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Biomedical subjects

K Ericson

Publications and source records attributed to K Ericson.

At least 19 recordsLinked to original sources

FDG-PET on irradiated brain tumor: ten years' summary.

PURPOSE: To evaluate FDG-PET in post-radiotherapy differentiation of tumor recurrence/malignant degeneration and radiation reaction, and to assess the role of PET in terms of survival. MATERIAL AND METHODS: 117 consecutive patients with a total of 156 FDG-PET examinations with positive but non-diagnostic MRI and/or CT were included. Final diagnosis was based on histopathology or correlated with radiologic and clinical follow-up. Brain metastases from lung carcinomas were further studied separately. Survival time was analysed using the Kaplan-Meier method. RESULTS: There were 61 true-positive, 2 false-positive, 15 false-negative, and 51 true-negative PET examinations; 5 positive and 22 negative PET examinations were indeterminate. The positive predictive value of a PET examination was 96% in all and 100% in brain metastases from lung carcinoma. The negative predictive value based on the histopathologic results was 55.6%. Survival time was significantly longer in patients with negative PET. CONCLUSION: FDG-PET is a valuable tool in the detection of tumor recurrence, especially lung carcinoma metastasis. FDG uptake is a prognostic marker.

Adolescent↗

No evidence for autoimmunity as a major cause of the empty sella syndrome.

OBJECTIVE: The cause of empty sella syndrome (ESS) remains largely unknown. We measured eleven organ-specific autoantibodies in serum in order to evaluate possible autoimmune components in ESS. PATIENTS: Thirty patients with ESS and 50 healthy blood donors participated in the study. MEASUREMENTS: Detection of pituitary autoantibodies was performed by immunoblotting with human pituitary cytosol as antigen. Thyroid peroxidase (TPO) and TSH receptor (TRAK) autoantibodies were analysed by radioimmunoassay. The remaining eight autoantibodies were detected by in vitro transcription and translation of the autoantigens and immunoprecipitation. RESULTS: The majority of the ESS patients (18/30) exhibited no immunoreactivity at all. None of the remaining 12 ESS patients reacted against more than one autoantigen. No immunoreactivity was found more frequently among ESS patients than healthy blood donors. Pituitary autoantibodies were not correlated to the ESS patients' pituitary function or sellar size, although the results indicated a tendency of increased autoimmunity in patients with hypopituitarism and normal sella size respectively. CONCLUSION: Detection of autoantibodies is a valuable tool in the diagnostic work-up of autoimmune diseases. By analysing a large number of organ-specific autoantibodies we found no evidence of ESS being associated with any specific autoimmune disease. The pathogenesis of ESS is believed to be heterogeneous and our findings suggest autoimmune components to be of minor importance. In some selective cases, ESS in combination with hypopituitarism may be the result of an autoimmune disease in the pituitary gland but this needs further investigation.

Adult↗

Familial risk of tumors associated with hereditary non-polyposis colorectal cancer: a Swedish population-based study.

BACKGROUND: Familial clustering, which may be due to inherited predisposition, is seen in several common cancer types. The aim of this study was to assess the familial risk of tumors that are associated with hereditary non-polyposis colorectal cancer (HNPCC), a familial cancer syndrome that confers an increased risk of several cancer types, and is associated with a low age at onset. METHODS: The National Swedish Cancer Registry and population registers were utilized to identify all tumors among the offspring of individuals who had developed any of the diagnoses included in the Amsterdam II criteria for HNPCC. In all, 204,358 offspring of 102,814 individuals with cancer of the colorectum, endometrium, upper urinary tract or small intestine were identified. RESULTS: Significantly increased risks for several tumor types were demonstrated. If the parent was below age 50 at diagnosis, the offspring Standard Incidence Ratios (SIRs) were 3.6 for colon cancer, 3.8 for rectal cancer, 2.8 for gastric cancer, and 2.3 for ovarian cancer. Offspring who had both a parent and a sibling with HNPCC-associated cancer showed even higher SIRs for cancer of the colorectum, endometrium, ovary, and urinary tract. The highest values were observed in the subgroup whose parent had developed multiple primary tumors; SIR 34.0 for colon cancer, 17.9 for rectal cancer, 21.8 for endometrial cancer, and 5.8 for ovarian cancer. CONCLUSIONS: The study demonstrates that there is an increased risk for several tumor types among individuals whose parents developed HNPCC-associated tumors, where a young age at diagnosis and development of multiple tumors in the parents lead to the highest SIRs.

