Micro-morphometrical assessment of the effect of Harpagophytum procumbens extract on articular cartilage in rabbits with experimental osteoarthritis using magnetic resonance imaging.

In vitro effects indicate a putative beneficial effect of Harpagophytum procumbens on cartilage turnover, however, in vivo protective effects on cartilage have yet to be demonstrated. A 7.1T MRI scanner was used to derive measurements of thickness, surface area and volume of the tibial condylar cartilage and to assess their precision (in the case of volume also accuracy) against the volumes of dissected cartilage measured by water displacement. Quantitative measurements were made in 16 rabbits, 6 months after unilateral medial meniscectomy and transection of the anterior cruciate ligament, after which eight of these were given a proprietary extract of Harpagophytum procumbens (HP). A semiquantitative MRI-based grading of the tibial cartilage was also compared with a 'macroscopic' grading based on direct visual inspection of dissected joints. The test-retest precision for MRI-based measurement was ≤6.4%. MRI-based measurements correlated well with volumes of surgically resected cartilage (r = 0.97, pair-wise random difference 4.2%). The medial tibial cartilage thickness and volume were about 35% smaller in the operated knees than in the non-operated contralateral knees (p < 0.05). The findings suggest that MRI is a precise and accurate tool for evaluating cartilage in a rabbit model of OA. The difference between the intact and operated knee in thickness and volume of the medial tibial cartilage was slightly but not significantly smaller in the HP-treated group than in the non-treated group.

["X-ray diagnostics - discipline-bound skeleton" and "magnetic resonance imaging - discipline-bound". Attempt at analysis of the achieved and the achievable]. / "Röntgendiagnostik - fachgebunden Skelett" und "Magnetresonanztomographie - fachgebunden". Versuch einer Analyse des Erreichten und Erreichbaren.

The presently valid regulation for professional advanced training from the year 2003 has already experienced much discussion about its meaningfulness and practicality. One of the essential changes for physicians active in discipline 6 (surgery) is the reform of X-ray analysis as specialist supplementary training. The discipline orthopedics and trauma surgery is particularly dependent on the application of economical diagnostics and therapy control with conventional X-ray imaging as well as modern computed tomography and magnetic resonance imaging. Simultaneously, there exist national government regulations for X-ray and radiation protection, which place already clear demands on the competence of individual physicians. The sometimes seemingly complicated regulations and their interaction will be described in this article and recommendations for planning one's own professional competence and demonstration of competence (advanced training) will be given.

Increase in degraded collagen type II in synovial fluid early in the rabbit meniscectomy model of osteoarthritis.

OBJECTIVE: The objective of this study was to determine whether collagen type II breakdown products in synovial fluid (SF), detected by an enzyme-linked immunoassay, represent a useful marker for early events in osteoarthritis (OA) in the rabbit medial meniscectomy model. DESIGN: Complete medial meniscectomy was performed on the right knee joints of 32 rabbits. Balanced groups of rabbits were then sacrificed at 2, 4, 8, and 12 weeks post-surgery. An additional 8 unoperated and 11 sham-operated animals served as controls. SF lavages were performed on right and left knee joints of the same animals at sacrifice. The proteolytic epitope of type II collagen was monitored using an enzyme-linked immunoassay. RESULTS: Macroscopically visible surface fibrillation and focal erosions appeared as early as 2 weeks after meniscectomy in the femorotibial joint (P<0.01). OA developed gradually during the later observation period, and then predominantly on the medial tibial plateau and medial femur. Significant histological alterations in cartilage, including a loss of proteoglycans, surface irregularities, and clefts, were detected at 2 weeks after meniscectomy (P<0.01). Collagen type II epitope levels in SF lavage samples were elevated peaking at 2 weeks after meniscectomy (P<0.02). Levels decreased at later time points, but they were still raised at 12 weeks (P< or =0.05). Highly significant correlations were found between the SF collagen type II epitope levels and the macroscopic and microscopic scoring results (Spearman rho correlation coefficient, macroscopy-collagen type II epitope r=0.222, P=0.025; microscopy-collagen type II epitope r=0.436, P< or =0.01). CONCLUSION: In this rabbit model of medial meniscectomy, levels of type II collagen fragments in SF appear to provide a useful marker of the early degenerative changes.

