and PSA-ACT.

Animals↗

PubMed1997

Annual risk for the first hemorrhage from untreated cerebral arteriovenous malformations.

To estimate the annual risk for the first hemorrhage, survival and life table statistics were used to analyze data from 2262 patients with cerebral arteriovenous malformations (AVM). We found that the risk for hemorrhage increases with increasing age. A validity test revealed, however, that life table statistics used on the total patient material underestimated the annual risk for hemorrhage, especially for patients 20-50 years of age. A method based on the fact that the distribution of the time at risk until the initial hemorrhage (= age at first rupture) reflects the risk for hemorrhage in untreated AVM was therefore also employed. The analysis yielded three conclusions: 1) the annual risk of hemorrhage increases with age; 2) small AVM are less prone to rupture; and 3) the risk of hemorrhage is higher in women during their fertile years as compared to males in the same age group. The risk related to age, AVM size and location assessed by survival statistics in the subgroup of patients with a known date for the initial hemorrhage gave similar results.

Adolescent↗