Adult↗

Defective mismatch-repair in patients with multiple primary tumours including colorectal cancer.

Individuals with an inherited predisposition to cancer development are at an increased risk of developing multiple tumours. Hereditary non-polyposis colorectal cancer (HNPCC) is one of the most common hereditary cancer syndromes and is estimated to account for approximately 2% of colorectal cancers. However, HNPCC individuals are at an increased risk of developing other tumour types such as cancers of the endometrium, urothelium and small intestine. We have utilised a population-based regional cancer registry to identify all patients with double primary colorectal cancers and at least one additional malignancy and characterised the tumour spectrum in this patient group. We subsequently selected those 47 individuals who had developed at least four malignancies, including two colorectal cancers, for studies of the tumour characteristics associated with HNPCC. In total, these individuals developed 209 tumours, 156 of which were successfully retrieved. Microsatellite instability (MSI), a phenomenon caused by defective mismatch-repair (MMR), was identified in 63/154 (41%) evaluable tumours with a MSI-high pattern in 59 and a MSI-low pattern in four tumours. All tumours were immunohistochemically stained for the MMR proteins MLH1 and MSH2, with loss of expression in 55/63 (87%) MSI tumours and in 2/89 (2%) microsatellite stable (MSS) tumours. This loss affected MLH1 in 24 tumours and MSH2 in 33 tumours. A concordant loss of expression for the same MMR protein in several tumours from the same individual, a pattern that strongly suggests an underlying germline MMR gene mutation, was found in 17/45 (38%) patients and affected MLH1 in 8 patients and MSH2 in 9 patients. We conclude that the development of multiple primary tumours, including synchronous or metachronous colorectal cancers, is associated with an increased frequency of MSI and loss of immunohistochemical expression of MLH1 and MSH2.

Adult↗

Diffusion-weighted MR and apparent diffusion coefficient in the evaluation of severe brain injury.

PURPOSE: To study apparent diffusion coefficient (ADC) maps in severely brain-injured patients. MATERIAL AND METHODS: Four deeply comatose patients with severe brain injury were investigated with single-shot, diffusion-weighted, spin-echo echoplanar imaging. The tetrahedral diffusion gradient configuration and four iterations of a set of b-values (one time of 0 mm2/s, and four times of 1000 mm2/s) were used to create isotropic ADC maps with high signal-to-noise ratio. ADC values of gray and white matter were compared among patients and 4 reference subjects. RESULTS: One patient was diagnosed as clinically brain dead after the MR examination. The patient's ADC values of gray and white matter were significantly lower than those of 3 other brain-injured patients. In addition the ADC value of white matter was significantly lower than that of gray matter. CONCLUSION: The patient with fatal outcome shortly after MR examination differed significantly from other patients with severe brain injury but non-fatal outcome, with regard to ADC values in gray and white matter. This might indicate a prognostic value of ADC maps in the evaluation of traumatic brain injury.

Adolescent↗

Patients with Primary brain tumours have elevated serum titres of antibodies to the myelin glycolipid sulphatide.

Primary and metastatic brain tumours may result in an altered exposure of normal cellular components to the immune system inducing an immune response measurable in autoantibodies. One potential immunogenic molecule is sulphatide, the major acidic glycolipid in myelin. Thirty-eight sera from 31 patients with primary and metastatic brain tumours have, therefore, been analyzed for the presence of antisulphatide antibodies by an ELISA performed on thin layer chromatography plates. Twenty-eight of the thirty-eight sera (74%) showed a positive antibody titre to sulphatide. The antibody titres were significantly higher (p < 0.01) in sera from patients with primary brain tumours than in sera from those with metastases. The study lends support to the possibility that antisulphatide antibodies could contribute to tissue damage and this might facilitate the invasive growth in primary brain tumours by demyelination. However, the pathogenic significance of these autoantibodies remains to be further elucidated.