Detection of thyroid peroxidase mRNA in peripheral blood of patients with malignant and benign thyroid diseases.

The aim of this study was to evaluate thyroid peroxidase (TPO) mRNA expression in peripheral blood of patients with benign and malignant thyroid disease. Included were 120 thyroid cancer patients, 85 patients with goitre or Graves' disease (GD) and 54 healthy volunteers. TPO mRNA expression was analysed in peripheral blood by nested RT-PCR. In cancer patients, RT-PCR results were compared with staging, grading and serum thyroglobulin (TG) measurement. TPO transcripts were detected in 7/10 (70%) patients with known metastases of thyroid cancer and in 39 of 110 (36%) patients without metastases (P<0.05), in 15/44 (34%) patients with goitre, in 17/41 (41%) cases with GD and in 4/54 (7.4%) subjects in the control group (P<0.05, controls vs all patients with thyroid disease). Among cancer patients without metastatic disease, RT-PCR results correlated positively with lymph node status (P=0.05), grading (P=0.01) and elevated serum thyroglobulin levels (P=0.03). This is the largest study investigating the use of the TPO-RT-PCR assay. Positivity in TPO-RT-PCR correlates significantly with metastatic disease in cancer patients and with the presence of thyroid disease in general. To date, TPO-RT-PCR cannot substitute for standard techniques in the diagnosis of local recurrence or metastatic spread in thyroid cancer patients. However, as results of TPO-RT-PCR correlate significantly with lymph node status, grading and serum TG measurements in patients with non-metastatic disease, TPO seems to be an interesting molecular marker to look at in follow-up studies.

Differences in tumor cell proliferation, HLA DR expression and lymphocytic infiltration in various types of thyroid carcinoma.

The proliferative activity of various thyroid carcinoma forms (papillary, follicular, medullary, anaplastic) was investigated using two second generation antibodies against Ki-67 that can be used on paraffin-embedded sections. Poorly-differentiated carcinomas had a higher proliferation than well-differentiated forms. Papillary carcinoma stained significantly more often with either antibody than follicular carcinoma. A solid growth pattern correlated with high Ki-67 expression while an increase in follicular elements and a high amount of psammoma bodies coincided with lower proliferation.HLA class II expression and infiltrating lymphocytes are prerequisites for an immune defense against cancer. In this study, HLA DR was increased in poorly-differentiated carcinomas, especially in the anaplastic type. The increase in HLA DR was correlated with Ki-67 positivity. On tumor-infiltrating lymphocytes, HLA DR was well expressed in papillary carcinoma and relatively poorly expressed in follicular carcinoma, but there was no significant correlation with carcinoma type or morphological parameters. CD 45 R0, which might recognize memory cells, was found mostly in anaplastic and papillary carcinomas, and correlated well with HLA DR expression. These findings imply that an active but variable immune response is present in thyroid carcinoma.

[Insular carcinoma of the thyroid: a differentiated thyroid carcinoma with poor prognosis]. / Das insuläre Schilddrüsencarcinom--ein differenziertes Schilddrüsencarcinom mit schlechter Prognose.

Insular carcinoma of the thyroid is a low differentiated type constituting about 5% of all thyroid cancers. Higher aggressiveness has been suggested as an important clinical feature. The value of preoperative fine-needle aspiration biopsy is not clearly proven for insular carcinoma. The criteria for histological diagnosis have been outlined by Carcangiu et al. Because of its aggressiveness, radical treatment at primary surgery appears advisable. Its clear distinction from undifferentiated (anaplastic) and medullary (C cell) cancers is important, as thyroglobulin is regularly synthesized by cancer cells. Enrichment of radioactive iodine makes such treatment feasible postoperatively and at relapse. Follow-up should be performed as in highly differentiated papillary and follicular thyroid cancer. A patient series of eight cases is presented. While all cancers were advanced at the initial diagnosis, the observed disease courses were in agreement with the assumption that insular carcinoma is a more aggressive form of differentiated thyroid cancer.

Molecular detection of thyroglobulin mRNA transcripts in peripheral blood of patients with thyroid disease by RT-PCR.

