Biomedical subjects

Lennart Johansson

Publications and source records attributed to Lennart Johansson.

15 recordsLinked to original sources

PubMed2006

Correction for scatter and septal penetration using convolution subtraction methods and model-based compensation in 123I brain SPECT imaging-a Monte Carlo study.

Scatter and septal penetration deteriorate contrast and quantitative accuracy in single photon emission computed tomography (SPECT). In this study four different correction techniques for scatter and septal penetration are evaluated for 123I brain SPECT. One of the methods is a form of model-based compensation which uses the effective source scatter estimation (ESSE) for modelling scatter, and collimator-detector response (CDR) including both geometric and penetration components. The other methods, which operate on the 2D projection images, are convolution scatter subtraction (CSS) and two versions of transmission dependent convolution subtraction (TDCS), one of them proposed by us. This method uses CSS for correction for septal penetration, with a separate kernel, and TDCS for scatter correction. The corrections are evaluated for a dopamine transporter (DAT) study and a study of the regional cerebral blood flow (rCBF), performed with 123I. The images are produced using a recently developed Monte Carlo collimator routine added to the program SIMIND which can include interactions in the collimator. The results show that the method included in the iterative reconstruction is preferable to the other methods and that the new TDCS version gives better results compared with the other 2D methods.

Algorithms↗

PubMed2006

In situ gamma-ray spectrometry for environmental monitoring: a semi empirical calibration method.

In situ gamma spectrometry using high-purity germanium (HPGe) detectors is a frequently used method for the determination of radionuclide ground deposition levels. Such measurements do, however, require an efficiency calibration based on detector sensitivity and parameters such as soil density and vertical activity distribution. In this work, a novel expression is used for the detector efficiency, incorporating both the influence of photon energy and incidence angle. Detector-specific efficiency data are determined empirically. For the theoretical calculation of the photon fluence at the detector, a three-layer model of finite thickness is developed for the description of soil density and vertical activity distribution. In order to facilitate the calibration of in situ measurements, a PC program has been developed to enable rapid, on-site calculations of radionuclide ground deposition levels. The semi empirical calibration method was tested on in situ measurements with two different detectors, and the results show good agreement with results obtained from traditional soil sampling.

Calibration↗

PubMed2006

High blood pressure despite treatment: results from a cross-sectional primary healthcare-based study in southern Sweden.

OBJECTIVE: To study degree of blood pressure (BP) control in primary healthcare (PHC) treated hypertensive patients in relation to sex, age, drug treatment, and concomitant diseases. DESIGN: Random sample of patients with hypertension. SETTING: Ten PHC centres in the Region of Skåne, Sweden. SUBJECTS: All the 30- to 95-year-old patients with hypertension who during the period 12 September to 24 September 2004 attended their PHC (146 men and 229 women). MAIN OUTCOME MEASURES: Achievement of BP control (< 140/90 mmHg) according to European guidelines. RESULTS: Some 90% had been treated > 12 months, 40% had mono-therapy, 15% > or = 3 drugs. Use of diuretics was more common in women while use of ACE inhibitors and calcium channel blockers was common in men. Inadequate BP control was related to age; only 22% had BP < 140/90 mmHg, 38% had a BP > or = 160/100 mmHg. BP decline was inversely related to BP measured 12 months or more prior to the present follow-up (r = - 0.64, p < 0.001, for systolic and r = - 0.67, p < 0.001, for diastolic BP). The systolic or diastolic BP had in every fifth patient during treatment increased by > or = 10 mmHg. No association was found between average BP decline and prescribed number of drugs. CONCLUSION: A minority of the patients had BP below the level (< 140/90 mmHg) recommended by European guidelines. This study illustrates the need for continued follow-up of defined groups of patients in order to improve quality of care.

Adult↗

PubMed2006

Radioactive iodine in thyroid medicine--how it started in Sweden and some of today's challenges.

In Sweden, radioactive iodine for thyroid diagnostics and therapy was introduced by Jan Waldenström (1906-1996) and Bengt Skanse (1918-1963). The paper describes the start of the clinical use of radioiodine, the various iodine isotopes available, measurement techniques and dosimetry. There are still problems to solve in relation to an optimal clinical use of radioiodine. One of the remaining challenges is to get consensus about the goal of the treatment of hyperthyreosis, as well as about a method for individual absorbed dose calculations. Careful dose estimates will prevent unnecessary radiation exposure and constitute a base for a future optimised radioiodine therapy. For the dose calculation, it is important to understand if there is any clinically significant temporary reduction in the ability of thyroid tissue to trap or retain 131I-iodide following prior administration of a diagnostic activity of 131I-iodide (stunning of the thyroid). This may be of special concern in connection with treatment of thyroid cancer and its metastases. Finally, the production capacity, availability and delivery of 123I have to be improved to increase clinical access to this radionuclide, which is optimal for diagnostic imaging and which gives lower absorbed dose and therefore also less risk for thyroid stunning than 131I.