Adolescent↗

Relationship of Chlamydia pneumoniae infection to severity of human coronary atherosclerosis.

BACKGROUND: Infection with Chlamydia pneumoniae has been postulated to play a pathogenic role in atherosclerosis. We examined the role of infection with C pneumoniae in relation to the extent of coronary atherosclerosis. METHODS AND RESULTS: Coronary atherosclerosis was graded microscopically on a postmortem basis in a blinded fashion in 60 subjects as mild (n=18) or severe (n=42) atherosclerosis. Serum antibodies to C pneumoniae were measured by microimmunofluorescence test. Paraffin-embedded coronary artery specimens were examined for the presence of chlamydia by use of a genus-specific direct immunofluorescence monoclonal antibody. Frozen coronary artery specimens were examined by immunoperoxidase for the presence of C pneumoniae by use of a specific monoclonal antibody RR-402. Direct immunofluorescence was reactive in 86% of cases with severe atherosclerosis but in only 6% of cases with mild atherosclerosis (P<0.01), whereas immunoperoxidase staining was reactive in 80% and 38% of cases with severe and mild atherosclerosis, respectively (P<0. 01). Elevated IgG and IgA levels against C pneumoniae were not different in cases with severe and mild atherosclerosis (61% and 30% for severe atherosclerosis and 67% and 42% for mild atherosclerosis, respectively). CONCLUSIONS: This study supports the hypothesis that intracellular infection with C pneumoniae may relate to the severity of atherosclerosis in some subjects. Serum antibody titers against C pneumoniae do not differentiate between severe and mild atherosclerosis.

Adult↗

[Familial hemophagocytic lymphohistiocytosis: diagnosis, treatment and pathophysiological mechanisms].

Familial hemophagocytic lymphohistiocytosis (FHL) is an invariably fatal disease typically seen in infancy and early childhood, with a median survival without therapy of two months. It is characterized by prolonged fever, hepatosplenomegaly, cytopenia, and deficient NK-cell activity and T-cell cytotoxic capacity. Severe neurological symptoms as well as coagulation disorders and abnormalities in liver function and lipid status may also develop. Since the mid 1980's there has been a remarkable increase in our understanding of this disease. In a large-scale international collaborative effort mediated through the Histiocyte Society, diagnostic criteria and an international treatment protocol (HLH-94) based on immunochemotherapy and BMT have been developed. A large proportion of affected children can now be cured and, moreover, successful chemotherapy in utero of FHL has been achieved. It has been shown that the symptoms and signs are mediated through a pronounced hypercytokinemia. Previous suggestions that FHL may be caused by a deficiency in apoptosis were recently confirmed when perforin gene defects were described, which may well explain the disastrous lymphohistiocytic accumulation and subsequent T-cell activation.

Apoptosis↗

Seropositivity against Chlamydia pneumoniae in patients with coronary atherosclerosis.

