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J Björnsson

Publications and source records attributed to J Björnsson.

At least 19 recordsLinked to original sources
PubMed2003

Orthotopic liver transplantation for hereditary fibrinogen amyloidosis.

Systemic amyloidosis results from the deposition of insoluble protein fibrils in various organs and tissues. To date, several different proteins have been associated with amyloid fibril formation, including immunoglobulin light chain, serum amyloid A protein, and transthyretin. Recent reports have shown that variant fibrinogen chains can form amyloid in certain kindreds. Hepatic transplantation has previously been reported in the treatment of hereditary amyloidosis associated with variant transthyretin proteins, which are mainly synthesized in the liver. This article reports the first use and long-term follow-up of combined hepatic and renal transplantation in the successful treatment of two patients with hereditary fibrinogen amyloidosis. Both patients experienced sustained improvement in renal function and nutritional status at 61/2 years and 28 months of follow-up, respectively. Orthotopic liver transplantation is effective and potentially curative treatment of hereditary fibrinogen amyloidosis.

Amyloidosis, Familial↗
PubMed2001

Malignant neoplasms: discordance between clinical diagnoses and autopsy findings in 3,118 cases.

BACKGROUND: During the past few decades, hospital autopsy rates have steadily declined throughout the Western world. This decline is mainly attributed to the introduction of advanced diagnostic techniques. Despite technological developments, discrepancy rates between clinical diagnoses and autopsy findings remain high. Few studies have addressed discrepancy rates exclusively with regard to malignant neoplasms. In the present study, we reviewed the records of 3,118 autopsies performed at Mayo Clinic during a 6-year period (1994-1999) and identified clinically undiagnosed malignancies found at autopsy and clinically diagnosed cancers not confirmed at postmortem examination. MATERIALS AND METHODS: Autopsy protocols, provisional and final anatomic diagnoses, and data from the Mayo Autopsy Pathology Quality Assurance program were reviewed in an attempt to identify discrepancies between clinical diagnoses and autopsy findings regarding malignant neoplasms. RESULTS: In 3,118 autopsies performed at Mayo Clinic between 1994 and 1999, a malignant tumor was identified in 768 cases (25%). In 128 of 3,118 cases (4.1%), the malignancy was not diagnosed clinically. In 14 of 3,118 cases (0.45%), autopsy failed to confirm a clinically diagnosed cancer. A review of the literature is presented. CONCLUSIONS: Autopsy remains an effective tool for the confirmation and refutation of clinical diagnostic findings regarding malignant neoplasms.

Autopsy↗
PubMed2000

Factor V leiden and morbid obesity in fatal postoperative pulmonary embolism.

HYPOTHESIS: Currently, the risk for postoperative acute pulmonary embolism (APE) is assessed clinically. We hypothesize that the expensive screening for the most common genetic thrombophilic clotting defect (factor V Leiden; R(506)Q) after exclusion of established clinical risk factors does not offer additional benefit to surgical patients. DESIGN: We reviewed protocols and histories from 8249 consecutive autopsies performed at the Mayo Clinic, Rochester, Minn. All patients who died of APE after routine surgery and who lacked any other clinical risk factors for APE were included and compared with matched controls. Genomic DNA was extracted from archival tissues and examined for R(506)Q by polymerase chain reaction amplification, restriction enzyme digestion, and direct sequencing. RESULTS: Acute pulmonary embolism was the immediate cause of death in 454 patients (5.5%). Of those, 32 (7.0%) had undergone routine surgery. These patients represent less than 0.07% of all case-adjusted surgical procedures in the same period. The rate of postoperative death from APE was higher after neurosurgical procedures (0.3%) than all other procedures (0.04%). Sixteen patients (50.0%) were morbidly obese. Only 1 patient was heterozygous and none were homozygous for R(506)Q. CONCLUSIONS: (1) Fatal APE is uncommon in surgical patients lacking clinically apparent risk factors for venous thromboembolism. (2) Neurosurgical patients are at increased risk for postoperative APE. (3) Morbid obesity is a major independent risk factor in cases of sudden death from APE postoperatively. (4) Routine preoperative screening for R(506)Q in the factor V gene does not appear to offer additional benefit in surgical patients without clinically recognizable thromboembolic risk factor(s).

