Comparison of diagnostic accuracy of (111)In-pentetreotide SPECT and (68)Ga-DOTATOC PET/CT: A lesion-by-lesion analysis in patients with metastatic neuroendocrine tumours.

OBJECTIVES: To compare the diagnostic accuracy of (111)In-pentetreotide-scintigraphy with (68)Ga-DOTATOC-positron emission tomography (PET)/computed tomography (CT) in patients with metastatic-neuroendocrine tumour (NET) scheduled for peptide receptor radionuclide therapy (PRRT). Incremental lesions (ILs) were defined as lesions observed on only one modality. METHODS: Fifty-three metastatic-NET-patients underwent (111)In-pentetreotide-scintigraphy (24 h post-injection; planar+single-photon emission CT (SPECT) abdomen) and whole-body (68)Ga-DOTATOC-PET/CT. SPECT and PET were compared in a lesion-by-lesion and organ-by-organ analysis, determining the total lesions and ILs for both modalities. RESULTS: Significantly more lesions were detected on (68)Ga-DOTATOC-PET/CT versus (111)In-pentetreotide-scintigraphy. More specifically, we observed 1,098 lesions on PET/CT (range: 1-105; median: 15) versus 660 on SPECT (range: 0-73, median: 9) (p<0.0001), with 439 PET-ILs (42/53 patients) and one SPECT-IL (1/53 patients). The sensitivity for PET/CT was 99.9 % (95 % CI, 99.3-100.0), for SPECT 60.0 % (95 % CI, 48.5-70.2). The organ-by-organ analysis showed that the PET-ILs were most frequently visualized in liver and skeleton. CONCLUSION: Ga-DOTATOC-PET/CT is superior for the detection of NET-metastases compared to (111)In-pentetreotide SPECT. KEY POINTS: Somatostatin receptor PET is superior to SPECT in detecting NET metastases. PET is the scintigraphic method for accurate depiction of NET tumour burden. The sensitivity of PET is twofold higher than the sensitivity of SPECT.

Use of bandage contact lenses for treatment of spontaneous chronic corneal epithelial defects in dogs.

OBJECTIVE: To determine whether polyxylon bandage contact lenses influence healing time and ocular comfort in the management of spontaneous chronic corneal epithelial defects in dogs. METHODS: Twenty dogs with spontaneous chronic corneal epithelial defects were included. All dogs were treated by debridement under topical anaesthesia at the first presentation. Ten dogs were assigned to the study group (application of a polyxylon bandage contact lens), and the remaining ten served as a control group. The healing time and ocular (dis)comfort were evaluated by assessment of the clinical findings and an owner-based questionnaire. All dogs received the same topical and systemic medication. RESULTS: Healing time for dogs in the study population was significantly shorter (mean 14±0 days) than for dogs in the control group (mean 36±17 days; P=0·005). The spontaneous chronic corneal epithelial defects had completely healed at the first recheck in all dogs with a polyxylon bandage contact lens. The duration of blepharospasm following debridement was significantly shorter in the study population (mean 4±4 days) than in the control group (mean 30±20 days; P=0·001). CLINICAL SIGNIFICANCE: The use of polyxylon bandage contact lenses is beneficial in the management of spontaneous chronic corneal epithelial defects.

Prevalence of residual excessive sleepiness during effective oral appliance therapy for sleep-disordered breathing.

