Absence of changes in the milk microbiota during Escherichia coli endotoxin induced experimental bovine mastitis

Changes in the milk microbiota during the course of mastitis are due to the nature of a sporadic occurring disease difficult to study. In this study we experimentally induced mastitis by infusion of Escherichia coli endotoxins in one udder quarter each of nine healthy lactating dairy cows and assessed the bacteriological dynamics and the milk microbiota at four time points before and eight time points after infusion. As control, saline was infused in one udder quarter each of additionally nine healthy cows that followed the same sampling protocol. The milk microbiota was assessed by sequencing of the 16 S rRNA gene and a range of positive and negative controls were included for methodological evaluation. Two different data filtration models were used to identify and cure data from contaminating taxa. Endotoxin infused quarters responded with transient clinical signs of inflammation and increased SCC while no response was observed in the control cows. In the milk microbiota data no response to inflammation was identified. The data analysis of the milk microbiota was largely hampered by laboratory and reagent contamination. Application of the filtration models caused a marked reduction in data but did not reveal any associations with the inflammatory reaction. Our results indicate that the microbiota in milk from healthy cows is unaffected by inflammation

Residual hip dysplasia at 1 year after treatment for neonatal hip instability is not related to degenerative joint disease in young adulthood: a 21-year follow-up study including dGEMRIC.

Developmental dysplasia of the hip (DDH) is associated with an increased risk of early hip osteoarthritis (OA). We aimed to examine the outcome at the completion of growth in a cohort of children who had residual acetabular dysplasia at age 1 year following early treatment for neonatal instability of the hip (NIH)

Local Flip Angle Correction for Improved Volume T1-Quantification in Three-Dimensional dGEMRIC Using the Look-Locker Technique

Purpose: To present an evaluation method for three-dimensional Look-Locker (3D-LL) based T1 quantification, calculating correct T1 values independent of local flip angle (FA) variations. The method was evaluated both in phantoms and in vivo in a delayed Gadolinium Enhanced MRI of Cartilage (dGEMRIC) study with 33 subjects. Materials and Methods: T1 was measured with 3D-LL, using both local FA correction and a precalculated FA slice profile. and compared with standard constant FA correction, for all slices in phantoms and in both femur condyles in vivo. T1 measured using two-dimensional Inversion Recovery (2D-IR) was used as gold standard. Results: Due to the FA being slice dependent, the standard constant FA correction results in erroneous T1 (systematic error = 109.1 ms in vivo), especially in the outer slices. With local FA correction. the calculated T1 is excellent for all slices in phantoms (<5% deviation from 2D-IR). In vivo the performance is lower (systematic error = -57.5ms), probably due to imperfect inversion. With precalculated FA correction the performance is very good also in vivo (systematic error = 13.3 ms). Conclusion: With the precalculated FA correction method, the 3D-LL sequence is robust enough for in vivo dGEMRIC, even outside the centermost slices

In vivo transport of Gd-DTPA(2-) into human meniscus and cartilage assessed with delayed gadolinium-enhanced MRI of cartilage (dGEMRIC)

Background: Impaired stability is a risk factor in knee osteoarthritis (OA), where the whole joint and not only the joint cartilage is affected. The meniscus provides joint stability and is involved in the early pathological progress of OA. Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) has been used to identify pre-radiographic changes in the cartilage in OA, but has been used less commonly to examine the meniscus, and then using only a double dose of the contrast agent. The purpose of this study was to enable improved early OA diagnosis by investigate the temporal contrast agent distribution in the meniscus and femoral cartilage simultaneously, in healthy volunteers, using 3D dGEMRIC at two different doses of the contrast agent Gd-DTPA(2-). Methods: The right knee in 12 asymptomatic volunteers was examined using a 3D Look-Locker sequence on two occasions after an intravenous injection of a double or triple dose of Gd-DTPA(2-) (0.2 or 0.3 mmol/kg body weight). The relaxation time (T-1) and relaxation rate (R-1 = 1/T-1) were measured in the meniscus and femoral cartilage before, and 60, 90, 120 and 180 minutes after injection, and the change in relaxation rate (Delta R-1) was calculated. Paired t-test and Analysis of Variance (ANOVA) were used for statistical evaluation. Results: The triple dose yielded higher concentrations of Gd-DTPA(2-) in the meniscus and cartilage than the double dose, but provided no additional information. The observed patterns of Delta R-1 were similar for double and triple doses of the contrast agent. Delta R-1 was higher in the meniscus than in femoral cartilage in the corresponding compartments at all time points after injection. Delta R-1 increased until 90-180 minutes in both the cartilage and the meniscus (p < 0.05), and was lower in the medial than in the lateral meniscus at all time points (p < 0.05). A faster increase in Delta R-1 was observed in the vascularized peripheral region of the posterior medial meniscus, than in the avascular central part of the posterior medial meniscus during the first 60 minutes (p < 0.05). Conclusion: It is feasible to examine undamaged meniscus and cartilage simultaneously using dGEMRIC, preferably 90 minutes after the injection of a double dose of Gd-DTPA(2-) (0.2 mmol/kg body weight)