Activated Protein C Resistance↗
PubMed1999

Death from pulmonary thromboembolism in severe obesity: lack of association with established genetic and clinical risk factors.

Several clinical and environmental conditions are causally related to sudden death from acute pulmonary thromboembolism (APT). Morbid obesity, despite its frequency and association with adverse health effects, is usually considered at most only an additive risk factor for APT. We reviewed protocols and histories from 7227 consecutive autopsies performed between 1985 and 1996 at the Mayo Clinic, including all deaths from APT where no clinical or environmental risk factor could be identified in the study. Body mass indices (BMI) were calculated and compared with those of age- and sex-matched controls who had died suddenly and naturally without evidence of APT. Resistance to activated protein C is the most common molecular clotting defect predisposing to APT, and it is caused by a point mutation in the factor V gene (R506Q). Genomic DNA was extracted from archival tissues of all cases and controls, and the R506Q status was determined by polymerase chain reaction amplification, restriction endonuclease digestion, and direct sequencing. APT was found as the immediate cause of death in 433 patients, with 36 (8%) having no previously established risk factors. Twenty-four of these persons (67%) were morbidly obese (BMI >30 kg/m2). compared with only five controls (14%, P<0.0001). Four patients in both groups, each with a BMI <30 kg/m2. had at least one allele positive for R506Q. Morbid obesity is an independent risk factor in cases of sudden death from APT after the exclusion of previously established clinical, environmental, and molecular risk factors.

Adult↗
PubMed1999

Formation of new vasa vasorum in vasculitis. Production of angiogenic cytokines by multinucleated giant cells.

Inflammation of the arterial wall in giant cell arteritis induces a series of structural changes, including the formation of new vasa vasorum. To study the regulation of neoangiogenesis in giant cell arteritis, temporal arteries were examined for the extent and localization of microvessel generation and for the production of angiogenic factors. In normal arteries, vasa vasorum were restricted to the adventitia, but in inflamed arteries, capillaries emerged in the media and the intima. These capillaries displayed a distinct topography with a circumferential arrangement in the external one-third of the intima. Neovascularization was closely correlated with the formation of lumen-obstructing intima, the fragmentation of the internal elastic lamina, and the presence of multinucleated giant cells. Comparison of tissue cytokine transcription in temporal arteries of giant cell arteritis patients with and without up-regulated neoangiogenesis identified interferon-gamma and vascular endothelial growth factor but not fibroblast growth factor-2 as mediators associated with vasa vasorum proliferation. Giant cells and CD68-positive macrophages at the media-intima junction were found to be the major cellular sources of vascular endothelial growth factor. These data demonstrate that formation of new vasa vasorum in vasculitis is regulated by inflammatory cells and not by arterial wall cells, raising the possibility that it represents a primary disease mechanism and not a secondary hypoxia-induced event. Increased neovascularization in interferon-gamma-rich arteries suggests that the formation of new vasa vasorum is determined by the nature of the immune response in the arterial wall, possibly resulting from the generation and functional activity of multinucleated giant cells.

Cytokines↗
PubMed1998

Primary chondrosarcoma of long bones and limb girdles.

BACKGROUND: Chondrosarcomas are common solid malignant tumors of bone, second in incidence only to osteosarcomas. The biologic evolution of chondrosarcomas is slow, requiring long follow-up intervals for meaningful survival analysis. METHODS: This study describes the clinicopathologic profiles of 344 patients, 194 male and 150 female (M:F, 1.3:1.0), with primary chondrosarcoma of long bones and limb girdles seen at 1 institution over a period of 80 years. RESULTS: The average age at presentation was 46 years (range, 5-82 years). The pelvis was the most common location (1.7% of all patients). Local pain was the most frequently reported initial symptom (81.4%). Survival analysis was limited to 233 patients whose primary treatment was given at the Mayo Clinic. All 233 patients had potential follow-up of at least 5 years. The overall 5-year survival rate was 77% (the expected rate was 96%). Local recurrence developed in 19.7% of patients and metastatic lesions in 13.7%. The recurrence rate was higher for tumors of the shoulder and pelvis than for tumors of long bones. Radiographically, chondrosarcomas had a characteristic appearance, including a combination of bone expansion and cortical thickening. Entering the tumor at surgery increased the risk of local recurrence. Histologic tumor grade was an important predictor of local recurrence and metastasis. CONCLUSIONS: With adequate initial surgical intervention, chondrosarcoma is primarily a local disease with a low metastatic rate.

