Graft mucosal blood flow is reduced prior to histologic evidence of rejection in mouse small bowel transplantation: a murine model.
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Animals↗
Biomedical subjects
O Nilsson
Publications and source records attributed to O Nilsson.
Clinical utility of biochemical markers in colorectal cancer: European Group on Tumour Markers (EGTM) guidelines.
In recent years, numerous serum and cell/tissue-based markers have been described for colorectal cancer (CRC). The aim of this article was to provide guidelines for the routine clinical use of some of these markers. Lack of sensitivity and specificity preclude the use of any available serum markers such as carcinoembryonic antigen (CEA), CA 19-9, CA 242, CA 72-4, tissue polypeptide antigen (TPA) or tissue polypeptide-specific antigen (TPS) for the early detection of CRC. However, preoperative measurement of CEA is desirable as this may give independent prognostic information, help with surgical management and provide a baseline level for subsequent determinations. For patients with stage 2 (Dukes' B) and 3 (Dukes' C) disease who may be candidates for liver resection, CEA levels should be measured every 2-3 months for at least 3 years after diagnosis. For monitoring treatment of advanced disease, CEA should also be tested every 2-3 months. Insufficient evidence is presently available to recommend the routine use of other serum markers for monitoring purposes. Similarly, the new cell and tissue-based markers (e.g, ras, P53) cannot yet be recommended for routine clinical use.
Antigens, Tumor-Associated, Carbohydrate↗
Adult coeliac patients do tolerate large amounts of oats.
OBJECTIVE: The aim of the present study was to investigate whether adult patients with coeliac disease in remission could include large amounts of oats in their daily gluten-free diet for an extended period of time without adverse effects. DESIGN, SUBJECTS AND METHODS: Twenty adult coeliac patients in remission included large amounts of uncontaminated rolled oats in their daily diet for a prolonged period. The examinations, performed four times during the study period, included small bowel endoscopy with biopsies, blood samples (nutritional status, serological analysis), height and body weight, gastrointestinal symptoms and dietary records. Gastrointestinal symptoms and diet were also investigated through unannounced telephone interviews once a month during the study period. RESULTS: No adverse effects of a large intake of oats were seen in small bowel histology, serology nor in nutritional status in the 15 subjects who completed the whole study period. Two of the subjects dropped out because of gastrointestinal symptoms and three for non-medical reasons. The median intake of oats was 93 g/day and the compliance to the oat diet was found to be good. Examinations of the patients after drop-out did not show any deterioration in small bowel histology or nutritional status nor raised levels of antibodies. CONCLUSION: Results from this study indicate that adult patients with coeliac disease in remission can include large amounts of controlled wheat-free rolled oats for an extended period of time without adverse effects.
Adult↗
Evaluation of (111)In labeled somatostatin analogs for targeted therapy of somatostatin receptor positive tumors.
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Carcinoma, Small Cell↗
Mucosal assessment for dysplasia and cancer in the ileal pouch mucosa in patients operated on for ulcerative colitis--a 30-year follow-up study.
PURPOSE: Sporadic reports of epithelial dysplasia and the occasional development of adenocarcinoma in the ileal pouch mucosa have recently appeared in the literature, pointing toward yet another long-term complication of the continent ileostomy and the pelvic pouch. The incidence of dysplasia and the risk for developing cancer has not been critically evaluated, however, and the reports are contradictory, with most having short observation times. The purpose of this study was to report long-term mucosal adaptation patterns and the incidence of dysplasia in Kock pouches after a mean follow-up of 30 years for patients previously operated on for ulcerative proctocolitis. METHODS: Two sets of two pathologists each (in Gothenburg, Sweden, and Manchester, United Kingdom) examined sequential, small-intestinal biopsy specimens from 40 patients with Kock pouch to observe long-term epithelial changes, with particular reference to the presence of dysplasia. RESULTS: There was full agreement between the two groups regarding the absence of high-grade dysplasia and invasive carcinoma (Categories 4 and 5 of the Vienna classification). There was, however, significant disagreement in reporting the frequency of low-grade and indefinite categories of dysplasia (Categories 2 and 3, of the Vienna classification). No attempt was made to report the differences within each set of pathologists. CONCLUSION: Because no case of high-grade dysplasia or invasive carcinoma was found in this study after a mean follow-up of 30 years, we conclude that it is very unlikely for invasive carcinoma to be a complication in ileal pouch mucosa.
