(18)F-fluoride PET for monitoring therapeutic response in Paget's disease of bone.

A prospective study was undertaken to evaluate PET with (18)F-fluoride for monitoring the response to bisphosphonates in Paget's disease of bones. METHODS: Fourteen patients with a monostotic (n = 9) or a polyostotic form (n = 5) of Paget's disease were scanned at baseline and at 1 and 6 mo after the beginning of treatment. Dynamic acquisition and arterial blood sampling were used to calculate the influx constant Ki (by both the Patlak [Ki-PAT] method and the nonlinear regression [Ki-NLR] method). Kinetic modeling was compared with maximal standardized uptake values (SUV(max)) and biochemical markers of bone remodeling. RESULTS: Baseline uptake of (18)F-fluoride by pagetic bones was significantly higher than in normal bones (P < 0.05). One month after the start of treatment, SUV(max), Ki-PAT, Ki-NLR, and K(1) (the unidirectional clearance of fluoride from plasma to the whole of the bone tissue) decreased significantly by 27.8%, 27.9%, 27.5%, and 23.6%, respectively. Biochemical markers were already normalized in 6 of 9 patients with monostotic disease, although all had high (18)F-fluoride uptake values. Six months after the start of treatment, (18)F-fluoride uptake further diminished by 22.3%-25.6%. Biochemical markers were normal in all but 2 patients, although 10 of 14 patients still showed high (18)F-fluoride uptake. One patient did not respond to treatment and maintained high uptake of (18)F-fluoride throughout the study. SUV(max) correlated with both Ki-PAT and Ki-NLR at baseline, 1 mo, and 6 mo (P < 0.05). Moreover, the change of SUV(max) between baseline and 1 mo, as well as between baseline and 6 mo, also correlated with the change of Ki-PAT and Ki-NLR (P < 0.05). CONCLUSION: Our results show that (18)F-fluoride PET can be used to noninvasively and accurately monitor the efficacy of treatment with bisphosphonates in Paget's disease of bones. SUV(max) correlates with Ki-PAT and Ki-NLR and, interestingly, varies in the same manner as kinetic indices. Therefore, the use of SUV(max) could avoid the need for dynamic acquisition and arterial blood sampling and would facilitate the use of whole-body PET in a clinical setting.     

The KHOALA cohort of knee and hip osteoarthritis in France

ObjectivesThis study aimed to describe the prevalence of symptomatic knee and hip osteoarthritis (OA) and its course over time, as well as identify prognostic factors of OA course and determinants of costs and access to care in France in a patient cohort.MethodsSubjects aged 40 to 75 years, with uni- or bilateral symptomatic hip and/or knee OA (ACR criteria), Kellgren and Lawrence (KL) stage 2 or greater, were recruited from a French national prevalence survey for the multicenter KHOALA cohort study. Data collected at baseline included sociodemographic and clinical data; WOMAC, IKS and Harris scores for pain and function; MAQ score for physical activity; functional comorbidity index; GHQ28 score for psychological status; and SF-36 (generic) and OAKHQOL (specific) scores for quality of life. Blood and urine samples were collected.ResultsEight hundred and seventy-eight subjects were included, 222 with OA of the hip (mean age 61.2 ± 8.8 years), 607 knee (mean age 62.0 ± 8.5 years) and 49 both hip and knee (mean age 64.9 ± 7.9 years). Mean body mass index was 26.9 ± 4.5 for hip OA and 30.3 ± 6.3 for knee OA. Hip and knee OA patients had 1.99 and 2.06 comorbidities, on average, respectively. Disease severity on X-rays for KL stages 2, 3 and 4 for hip OA was 69.8, 26.1 and 4.1%, respectively, and for knee OA, 44.5, 30.3, and 25.2%. As compared with population norms, age- and sex-standardized SF-36 scores were greatly decreased for both knee and hip OA in all dimensions, particularly physical and emotional dimensions.PerspectivesPatients will be followed up annually, alternately by mail and clinical visit. This cohort of representative patients with knee and hip OA will be an opportunity for future collaborative research.     