Adolescent↗
PubMed1998

Platelet-derived growth factor, intimal hyperplasia, and ischemic complications in giant cell arteritis.

OBJECTIVE: To explore whether vasoocclusion in giant cell (temporal) arteritis (GCA) is related to intimal hyperplasia and in situ production of platelet-derived growth factor (PDGF). METHODS: Temporal artery biopsy specimens from patients with GCA were analyzed for the presence of intimal hyperplasia. Expression of PDGF-A and PDGF-B was assessed by immunohistochemistry and digitized image analysis. RESULTS: PDGF-A and PDGF-B were widely expressed in inflamed arteries. CD68+ macrophages, smooth muscle cells, and multinucleated giant cells produced PDGF, whereas hyperplastic intimal tissue did not. Arteries with marked luminal narrowing and those with no or minimal luminal narrowing differed in the extent and distribution of PDGF expression. Concentric intimal hyperplasia was associated with the accumulation of PDGF-A- and PDGF-B-producing CD68+ macrophages at the media-intima junction. PDGF+,CD68+ macrophages in close proximity to the internal elastic lamina frequently coproduced matrix metalloproteinase 2. Intimal hyperplasia of the temporal artery correlated with ischemic complications of GCA, such as ocular involvement, jaw claudication, and aortic arch syndrome. CONCLUSION: Production of PDGF has a role in arterial occlusion in GCA. The excessive fibroproliferative response leading to luminal narrowing can be distinguished from the stenosing process in atherosclerosis and postangioplasty restenosis, suggesting that there are different response patterns to arterial injury. In GCA, macrophages at the media-intima border are the dominant source of PDGF. Since vasoocclusion is associated with a number of serious complications in GCA, inhibition of intimal proliferation should be a major goal of treatment.

Brain Ischemia↗
PubMed1997

Disease patterns and tissue cytokine profiles in giant cell arteritis.

OBJECTIVE: To determine whether clinical heterogeneity in patients with giant cell arteritis (GCA) is correlated with different patterns in the tissue-specific inflammatory response. METHODS: Twenty-three patients with typical histomorphologic findings of GCA were grouped according to the presence or absence of jaw claudication and/or visual abnormalities, fever, concomitant polymyalgia rheumatica (PMR), and histologic evidence of giant cell formation. The inflammatory response in temporal artery biopsy specimens was characterized by semiquantification of cytokine messenger RNA (mRNA) transcripts using reverse transcriptase-polymerase chain reaction, followed by oligonucleotide hybridization with cytokine-specific probes. Clinical patterns were then correlated with profiles of tissue cytokines. RESULTS: Inflammatory cytokines were expressed in all temporal artery tissues. In situ synthesis of interleukin-2 (IL-2), interferon-gamma (IFN gamma), and IL-1 beta mRNA, but not of IL-10 and IL-12 mRNA, distinguished different patterns of inflammation, and these patterns correlated with clinical manifestations of the disease. Patients with evidence of ischemic symptoms, indicated by jaw claudication and/or visual symptoms, typically expressed higher concentrations of IFN gamma mRNA (P = 0.008) and IL-1 beta mRNA (P = 0.02). Presence of fever was correlated with lower copy numbers of IFN gamma (P = 0.02). Formation of giant cells in the granulomatous infiltrates was associated with the local synthesis of IFN gamma mRNA (P = 0.003). Tissue from GCA patients with concomitant PMR contained higher levels of IL-2 mRNA transcripts (P = 0.001). CONCLUSION: Variations in the clinical presentation of GCA were correlated with cytokine mRNA expression in the affected temporal arteries. Differences in the effector functions of tissue-infiltrating T cells distinguished disease patterns in which either local ischemic symptoms or systemic involvement was dominant, or in which there was co-occurrence of PMR. Definition of different patterns of inflammation in GCA might, therefore, facilitate the design of differentiated therapeutic approaches.