BACKGROUND: Oral appliance therapy with a mandibular advancement device (OAm) can yield to complete therapeutic response (apnea-hypopnea index [AHI]<5 events/h), though some patients show little or no improvement in daytime sleepiness. The prevalence of residual excessive sleepiness (RES) despite effective treatment with OAm therapy is unknown. We aimed to determine the prevalence of RES in patients treated with a titratable custom-made duobloc OAm. METHODS: A prevalence study was performed, collecting data from 185 patients with an established diagnosis of sleep-disordered breathing (SDB) under OAm therapy with a titratable custom-made duobloc device (baseline data were male:female ratio, 129:56; age, 48±9 years; body mass index [BMI], 27±4 kg/m2; Epworth Sleepiness Scale [ESS] score, 10±5; and AHI, 19±12 events/h). A full-night polysomnography was performed at baseline and after 3 months of OAm therapy. Daytime sleepiness was assessed using the ESS with RES defined as an ESS score of 11 or higher out of 24, despite complete therapeutic response. RESULTS: Out of 185 patients, 84 patients (45%) showed a complete therapeutic response with an AHI of <5 events per hour after 3 months of OAm therapy. Despite this normalization of AHI, 27 out of these 84 patients (32%) showed RES and had a significantly higher baseline ESS (15±4 vs. 9±4; P<.001) and were younger (43±9 vs. 47±9; P=.028) compared to patients without RES. CONCLUSION: RES under OAm therapy showed a prevalence of up to 32% in SDB patients effectively treated with respect to AHI. Patients with RES were younger and had higher baseline daytime sleepiness.

Preclinical evaluation of [(18)F]JNJ42259152 as a PET tracer for PDE10A.

Phosphodiesterase-10A (PDE10A) is implicated in several neuropsychiatric disorders involving basal ganglia neurotransmission, such as schizophrenia, obsessive-compulsive disorder and Huntington's disease. To confirm target engagement and exposure-occupancy relationships of clinical candidates for treatment, and to further explore the in vivo biology of PDE10A, non-invasive imaging using a specific PET ligand is warranted. Recently we have reported the in vivo evaluation of [(18)F]JNJ41510417 which showed specific binding to PDE10A in rat striatum, but with relatively slow kinetics. A chemically related derivative JNJ42259152 was found to have a similar in vivo occupancy, but lower lipophilicity and lower PDE10A in vitro inhibitory activity compared to JNJ41510417. (18)F-labeled JNJ42259152 was therefore evaluated as a potential PDE10A PET radiotracer. Baseline PET in rats and monkey showed specific retention in the PDE10A-rich striatum, and fast wash-out, with a good contrast to non-specific binding, in other brain regions. Pretreatment and chase experiments in rats with the selective PDE10A inhibitor MP-10 showed that tracer binding was specific and reversible. Absence of specific binding in PDE10A knock-out (KO) mice further confirmed PDE10A specificity. In vivo radiometabolite analysis using high performance liquid chromatography (HPLC) showed presence of polar radiometabolites in rat plasma and brain. In vivo imaging in rat and monkey further showed faster brain kinetics, and higher striatum-to-cerebellum ratios for [(18)F]JNJ42259152 compared to [(18)F]JNJ41510417. The arterial input function corrected for radiometabolites was determined in rats and basic kinetic modeling was established. For a 60-min acquisition time interval, striatal binding potential of the intact tracer referenced to the cerebellum showed good correlation with corresponding binding potential values of a Simplified Reference Tissue Model and referenced Logan Plot, the latter using a population averaged reference tissue-to-plasma clearance rate and offering the possibility to generate representative parametric binding potential images. In conclusion we can state that in vivo imaging in PDE10A KO mice, rats and monkey demonstrates that [(18)F]JNJ42259152 provides a PDE10A-specific signal in the striatum with good pharmacokinetic properties. Although presence of a polar radiometabolite in rat brain yielded a systematic but reproducible underestimation of the striatal BPND, a Logan reference tissue model approach using 60 min acquisition data is appropriate for quantification.

Synthesis of 18F-labelled 2-(4'-fluorophenyl)-1,3-benzothiazole and evaluation as amyloid imaging agent in comparison with [11C]PIB.