Reliability of a quantification imaging system using magnetic resonance images to measure cartilage thickness and volume in human normal and osteoarthritic knees

OBJECTIVE: The aim of this study was to evaluate the reliability of a software tool that assesses knee cartilage volumes using magnetic resonance (MR) images. The objectives were to assess measurement reliability by: (1) determining the differences between readings of the same image made by the same reader 2 weeks apart (test-retest reliability), (2) determining the differences between the readings of the same image made by different readers (between-reader agreement), and (3) determining the differences between the cartilage volume readings obtained from two MR images of the same knee image acquired a few hours apart (patient positioning reliability). METHODS: Forty-eight MR examinations of the knee from normal subjects, patients with different stages of symptomatic knee osteoarthritis (OA), and a subset of duplicate images were independently and blindly quantified by three readers using the imaging system. The following cartilage areas were analyzed to compute volumes: global cartilage, medial and lateral compartments, and medial and lateral femoral condyles. RESULTS: Between-reader agreement of measurements was excellent, as shown by intra-class correlation (ICC) coefficients ranging from 0.958 to 0.997 for global cartilage (P<0.0001), 0.974 to 0.998 for the compartments (P<0.0001), and 0.943 to 0.999 for the condyles(P<0.0001). Test-retest reliability of within-reader data was also excellent, with Pearson correlation coefficients ranging from 0.978 to 0.999 (P<0.0001). Patient positioning reliability was also excellent, with Pearson correlation coefficients ranging from 0.978 to 0.999 (P<0.0001). CONCLUSIONS: The results of this study establish the reliability of this MR imaging system. Test-retest reliability, between-reader agreement, and patient positioning reliability were all extremely high. This study represents a first step in the overall validation of an imaging system designed to follow progression of human knee OA.     

Upper-limb function and recovery in the acute phase poststroke

This study evaluates stroke patients with upper-limb (UL) motor deficits using measures of impairment and "activity limitation" to quantify recovery of UL function poststroke and to identify predictors of UL function and predictors of UL recovery following stroke. The study also compares the recovery of UL function with that of the lower limb (LL). Measures of impairment and "activity limitation" of the UL and LL improved over the first 5 weeks. The Box and Block Test performance improved the most over 5 weeks (standardized response mean [SRM] = 1.34), followed closely by the 5-meter walk test (SRM = 0.97). Performances on measures of UL "activity limitation" measured at 1 week poststroke were the most important predictors of UL function 5 weeks poststroke. The results of this study do not support the belief that recovery of LL function is faster than that of UL.     

Segment of rat chromosome 20 regulates diet-induced augmentations in adiposity,glucose intolerance,and blood pressure

Previous linkage and association studies have suggested that a region of human chromosome 6 containing the tumor necrosis factor (TNF)-alpha gene is involved in the pathogenesis of obesity and obesity-associated hypertension. The aim of the present investigation was to establish whether a segment of rat chromosome 20 (RNO20), which also contains the TNF-alpha gene, determines diet-induced changes in adiposity and blood pressure (BP). The results showed that a transfer of the RNO20 segment from the normotensive Brown Norway (BN) rat onto the background of the spontaneously hypertensive rat (SHR) is associated with a significantly greater increase in adiposity, glucose intolerance, circulating leptin levels, and BP during 12-week, high-fat-diet feeding. In contrast, the transfer is not associated with significant changes in these variables during 12-week, normal-diet feeding. In addition, sequencing of the TNF-alpha gene revealed differences between SHR and BN in the 5'- and 3'-regulatory regions of the gene. Subsequent analyses of TNF-alpha gene expression in fat, muscle, and liver, however, did not provide support for the functional involvement of these differences. In summary, the investigated RNO20 segment contains 1 or more gene variants that affect adiposity, glucose tolerance, serum leptin levels, and BP, but only when the animals are exposed to a particular environment, ie, high-fat-diet feeding. Further studies are needed to identify genes mediating these effects. Considering current changes in our lifestyle involving an increased calorie and fat intake, we believe that gene-environment interactions, such as those described here, play an important role in the current epidemic of obesity and obesity-associated hypertension.     

Fine motor dexterity is correlated to social functioning in schizophrenia

OBJECTIVE: To identify neuropsychological domains, including fine motor dexterity, that are related to social functioning in schizophrenia. METHOD: Thirty-six DSM-IV schizophrenic subjects were assessed using the Purdue Pegboard test, the Modified Wisconsin Card Sorting test, the Tower of London, Schwartz' Reaction Time and Wechsler's Associate Learning and Digit Span tests. Social functioning was measured by the Social and Occupational Functional Assessment Scale. RESULTS: Univariate regression analyses showed that the Purdue Pegboard, the Modified Card Sorting test, the Tower of London and Wechsler's Associate Learning subtest were significantly linked to social functioning. The best fitting multivariate model to explain social functioning included fine motor dexterity and executive functioning. CONCLUSION: Various neuropsychological measures correlated to social functioning, the correlation involving fine motor dexterity being the strongest one. Future studies of the prediction of social functioning in schizophrenia should include fine motor dexterity.