Comparison of Compressive Stress-Relaxation Behavior in Osteoarthritic (ICRS Graded) Human Articular Cartilage.

Osteoarthritis (OA) is a common joint disorder found mostly in elderly people. The role of mechanical behavior in the progression of OA is complex and remains unclear. The stress-relaxation behavior of human articular cartilage in clinically defined osteoarthritic stages may have importance in diagnosis and prognosis of OA. In this study we investigated differences in the biomechanical responses among human cartilage of ICRS grades I, II and III using polymer dynamics theory. We collected 24 explants of human articular cartilage (eight each of ICRS grade I, II and III) and acquired stress-relaxation data applying a continuous load on the articular surface of each cartilage explant for 1180 s. We observed a significant decrease in Young's modulus, stress-relaxation time, and stretching exponent in advanced stages of OA (ICRS grade III). The stretch exponential model speculated that significant loss in hyaluronic acid polymer might be the reason for the loss of proteoglycan in advanced OA. This work encourages further biomechanical modelling of osteoarthritic cartilage utilizing these data as input parameters to enhance the fidelity of computational models aimed at revealing how mechanical behaviors play a role in pathogenesis of OA.

Sustainable Development of Pathology in Sub-Saharan Africa: An Example From Ghana.

CONTEXT: - Pathology services are poorly developed in Sub-Saharan Africa. Komfo Anokye Teaching Hospital in Kumasi, Ghana, asked for help from the pathology department of the University Hospital of North Norway, Tromsø. OBJECTIVE: - To reestablish surgical pathology and cytology in an African pathology department in which these functions had ceased completely, and to develop the department into a self-supporting unit of good international standard and with the capacity to train new pathologists. DESIGN: - Medical technologists from Kumasi were trained in histotechnology in Norway, they were returned to Kumasi, and they produced histologic slides that were temporarily sent to Norway for diagnosis. Two Ghanaian doctors received pathology training for 4 years in Norway. Mutual visits by pathologists and technologists from the 2 hospitals were arranged for the introduction of immunohistochemistry and cytology. Pathologists from Norway visited Kumasi for 1 month each year during 2007-2010. Microscopes and immunohistochemistry equipment were provided from Norway. Other laboratory equipment and a new building were provided by the Ghanaian hospital. RESULTS: - The Ghanaian hospital had a surgical pathology service from the first project year. At 11 years after the start of the project, the services included autopsy, surgical pathology, cytopathology, frozen sections, and limited use of immunohistochemistry, and the department had 10 residents at different levels of training. CONCLUSIONS: - A Ghanaian pathology department that performed autopsies only was developed into a self-supported department with surgical pathology, cytology, immunohistochemistry, and frozen section service, with an active residency program and the capacity for further development that is independent from assistance abroad.

Optical investigation of osteoarthritic human cartilage (ICRS grade) by confocal Raman spectroscopy: a pilot study.

Biomolecular changes in the cartilage matrix during the early stage of osteoarthritis may be detected by Raman spectroscopy. The objective of this investigation was to determine vibrational spectral differences among different grades (grades I, II, and III) of osteoarthritis in human osteoarthritic cartilage, which was classified according to the International Cartilage Repair Society (ICRS) grading system. Degenerative articular cartilage samples were collected during total joint replacement surgery and were classified according to the ICRS grading system for osteoarthritis. Twelve cartilage sections (4 sections of each ICRS grades I, II, and III) were selected for Raman spectroscopic analysis. Safranin-O/Fast green was used for histological staining and assignment of the Osteoarthritis Research Society International (OARSI) grade. Multivariate principal component analysis (PCA) was used for data analysis. Spectral analysis indicates that the content of disordered coil collagen increases significantly during the early progression of osteoarthritis. However, the increase was not statistically significant during later stages of the disease. A decrease in the content of proteoglycan was observed only during advanced stages of osteoarthritis. Our investigation shows that Raman spectroscopy can classify the different stage of osteoarthritic cartilage and can provide details on biochemical changes. This proof-of-concept study encourages further investigation of fresh cartilage on a larger population using fiber-based miniaturized Raman probe for the development of in vivo Raman arthroscopy as a potential diagnostic tool for osteoarthritis.

[Middle-aged female presenting with headache, blurred vision and skin rash]. / Ei kvinne i 50-åra med hovudverk, uklart syn og utslett.