2-(4'-[(18)F]fluorophenyl)-1,3-benzothiazole was synthesized as a fluorine-18 labelled derivative of the Pittsburg Compound-B (PIB), which has known affinity for amyloid beta and promising characteristics as tracer for in vivo visualisation of amyloid deposits in patients suffering from Alzheimer's disease (AD). Both the nitro-precursor 2-(4'-nitrophenyl)-1,3-benzothiazole and the non-radioactive reference compound were synthesized using a 1-step synthesis pathway. Labelling was achieved by direct aromatic nucleophilic substitution of the nitro-precursor using [(18)F]fluoride by heating for 20 min at 150 degrees C and with a radiochemical yield of 38%. The reference compound showed high affinity for amyloid in an in vitro competition binding study using human AD brain homogenates (K(i)=9.0 nM) and fluorescence imaging of incubated transgenic APP mouse brain slices confirmed binding to amyloid plaques. A biodistribution study in normal mice showed a high brain uptake at 2 min pi (3.20%ID/g) followed by a fast washout (60 min pi: 0.21%ID/g). A dynamic microPET study was performed in a transgenic APP and normal WT mouse, but, similar to [(11)C]PIB, no difference was seen in tracer retention between both kind of mice. The new (18)F-labelled 2-phenylbenzothiazole showed excellent preclinical characteristics comparable with those of the (11)C-labelled PIB.

11C-labelled PIB analogues as potential tracer agents for in vivo imaging of amyloid beta in Alzheimer's disease.

Pittsburgh Compound-B (PIB) is currently being evaluated clinically for in vivo visualization of amyloid plaques in patients with Alzheimer's disease (AD). We have synthesized three structural isomers of 6-hydroxy-2-(4'-aminophenyl)-1,3-benzothiazole, performed radiolabelling with carbon-11 and investigated their in vivo and in vitro properties. Specific binding to amyloid plaques was demonstrated in vitro using post-mortem brain homogenates of AD patients, transgenic AD mice brain sections and post-mortem human AD brain sections. In normal mice, initial brain uptake (at 2 min p.i.) was high and was followed by a fast wash-out. The three structural analogues have a high potential as tracer agents for in vivo visualization of amyloid plaques in AD patients.

Synthesis and evaluation of a (99m)Tc-BAT-phenylbenzothiazole conjugate as a potential in vivo tracer for visualization of amyloid beta.

We have conjugated S,S'-bis-trityl-N-BOC-N'-acetic acid-1,2-ethylenedicysteamine, a protected bis-amino-bis-thiol (BAT) tetraligand, with 2-(4'-aminophenyl)-1,3-benzothiazole, a derivative of thioflavin-T with known affinity for amyloid. The conjugate was efficiently labelled with (99m)Tc by heating of the protected precursor in diluted hydrochloric acid followed by neutralization and heating in the presence of (99m)Tc-tartrate. It was demonstrated that the (99m)Tc-BAT-phenylbenzothiazole conjugate binds in vitro to amyloid beta present in postmortem brain slices of Alzheimer's patients. Despite its high lipophilicity and neutral character, the radiolabelled conjugate did not cross the blood-brain barrier to a sufficient degree and therefore is not useful for detection of Alzheimer's disease. Further evaluation of this (99m)Tc-labelled tracer agent could elucidate its potential usefulness to visualize amyloid plaques in peripheral amyloidosis.

Level of acceptability of EULAR recommendations for the management of knee osteoarthritis by practitioners in different European countries.

OBJECTIVE: To evaluate the level of acceptability of the EULAR recommendations for the management of knee osteoarthritis (KOA) in practice. METHODS: A questionnaire was sent to general practitioners, rheumatologists, rehabilitators, and orthopaedic surgeons in five European countries (France, Spain, Belgium, Switzerland, Italy). Practitioners were asked to give their opinion on the 10 EULAR recommendations and on 23 treatment modes for KOA. Practitioners' opinions were compared with those of the expert task force involved in the development of these recommendations. RESULTS: The overall response rate was 10.4% (4204 replies). Results were similar across countries and specialties. Of the 23 treatment modes proposed, only joint lavage and intra-articular (IA) corticosteroid injections were more strongly recommended by the expert task force than by the responders as a whole, while the opposite was true for spa therapy. Principal component analysis showed: (1) some practitioners preferred "hard line" treatments (surgery, IA injections, or non-steroidal anti-inflammatory drugs (NSAIDs)); (2) there was a difference between those prescribing pharmacological (paracetamol) or non-pharmacological measures with low iatrogenicity (exercises, sticks, education), and those prescribing less well validated treatments closer to "alternative" medicine; (3) each specialist tended to advocate modes that they were most familiar with: rheumatologists were more likely to recommend IA injections and NSAIDs; orthopaedic surgeons, surgical procedures; rehabilitators, education and all non-pharmacological modes; general practitioners, spa therapy and opioids. CONCLUSIONS: A multidisciplinary approach is optimal in the management of this chronic disease with its variable course.