The sensitive detection of circulating tumour cells in patients with differentiated thyroid cancer may precede the detection of relapse by other diagnostic studies--such as serum thyroglobulin-and thus may have important therapeutic and prognostic implications. We performed reverse transcription-polymerase chain reaction (RT-PCR) on blood samples from patients diagnosed with thyroid disease using two different RT-PCR sensitivities. Additionally, tissue specificity of TG mRNA-expression was determined using RNA extracts from 27 different human tissues. The lower limit of detection was 50-100 TG mRNA producing cells/ml blood using a 'normal' RT-PCR sensitivity and 10-20 cells/ml blood using a 'high' sensitivity. With the normal sensitivity TG mRNA was detected in 9/13 patients with thyroid cancer and metastasis, 63/137 patients with a history of thyroid cancer and no metastasis, 21/85 with non-malignant thyroid disease and 9/50 controls. With the high sensitivity TG mRNA was detected in 11/13 patients with thyroid cancer and metastasis, 111/137 patients with a history of thyroid cancer and no metastasis, 61/85 with non-malignant thyroid disease and 41/50 controls. Interestingly, using the normal RT-PCR sensitivity TG mRNA transcripts are specific for thyroid tissue and detectable in the peripheral blood of controls and patients with thyroid disease, which correlates with a diagnosis of metastasized thyroid cancer. However, with a high RT-PCR sensitivity, TG mRNA expression was found not to be specific for thyroid tissue and was not correlated with a diagnosis of thyroid cancer in patients. As a consequence, to date TG mRNA detected by RT-PCR in the peripheral blood cannot be recommended as a tumour marker superior to TG serum-level.

Longitudinal characterization of synovial fluid biomarkers in the canine meniscectomy model of osteoarthritis.

Damage to the meniscus can lead to posttraumatic osteoarthritis. Early markers of joint injury and tissue disease may be useful in developing and administering clinical treatment. We investigated the effects of total medial meniscectomy on biomarkers measured serially in synovial lavage fluid each month for 3 months. Following meniscectomy in dogs, four biomarkers were evaluated: cartilage oligomeric matrix protein, keratan sulfate epitope (5D4), the 3B3(-) neoepitope of chondroitin-6-sulfate, and the 3B3(+) chondroitinase-generated epitope of chondroitin-6-sulfate. Meniscectomy led to statistically significant elevations of all four biomarkers, with levels peaking at 4 weeks. By 12 weeks, the level of the 5D4 epitope returned to the preoperative baseline level whereas that of cartilage oligomeric matrix protein, 3B3(-), and 3B3(+) remained above the baseline. Concentrations of these biomarkers in the knees not operated on did not change significantly from the baseline. The levels of cartilage oligomeric matrix protein and 3B3(-) relative to 3B3(+) remained constant in all knees. In contrast, the level of 5D4 relative to 3B3(+) declined over time in the knee operated on but remained constant in the knee not operated on. These results demonstrate a quantitative change in the molecular components of synovial fluid after meniscectomy, as well as a qualitative change evinced by an alteration in the relative proportions of these epitopes. Extensive analyses showed a strong correlation between serum levels of 3B3(-) from the femoral and cephalic veins; however, serum 3B3(-) was not correlated with synovial fluid 3B3(-). These findings support the hypothesis that the concentrations of select cartilage biomarkers in synovial fluid are altered following meniscectomy and are promising tools for objectively monitoring the induction of osteoarthritis in this model system.

Occurrence of carcinoma-associated antigen 494 in colorectal cancer tissue and in Patients' sera during metastatic disease.

CA 494 is a new carbohydrate epitope on a high-molecular-weight mucin-type glycoprotein which has been intensively investigated in pancreatic cancer. In this study, the occurrence of CA 494 was characterized in colorectal cancer tissue and in patients' sera during metastatic disease. CA 494 was detected in cancer tissue from 82% of the 49 patients studied. Serum levels of CA 494 were elevated (>40 U/ml) in 66% of the same patients during metastatic disease (n = 41). The well-established tumor markers carcinoembryonic antigen (CEA) and CA 19-9 were increased (CEA >5 ng/ml; CA 19-9 >37 U/ml) in about 79% of these patients. The correlation of CA 494 with CA 19-9 levels was lower (r = 0.532) than previously reported in pancreatic cancer.

[Esophageal perforation. A rare complication after operation of degenerative and traumatic pathology of the cervical spine]. / Die Osophagusperforation. Eine seltene Komplikation der Operation degenerativer und traumatischer Halswirbelsäulenleiden.