BACKGROUND: Autoimmune hyperlipidemia (AIH) is a rare cause of secondary hyperlipidemia. A few cases of AIH have been reported in multiple myeloma. MATERIAL AND METHODS: A female in her fifties was referred to the outpatient clinic presenting with headache, blurred vision and skin rash. Physical examination with subsequent laboratory and histological examinations revealed severe hyperlipidemia secondary to secretory multiple myeloma with monoclonal IgG kappa protein and erythrocytosis secondary to a erythropoietin secreting adenoma in the liver. RESULTS AND INTERPRETATION: Treatment for multiple myeloma (induction treatment and autologous hematological stem cell transplantation) gained partial remission and was associated with normalization of serum lipids. There was no need for further medical treatment of the hyperlipidemia. Three years after the initial treatment, serum concentrations of triglycerides and total cholesterol increased in parallel with monoclonal IgG kappa protein. Total cholesterol and triglycerides decreased and remained within the reference ranges after retreatment with a second autologous stem cell transplantation. Surgical removal of the hepatic adenoma caused normalisation of the erythropoietin concentration and resolution of the erythrocytosis. The present case reports two rare complications (AIH and erythrocytosis) to multiple myeloma and hepatic adenoma, with regression of complaints and normalisation of laboratory tests after adequate treatment of underlying diseases.

Erythropoietin production by a hepatic adenoma in a patient with severe erythrocytosis.

A 53-year-old woman with severe erythrocytosis (hemoglobin concentration 19.5 g/dl and hematocrit 0.59) was admitted to our hospital because of fatigue and headache. The serum erythropoietin (Epo) concentration was 68.6 U/l (reference range; 3.7-31.5). Further investigations excluded polycythemia vera or any lung or heart disease. Radiological examination showed a tumor in the left hepatic lobe. Needle biopsies were performed and the histopathological diagnosis was hepatocellular adenoma. Immunohistochemistry demonstrated erythropoietin expression in the adenomatous cells. Liver adenoma is a rare cause of erythrocytosis. For the first time, we report erythropoietin-positive immunoreactivity in liver adenomatous cells in a patient with erythrocytosis.

Preoperative staging and treatment options in T1 rectal adenocarcinoma.

BACKGROUND: Major rectal resection for T1 rectal cancer offers more than 95% cancer specific five-year survival to patients surviving the first 30 days after surgery. A significant further improvement by development of the surgical technique may not be possible. Improvements in the total survival rate have to come from a more differentiated treatment modality, taking patient and procedure related risk factors into account. Subgroups of patients have operative mortality risks of 10% or more. Operative complications and long-term side effects after rectum resection are frequent and often severe. RESULTS: Local treatment of T1 cancers combined with close follow-up, early salvage surgery or later radical resection of local recurrences or with chemo-radiation may lead to fewer severe complications and comparable, or even better, long-term survival. Accurate preoperative staging and careful selection of patients for local or non-operative treatment are mandatory. As preoperative staging, at present, is not sufficiently accurate, strategies for completion, salvage or rescue surgery is important, and must be accepted by the patient before local treatment for cure is initiated. RECOMMENDATIONS: It is recommended that polyps with low-risk T1 cancers should be treated with endoscopic snare resection in case of Haggitt's stage 1 or 2. TEM is recommended if resection margins are uncertain after snare resection for Haggitt's stage 3 and 4, and for sessile and flat, low-risk T1 cancers. Average risk patients with high-risk T1 cancers should be offered rectum resection, but old and comorbid patients with high-risk T1 cancers should be treated individually according to objective criteria as age, physical performance as well as patient's preference. All patients treated for cure with local resection or non-surgical methods should be followed closely.

Diagnostic and prognostic markers for gastrointestinal stromal tumors in Norway.

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor in the gastrointestinal tract. The diagnosis of GIST is based on histology together with a panel of immunohistochemical markers; the most important is KIT (CD117). A total of 434 cases of GISTs were confirmed by histology and immunohistochemistry, and incorporated into tissue microarrays. Validation of histological features as well as the prognostic value of two immunohistochemical biomarkers (p16 and L1) was assessed. High mitotic rate, large tumor size, nuclear atypia, and small bowel primary site were all validated as negative prognostic factors in GISTs. Expression of p16 was significantly correlated with unfavorable prognosis, whereas L1 expression was not.

A randomized trial comparing autologous chondrocyte implantation with microfracture. Findings at five years.

BACKGROUND: The optimal treatment for cartilage lesions has not yet been established. The objective of this randomized trial was to compare autologous chondrocyte implantation with microfracture. This paper represents an update, with presentation of the clinical results at five years. METHODS: Eighty patients who had a single chronic symptomatic cartilage defect on the femoral condyle in a stable knee without general osteoarthritis were included in the study. Forty patients were treated with autologous chondrocyte implantation, and forty were treated with microfracture. We used the International Cartilage Repair Society, Lysholm, Short Form-36, and Tegner forms to collect clinical data, and radiographs were evaluated with use of the Kellgren and Lawrence grading system. RESULTS: At two and five years, both groups had significant clinical improvement compared with the preoperative status. At the five-year follow-up interval, there were nine failures (23%) in both groups compared with two failures of the autologous chondrocyte implantation and one failure of the microfracture treatment at two years. Younger patients did better in both groups. We did not find a correlation between histological quality and clinical outcome. However, none of the patients with the best-quality cartilage (predominantly hyaline) at the two-year mark had a later failure. One-third of the patients in both groups had radiographic evidence of early osteoarthritis at five years. CONCLUSIONS: Both methods provided satisfactory results in 77% of the patients at five years. There was no significant difference in the clinical and radiographic results between the two treatment groups and no correlation between the histological findings and the clinical outcome. One-third of the patients had early radiographic signs of osteoarthritis five years after the surgery. Further long-term follow-up is needed to determine if one method is better than the other and to study the progression of osteoarthritis.