BACKGROUND: Results of therapy in patients with unstable coronary syndromes with antibiotics directed against Chlamydia pneumoniae have been variable, perhaps due to the heterogeneity of patients in these trials. HYPOTHESIS: The aim of the present study was to correlate the severity of coronary artery disease (CAD) with seropositivity against C. pneumoniae prospectively. METHODS: We measured the frequency of seropositivity (IgG levels > or = 1/64 and IgA levels > or = 1/16 against Chlamydia pneumoniae) in 110 patients with CAD and in 49 controls. RESULTS: As expected, traditional CAD risk factors were seen more often in patients with CAD than in controls. Mean values of total cholesterol (184 +/- 52 and 166 +/- 44 mg/dl, respectively) and triglyceride (143 +/- 60 and 112 +/- 63 mg/dl, respectively) in serum were significantly higher in patients with CAD than in controls (both p < 0.04). There were no significant differences between the two groups in serum high-density lipoprotein cholesterol (34 +/- 13 and 32 +/- 14 mg/dl, respectively) and lipoprotein (a) (Lp(a):241 +/- 247 and 223 +/- 263 mg/l, respectively) levels. The rate of IgG seropositivity was 52% (28/54) in patients with stable CAD, 41% (23/56) in patients with unstable CAD, and 35% in controls (p = NS). The rate of IgA seropositivity was 25% (14/54) in patients with stable CAD, 12% (6/49) in patients with unstable angina, and 12% (6/49) in controls (all p = NS). CONCLUSIONS: Only a small percentage of patients with CAD demonstrate seropositivity against Chlamydia pneumoniae. Antibiotic therapy in these selected patients, but not in the remaining patients, may be considered rational. These considerations may underlie the failure to see consistent benefits of antibiotic therapy in patients with CAD.

Analysis of Variance↗

Volume measurement of cerebral arteriovenous malformations from angiography.

We designed software for measuring the volume of cerebral arteriovenous malformations from angiography and validated it against prescription volumes in radiosurgery. We aimed to create a model for the risk for complications as a function of volume, based on established outcome prediction models for Gamma Knife radiosurgery, but without the need for dose planning. We created an application for computing the volume of cerebral arteriovenous malformations from the intersection of two X-ray cones in stereotactic space. Volume measurements were compared with prescription volumes from dose planning, in phantoms and in patients treated with Gamma Knife radiosurgery for cerebral arteriovenous malformations. Previous studies of 1128 treated patients were used to calculate the risk for complication as a function of the nidus volume. In 63 patients volumes measured with either method correlated, R2 = 0.85. Volume as measured with the intersecting cone model (ICM) correlated with predicted Gamma Knife radiosurgery complication rate, R2 = 0.84. The ICM can thus be used for measurement of AVM volumes less than 10 cm3 from angiography. Outcome models from Gamma Knife radiosurgery may be applied, but with reduced exactness. Standardised AVM volume measurement is valuable for comparing outcome and for quantification of volume reduction after therapy, notably embolisation. Thus the optimal management plan may be selected in conjunction with diagnostic or therapeutic angiography.

Cerebral Angiography↗

Tumor suppressor INK4: determination of the solution structure of p18INK4C and demonstration of the functional significance of loops in p18INK4C and p16INK4A.

Since the structures of several ankyrin-repeat proteins including the INK4 (inhibitor of cyclin-dependent kinase 4) family have been reported recently, the detailed structures and the functional roles of the loops have drawn considerable interest. This paper addresses the potential importance of the loops of ankyrin-repeat proteins in three aspects. First, the solution structure of p18INK4C was determined by NMR, and the loop structures were analyzed in detail. The loops adapt nascent antiparallel beta-sheet structures, but the positions are slightly different from those in the crystal structure. A detailed comparison between the solution structures of p16 and p18 has also been presented. The determination of the p18 solution structure made such detailed comparisons possible for the first time. Second, the [1H,15N]HSQC NMR experiment was used to probe the interactions between p18INK4C and other proteins. The results suggest that p18INK4C interacts very weakly with dna K and glutathione S-transferase via the loops. The third aspect employed site-specific mutagenesis and functional assays. Three mutants of p18 and 11 mutants of p16 were constructed to test functional importance of loops and helices. The results suggest that loop 2 is likely to be part of the recognition surface of p18INK4C or p16INK4A for CDK4, and they provide quantitative functional contributions of specific residues. Overall, our results enhance understanding of the structural and functional roles of the loops in INK4 tumor suppressors in particular and in ankyrin-repeat proteins in general.

Amino Acids↗

MR imaging with gadolinium in patients with and without post-lumbar puncture headache.