Dopamine transporter SPECT using fast kinetic ligands: 123I-FP-beta-CIT versus 99mTc-TRODAT-1.

A comparative study was carried out on two promising presynaptic dopamine transporter single-photon emission tomography (SPECT) radioligands with a fast pharmacokinetic profile, 123I-FP-beta-CIT (FP) and 99mTc-TRODAT-1 (TR), in order to assess their differential diagnostic power in early parkinsonism and their sensitivity for detection of disease progression. This cross-sectional study was conducted on 96 patients with early-stage parkinsonism referred in a tertiary clinical setting. Mean disease duration was 2.0+/-1.3 years, and patients had a modified Hoehn and Yahr (H&Y) stage of 1-2 (average 1.2). Forty-seven patients received TR, and 49 received FP. In both groups, ten patients with normal presynaptic function were included as a control population; all other patients were clinically diagnosed as having idiopathic Parkinson's disease. Groups were matched for gender, age, disease duration and modified H&Y stage. Triple-head gamma camera SPECT was analysed using a semiquantitative index of transporter binding (BI). Discriminant analysis with cross-validation resulted in a maximal classification accuracy for FP of 93% (sensitivity 95% and specificity 86%) for the contralateral putamen BI. For TR, the corresponding values were 87% accuracy, 92% sensitivity and 70% specificity. For FP, disease duration was correlated with both the putamen BI (-8.8%/year, rho=-0.41, P=0.025) and the putamen/caudate ratio (-7.4%/year, rho=-0.51, P=0.004), but for TR no significant correlation was found (all P values >0.5). In conclusion, both FP and TR show high sensitivity in a clinically relevant setting, but FP has superior accuracy for early differential diagnosis of idiopathic parkinsonism and non-degenerative extrapyramidal disorders, as well as better sensitivity for disease follow-up.

Results of the international Pu-2000 exercise for plutonium isotopic composition measurements.

An international comparison for plutonium isotopic composition measurement, known as the Pu-2000 exercise, was organized by the ESARDA NDA-WG (European Safeguards Research and Development Association, Working Group on Techniques and Standards for Non-Destructive Assay). The aim of this comparison was to test X- and gamma-ray spectrometry methods over a large range of isotopic ratios. These methods are based on the complex analysis of several X- and gamma-rays in the KX region of the plutonium spectrum and also in the 120-700 keV energy range. The results obtained by the participants with their corresponding uncertainties are presented in this document and compared to the declared values. The main conclusions of the work are also given. No important bias due to an inadequate knowledge of the nuclear data for plutonium isotopes was observed.

RP-HPLC separation of the diastereomers of technetium-99m labelled tropanes and identity confirmation using radio-LC-MS.

99mTc-TRODAT-1 (technetium(V)-oxo-2-[[2-[[[3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3.2.1]oct-2-yl]methyl](2-mercaptoethyl)amino]ethyl]]amino]-ethanethiolato(3-)) and 99mTc-TRODAT-M, the 4-methylphenyl derivative of 99mTc-TRODAT-1, are at this moment being evaluated in clinical trials as imaging agents for the central nervous dopamine transporter system. Both compounds are formed as a mixture of two major diastereomers. As the tracer concentration in preparations for clinical investigations is very low (30-150 pmol/ml), identification of these 99mTc-complexes was, up to now, carried out indirectly using X-ray diffraction analysis of the corresponding rhenium complexes which can be synthesized in gram amounts. In this study, we developed a convenient and practical reversed phase HPLC-method for purification and isolation of the respective diastereomers of 99mTc-TRODAT-1 and three of its derivatives using mixtures of solvents which are compatible with biological studies, i.e. aqueous buffers and ethanol. Furthermore, direct identity confirmation of the 99mTc-complexes using radio-LC-MS was successfully elaborated.

