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W2013127079 abstract "Background. Gallium-67 (67Ga) scintigraphy may be useful in evaluating patients with retroperitoneal fibrosis (RPF), but a systematic assessment of its value is lacking. Objective. Prospective evaluation of the value of 67Ga scintigraphy in assessing active RPF disease and in predicting treatment response. Methods. Thirty-four patients with nonmalignant RPF treated with tamoxifen underwent 67Ga scintigraphy at baseline and – if baseline gallium scan was positive – at 3 months follow-up. Gallium scans were visually scored according to pathologic 67Ga-uptake compared to normal bone marrow 67Ga-uptake. Results were correlated with other (follow-up) measurements. Value of (follow-up) 67Ga scintigraphy in predicting treatment response was also assessed. Results. Gallium scans were positive in 24 patients (71%). Mass thickness was greater in patients with positive gallium scan compared with patients with negative gallium scan (P = 0.006). Visual gallium score correlated with mass thickness (P = 0.006). Visual gallium score decreased significantly following tamoxifen treatment (P < 0.0001). Decrease in visual gallium score correlated with decreases in C-reactive protein and erythrocyte sedimentation rate (P = 0.019) and with decrease in mass thickness (P < 0.01). Positive predicting value (PPV) of positive baseline gallium scan was 0.71; PPV of negative follow-up gallium scan in patients with initial positive scan was 0.89. 67Ga scintigraphy detected extra-abdominal involvement in one patient and recurrent active disease in two symptomatic patients with normal acute-phase reactants and stable residual mass. Conclusion. 67Ga scintigraphy is useful in assessing (recurrent) activity of RPF disease and in evaluating treatment response in patients with initial positive gallium scan. Retroperitoneal fibrosis (RPF) is a rare collagen vascular disease, characterized by a chronic nonspecific inflammation of the retroperitoneum which can entrap and obstruct retroperitoneal structures [1, 2]. Nowadays, through awareness of its manifestations and routine application of computed tomography (CT) or magnetic resonance imaging (MRI), a diagnosis of RPF can be made with near-certainty, thereby obviating the need for laparotomic or percutaneous biopsy [1, 2]. In addition, immunosuppressive and/or hormonal therapy seems to be replacing surgical treatment as the treatment of choice [3–7]. However, in the absence of a histologic substrate of RPF, it is unclear how to determine with certainty the stage of the disease, i.e. whether the disease is in the active, cellular or in the late, fibrotic stage [1, 2]. This is important as medical treatment may only be effective in the early, active stage of RPF [1, 2]. Anecdotal data suggest that enhanced Gallium-67 (67Ga) uptake at the level of the retroperitoneal mass reflects disease activity, thereby indicating potential success of medical treatment [8–15]. To address this issue, we prospectively studied the use of 67Ga scintigraphy in a relatively large group of patients with nonmalignant RPF who were treated with tamoxifen monotherapy. From April 1998 through August 2006, 34 patients with active nonmalignant RPF were treated with tamoxifen (20 mg twice-daily) monotherapy at the department of internal medicine of the Albert Schweitzer Hospital, Dordrecht, the Netherlands. In eight of these 34 patients, it concerned a recurrent episode after initial successful treatment with steroids. Study patients were recruited from a pool of 38 consecutive patients during this period. Four patients were excluded from this study because of concurrent systemic disease (polyarteritis nodosa, n = 1; acute tubulo-interstitial nephritis, n = 1) necessitating immunosuppressive therapy or because of concurrent malignancy (urothelial cell carcinoma, n = 2). After the careful exclusion of (occult) malignancy, the diagnosis of active nonmalignant RPF was based on the typical clinical picture and the presence of characteristic computed tomographic (CT) findings [1–3]. In six patients the diagnosis was confirmed by histological examination of biopsy material. None of the patients had a history of infection or of taking drugs that could have been associated with RPF. Emergency renal drainage was performed in case of severe obstructive renal failure. 