PURPOSE: To study frequency and extent of meningeal enhancement in patients with and without post-lumbar puncture headache (PLPH) with cerebral MR with Gd-DTPA. MATERIAL AND METHODS: Ten consecutive patients with PLPH and 9 consecutive patients without PLPH were included in the study. Nine of the PLPH patients were reinvestigated when the PLPH was over and all non-PLPH patients during the week after the lumbar puncture. RESULTS: Eight of the 9 patients with PLPH showed more enhancement of meningeal structures during PLPH than when PLPH had disappeared. The differences were slight in 5, more marked in 2, and pronounced in 1 patient. The 9th patient showed no change at all. In the 9 patients without PLPH, there was mainly slight enhancement before lumbar puncture and no change in enhancement after lumbar puncture as compared with before. CONCLUSION: PLPH is related to increased Gd-DTPA enhancement of the meninges, although the increase in enhancement during PLPH is minor in most cases. Pronounced enhancement of the meninges after lumbar puncture may predict long duration of the PLPH.

Adult↗

An algorithm for correction of distortion in stereotaxic digital subtraction angiography.

An algorithm for correction of the geometrical distortion in digital subtraction angiography (DSA) images was developed. Originally invented for 3D X-ray angiography, the algorithm was implemented in a computer program designed to fulfil the specific needs of stereotaxic DSA. The algorithm is based on transformation of an image of a grid from a distorted image back into its original pattern. The same transformation is then applied pixel-by-pixel to the angiographic images, which are acquired in direct conjunction with the grid image, without moving the gantry. The algorithm was tested in phantom studies and in the clinical situation with seven patients in ten examinations. Comparisons were made between co-ordinate determinations made on conventional full-size cut film and those performed on uncorrected and corrected DSA images, using 30- and 23-cm fields of view. With our method of measurement we could not shown any remaining geometric distortion in the corrected DSA images. This distortion correction can, if properly applied, be used for high-precision stereotaxic DSA.

Algorithms↗

Tumor suppressor p16INK4A: determination of solution structure and analyses of its interaction with cyclin-dependent kinase 4.

The solution structure of the tumor suppressor p16INK4A has been determined by NMR, and important recognition regions of both cdk4 and p16INK4A have been identified. The tertiary structure of p16INK4A contains four helix-turn-helix motifs linked by three loops. Twelve tumorigenic mutants of p16INK4A have been constructed and analyzed for their structure and activity, and new mutants have been designed rationally. A fragment of 58 residues at the N terminus of cdk4 important for p16INK4A binding has been identified. The importance of this region was further verified by mutational analysis of cdk4. These results and docking experiments have been used to assess possible modes of binding between p16INK4A and cdk4.

Binding Sites↗

Optimising contrast-enhanced cranial CT for detection of brain metastases.

PURPOSE: In order to optimise contrast-enhanced CT in the detection of brain metastases, we investigated how sensitivity was affected by an increase in contrast medium dose and a reduction in slice thickness. MATERIAL AND METHODS: A total of 198 cases of known primary malignancy with suspected brain metastases were investigated in three consecutive contrast-enhanced CT examinations. The first was a standard CT examination with an injection of 100 ml contrast medium (300 mg I/ml) and a slice thickness of 10 mm. A further 100 ml contrast medium was given and the second examination was performed immediately afterwards with the same slice thickness as the first. This was followed by the third examination, which used a slice thickness of 5 mm. The standard contrast-enhanced CT images were compared with the double-dose images and with the images of reduced slice thickness (5 mm instead of 10 mm). RESULTS: The double-dose images demonstrated an 8-18% increase in the number of brain metastases detected compared to the standard contrast-enhanced CT; the images of the 5-mm-thick slices showed a further 22-33% increase. The comparison between the standard contrast-enhanced CT images and the images with both thinner slices and the double dose of contrast medium demonstrated a 32-55% increase in the number of metastases detected. CONCLUSION: A considerable increase in sensitivity (32-55%) in contrast-enhanced CT can be obtained by reducing the slice thickness and increasing the contrast medium dose. This optimised technique should be the method of choice in patients with known primary malignancy and suspected brain metastases.

Adult↗