Adenocarcinoma↗
Initial experience with multivisceral, cluster, and combined liver and small bowel transplantation in Sweden.
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Drug Therapy, Combination↗
Impacted corticocancellous allografts and cement for revision of the femur component in total hip arthroplasty.
Revision of the femur component in total hip arthroplasty using impacted morcellized bone allografts and cemented Lubinus SP-II prosthesis or Charnley standard prosthesis was performed in patients with loss of bone stock grade II through IV according to the Endo-Klinik classification from 1st to 8th revision. We report the results from 57 hips in 56 patients, with a median of 64 months' follow-up. Modified Merle d'Aubigne-Postel postoperative scores increased significantly from preoperative to postoperative values for the Lubinus group and for the Charnley group. Few complications were seen in this follow-up period. Five stems had minor subsidence. Rate of mechanical failure was 4% for both groups. Radiologic examinations provided evidence of frequent trabecular remodeling of the graft, especially for the Lubinus prosthesis.
Aged↗
Expression and localization of Indian hedgehog (Ihh) and parathyroid hormone related protein (PTHrP) in the human growth plate during pubertal development.
Indian Hedgehog (Ihh) has been reported to control the rate of cartilage differentiation during skeletal morphogenesis in rodents through a negative feedback loop involving parathyroid hormone related protein (PTHrP). The role of Ihh and PTHrP in the regulation of human epiphyseal chondrocytes is unknown. The aim of the current study was to examine the expression and localization of Ihh and PTHrP in the human growth plate at various pubertal stages. Growth plate biopsies were obtained from patients subjected to epiphyseal surgery and the expression of Ihh and PTHrP was detected by immunohistochemistry. We show that Ihh and PTHrP are expressed mainly in early hypertrophic chondrocytes in the human growth plate. The levels of expression of Ihh and PTHrP are higher in early stages of puberty than later. Our results suggest that Ihh and PTHrP are present in the human growth plate and that Ihh and PTHrP may be involved in the regulation of pubertal growth in humans.
Adolescent↗
Dosimetric comparison of radionuclides for therapy of somatostatin receptor-expressing tumors.
PURPOSE: Therapy of tumors expressing somatostatin receptors, sstr, has recently been clinically tested using somatostatin analogues labeled with (111)In and (90)Y. Several other radionuclides, i.e., (131)I, (161)Tb, (64)Cu, (188)Re, (177)Lu, and (67)Ga, have also been proposed for this type of therapy. The aim of this work was to investigate the usefulness of the above-mentioned radionuclides bound to somatostatin analogues for tumor therapy. METHODS: Biokinetic data of (111)In-labeled octreotide in mice and man were used, primarily from our studies but sometimes from the literature. Dosimetric calculations were performed with the assumption that biokinetics were similar for all radionuclides bound to somatostatin analogues. The cumulated tumor:normal-tissue activity concentration, TNC was calculated for the various physical half-lives of the radionuclides. Using mathematical models, the tumor:normal-tissue mean absorbed dose rate ratio, TN D and tumor:normal-tissue mean absorbed dose ratio, TND, were calculated for various tumor sizes in mice and humans. RESULTS: TNC of radionuclide-labeled octreotide increased with physical half-life for most organs, both in mice and in humans. TN D showed that radionuclides emitting electrons with too high energy are not suitable for therapy of small tumors. Furthermore, radionuclides with a higher frequency of photon emissions relative to electron emissions will yield lower TN D and are thus less suitable for therapy than radionuclides with a lower frequency of photon emissions. The TND was highest for (161)Tb in both mice and humans. CONCLUSIONS: The results demonstrate that long-lived radionuclides, which emit electrons with rather low energy and which have low frequency of photon emissions, should be the preferred therapy for disseminated small sstr-expressing tumors.