67Ga scintigraphy was performed in all recruited patients at baseline and – if positive (see below) – after 3 months treatment with tamoxifen. All study patients provided informed consent prior to the start of treatment and the scheduling of baseline Ga67 scintigraphy. Tamoxifen treatment was started within 1 week after performing baseline Ga67 scintigraphy and regardless of these results. Tamoxifen was continued for 2 years [7]. Follow-up included periodic clinical and laboratory examination (initially 6-week interval; after 6 months 3-month interval) and repeated CT scanning (initially 4-month intervals; after 8 months 6–12 month interval). In case of diagnostic doubt during follow-up, histological examination of CT-guided biopsy was performed. Because of its potential value in assessing disease activity, 67Ga imaging was performed in all patients. Whole-body scanning after intravenous administration of 150 Mbq 67Ga-citrate was carried out with a large field, dual head, multipeak gammacamera (double head Siemens Ecam; Siemens Inc., Hoffman Estates, IL, USA or Adac Vertex, Adac laboratories, Milpitas, CA, USA), using a medium-energy collimator and the three main energy peaks of 67Ga (i.e. 93, 184 and 300 keV). The whole body images at 48 h postinjection were acquired with a 1024 × 256 matrix at a speed of 6 cm min−1. Planar images of the abdomen at 72 h postinjection were obtained in a 256 × 256 matrix for a total of 500 kcounts. In addition of the planar images, single photon emission computed tomography (SPECT) of the abdomen were obtained 48 h postinjection (128 × 128 matrix; 360 grades rotation; 6-grade angle step and 40 s per frame acquisition time). Data were reconstructed by filtered backprojection using a butterworth filter. If there was enhanced (i.e. pathologic) 67Ga uptake in the paravertebral midline at the same position as the retroperitoneal mass as determined with CT scanning, gallium scan was classified as positive. If there was no pathologic uptake in this region, gallium scan was classified as negative. In patients with a positive gallium scan at presentation, follow-up 67Ga scanning was performed after 3 months of tamoxifen treatment. All gallium scans were independently reviewed by two experienced nuclear medicine physicians who were unaware of the patient's status and visually scored the pathologic 67Ga uptake compared with (normal) bone marrow 67Ga uptake [16]: 0 (no pathologic uptake); 1+ (pathologic uptake but less than bone marrow uptake); 2+ (pathologic uptake similar to bone marrow uptake); 3+ (pathologic uptake more than bone marrow uptake). Disagreements were resolved by consensus. Decrease in pathologic 67Ga uptake following initiation of tamoxifen was measured as the absolute difference between the visual gallium score on the first and second gallium scan (ΔGa67 score). Performance of repeat gallium scanning at later points in time during follow-up were at the discretion of the treating physician and not prescribed by the protocol (e.g. evaluation of suspected recurrence; evaluation of second-line treatment). All CT scans were independently reviewed by two experienced radiologists who were unaware of the patient's status. The maximal thickness of the mass was measured in three different view directions (i.e. anterior–posterior, left lateral and transversal direction). To objectivate changes within patients during follow-up, the largest value of the initial three different measurements of maximal thickness was compared with the thickness of the mass at each follow-up CT scan, using the same measurement direction and the same level from which the largest value was obtained on the first CT scan. In addition, the initial measurement of craniocaudal length was compared with the craniocaudal length of the mass at each follow-up CT scan. At each time of CT follow-up, the absolute decrease in thickness (Δ thickness; mm) and length were calculated (Δ length; mm). Age, sex, clinical signs and symptoms, duration of symptoms, laboratory parameters [erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), creatinine] and gallium and CT scan findings were documented at baseline. Follow-up measurements included clinical improvement, time to substantial resolution of symptoms (weeks), changes in laboratory parameters and repeated gallium and CT scan findings. Apart from the documentation of overall subjective improvement as felt by the patient, we used the 100 mm horizontal visual analogue scale (VAS) to objectivate changes of primary symptoms within individuals during follow-up, using pain (i.e. area of the body where the most pain is felt) and discomfort as variables [17]. Treatment success was defined as such satisfactory clinical, laboratory and radiological (i.e. CT-documented) response to tamoxifen during the first 8 months that there was no need to alter therapy. Results of follow-up gallium scanning at 3 months in patients with initial positive gallium scan were not part of the predefined aggregate measure of treatment success. Treatment outcome analysis included those patients who had follow-up of 8 months or longer and who underwent the prescribed CT scan