Aged↗
PubMed1997

Diffuse proliferative glomerulonephritis and acute renal failure associated with acute staphylococcal osteomyelitis.

A 72-year-old man developed acute renal failure after coronary bypass surgery that had been complicated by sternal osteomyelitis caused by the Staphylococcus aureus bacterium. Bacteremia and sepsis were not present. Renal biopsy demonstrated a florid, diffuse, proliferative glomerulonephritis with glomerular immune complex deposition. Management included hemodialysis, prolonged antibiotic therapy, and repeated surgical debridement. Spontaneous recovery of renal function occurred after eradication of infection and final surgical wound repair. The relationship between acute bacterial infections and glomerulonephritis and, in particular, the causal role of staphylococcal antigens in the pathogenesis of such lesions is discussed.

Acute Kidney Injury↗
PubMed1996

Correlation of the topographical arrangement and the functional pattern of tissue-infiltrating macrophages in giant cell arteritis.

End organ ischemia, fragmentation of elastic membranes, and aneurysm formation in patients with giant cell vasculitis results from an inflammation destroying the mural layers of large and medium sized arteries. Although the inflammatory infiltrate extends through all layers of the affected blood vessel, the most pronounced changes involve the intima and the internal elastic lamina. Analysis of the functional profile of tissue infiltrating CD68+ cells demonstrates that different subsets of macrophages can be distinguished. TGFbeta1-expressing CD68+ cells coproduce IL-1beta and IL-6, are negative for inducible nitric oxide synthase (iNOS), and exhibit a strong preference for localization in the adventitia. The adventitial homing of TGFbeta1+ CD68+ cells places them in the vicinity of IFN-gamma secreting CD4+ T cells which also accumulate in the exterior layer of the artery. Conversely, iNOS expressing CD68+ cells are negative for TGFbeta and are almost exclusively found in the intimal layer of the inflamed artery. The intimal-medial junction is the preferred site for 72-kD collagenase expressing CD68+ cells. Thus, TGFbeta1-producing macrophages colocalize with activated CD4+ T cells and home to an area of inflammation which is distant from the site of tissue damage but critical in regulating cellular influx, suggesting that TGFbeta1 functions as a proinflammatory mediator in this disease. iNOS- and 72-kD collagenase-producing macrophages accumulate at the center of pathology implying a role of these products in tissue destruction. These data indicate that the microenvironment controls the topographical arrangement as well as the functional commitment of macrophages.

Antigens, CD↗
PubMed1996

Altered expression of CA-125 in breast carcinomas.

CA-125 is a high molecular weight glycoprotein that is best known as a tumour marker for ovarian carcinoma but has been found to be present on various epithelial surfaces including normal tissues. Elevated serum levels of CA-125 have been described in malignancies other than ovarian carcinoma as well as in inflammatory conditions. The expression of CA-125 was studied in paraffin-embedded tissue from 48 mammary carcinomas and 11 samples of normal mammary gland using two monoclonal antibodies, M2 and M11. CA-125 was detected in all normal tissue samples and 64% of the breast carcinomas. Eight of the thirty CA-125-positive carcinomas reacted with only one of the antibodies, indicating molecular change. In normal mammary tissue, CA-125 was seen on apical surfaces and in ductal contents, whilst the majority of the carcinomas (90%) expressed CA-125 in cytoplasmic granules, often showing membranous staining as well. In 16 samples of lymph node metastases CA-125 expression was similar to that seen in the primary tumour. Elevated serum levels of CA-125 were detected in only 3 out of 41 samples available from this patient group. No significant associations were detected with various clinical parameters. We conclude that CA-125 is normally expressed in the mammary gland and that the expression is frequently altered and sometimes absent in mammary carcinoma, possibly reflecting the loss of cellular polarity. Measuring serum levels of CA-125 is not relevant in breast carcinoma patients since one third of breast carcinomas were CA-125 negative and even patients with strongly CA-125-positive tumors had undetectable CA-125 serum levels.

Breast Neoplasms↗
PubMed1996

Interferon-gamma-producing T cells in giant cell vasculitis represent a minority of tissue-infiltrating cells and are located distant from the site of pathology.