History, 20th Century↗

PubMed2005

In vivo clearing of idiotypic antibodies with antiidiotypic antibodies and their derivatives.

At immunolocalization of experimental tumors, idiotypic monoclonal antibodies, such as TS1 against cytokeratin 8, can be used to carry and deposit in vivo terapeutics in the tumor. These carriers also remain in the circulation and may cause negative side-effects in other tissues. In this report, several derivatives of the antiidiotypic antibody alphaTS1 were produced and tested for their clearing capacity of the idiotypic carrier antibody TS1. Intact monoclonal alphaTS1, scFv of a alphaTS1 and alphaTS1 Fab'2 and fragments were produced by recombinant technology or by cleavage with Ficin. The scFv was tailored by use of the variable domain genes of the light and heavy chain from the hybridoma clone in combination with a (Gly4Ser)3-linker, followed by expression in E. coli. When tested for clearing capacity, the intact divalent antiidiotypic IgG was found to be the most efficient. The divalent and the monovalent Fab fragment also demonstrated significant clearing, but lower than the intact antiidiotypic IgG. The alphaTS1 scFv antibody when injected separately was not found to clear the idiotype, but could do so when preincubated with the idiotype. Rapid excretion and in vivo instability of this low molecular weight antibody fragment may be the major reasons. Similar results were obtained when the system was reversed and the 131I-labeled antiidiotype IgG was cleared with the idiotype fragment. It is concluded that both intact antiidiotypic IgG, and Fab'2 fragments are able to clear the idiotypic antibodies. The experimental data support the conclusion that the Fc parts from both the idiotype and the antiidiotype may contribute to this elimination.

Antibodies, Anti-Idiotypic↗

PubMed2005

Does electron and proton therapy reduce the risk of radiation induced cancer after spinal irradiation for childhood medulloblastoma? A comparative treatment planning study.

The aim of this treatment planning comparison study was to explore different spinal irradiation techniques with respect to the risk of late side-effects, particularly radiation-induced cancer. The radiotherapy techniques compared were conventional photon therapy, intensity modulated x-ray therapy (IMXT), conventional electron therapy, intensity/energy modulated electron therapy (IMET) and proton therapy (IMPT).CT images for radiotherapy use from five children, median age 8 and diagnosed with medulloblastoma, were selected for this study. Target volumes and organs at risk were defined in 3-D. Treatment plans using conventional photon therapy, IMXT, conventional electron therapy, IMET and IMPT were set up. The probability of normal tissue complication (NTCP) and the risk of cancer induction were calculated using models with parameters-sets taken from published data for the general population; dose data were taken from dose volume histograms (DVH). Similar dose distributions in the targets were achieved with all techniques but the absorbed doses in the organs-at-risk varied significantly between the different techniques. The NTCP models based on available data predicted very low probabilities for side-effects in all cases. However, the effective mean doses outside the target volumes, and thus the predicted risk of cancer induction, varied significantly between the techniques. The highest lifetime risk of secondary cancers was estimated for IMXT (30%). The lowest risk was found with IMPT (4%). The risks associated with conventional photon therapy, electron therapy and IMET were 20%, 21% and 15%, respectively. This model study shows that spinal irradiation of young children with photon and electron techniques results in a substantial risk of radiation-induced secondary cancers. Multiple beam IMXT seems to be associated with a particularly high risk of secondary cancer induction. To minimise this risk, IMPT should be the treatment of choice. If proton therapy is not available, advanced electron therapy may provide a better alternative.

Child↗

PubMed2003

Scatter-to-primary based scatter fractions for transmission-dependent convolution subtraction of SPECT images.

In single photon emission computed tomography (SPECT), transmission-dependent convolution subtraction has been shown to be useful when correcting for scattered events. The method is based on convolution subtraction, but includes a matrix of scatter fractions instead of a global scatter fraction. The method can be extended to iteratively improve the scatter estimate, but in this note we show that this requires a modification of the theory to use scatter-to-total scatter fractions for the first iteration only and scatter-to-primary fractions thereafter. To demonstrate this, scatter correction is performed on a Monte Carlo simulated image of a point source of activity in water. The modification of the theory is compared to corrections where the scatter fractions are based on the scatter-to-total ratio, using one and ten iterations. The resulting ratios of subtracted to original counts are compared to the true scatter-to-total ratio of the simulation and the most accurate result is found for our modification of the theory.