follow-up. Recurrences were defined as aggravation or return of signs and symptoms after 8 months of follow-up in patients with initial satisfactory response. Normality testing with the Kolmogorov–Smirnov test showed that many variables did not follow a normal distribution. For consistency, all continuous variables were therefore reported as median and interquartile range (25th to 75th percentile). In addition, all analyses were performed with nonparametric tests. Characteristics of patients with either a positive or negative gallium scan at presentation were compared. Differences between continuous variables were analyzed by using Mann–Whitney test and Wilcoxon signed rank-sum test, where appropriate. Differences between more than two groups were analyzed by using the Kruskal–Wallis statistic and a post-test to determine differences between any two groups. Categorical variables were expressed as proportions and compared with Fisher exact test. Spearman rank correlation coefficient was used to test the association between the degree of 67Ga uptake at presentation, expressed by the ordinal variable visual gallium score, and other parameters of disease activity. Similar exploration was made to test the association between the decrease in visual gallium score and changes in other parameters during follow-up. Differences between the visual gallium score at baseline and follow-up were studied using the Wilcoxon signed rank-sum test. Sensitivity and specificity of positive baseline gallium scan and sensitivity and specificity of negative follow-up gallium scan in predicting treatment success were calculated. All reported P-values are two-sided. A P-value of <0.05 was considered significant. All statistical analyses were performed with SPSS software (version 11.0.1; SPSS Inc., Chicago, IL, USA). Demographic and clinical characteristics of the 34 study patients are depicted in Table 1. Median follow-up was 26 months (range 9–32). During careful follow-up, no other pathology was found that could have accounted for the findings at presentation (e.g. malignant lymphoma). Baseline gallium scan was positive in 24 (71%) patients (Fig. 1). Patients with a positive gallium scan at presentation were younger and tended to present earlier with less impaired renal function when compared with patients with a negative gallium scan at presentation (Table 2]. ESR and CRP were within the normal range in five (21%) and six (25%) patients with a positive gallium scan at presentation, respectively. Two patients presenting with hydro-ureteronephrosis felt well without any complaint other than pollakisuria, had also normal baseline ESR and CRP levels but had a positive gallium scan. The thickness of the retroperitoneal mass in patients with a positive gallium scan was significantly greater compared with the mass thickness in patients with a negative gallium scan at presentation (Table 2). In one patient, gallium scanning revealed extra-abdominal involvement of disease (i.e. mediastinal fibrosis). Transverse, sagittal and coronal 67Ga-images in a 57-year-old woman with retroperitoneal fibrosis before (a) and after (b) 3 months treatment with tamoxifen (20 mg orally twice daily). At presentation, there was intense pathologic 67Ga-uptake in the prevertebral midabdominal region (visual gallium score 3+), which disappeared at follow-up gallium scanning. Subsequent CT scanning at 4 months showed significant regression of the retroperitoneal mass. Stratification according to the visual gallium score at presentation showed significant differences in the VAS score for pain and the CT-documented thickness of the retroperitoneal mass, but not in ESR or CRP levels (Table 3). Maximal thickness but not the craniocaudal length of the mass correlated significantly with the visual gallium score at presentation (Fig. 2). Following tamoxifen treatment, the visual gallium score decreased significantly in patients with initial positive gallium scan (Fig. 3). The decrease in visual gallium score at 3 months correlated with the absolute decrease in CT-documented mass thickness at 4 and 8 months follow-up, respectively (4, 5). Box-and-whiskers plot showing the CT-documented maximal thickness and craniocaudal length of the retroperitoneal mass according to the visual gallium score at presentation. The visual gallium score correlated significantly with the maximal thickness (rs = 0.47 [CI 0.13–0.70], P < 0.01) but not the craniocaudal length (rs = −0.19 [CI −0.50 to 0.17], P = 0.287) of the mass. Change in the visual gallium score in patients with initial positive gallium scan (visual gallium score ≥1+) following 3 months treatment with tamoxifen (n = 24). There was a significant decrease in the visual gallium score over time (P < 0.0001). Only three