[A 53-year-old man with headache and concentration difficulties]. / Ein 53 år gammal mann med hovudverk og konsentrasjonsvanskar.

BACKGROUND: Polycythaemia vera is a chronic myeloproliferative disease with no single diagnostic marker. The Polycythaemia Vera Study Group used a combination of major and minor diagnostic criteria. In the presence of newer diagnostic tools, low serum erythropoietin level has been proposed as an important diagnostic criterion for polycythaemia vera, whereas an elevated erythropoietin value contradicts the diagnosis. We report a case of polycythaemia vera with extreme haemoconcentration in which the serum level of erythropoietin was above the upper reference limit. MATERIAL AND METHODS: A 53-year-old man with erythrocytosis (packed cell volume 0.68, hemoglobin 23.6 g/dl), thrombocytosis, leukocytosis and no underlying disease had a serum level of erythropoietin of 29.0 U/l (normal range 1.3-21.5 U/l). RESULTS AND INTERPRETATION: The patient was treated with venesection. After one month the haemoglobin level had decreased to 15.7 g/dl and packed cell volume to 0.48. The symptoms of polycythaemia disappeared and the serum level of erythropoietin declined to low normal values (2.2 U/l after five weeks and 5.4 U/l after 1.5 year). We propose that local hypoxia in the kidneys might be responsible for the elevated erythropoietin value at the time of diagnosis. The present case shows that high erythropoietin values may not necessarily exclude the diagnosis of polycythaemia vera.

Autologous chondrocyte implantation compared with microfracture in the knee. A randomized trial.

BACKGROUND: New methods have been used, with promising results, to treat full-thickness cartilage defects. The objective of the present study was to compare autologous chondrocyte implantation with microfracture in a randomized trial. We are not aware of any previous randomized studies comparing these methods. METHODS: Eighty patients without general osteoarthritis who had a single symptomatic cartilage defect on the femoral condyle in a stable knee were treated with autologous chondrocyte implantation or microfracture (forty in each group). We used the International Cartilage Repair Society, Lysholm, Short Form-36 (SF-36), and Tegner forms to collect data. An independent observer performed a follow-up examination at twelve and twenty-four months. Two years postoperatively, arthroscopy with biopsy for histological evaluation was carried out. The histological evaluation was done by a pathologist and a clinical scientist, both of whom were blinded to each patient's treatment. RESULTS: In general, there were small differences between the two treatment groups. At two years, both groups had significant clinical improvement. According to the SF-36 physical component score at two years postoperatively, the improvement in the microfracture group was significantly better than that in the autologous chondrocyte implantation group (p = 0.004). Younger and more active patients did better in both groups. There were two failures in the autologous chondrocyte implantation group and one in the microfracture group. No serious complications were reported. Biopsy specimens were obtained from 84% of the patients, and histological evaluation of repair tissues showed no significant differences between the two groups. We did not find any association between the histological quality of the tissue and the clinical outcome according to the scores on the Lysholm or SF-36 form or the visual analog scale. CONCLUSIONS: Both methods had acceptable short-term clinical results. There was no significant difference in macroscopic or histological results between the two treatment groups and no association between the histological findings and the clinical outcome at the two-year time-point. LEVEL OF EVIDENCE: Therapeutic study, Level I-1a (randomized controlled trial [significant difference]). See Instructions to Authors for a complete description of levels of evidence.

Diagnostic accuracy of second-opinion diagnoses based on still images.

Second opinion of histological specimens is an important part of the daily routine in anatomic pathology practices. Today, extramural second opinion can be easily obtained by sending still images via an electronic network. The aim of this study was to examine the diagnostic accuracy of second opinion diagnosis based on still images selected from glass slides of 90 archived cases originally referred for extramural second opinion. Two pathologists together diagnosed first the still images (phase 1) and then the glass slides (phase 2). Phase 1 and phase 2 diagnoses were compared with the original second opinion diagnoses (OSODs). The pathologists achieved the same diagnostic results in phase 1 and in phase 2 measured against the OSOD, 67.8% (n = 61) and 68.9% (n = 62) complete agreement, respectively. In 29 cases in phase 1, the diagnoses were discordant with the OSOD. Three cases had incorrect benign diagnoses and 8 cases had incorrect malignant diagnoses. There were 8 false-negative diagnoses regarding malignancy, 6 false-positive diagnoses regarding malignancy, and 4 other discordant diagnoses. Eleven of the 29 discordant diagnoses could have had clinical implications. In interpreting these results, it is important to acknowledge the observer variability in diagnostic histopathology in general. In conclusion, the results support the concept of using still images to obtain second opinion diagnosis.