Computer Simulation↗

PubMed2003

Combined low dose radio- and radioimmunotherapy of experimental HeLa Hep 2 tumours.

Radiation therapy of malignant tumours can be delivered by external beam radiation (RT) or radioimmunotherapy (RIT), using nuclides attached to monoclonal antibodies (mAbs). These treatment modalities have now been combined in order to investigate putative therapeutic advantages and elucidate the biological responses involved. Nude mice were transplanted subcutaneously on the back with human HeLa Hep2 tumour cells. RT (3x5 Gy) and/or 100 microg (131)I-labelled mAb H7, against placental alkaline phosphatase, or (131)I-labelled mAb TS1, against cytokeratin, was administered separately or in combination (specific activity of 120-200 MBq/mg antibody). Significant tumour growth retardation was observed both with RT alone and with RIT alone. Combining these regimens enhanced the therapeutic effects further, and a significant reduction in tumour volume could be demonstrated. The tumours were subjected to extensive histochemical and immunohistochemical investigations in order to elucidate changes in biology and histology within them. The following stainings were used: haematoxylin-eosin (morphology), Ki67 (proliferation), M30 (apoptosis), TUNEL (apoptosis) and endoglin (vascularisation). Tumours in the control group grew fast, with an average tumour doubling time of 9 days. These tumours contained large viable tumour cell masses displaying vast proliferation zones of Ki67-positive tumour cells, as well as necrotic regions and small amounts of connective tissue. Apoptotic cells could be identified both with M30 and TUNEL staining. When RT was applied, the growth rate was significantly reduced (doubling time 19 days) and typical alterations in morphology were seen, with a relative increase in connective tissue and a decrease in necrotic regions. Apoptotic cells were identified and a decrease in cell density was also observed. When RIT alone was applied, the growth parameters indicated a longer lasting growth reduction, especially when TS1 was used separately or in combination with H7. The histological appearances of these tumours were somewhat different from the RT-treated tumours, with a larger portion of intratumoural cysts. These tumours also presented a reduced tumour cell density. Dramatic effects were observed when RT was combined with RIT, with a pronounced growth reduction seen in all combination treatment groups. Pronounced tumour volume reduction was also evident in both the RT + RIT ((131)I-TS1) group and RT + RIT ((131)I-TS1/(131)I-H7) group, and in some animals no tumour remained at all. The morphology of the tumour remnants at day 22 was chaotic with a drastically changed histology, with presence of abundant cysts, low fractions of Ki67-positive cells, reduction in cell density, increased amounts of connective tissue and a decrease in necrotic regions. Again, apoptotic cells could be identified, scattered throughout the viable regions. Combining RT and RIT seems to generate an efficient treatment with convincing and long-lasting tumour growth inhibition, which is reflected in a highly aberrant histology within the tumour. Results obtained in this study indicate that both necrosis and apoptosis may be involved in the process leading to this efficient therapy of epithelially derived tumours.

Animals↗

PubMed2003

Hormesis, an update of the present position.

The ongoing debate over the possible beneficial effects of ionising radiation on health, hormesis, is reviewed from different perspectives. Radiation hormesis has not been strictly defined in the scientific literature. It can be understood as a decrease in the risk of cancer due to low-dose irradiation, but other positive health effects may also be encompassed by the concept. The overwhelming majority of the currently available epidemiological data on populations exposed to ionising radiation support the assumption that there is a linear non-threshold dose-response relationship. However, epidemiological data fail to demonstrate detrimental effects of ionising radiation at absorbed doses smaller than 100-200 mSv. Risk estimates for these levels are therefore based on extrapolations from higher doses. Arguments for hormesis are derived only from a number of epidemiological studies, but also from studies in radiation biology. Radiobiological evidence for hormesis is based on radio-adaptive response; this has been convincingly demonstrated in vitro, but some questions remain as to how it affects humans. Furthermore, there is an ecologically based argument for hormesis in that, given the evolutionary prerequisite of best fitness, it follows that humans are best adapted to background levels of ionising radiation and other carcinogenic agents in our environment. A few animal studies have also addressed the hormesis theory, some of which have supported it while others have not. To complete the picture, the results of new radiobiological research indicate the need for a paradigm shift concerning the mechanisms of cancer induction. Such research is a step towards a better understanding of how ionising radiation affects the living cell and the organism, and thus towards a more reliable judgement on how to interpret the present radiobiological evidence for hormesis.

Dose-Response Relationship, Radiation↗

PubMed2003

Internal radionuclide dosimetry: diagnostic and therapeutic nuclear medicine, occupational and environmental exposures. Differences and similarities.