patients exhibited no decrease in the visual gallium score. Scatter plot showing a significant correlation between the decrease in visual gallium score at 3 months and the CT-documented decrease in mass thickness at 4 months (rs = 0.76 [CI 0.48–0.89], P < 0.0001) and 8 months (rs = 0.75 [CI 0.40–0.91], P = 0.0007) follow-up, respectively. Lines depict regression line of y on x and 95% confidence intervals for regression line. (a) Contrast-enhanced computed tomography (CT) in a 57-year-old man demonstrating a well-delineated peri-aortic soft tissue mass (arrows). (b) Repeat CT scanning after 4 months of tamoxifen treatment (20 mg orally twice daily) showed significant regression of the mass. Baseline 67Ga scan in this patient was strongly positive (visual gallium score 3+), which became normal at 3 months follow-up. No significant correlation was found between the decrease in visual gallium score and the time to substantial resolution of symptoms (P = 0.895), decrease in VAS score for pain (P = 0.169) and discomfort (P = 0.093). The decrease in visual gallium score correlated with the decrease in CRP at 6-week (ΔCRP 11 [0–33] mg L−1; P = 0.043) and at 4-month (ΔCRP 16 [1–41] mg L−1; P = 0.019) follow-up, respectively, and with the decrease in ESR at 4-month follow-up (ΔESR 15 [8–33] mm h−1; P = 0.019). The follow-up gallium scan at 3 months normalized in 12 of 24 (50%) patients with initial positive gallium scan (Fig. 1). Patients with a persistently positive gallium scan did not differ from patients with a negative follow-up gallium scan in terms of ESR and CRP levels at 6-week, 4-month and 8-month follow-up, respectively (P > 0.2). Of the 34 study patients, 31 were evaluable for treatment outcome analysis. Fifteen of 21 (71%) patients with a positive baseline gallium scan were treated successfully, compared with six of 10 (60%) patients with a negative baseline gallium scan. Sensitivity of positive baseline Ga67 scintigraphy in predicting treatment success was 0.71; specificity was 0.40. The positive predicting value (PPV) was 0.71; negative predicting value (NPV) was 0.40. Eight of nine (89%) patients in whom the gallium scan had normalized at 3-month follow-up were treated successfully, compared with 7 of 12 (58%) patients in whom the gallium scan was still positive. Sensitivity of negative follow-up Ga67 scintigraphy in predicting treatment success in patients with initial positive gallium scan was 0.53; specificity was 0.83 (PPV 0.89; NPV 0.42). Three patients treated successfully developed a symptomatic recurrence requiring re-introduction of tamoxifen (n = 1) or change of therapy (n = 2). All patients had a positive gallium scan at initial presentation, which became normal at standard follow-up gallium scanning at 3 months. Two of these patients with recurrent typical complaints had no concomitant increase in acute-phase reactants or in residual mass thickness on repeat CT scan. Repeat gallium scanning at the time of recurrence in these patients was again positive, which became negative during subsequent treatment. In two patients who failed tamoxifen treatment and who exhibited a persistently positive gallium scan at 3 months, repeat gallium scanning during evaluation of second-line treatment (prednisone/azathioprine) showed disappearance of pathologic 67Ga activity, concurrent with clinical improvement and subsequent CT-documented mass regression. This first prospective study in a large group of patients with RPF indicates that 67Ga SPECT scintigraphy can be of added value in the diagnostic and therapeutic evaluation of RPF. Patients with a positive gallium scan had a significantly larger retroperitoneal mass compared with patients with a negative gallium scan at baseline and tended to present earlier. As such, it can help in establishing severity and extent of RPF disease. In addition, the decrease in visual gallium score following treatment at 3-month follow-up correlated strongly with the subsequent decrease of the retroperitoneal mass as documented on repeat CT scanning at 4 and 8 months, respectively. Repeated 67Ga scintigraphy may thus be useful as an additional tool in weighing the response to treatment, which is further illustrated by the PPV of 0.89 of negative follow-up gallium scan in patients with initial positive gallium scan. It suggests that in most patients in whom the pathologic 67Ga uptake disappears, treatment will be successful. The subsequent disappearance of pathologic 67Ga activity during second-line treatment in patients who failed tamoxifen treatment underscores the potential of 67Ga scintigraphy in evaluating treatment response. Determining the stage of disease without performing biopsy – as is clinical practice these days – may be difficult [1]. This is important