An efficient HPLC method for the analysis of isomeric purity of technetium-99m-exametazime and identity confirmation using LC-MS.

99mTc-exametazime (99mTc-d,l-HMPAO, 99mTc-d,l-hexamethylpropyleneamine oxime) is a neutral rather unstable complex of short-lived 99mTc (t(1/2)=6 h) with the d,l-isomer (mixture of D,D- and L,L-isomers) of a bis-amine bis-oxime tetraligand. It is widely used for measurement of regional cerebral perfusion in nuclear medicine. The meso-isomer (D,L-form) should not be present in a preparation as it is not retained in brain and thus does not provide clinically useful information. Meso-HMPAO is removed from the ligand during the synthesis procedure by repeated recrystallization, but can still be present as impurity in d,l-isomer. Due to the lack of a suitable chromatographic method for analysis of the isomeric purity of 99mTc-exametazime preparations, United States Pharmacopoeia 25 (USP 25) prescribes a biological test in rats for quality control purpose. In this study, we developed a suitable high-performance liquid chromatography (HPLC) method which allows to demonstrate the relative amounts of d,l- and meso-isomer in 99mTc-exametazime and so obviates the need for a biodistribution test in animals as part of the quality control. Due to the low concentrations in which 99mTc-d,l-HMPAO is obtained (typically 2-6 ng/ml), confirmation of the identity of 99mTc-d,l-HMPAO in the monograph of the European Pharmacopoeia is now performed only indirectly by TLC and assessment of its retention time on RP-HPLC. To investigate the potential of radio-LC-MS for assessment of the identity of 99mTc-exametazime, 99mTc-d,l-HMPAO and 99mTc-meso-HMPAO prepared using a Tc-rich eluate were analyzed using a radio-LC-MS system equipped with a time-of-flight mass spectrometer with electrospray ionization. The main peak in the radiometric channel coincided with the molecular ion mass of 99mTc-d,l-HMPAO in the mass spectrometer channel and the measured accurate mass differed only by 0.26 ppm from the theoretical mass. The identity of 99mTc-meso-HMPAO was also confirmed. Thus, radio-LC-MS allowed to obtain strong evidence for the structure of 99mTc-d,l-HMPAO and 99mTc-meso-HMPAO at nanomolar concentration. It is concluded that radio-LC-MS can become a sensitive aid in quality control of "no carrier added" radiopharmaceutical preparations.

Preparation and preliminary evaluation of 99mTc-EC-For-MLFK.

For-Met-Leu-Phe-Lys (For-MLFK), a chemotactic peptide that binds with high affinity to granulocytes and monocytes, was labeled with 99mTc using ethylene dicysteine (EC) as the metal chelating system. EC was selected because of the rapid renal excretion of its 99mTc-complex and therefore, was expected to enhance the degree of urinary elimination of the peptide-conjugate. 99mTc-EC-For-MLFK was prepared using a preformed chelate approach. After incubation of 99mTc-EC-For-MLFK with total blood, 68.1% of the labeled peptide was associated with WBC and 86% of this cell-associated activity was bound to granulocytes. Biodistribution studies in normal mice revealed a very fast blood clearance (4.1% and 0.6% of I.D. in blood at respectively 5 and 60 min p.i.). However, elimination of the labeled peptide proceeds mainly via the hepatobiliary system (24.5% of I.D. in liver and 48.8% of I.D. in intestines at 60 min p.i.) and to a much lower degree via the kidneys (17.9% in renal system at 60 min p.i.). From these results, it is concluded that 99mTc-EC-For-MLFK is not suited to image infections, despite its high binding to granulocytes, since it leads to high, non-specific, abdominal activity.