Knee cartilage quality assessed with dGEMRIC in rheumatoid arthritis patients before and after treatment with a TNF inhibitor.

BACKGROUND: TNF-α inhibitors are potent anti-inflammatory drugs that have revolutionized the treatment of rheumatoid arthritis (RA). Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) is a non-invasive method to study cartilage quality, in particular the glycosaminoglycan (GAG) content. PURPOSE: To evaluate knee cartilage quality before and after treatment with a TNF-α inhibitor (infliximab) in patients with RA using dGEMRIC and to study clinical parameters and serum cartilage oligomeric protein (COMP) after the same treatment. MATERIAL AND METHODS: Seven patients with chronic RA received infusions of 3 mg/kg infliximab at weeks 0, 2, 6, 14, and 22. Clinical examination, serum COMP level, and dGEMRIC scans (1.5 T) were performed at baseline and after 7 months. The dGEMRIC index (ms), reflecting cartilage GAG content, was calculated using an inversion recovery sequence in the femoral weight-bearing cartilage. Seven years after treatment, charts were reviewed regarding joint replacement surgery (TKA). RESULTS: Clinical parameters showed an improvement for all patients after the 7-month treatment period. Serum COMP decreased from 13±4.5 to 11±3.4 (μg, mean ± SD) μg/ml (P<0.05). The dGEMRIC index was lower at follow-up than at baseline, 332±85 and 382±69 (ms, mean ± SD), respectively (P<0.05), indicating loss of GAG. The two patients with the lowest dGEMRIC index had received a TKA 7 years after treatment. CONCLUSION: This longitudinal study indicates a substantial GAG loss from the knee cartilage matrix in patients with chronic RA. Treatment with infliximab does not seem to protect the cartilage from further deterioration despite improvements in clinical parameters and decreased serum COMP

Association between findings on delayed gadolinium-enhanced magnetic resonance imaging of cartilage and future knee osteoarthritis.

OBJECTIVE: To examine the predictive value of the delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) index with regard to future radiographic osteoarthritis (OA). METHODS: In 1998, 17 knees in 11 men and 4 women with knee pain, normal results of weight-bearing radiography, and arthroscopic cartilage changes ranging from superficial fibrillation to fissuring and softening were examined using dGEMRIC. Six years later, 16 of the 17 knees were reassessed for radiographic OA changes. RESULTS: At followup, 9 of the 16 knees showed radiographic OA changes. Two of them had undergone a knee joint replacement due to OA. In the knees with radiographic OA, the dGEMRIC index at baseline was lower than that in the knees without radiographic OA (P = 0.03). CONCLUSION: The results of the present study support the dGEMRIC index as a clinically relevant measure of cartilage integrity and suggest that a low index may be predictive of the development of knee OA

In Vivo Transport Of Gd-Dtpa(2-) In Human Knee Cartilage Assessed By Depth-Wise Dgemric Analysis