Giant cell vasculitis is an arteritis that predominantly affects medium- and large-sized arteries. Genetic risk factors and clonal expansion of selected CD4+ T cell specificities in the vascular lesions support the model that giant cell arteritis is a T-cell-driven disease. Interferon (IFN)-gamma production in the tissue is intimately associated with the formation of the inflammatory infiltrates. Antigens inducing stimulation of T cells are unknown. To provide indirect evidence for the type and the tissue localization of the antigen, we examined CD4+ T cells in the lesions that secrete IFN-gamma. Temporal artery specimens from patients with giant cell arteritis were analyzed bu two-color immunohistochemistry applying antibodies to T cell markers. IFN-gamma, the interleukin-2 receptor alpha-chain (CD25) and talin, a cytoskeletal protein that is reorganized in T cells interacting with antigen-presenting cells. Proliferating cells in the lesions were identified through the expression of the Ki-67 nuclear antigen. More than 90% of tissue-infiltrating IFN-gamma-producing cells were CD4+ CD45RO+. They represented a minute subset (2 to 4%) of tissue-infiltrating T cells. IFN-gamma+ T cells aggregated in the adventitial layer of the inflamed artery where they were either diffusely distributed or arranged in clusters. The majority of IFN-gamma-secreting T cells expressed CD25. IFN-gamma+ T cells included a fraction of cells that had reorganized the cytoskeletal protein talin, indicating an interaction of the T cell receptor and an antigen-presenting cell. A subset of IFN-gamma-expressing T cells was undergoing proliferation in the tissue. IFN-gamma-producing T cells in vasculitic lesions of giant cell arteritis express several markers that identify them as T cells that have recently been stimulated through their antigen-specific receptor. These putatively disease-relevant T cells represent only a very minor fraction of tissue-infiltrating cells. Their preferential accumulation in the adventitia is most compatible with the model that they contact the relevant antigen primarily in this particular region of the artery. Their regulatory function appears to extend into the inner media and intima where pathological changes in giant cell arteritis are most pronounced.

Arteritis↗
PubMed1995

TP53 mutations and abnormal p53 protein staining in breast carcinomas related to prognosis.

Abnormalities in the TP53 tumour suppressor gene were evaluated in 106 unselected breast carcinomas and compared to clinical outcome of the disease. Tumours were screened for p53 abnormalities using immunohistochemical staining and polymerase chain reaction-constant denaturant gel electrophoresis (PCR-CDGE) analysis, followed by PCR and direct sequencing. Allelic loss at the TP53 locus was determined with polymorphic markers by comparing normal and tumour DNA. For approximately half of the patients, abnormal p53 protein expression in serum was determined by an ELISA assay. p53 abnormalities, detected as mutations and/or nuclear staining, were found in 37.6 (38/101) of cases. Nuclear staining for p53 protein could be identified in 33.7% of the tumours. Mutations in exons 5-8 were detected in 18.9% of the tumours, and an association was found between mutations and nuclear staining. Allelic loss in the TP53 region on 17p was more frequent in tumours showing changes in the TP53 gene (72.7%) compared to tumours with no mutation (45.8%). Serum levels of p53 antibodies showed no association with either TP53 mutations or nuclear staining. Women with TP53 mutations in their tumours had an elevated risk of dying during the study period (RR (relative risk) = 3.4, P = 0.014). The effects of p53 positive staining were similar (RR = 3.2, P = 0.013). Considering all abnormalities, mutation and/or staining, the relative risk of dying from breast cancer was 3.5 (P = 0.008).

Adult↗
PubMed1995

Extrapulmonary lymphangioleiomyomatosis and lymphangiomatous cysts in tuberous sclerosis complex.