Passage of intratracheally instilled ultrafine particles from the lung into the systemic circulation in hamster.

The mechanisms of particulate pollution-related cardiovascular morbidity and mortality are not well understood. We studied the passage of radioactively labeled ultrafine particles after their intratracheal instillation. Hamsters received a single intratracheal instillation of 100 microg albumin nanocolloid particles (nominal diameter < or = 80 nm) labeled with 100 microCi technetium-99m and were killed after 5, 15, 30, and 60 min. In blood, radioactivity, expressed as percentage of total body radioactivity per gram blood, amounted to 2.88 +/- 0.80%, 1.30 +/- 0.17%, 1.52 +/- 0.46%, and 0.21 +/- 0.06% at 5, 15, 30, and 60 min, respectively. Thin-layer chromatography showed only one peak of radioactivity corresponding to unaltered (99m)Tc-albumin nanocolloid. In the liver, radioactivity, expressed as percentage of total radioactivity per organ, amounted to 0.10 +/- 0.07%, 0.23 +/- 0.06%, 1.24 +/- 0.27%, and 0.06 +/- 0.02% at 5, 15, 30, and 60 min, respectively. Lower values were observed in the heart, spleen, kidneys, and brain. Dose dependence was assessed at 30 min following instillation of 10 microg and 1 microg (99m)Tc-albumin per animal (n = 3 at each dose), and values of the same relative magnitudes as after instillation of 100 microg were obtained. We conclude that a significant fraction of (99m)Tc-albumin, taken as a model of ultrafine particles, rapidly diffuses from the lungs into the systemic circulation.

Evaluation of 99mTc-MAMA-chrysamine G as an in vivo probe for amyloidosis.

To date, systemic amyloidosis is diagnosed histologically using Congo red staining or in vivo using iodine-123 labelled serum amyloid P component (123I-SAP) scintigraphy. We developed 99mTc-MAMA-CG, a 99mTc-labelled derivative of the lipophilic Congo red analogue chrysamine G (CG), as a possible alternative to 123I-SAP. In vivo 99mTc-MAMA-CG scintigraphy, performed in chickens with spontaneous joint amyloidosis, resulted as soon as 10 min after injection in scintigraphic images showing uptake of activity in amyloid-loaded organs (liver, joints). One of these chickens was studied also with 123I-SAP resulting in scintigraphic images revealing 123I-SAP binding to amyloid deposits in the liver. However, up to 11 h after injection no radioactivity was visible in the amyloid positive joints. In vitro autoradiography, performed on sections of chicken joints with Enterococcus faecalis induced amyloid arthropathy (chjAA), demonstrated the failure of 99mTc-MAMA-CG to bind significantly to amyloid deposits in the presence of 10 microM Congo red The specificity of 99mTc-MAMA-CG localisation was also established by the absence of 99mTc-MAMA-CG binding in non-amyloidotic organs in vitro and in vivo. 99mTc-MAMA-CG did not show any sign of acute toxicity. These findings establish the usefulness of 99mTc-MAMA-CG as a non-invasive in vivo diagnostic probe in chickens with amyloid arthropathy and suggest that it may also be applicable to human amyloidosis.

In vitro affinity of 99Tcm-labelled N2S2 conjugates of chrysamine G for amyloid deposits of systemic amyloidosis.

To date, systemic amyloidosis is diagnosed histologically in vitro using Congo red staining or in vivo using iodine-123 serum amyloid P component (123I-SAP) scintigraphy. 99Tcm-labelled derivatives of chrysamine G (CG), a lipophilic analogue of Congo red, were synthesized as potential tracer agents for direct and quantitative scintigraphic evaluation of amyloid deposits. To determine the affinity of 99Tcm-MAMA-CG, 99Tcm-Me4MAMA-CG and 99Tcm-MAMA-CG diethyl ester for amyloid, in vitro autoradiography was performed on sections of human kidney biopsy cylinders from kidneys with amyloid deposits (types AA, Alambda and Akappa) or control kidney tissue after incubation with the respective tracer agents. The binding of 99Tcm-MAMA-CG and its tetramethyl derivative was higher to kidney biopsy material with amyloid deposits of the AA, Alambda or Akappa type compared with control kidney tissue. This higher binding was prevented by the presence of 10 microM Congo red in the incubation medium. The diethyl ester of 9Tcm-MAMA-CG did not demonstrate increased binding to Congo red-positive kidney tissue. In conclusion, 99Tcm-MAMA-CG and 99Tcm-Me4MAMA-CG localize specifically to amyloid deposits in human kidney tissue, suggesting that these tracer agents may be applicable as specific targeting agents for diagnostic purposes in clinical amyloidosis.