In diagnostic nuclear medicine, model-derived effective dose estimates have been considered adequate for risk estimates for various patient groups. Average anthropomorphic models (normally MIRD models) and representative biokinetic models are used, with the main uncertainty being due to limited information on the biokinetics of the substance in representative groups of patients. In nuclear medicine therapy it is necessary to make patient-specific absorbed dose estimates, especially to dose-limiting risk organs and to the tumor tissue. Together with information on the time-activity curve (which may differ for the low test activity and the high therapeutic activity) in different organs and tissues, there is a need for detailed anatomical information, normally collected through CT- and/or MR-imaging through the body volumes of interest. The wish to get the radionuclide localized in the tumor cells and preferentially in the cell nuclei makes it essential to consider the increased biological effect resulting from the nonuniform distribution of the absorbed energy in tumors as well as in dose-limiting organs such as bone marrow, liver, and kidneys. The situation in occupational and environmental internal dosimetry resembles that of diagnostic nuclear medicine. However, biokinetic models derived for the former purposes are often constructed for relatively long-lived isotopes, and cannot be used for the short-lived isotopes of the same element, which are used in diagnostic nuclear medicine. Similarities and differences in objectives and methods for dosimetry in the different areas are discussed.

Diagnostic Techniques, Radioisotope↗

PubMed2003

Rapid test, throat culture and clinical assessment in the diagnosis of tonsillitis.

OBJECTIVES: Our aim was to identify a group of patients with clinical signs of tonsillitis to whom antibiotics could be prescribed without further diagnostic actions, and to compare the outcome of clinical assessment with the result of an antigen detection test using culture as the gold standard. METHODS: During two winter months, patients aged > or =4 years attending for sore throat at three primary health care centres in Malmö, Sweden, were examined. Odds ratios, sensitivities, specificities and predictive values were calculated for clinical assessment and for an antigen detection test. RESULTS: Among the 169 participating patients, growth of group A beta-haemolytic streptococci (GAS) was found in 53 cultures, and 23 patients (14%) were clinically assessed as 'absolutely positive', representing positive clinical assessment. Nineteen had positive cultures for GAS. The sensitivity, specificity and predictive positive and negative value for the antigen detection test were 82, 96, 90 and 93%, respectively, and for positive clinical assessment 36, 97, 83 and 77%. CONCLUSION: It is possible to identify a small group of patients with convincing signs of tonsillitis in which the specificity as well as the predictive positive value of the rapid test and the clinical assessment are close to equal. Antibiotics may be prescribed to these patients without further diagnostic actions.

Adolescent↗

PubMed2002

Apoptosis induced by low-dose and low-dose-rate radiation.

BACKGROUND: It has been claimed that external radiation, as a treatment modality for malignant diseases, partly induces apoptosis. It is not known, however, whether therapeutic low-dose and low-dose-rate radiation are able to induce apoptosis. METHODS: The effect of low-dose radiation on apoptosis induction in HeLa Hep2 cells was studied, and quantitation of the apoptotic cells was performed by immunocytochemistry using TdT-mediated dUtp-x Nick End Labeling (TUNEL) technology and the M30 CytoDEATH antibody method. RESULTS: When TUNEL staining was used to quantify apoptosis in untreated HeLa Hep2 cells kept in culture, approximately 5 plus minus 3% of the cells showed positive staining without any treatment. In the first experiment, the HeLa Hep2 cells were exposed to gamma radiation (i.e., 0.5, 1, 2, 5, 10, and 15 grays [Gy]) from a cobalt-60 radiation source delivering a dose rate of 0.80 Gy/min. The radiated cells were cultivated for 5, 10, 24, 48, 72 and 168 hours after irradiation. Radiation doses below 2 Gy did not cause any significant apoptosis, but between 5 and 15 Gy significant apoptosis was observed, with peak values at 5 Gy (P < 0.001). Up to 60% of the investigated cells were shown to display apoptosis. Time to this peak value was 168 hours after irradiation. The HeLa Hep2 cells were exposed to doses of 2, 5, and 10 Gy at a 10-fold lower dose rate (0.072 Gy/min). The cells that achieved a dose below 2 Gy did not present increased apoptosis. At doses above 2 Gy, however, the cells again demonstrated significant apoptosis. Up to 24 hours following irradiation, no apoptosis could be documented, whereas beyond 24 and up to 168 hours a highly significant apoptosis induction was observed. Significant cytotoxicity was confirmed by chromium-51 release from the cells at 5 Gy. CONCLUSIONS: Low-dose and low-dose-rate radiation are able to induce significant apoptosis, and apoptosis may be one of the mechanisms by which low-dose radiation causes growth inhibition.