PURPOSE: To investigate the transport of Gd-DTPA(2-) in different layers of femoral knee cartilage in vivo. MATERIALS AND METHODS: T(1) measurements (1.5 Tesla) were performed in femoral knee cartilage of 23 healthy volunteers. The weight-bearing central cartilage was analyzed before contrast and at eight time points after an intravenous injection of Gd-DTPA(2-) : 12-60 min (4 volunteers) and 1-4 h (19 volunteers). Three regions of interest were segmented manually: deep, middle, and superficial. RESULTS: Before contrast injection, a depth-wise variation of T(1) was observed with 50% higher values in the superficial region compared with the deep region. In the deep region, the uptake of Gd-DTPA(2-) was not detected until 36 min and the concentration increased until 240 min, whereas in the superficial region, the uptake was seen already at 12 min and the concentration decreased after 180 min (P < 0.01). There was a difference between medial and lateral compartment regarding bulk, but not superficial Gd-DTPA(2-) concentration. The bulk gadolinium concentration was negatively related to the cartilage thickness (r = -0.68; P < 0.01). CONCLUSION: The depth-wise and thickness dependent variations in Gd-DTPA(2) transport influence the interpretation of bulk dGEMRIC analysis in vivo. In thick cartilage, incomplete penetration of Gd-DTPA(2) will yield a falsely too long T(1) . J. Magn. Reson. Imaging 2011;. © 2011 Wiley-Liss, Inc

dGEMRIC (delayed gadolinium-enhanced MRI of cartilage) indicates adaptive capacity of human knee cartilage.

Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) is a new imaging technique to estimate joint cartilage glycosaminoglycan content by T1-relaxation time measurements after penetration of the hydrophilic contrast agent Gd-DTPA2-. This study compares dGEMRIC in age-matched healthy volunteers with different levels of physical activity: Group 1 (n = 12): nonexercising individuals; Group 2 (n = 16): individuals with physical exercise averaging twice weekly; Group 3 (n = 9): male elite runners. dGEMRIC was performed 2 hr after an intravenous injection of Gd-DTPA2- at 0.3 mmol/kg body weight. T1 differed significantly between the three different levels of physical exercise. T1 values (mean of medial and lateral femoral cartilage) for Groups 1, 2, and 3 were: 382 ± 33, 424 ± 22 and 476 ± 36, respectively (ms, mean ± SD) (P = 0.0004, 1 vs. 2 and 0.0002, 2 vs. 3). Irrespective of the exercise level, T1 was longer in lateral compared to medial femoral cartilage (P = 0.00005; n = 37). In conclusion, this cross-sectional study indicates that human knee cartilage adapts to exercise by increasing the glycosaminoglycan content. Furthermore, results suggest a compartmental difference within the knee with a higher glycosaminoglycan content in lateral compared to medial femoral cartilage. A higher proportion of extracellular water, i.e., larger distribution volume, may to some extent explain the high T1 in the elite runners

In vivo transport of Gd-DTPA(2-) in human knee cartilage assessed by depth-wise dGEMRIC analysis.

PURPOSE: To investigate the transport of Gd-DTPA(2-) in different layers of femoral knee cartilage in vivo. MATERIALS AND METHODS: T(1) measurements (1.5 Tesla) were performed in femoral knee cartilage of 23 healthy volunteers. The weight-bearing central cartilage was analyzed before contrast and at eight time points after an intravenous injection of Gd-DTPA(2-) : 12-60 min (4 volunteers) and 1-4 h (19 volunteers). Three regions of interest were segmented manually: deep, middle, and superficial. RESULTS: Before contrast injection, a depth-wise variation of T(1) was observed with 50% higher values in the superficial region compared with the deep region. In the deep region, the uptake of Gd-DTPA(2-) was not detected until 36 min and the concentration increased until 240 min, whereas in the superficial region, the uptake was seen already at 12 min and the concentration decreased after 180 min (P < 0.01). There was a difference between medial and lateral compartment regarding bulk, but not superficial Gd-DTPA(2-) concentration. The bulk gadolinium concentration was negatively related to the cartilage thickness (r = -0.68; P < 0.01). CONCLUSION: The depth-wise and thickness dependent variations in Gd-DTPA(2) transport influence the interpretation of bulk dGEMRIC analysis in vivo. In thick cartilage, incomplete penetration of Gd-DTPA(2) will yield a falsely too long T(1) . J. Magn. Reson. Imaging 2011;. © 2011 Wiley-Liss, Inc