Surgical correction of vesicoureteral reflux: 5-year follow-up with 99Tcm-DMSA scintigraphy.

AIM: To evaluate kidney function before and after surgical correction of vesicoureteral reflux. The long-term effect was measured with quantitative nephro-scintigraphy using 99Tcm labelled dimercaptosuccinic acid (99Tcm-DMSA). METHODS: Forty-five children with a history of urinary tract infections due to vesicoureteral reflux (VUR) were studied. VUR grade was determined with contrast voiding cystourethrography. Planar scintigraphy was performed with 99Tcm-DMSA and uptake measured as a percentage of injected dose. Kidney function was evaluated at baseline and 5 years after corrective surgery. RESULTS: Three months after surgery, persistent mild reflux was found in eight of 76 treated renal units. Kidney uptake at 5-year follow-up was unchanged in the majority of children, indicating preservation of renal function found at baseline. The split renal function showed an excellent correlation (r = 0.99) between baseline and follow-up studies (regression slope 1.01). Percentage uptake had a regression slope of 0.89 significantly different from unity (P<0.05). Empirical kidney-depth correction techniques were compared. The scintigraphic pattern worsened in six kidneys, indicative of increased scarring in a minority of children. CONCLUSION: Planar nephro-scintigraphy with 99Tcm-DMSA was well tolerated in our paediatric population, and appeared appropriate to evaluate kidney function in time. After surgical correction of VUR, the baseline function was maintained in 94% of kidneys.

EULAR recommendations for the management of knee osteoarthritis: report of a task force of the Standing Committee for International Clinical Studies Including Therapeutic Trials (ESCISIT).

BACKGROUND: Osteoarthritis (OA) is the most common joint disease encountered throughout Europe. A task force for the EULAR Standing Committee for Clinical Trials met in 1998 to determine the methodological and logistical approach required for the development of evidence based guidelines for treatment of knee OA. The guidelines were restricted to cover all currently available treatments for knee OA diagnosed either clinically and/or radiographically affecting any compartment of the knee. METHODS: The first stage was the selection of treatment modalities to be considered. The second stage comprised a search of the electronic databases Medline and Embase using a combination of subject headings and keywords. All European language publications in the form of systematic reviews, meta-analyses, randomised controlled trials, controlled trials, and observational studies were included. During stage three all the relevant studies were quality scored. The summary statistics for validated outcome measures, when available, were recorded and, where practical, the numbers needed to treat and the effect size for each treatment were calculated. In the fourth stage key clinical propositions were determined by expert consensus employing a Delphi approach. The final stage ranked these propositions according to the available evidence. A second set of propositions relating to a future research agenda was determined by expert consensus using a Delphi approach. RESULTS: Over 2400 English language publications and 400 non-English language publications were identified. Seven hundred and forty four studies presented outcome data of the effects of specific treatments on knee OA. Quantitative analysis of treatment effect was possible in only 61 studies. Recommendations for the management of knee OA based on currently available data and expert opinion are presented. Proposals for a future research agenda are highlighted. CONCLUSIONS: These are the first clinical guidelines on knee OA to combine an evidence based approach and a consensus approach across a wide range of treatment modalities. It is apparent that certain clinical propositions are supported by substantial research based evidence, while others are not. There is thus an urgent need for future well designed trials to consider key clinical questions.