as medical treatment may only be effective in the early, active stage of RPF [1, 2, 10, 11, 18]. The combination of severe symptoms and significantly increased acute-phase reactants is usually taken as an indication to start a trial of medical treatment in patients with RPF. However, it is unknown whether (sequential) measurement of ESR or CRP is of any value in the diagnosis and follow-up of this inflammatory condition. The degree of enhancement of the mass upon CT scanning following i.v. contrast administration may help in determining the stage of the disease, this being less in the advanced fibrotic stage and greater in an active, inflammatory stage [1, 2]. However, in the presence of severe renal failure the administration of i.v. contrast may be contraindicated. Our study shows that RPF disease may present without (serious) symptoms and/or increased acute-phase reactants. In these cases, additional gallium scanning may be of particular help in establishing whether the disease is in the active, cellular stage. In addition, in the absence of symptoms and increased acute-phase reactants, 67Ga scintigraphy may be the only follow-up parameter in monitoring treatment response. The present study also shows that a positive gallium scan can be the only indication of RPF disease relapse during or after treatment in patients with normal acute-phase reactants and stable residual mass on CT scanning. However, we did not have patients in whom active RPF was suspected and a gallium scan was performed, but in whom the diagnosis of active RPF was rejected and hence not treated. Therefore, results should be interpreted with care. To date, only anecdotal case reports and one small retrospective case series comprising five patients have been published on the potential value of 67Ga scintigraphy in the diagnostic work-up and follow-up evaluation of RPF [8–15]. Pathologic peri-aortic 67Ga uptake was observed in a total of nine patients with a (subsequent) diagnosis of RPF. Follow-up gallium scanning in five of these patients after 4 weeks to 3 months of treatment with corticosteroids (n = 4) or corticosteroids and azathioprine (n = 1) showed diminution of this pathologic 67Ga uptake [8, 12–14]. However, these limited data, prone to positive reporting bias, do not tell whether all patients with a positive gallium scan at presentation will respond to medical treatment. In addition, these data do not tell whether a negative baseline gallium scan precluded successful medical treatment. Our data indicate that not all patients with a positive baseline gallium scan will have a satisfactory response to treatment. The present study also shows that a negative gallium scan at baseline does not preclude successful treatment with tamoxifen. Whether this also holds true for other medical treatment regimens, such as corticosteroids and azathioprine, remains unknown. Our findings may also suggest the potential efficacy of tamoxifen in both early and late(r) stages of the disease. If immunosuppressive treatment would only be effective in the early stage of disease [1–5], a negative gallium scan at presentation could thus drive therapeutic decisions. Of note, some patients with persistently positive gallium scan at 3 months did have a satisfactory response to tamoxifen treatment at the end of follow-up. Possibly, repeated gallium scanning also separates rapid from slow responders during therapy. If this were to be true, repeat gallium scanning at a later stage (e.g. after 6 months therapy) may be more useful and possibly improve its sensitivity and specificity. The exact pathway by which 67Ga localizes in an area of inflammation is not completely understood. Suggested mechanisms include leucocyte labelling, lactoferrin and transferrin binding at inflammatory cells, leakage of 67Ga through capillaries with increased permeability and direct bacterial uptake [19–21]. However, active RPF is characterized by a predominantly lymphocytic and not leucocytic infiltrate [18]. Dhawan et al. [22] showed 67Ga uptake at inflammatory sites in the absence of circulating leucocytes. In addition, activated lymphocytes have been shown to express a high amount of transferrin receptors [12]. Hence, it may be that lymphocytes provide the pathway for delivery and uptake of 67Ga in active RPF [9]. With conventional 67Ga scintigraphy, it may sometimes be difficult to differentiate the ‘typical’ pathologic 67Ga uptake in the paravertebral midline from focal abdominal activity related to the colonic lumen and normal gastrointestinal radioactivity. In these cases, 72-h images are usually required [16]. Axial imaging with SPECT however, as performed in this study, allows a more clear distinction between normal and abnormal abdominal gallium activity. It offers