Esophageal perforation is a rare complication in the surgical treatment of diseases of the cervical spine. Following cervical discectomy for degenerative arthritis at the C6/C7 level, a 42-year-old male patient experienced a progressive dislocation of a PMMA-implant with impending esophageal perforation. Neurological symptoms including dysphagia worsened and a new fusion had to be performed 3.5 months after initial surgery. On the 2nd postoperative day, a laceration of the esophagus was diagnosed clinically and on esophagogram. After drainage, the perforation healed under antibiotic treatment and enteral nutrition through a percutaneous endoscopic gastrostomy within 5 weeks.

On the possible role of positive end-expiratory pressure ventilation in the treatment of chylothorax caused by blunt chest trauma.

Recent reports on the treatment of chylothorax postulate a benefit to ventilator therapy, especially using positive end-expiratory pressure (PEEP). This report describes the use of mechanical ventilation with PEEP in the management of a 24-year-old male motorcyclist who sustained a ligamentous Chance fracture of the thoracic spine at the T6-7 level with bilateral traumatic chylothorax. Treatment of the chylothorax consisted of high PEEP ventilation, bilateral chest tube thoracostomies, and total parenteral nutrition. The chylothoraces resolved within 4 days of treatment and mechanical ventilation was stopped. Ventilator therapy of traumatic chylothorax and the physiologic grounds for its use are discussed. A review of the literature and experimental evidence seem to suggest that ventilator treatment of traumatic chylothoraces is effective.

Acute inflammation, acute phase serum amyloid A and cholesterol metabolism in the mouse.

Acute inflammation results in a profound change in the apolipoprotein composition of high density lipoprotein (HDL). Several isoforms of the serum amyloid A (SAA) family, SAA1 and SAA2, become major components of HDL. This structural relationship has suggested that acute phase SAA plays some as yet unidentified role in HDL function, possibly related to cholesterol transport, during the course of acute inflammation. Using subcutaneous AgNO3 to induce a sterile abscess changes in plasma cholesterol and SAA were monitored over the subsequent 144 h. Total plasma cholesterol began to increase within 12 h of the induction of inflammation and reached a peak in 24 h. Thereafter its plasma levels fell returning to normal values by 96-120 h. The bulk of the increase in plasma cholesterol was found in the free cholesterol fraction of HDL. This pattern of cholesterol increase corresponds to the established temporal changes for acute phase SAA (AP-SAA). AP-SAA levels increased within 8 h of the induction of inflammation and reached a peak at 24 h. They began to decrease by 48 h with small quantites still present 120 h later. In concert, but inversely, with the changes in AP-SAA the apoA-I, apoA-II, and apo-E, content of HDL decreased during the AP-SAA increases and increased as AP-SAA levels fell. The plasma appearance of cholesterol from the periphery, and central parts of the inflammatory site was assessed by the use of radiolabelled cholesterol. The peripherally placed cholesterol rapidly reached a peak plasma concentration within 24 h of injection. Cholesterol placed in the central part of the sterile abscess, a site relatively inaccessible to the vasculature required 48 h to reach its peak and was 5-times lower than that placed peripherally. The influence of AP-SAA on neutral cholesterol ester hydrolase (nCEH) activity in mouse liver homogenates, mouse peritoneal macrophage homogenates, and a purified porcine pancreatic enzyme with nCEH activity was also assessed. Following optimization with regard to pH, bile salt concentration, protein concentration and incubation time, mouse peritoneal macrophages had a significantly higher nCEH specific activity than that found in liver (7-8 fold). Purified AP-SAA, assessed over a concentration range of 0-10 microg/ml, enhanced nCEH activity at concentrations above 2 microg/ml. The nCEH activity, regardless of its source, increased by 3-7 fold in the presence of AP-SAA. Equivalent concentrations of apolipoprotein A-I (apo A-I) and bovine serum albumin (BSA) failed to alter the activity of nCEH. The effect of AP-SAA on a purified form of nCEH suggests that AP-SAA may have a direct effect on the activity of this enzyme. The temporal correlation of circulating AP-SAA and plasma cholesterol and the significant stimulation of nCEH by AP-SAA (but not apoA-I or BSA) provides further evidence that AP-SAA plays a role in cholesterol metabolism during the course of acute inflammation.