Algorithms↗
[Phenotypic expression of a mutation in MEN 2A documented in a family in the western part of Sweden].
A missense mutation at codon 618 of the RET proto-oncogene is a rather unusual cause of multiple endocrine neoplasia 2A. We report the phenotypic expression of this specific RET mutation in a large Swedish family. The family was mapped back to the 18th century. Since 1971 the family has been included in a biochemical screening program, and since 1994 has undergone genetic screening. Twenty-seven individuals were found to have medullary thyroid carcinoma (MTC). Eighteen were detected by screening. The incidence of pheochromocytoma (4%) and hyperparathyroidism (7%) was low. Five individuals died of MTC, but of these none had been included in the screening program. One patient underwent prophylactic thyroidectomy after positive genetic screening. MTC tumor aggressivity differed markedly between gene carriers. The screening program shows that the clinical aggressivity of MTC can be mitigated by early and adequate surgical intervention.
Female↗
[Hereditary thyroid cancer can be cured by prophylactic surgery].
Multiple endocrine neoplasia type 2 (MEN 2) is a rare syndrome in which the consequences for the patient and family members are considerable. Mutation analysis of the RET proto-oncogene is crucial for decision-making regarding each patient. Today, carriers of MEN 2 mutations should be offered prophylactic thyroidectomy with the potential to eliminate the risk for potentially lethal medullary thyroid carcinoma (MTC). Here, we present the first Swedish experience of such operations performed mainly on the basis of genetic analysis. Twenty patients underwent total thyroidectomy at a mean age of 13.5 (6-43) years. In all cases, either manifest MTC (n = 11) or C-cell hyperplasia was found. So far, no patient has any sign of recurrence or developmental insufficiency at 1-5 years follow-up. As the medical and ethical problems in this group of patients are substantial, and as the operations are performed in otherwise healthy children, they should be treated at centers with adequate multidisciplinary expertise and competence.
Adolescent↗
New halogen-specific detector applied to the analysis of chlorinated fatty acids.
A new halogen-specific detection method (XSD) was tested for determination of chlorinated fatty acids in marine biota. In XSD, an increased emission of ions and electrons is caused by the high-temperature combustion of halogen-containing compounds. The detection limit of methyl dichlorooctadecanoate and the selectivity at a reactor temperature of 900 degrees C match those of electrolytic conductivity detection (ELCD). The relative standard deviation is less than 11% for > or =0.2 ng methyl dichlorooctadecanoate. An XSD chromatogram of a complex sample, chlorinated fatty acid methyl esters liberated from fish lipids, agreed with a previously obtained ELCD chromatogram.
Chlorine↗
Differential expression of vesicular monoamine transporter (VMAT) 1 and 2 in gastrointestinal endocrine tumours.
Neuroendocrine tumours are characterized by their capacity to produce hormones, which are stored in vesicles and secretory granules. Demonstration of granule/vesicle proteins in tumours is taken as evidence of neuroendocrine differentiation. Vesicular monoamine transporters (VMAT1 and VMAT2) mediate the transport of amines into vesicles of neurons and endocrine cells. The expression of VMAT1 and VMAT2 and the usefulness of VMAT1 and VMAT2 in the histopathological diagnosis of gastrointestinal endocrine tumours have not been fully explored. This study therefore investigated the expression of VMAT1 and VMAT2 in 211 human gastrointestinal tumours by immunocytochemistry and western blotting. VMAT1 and/or VMAT2 were demonstrated in the majority of amine-producing endocrine tumours of gastric, ileal, and appendiceal origin. Serotonin-producing endocrine tumours (ileal and appendiceal carcinoids) expressed predominantly VMAT1, while histamine-producing endocrine tumours (gastric carcinoids) expressed VMAT2 almost exclusively. In peptide-producing endocrine tumours such as rectal carcinoids and endocrine pancreatic tumours, only a small number of immunopositive tumour cells were observed. No labelling was found in non-endocrine tumours, including gastric, colorectal and pancreatic adenocarcinomas and gastrointestinal stromal tumours. In conclusion, VMAT1 and VMAT2 are differentially expressed by gastrointestinal endocrine tumours, with a pattern specific for each tumour type, reflecting their neuroendocrine differentiation and origin. VMAT1 and VMAT2 may therefore become valuable markers in the classification of neuroendocrine tumours and may also indicate patients suitable for radioisotope treatment operating via these transporter systems.