the advantage of cross-sectional imaging when compared with conventional planar imaging. Furthermore, computer-aided, three-dimensional reconstruction of SPECT data helps to make measurements directly in the region of interest, to obtain a higher image contrast and a clear cut signal of the investigated area. It should be noted that 67Ga scintigraphy allows whole-body imaging. As illustrated in our study, it may also reveal other sites of disease (e.g. Riedel's thyroiditis; mediastinal fibrosis) or it may detect inflammatory or neoplastic processes to which RPF may be associated or secondary [11]. Indeed, one patient met exclusion criteria for our study after gallium scanning revealed intense renal uptake, which was found to be due to acute tubulo-interstitial nephritis. Patients with a positive baseline gallium scan not only had a larger retroperitoneal mass but were also younger. Younger patients possibly present with a more intense inflammatory response, with more vascularization and oedema, compared with older patients. Conversely, patients with a negative baseline gallium scan had more severely impaired renal function compared with patients with a positive baseline gallium scan. The number of patients with hydronephrosis did not differ between groups. As these patients were older, it may be that atherosclerotic renal disease was more prevalent amongst the patients with negative baseline gallium scan. Advanced atherosclerosis is a prominent feature in many patients with RPF [1, 2]. Positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) has recently been described as useful in the diagnosis and follow-up of RPF [23, 24], but these limited observations have not yet been confirmed. It may probably be expected that FDG-PET will show similar beneficial results in RPF as 67Ga scintigraphy. As CT is the major imaging modality in the clinical scenario of RPF, combined PET-CT with FDG may become the most appropriate modality in the future. At the present however, 67Ga scintigraphy is more widely available and – at least in the Netherlands – less than half the cost of FDG-PET scanning. The strength of our study is that it is the largest prospective study of any kind in this uncommon disease and the first to study prospectively the use of 67Ga scintigraphy in RPF. Our study also has limitations. As prescribed by the protocol, all patients received tamoxifen treatment regardless of baseline gallium scan results. However, as the study was unblinded, one cannot exclude the possibility that results from repeat gallium scanning influenced treatment decisions during follow-up (e.g. at the time of suspected disease relapse). In addition, as all study patients underwent (repeated) gallium scanning, the attributable portion of this imaging technique on top of CT scanning cannot be ascertained. For this, a study randomizing patients to receive either combined CT and 67Ga scintigraphy or CT scanning only would be required. In conclusion, the present study shows that 67Ga scintigraphy may be a useful additional tool in RPF. It may be particularly useful in evaluating treatment response in patients with initial positive gallium scan. It may also help in assessing (recurrent) activity of RPF disease. Whereas CT scanning and MRI more clearly delineate the extent of the retroperitoneal mass, 67Ga scintigraphy not only shows the mass lesion but also the inflammatory component. In case of absence of serious complaints and/or increased acute-phase reactants, it may thus be the only indication of (recurrent) active disease. Similarly, it may be the only follow-parameter in monitoring response to treatment. Finally, it may show diseased sites elsewhere. None. We are indepted to A. Jannink for his help in preparing the photographs." @default.
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W2013127079 title "Clinical value of gallium-67 SPECT scintigraphy in the diagnostic and therapeutic evaluation of retroperitoneal fibrosis: a prospective study" @default.
W2013127079 cites W1530965271 @default.
W2013127079 cites W1973853289 @default.
W2013127079 cites W1989874924 @default.
W2013127079 cites W1999529346 @default.
W2013127079 cites W2007686638 @default.
W2013127079 cites W2013032248 @default.
W2013127079 cites W2056952466 @default.
W2013127079 cites W2068830939 @default.
W2013127079 cites W2085425054 @default.
W2013127079 cites W2093792967 @default.
W2013127079 cites W2120263268 @default.
W2013127079 cites W2133194893 @default.
W2013127079 cites W2139516137 @default.
W2013127079 cites W2160399009 @default.
W2013127079 cites W2320695267 @default.
W2013127079 cites W2508804216 @default.
W2013127079 cites W4233240948 @default.
W2013127079 cites W4386007333 @default.
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