Apoptosis↗

PubMed2002

The combination of external beam radiotherapy and experimental radioimmunotargeting with a monoclonal anticytokeratin antibody.

BACKGROUND: Doses to tumors of up to 80 grays (Gy) have been postulated to eradicate solid experimental tumors with radiommunotargeting, but this value has proved difficult to reach. Combining two treatment modalities, external beam radiotherapy and radioimmunotargeting, could potentially give rise to a number of advantages. METHODS: The purpose of this study was to detect potential benefits with different treatment timing strategies when combining external beam radiotherapy and radioimmunotargeting, with the anticytokeratin monoclonal antibody (MAb) TS1 injected into a nude mouse model carrying subcutaneous human HeLa Hep 2-cell tumors. Cytokeratins are present in necrotic regions within tumors, thereby providing a potential increase in binding sites for TS1 if combined with external beam radiotherapy. External beam radiotherapy was given before, after, and simultaneously with injection of radiolabeled MAb. RESULTS: The highest yields in terms of total accumulated dose (Gy), percentage of injected activity per gram of tumor tissue, and accumulated dose per injected activity (Gy/MBq) were seen in the group receiving external beam radiotherapy prior to MAb-injection. CONCLUSIONS: Enhanced effects may be achievable by combining external beam radiotherapy with experimental radioimmunotargeting using the monoclonal anticytokeratin antibody TS1, if the radiotherapy is given prior to MAb injection.

Animals↗

PubMed2002

Increased incidence of parathyroid adenomas following X-ray treatment of benign diseases in the cervical spine in adult patients.

OBJECTIVE: To determine whether or not exposure to ionizing radiation as an adult increases the risk of developing parathyroid adenomas. DESIGN AND PATIENTS: A cohort of 27 415 patients had received X-ray treatment to palliate pain originating from arthrosis and spondylosis from 1950 to 1964. In a subcohort of 8144 patients the cervical spine was the target, or one of the targets for the treatment. With the technique used it could be assumed that, as a rule, the parathyroid glands had been included in the treated volume. Patients with parathyroid adenomas were obtained from the Swedish Cancer Register from 1958 to 1995. The standardized incidence ratio (SIR) was calculated. RESULTS: The number of person-years at risk was 180 492 in the cohort exposed at the cervical spine, and 412 994 in the control cohort irradiated only at other sites. The calculated dose in the parathyroid region in the study cohort was about 1 Gy. The observed number of parathyroid adenomas in the study cohort was 22, and 24 in the control cohort. Expected numbers based on population data were 12.0 and 24.7, respectively, giving an SIR of 1.83 (95% CI 1.14-2.76) and 0.97 (CI 0.62-1.45), respectively. Mean age at exposure was 48.9 years (SD 10.2) and at diagnosis 71.5 years (SD 8.3). The time from exposure to diagnosis varied from 2 to 34 years (median 26 years). The excess relative risk was about 0.8 per Gy. CONCLUSION: Exposure to ionizing radiation to the cervical spine in adult age seems to be associated with an increased risk of developing parathyroid adenomas.

Adenoma↗

PubMed2002

Thyroid cancer after X-ray treatment of benign disorders of the cervical spine in adults.

While there is very good epidemiological evidence for induction of thyroid cancer by radiation exposure in children, the risk for adults after exposure is still uncertain, especially when concerning relatively small radiation doses. A cohort of 27,415 persons which in 1950 through 1964 had received x-ray treatment for various benign disorders in the locomotor system (such as painful arthrosis and spondylosis) was selected from three hospitals in Northern Sweden. A proportion of this cohort, consisting of 8 ,44 persons (4,075 men and 4,069 women), had received treatment to the cervical spine and thereby received an estimated average dose in the thyroid gland of about 1 Gy. Standard incidence rates (SIR) were calculated by using the Swedish Cancer Register. In the cervical spine cohort, 22 thyroid cancers were found versus 13.77 expected (SIR 1.60, CI 1.00-2.42). The corresponding figures for women were 16 observed cases versus 9.60 expected cases (SIR 1.67: Cl 0.75-2.71). Most thyroid cancers (15 out of 22) were diagnosed > 15 years after the exposure. In the remaining part of the total cohort, i.e. those without cervical spine exposure, no increased risk of thyroid cancer was found (SIR 0.98, CI 0.64-1.38). The study strongly suggests that external radiation exposure of adults at relatively small doses increases the risk of thyroid cancer but also that this increase is very much lower than that reported after exposure in children.

Adolescent↗