Blotting, Western↗
Intraoperative tumour detection using 111In-DTPA-D-Phe1-octreotide and a scintillation detector.
Intraoperative tumour detection has been used in many applications. The examined tumour forms have varied and different detector systems and radiopharmaceuticals have also been used. The aim of this study was to evaluate and compare the ability of an NaI(T1) scintillation detector to detect primary tumours and metastases in patients with different endocrine tumour types (e.g. carcinoid tumours, endocrine pancreatic tumours and thyroid tumours) and in patients with breast carcinoma or benign thyroid lesions, on the basis of their somatostatin receptor expression after i.v. injection of 111In-DTPA-D-Phe1-octreotide. Thirty patients were injected with 111In-DTPA-D-Phe1-octreotide intravenously. Scintigraphic images were taken 1 day after injection of the radiopharmaceutical, and surgery was performed 1-7 days post injection. An NaI(T1) scintillation detector was used for intraoperative tumour detection. Tissue samples were collected during surgery for determination of 111In activity concentration and histopathological examination. The scintigraphic images were positive in 29 out of 30 patients. Intraoperative tumour detection was successful in 43 of 66 collected biopsies: 10 out of 11 for carcinoid tumours, 7 out of 10 for medullary thyroid carcinoma (MTC) and 14 out of 22 for breast cancer. On the basis of our findings we conclude that intraoperative tumour detection with 111In-DTPA-D-Phe1-octreotide using this NaI(T1) detector can be successful especially for carcinoid tumours and endocrine pancreatic tumours, due to the relatively high activity concentrations in these tumour types, but is less successful in other forms of thyroid cancer, including MTC, and breast cancer. For successful intraoperative detection, the detector characteristics are also very important, and further improvement of the detector systems is required to increase the sensitivity and specificity.
Adolescent↗
Cytotoxic treatment of adrenocortical carcinoma.
Adrenocortical carcinoma (ACC) is a rare, aggressive tumor that is often detected in an advanced stage. Medical treatment with the adrenotoxic drug mitotane has been used for decades, but critical prospective trials on its role in residual disease or as an adjuvant agent after surgical resection are still lacking. The concept of a critical threshold plasma level of the drug must be confirmed in controlled studies. Because individual responsiveness cannot be predicted, the use mitotane is still advised for nonresectable disease. In case of cortisol or other steroid overproduction, several drugs (e.g., ketoconazole or aminoglutethimide) may be used. Chemotherapy with single agents (e.g., doxorubicin or cisplatin) have been disappointing, with low response rates (< 30%) and a short response duration. Part of this refractoriness may be explained by the fact that ACC tumors express the multidrug-resistance gene MDR-1. Chemotherapy with multiple agents has been tested in smaller series and has resulted in significant side effects. The best results were achieved by the combination of etoposide, doxorubicin, and cisplatin associated with mitotane, achieving a response rate of 54%, including individual complete responses. To be able to make progress in treating advanced ACC disease, adjuvant multicenter trials must be encouraged. When mitotane-based therapies are used, monitored drug levels are mandatory.
Adrenal Cortex Neoplasms↗
A transplantable human carcinoid as model for somatostatin receptor-mediated and amine transporter-mediated radionuclide uptake.