OBJECTIVE: To describe the clinical manifestations, imaging findings, and histologic features of extrapulmonary lymphangioleiomyomatosis (LAM) in the tuberous sclerosis complex (TSC). DESIGN: We retrospectively reviewed institutional medical records since 1940 to identify patients with TSC and extrapulmonary LAM. MATERIAL AND METHODS: Of 403 patients with TSC, 3 had pulmonary and extrapulmonary LAM and retroperitoneal lymphangiomatous cysts. The clinical, imaging, and histologic features of these three patients were summarized, including analysis of biopsy specimens by conventional histology, immunohistology, radiolabeled ligand-binding assays, and tissue culture. RESULTS: The three young women had characteristic dermatologic findings of TSC and pulmonary LAM. Two patients were of normal intelligence, and one had a recent history of contraceptive use. All three patients had intra-abdominal lymphangiomatous cysts, uterine LAM, and renal angiomyolipomas. Renal and uterine biopsy specimens demonstrated positive immunostaining for melanoma-related antigens and expression of estrogen and progesterone receptors by ligand-binding assay and immunohistology. Cells cultured from LAM tissue of one of the patients exhibited a mitogenic response to estradiol. CONCLUSION: Clinically significant extrapulmonary LAM is a rare manifestation of TSC and may occur in women with this disease who also have pulmonary LAM. The clinical features of these patients confirm the importance of sex steroids in the development of these lesions. Immunohistochemical findings suggest that LAM and angiomyolipomas have a neuroectodermal origin. The development of lymphangiomatous cysts in these patients is probably due to smooth muscle proliferation in lymph vessels, which can result in lymphatic obstruction.

Abdominal Neoplasms↗
PubMed1994

Giant cell arteritis in Iceland. An epidemiologic and histopathologic analysis.

OBJECTIVE: To investigate the incidence and clinical and histopathologic features of giant cell (temporal) arteritis (GCA) in the Caucasian population of Iceland. METHODS: All patients diagnosed between 1984 and 1990 were included. Case ascertainment for the study was done in 2 ways: 1) a computerized search from all hospitals and primary care clinics for the diagnosis of GCA, and 2) a review of all temporal artery biopsies performed during the 7-year period. RESULTS: One hundred thirty-three patients with GCA were identified. All fulfilled the 1990 American College of Rheumatology criteria for the classification of GCA. The incidence rate for the population 50 years and older was 27/100,000 (36/100,000 and 18/100,000 for women and men, respectively). Clinical findings included the following: mean age at diagnosis 72.5 years for women and 70.3 years for men, new headache 63.2%, abnormal temporal artery on palpation 43.6%, mean erythrocyte sedimentation rate 88 mm/hour, symptoms of polymyalgia rheumatica 48.1%, and visual disturbances 14.3%. A total of 744 patients underwent temporal artery biopsy during the 7-year period; 16.8% had a positive biopsy result. All 133 patients with the diagnosis of GCA underwent a temporal artery biopsy; 94% had a positive result. Histopathologic findings from the positive biopsies included a fragmented internal elastic lamina in 99.2%, giant cells in 65.6%, and fibrinoid necrosis in 12%. CONCLUSION: Compared with previous epidemiologic surveys, this study shows a high incidence of biopsy-proven GCA in Iceland.

Aged↗
PubMed1994

Arterial fibromuscular dysplasia associated with severe alpha 1-antitrypsin deficiency.

OBJECTIVE: To elucidate the putative arteriopathy associated with alpha 1-antitrypsin (alpha 1-AT) deficiency. DESIGN: We retrospectively studied the frequency of occurrence of fibromuscular dysplasia (FMD) in patients with alpha 1-AT deficiency in whom a postmortem examination had been done during a 10-year period at the Mayo Clinic. MATERIAL AND METHODS: The medical records of all patients in whom an autopsy was done at the Mayo Clinic between 1983 and 1992 were reviewed to identify all those with a diagnosis of alpha 1-AT deficiency or FMD. RESULTS: Arterial FMD was found in 2 of 6 patients with alpha 1-AT deficiency (33.3%; 95% confidence interval, 4.3 to 77.7%) in comparison with 23 of 6,690 patients without alpha 1-AT deficiency (0.3%; 95% confidence interval, 0.2 to 0.5%). In both patients with alpha 1-AT deficiency and FMD, the arterial media was thickened and composed of irregular arrays of muscular and connective tissue fibers in a background of mucoid ground substance. CONCLUSION: These findings provide further evidence for an underlying arteriopathy in patients with alpha 1-AT deficiency and suggest that FMD may be a non-specific disorder.

Adult↗