A human midgut carcinoid tumor was successfully transplanted into nude mice and propagated for five consecutive generations (30 months) with well-preserved phenotype. Tumor cells in nude mice expressed identical neuroendocrine markers as the original tumor, including somatostatin receptors (somatostatin receptors 1 to 5) and vesicular monoamine transporters (VMAT1 and VMAT2). Because of the expression of somatostatin receptors and VMAT1 and VMAT2 the grafted tumors could be visualized scintigraphically using the somatostatin analogue 111In-octreotide and the catecholamine analogue 123I-metaiodobenzylguanidine. The biokinetics of the somatostatin analogue 111In-octreotide in the tumors was studied and showed a high retention 7 days after administration. Cell cultures were re-established from transplanted tumors. Immunocytochemical and ultrastructural studies confirmed the neuroendocrine differentiation. The human origin of transplanted tumor cells was confirmed by cytogenetic and fluorescence it situ hybridization analyses. Spontaneous secretion of serotonin and its metabolite, 5-hydroxyindole acetic acid, from tumor cells was demonstrated. The tumor cells increased their [Ca2+]i in response to beta-adrenoceptor stimulation (isoproterenol) and K+-depolarization. All somatostatin receptor subtypes could be demonstrated in cultured cells. This human transplantable carcinoid tumor, designated GOT1, grafted to nude mice, will give unique possibilities for studies of somatostatin receptor- and VMAT-mediated radionuclide uptake as well as for studies of secretory mechanisms.
3-Iodobenzylguanidine↗
Increase in serum S100A1-B and S100BB during cardiac surgery arises from extracerebral sources.
BACKGROUND: Elevated levels of serum S100B after coronary artery bypass grafting may arise from extracerebral contamination. Serum S100B content was analyzed in several tissues, and the two dimers S100A1-B and S100BB were analyzed separately in blood. METHODS: Serum, shed blood, marrow, fat, and muscle were studied in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass using suction either to the cardiotomy reservoir (group 1, n = 10) or to a cell-saving device (group 2, n = 10), or operated on off-pump (group 3, n = 10). RESULTS: Serum S100B was sixfold higher in group 1 than in groups 2 and 3, which were identical. The same ratio between S100A1-B and S100BB was found in all groups. When compared with serum, S100B was 10(2) to 10(4) times higher in marrow, fat, muscle tissue, and shed blood. CONCLUSIONS: Separate analysis of S100A1-B and S100BB did not distinguish between S100B of cerebral and extracerebral origin. The concept that S100B only originates in astroglial and Schwann cells is wrong. Fat, muscle, and marrow in mediastinal blood contain high levels of S100B. Cardiopulmonary bypass caused no increase in S100B.
Adult↗
Prostasome-like granules from the PC-3 prostate cancer cell line increase the motility of washed human spermatozoa and adhere to the sperm.
OBJECTIVE: Prostasome-like granules are present in the PC-3 prostate cancer cells. Since the seminal prostasomes are able to promote the forward motility of human spermatozoa, we conducted a study to determine whether PC-3 prostasomes exerted effects similar to those of seminal prostasomes on buffer-washed spermatozoa from normospermic semen samples. STUDY DESIGN: We used computer-assisted sperm analysis (CASA) and immunostaining of prostasomes to find out where these granules are located on the spermatozoa. RESULTS: Addition of PC-3 prostasomes increased the proportion of motile spermatozoa from 12-15% to 50-70% (p<0.001). The optimal protein concentration of these prostasomes was 0.1mg/ml. Heat treatment of PC-3 prostasomes did not decrease their motility-promoting effect. Immunostaining with anti-prostasome monoclonal antibody (mAb78) revealed that the PC-3 prostasomes and seminal prostasomes adhered to the sperm cells. The staining, which occurred all over the spermatozoa, was intense on the mid-pieces and weaker on the sperm heads. Herewith, some prostasome component may activate the spermatic mitochondrial function, thus increasing sperm motility. CONCLUSION: It is concluded that PC-3 prostasomes bear a functional resemblance to seminal prostasomes as regards sperm motility promotion.
Cell Adhesion↗