Despite steadily growing numbers of children diagnosed with autism spectrum disorders (ASD), causative treatment is unavailable. Recently, biological cell therapies involving pluripotent cells have ...raised hopes towards sustained beneficial outcome. We herein report data of four children diagnosed with ASD, who were treated with autologous, bone marrow (BM)-derived, intrathecally and simultaneously intravenously applied, point-of-care stem cell transplant (SCT). The three boys and one girl received the diagnosis at ages between 2-4 years. The decision to perform the procedure was preceded by limited beneficiary impact of conventional symptom-based, psychological and pharmacological interventions. At ages of 4-14 years the children received their SCT, no immediate or late adverse events were reported. Disappearance of symptoms were observed by the parents during the following year and consequently improved Autism Treatment Evaluation Checklist (ATEC) scores were reported. The SCT procedure, in trained hands, can be a safe and promising treatment option in children with ASD, responding in a non-satisfactory manner to conventional treatments. It is postulated that SCT may, among others, assert its positive effect by counteracting a cerebral inflammatory autoimmune process which in turn supports the responsiveness to behavioral and pharmacological interventions. Our results in this small group are encouraging, but certainly need further investigation in larger cohorts.
(177)Lu-labeled ethylenediamine-N,N,N',N'-tetrakis methylene phosphonic acid ((177)Lu-EDTMP), was used to palliate metastatic bone pain as a new bone-seeking radiopharmaceutical. In this phase II ...study, we assessed the efficacy and safety of (177)Lu-EDTMP for bone pain palliation in patients with breast cancer and hormone refractory prostate cancer with bone metastases.
Sixteen patients were enrolled in the trial and were subsequently divided into 2 groups, the low-dose group (1295 MBq) and the high dose group (2590 MBq) to determine differences in toxicities and response rates. Pain scores, Karnofsky indices, mobility scores, and requirement of analgesic administration were assessed at 0, 2, 4, 6, 8, and 12 weeks after injection of (177)Lu-EDTMP. Toxicity was assessed by analyzing hemoglobin, leukocyte, and platelet counts.
An obvious reduction in the mean pain score was observed at 2 to 6 weeks after the administration of (177)Lu-EDTMP. The rate of complete responses in bone pain palliation was 55% in group 1 and 80% in group 2 at 6 weeks after treatment. Of the 5 patients who required additional analgesics, all were able to reduce or completely stop taking these medications by 4 weeks after therapy. Mean (SD) Karnofsky indices of 58.18 (9.82) (range, 50-70) and 56.00 (8.94) (range, 50-70) at baseline increased to 82.73 (9.05) (range, 60-90) at 6 weeks after (177)Lu-EDTMP treatment in group 1 and 85.00 (5.77) (range, 80-90) at 8 weeks after injection in group 2, respectively. Mobility scores decreased from 2.91 (1.04) (range, 1-4) and 2.80 (0.84) (range, 2-4) at baseline to 1.00 (0.67) (range, 0-2) and 0.50 (0.58) (range, 0-1) at 8 weeks after administration of (177)Lu-EDTMP in groups 1 and 2, respectively, primarily owing to improved mobility. In group 1, 1 patient experienced grade III toxicity in both hemoglobin and platelet counts. No grade IV toxicities were observed. In group 2, there were no grade III or IV toxicities found in hemoglobin, platelets, or leukocytes counts. Moreover, no clinically significant adverse effects were observed, and no significant differences in either efficacy or safety were detected between the 2 dose levels.
This study indicated that (177)Lu-EDTMP was an effective and safe treatment for palliation of metastatic bone pain in patients with prostate or breast cancer. A dose of 1295 MBq (35 mCi) was sufficient for bone pain palliation therapy, and doses as high as 2590 MBq (70 mCi) were well tolerated.
Background
Radiosynovectomy (RSO) is widely used in rheumatoid arthritis (RA). Commercially available radiopharmaceuticals are costly, and therefore new agents may be of interest. Radiocolloids ...labelled with less costly and more accessible radionuclides are of interest to developing countries. We investigated the efficacy of different formulations in RA.
Methods
In a multicentre effort, a cohort of 99 RA patients with knee involvement underwent RSO. Sixty-eight patients were treated with 184 ± 4 MBq Y-90 silicate (Y-90), 15 patients with 53 ± 11 MBq P-32 colloid (P-32), and 16 patients with 451 ± 110 MBq of Re-188 tin colloid (Re-188). Corticosteroid group (CSG) consisting of 46 patients received an intra-articular instillation of 20–40 mg triamcinolone. Pain response was evaluated by a 10-step visual analogue scale (VAS) before, 1 month, 3 months, 6 months and 12 months following the procedure.
Results
In the RSO group (
n
= 99), pain relief by VAS from 6 ± 2 before to 5 ± 3, 4 ± 2, 3 ± 2 and 4 ± 2 at 1, 3, 6, 12 months after RSO was documented (Y-90 group: 6 ± 2 to 3 ± 2; P-32: 5 ± 2 to 3 ± 2, Re-188: 7 ± 2 to 4 ± 2 before vs. 6 months after therapy, respectively). The CSG VAS values were 6 ± 2 before and 5 ± 2, 4 ± 3, 5 ± 2 and 6 ± 2 at 1, 3, 6 and 12 months after corticosteroid instillation, respectively. Pain relief achieved with the three radiocolloid formulations did not differ significantly (
P
> 0.1). Pain relief at 12 months was more durable in RSO compared to CSG,
P
< 0.05. At 3 months, pain relief (>2 steps) was reported by 86% of RSO versus 67% of CSG, at 6 months 72 versus 46% and at 12 months 46 versus 21%. Side effects, i.e. swelling or transient pain increase, were recorded in 16% of patients but resolved within 1 month.
Conclusion
Therapeutic efficacy of RSO for RA of the knee applying either P-32, Re-188 or Y-90 provides comparable results. Pain relief by RSO is longer lasting as compared to corticosteroid instillation.
This article describes trends in nuclear medicine in the developing world as noted by nuclear medicine professionals at the International Atomic Energy Agency (IAEA). The trends identified are based ...on data gathered from several sources, including information gathered through a database maintained by the IAEA; evaluation of country program frameworks of various IAEA Member States; personal interactions with representatives in the nuclear medicine field from different regions of the world; official proceedings and meeting reports of the IAEA; participation in numerous national, regional, and international conferences; discussions with the leadership of major professional societies; and relevant literature. The information presented in this article relied on both objective and subjective observations. The aims of this article were to reflect on recent developments in the specialty of nuclear medicine and to envision the directions in which it is progressing. These issues are examined in terms of dimensions of practice, growth, and educational and training needs in the field of nuclear medicine. This article will enable readers to gain perspective on the status of nuclear medicine practice, with a specific focus on the developing world, and to examine needs and trends arising from the observations.
Ever since the first descriptions as an aid for sentinel lymph node biopsy in the early 1990s 1, 2, interest in radio-guided surgery has been rising sharply and continues to do so with respect to ...both the number of articles published in the medical literature and the amount of procedures performed. In Europe, lymphoscintigraphic imaging procedures for sentinel lymph node biopsy have markedly increased, by about 17.5%, between the years 2005 and 2008 (source
Under the auspices of the International Atomic Energy Agency, a new-generation, platform-independent, and x86-compatible software package was developed for the analysis of scintigraphic renal dynamic ...imaging studies. It provides nuclear medicine professionals cost-free access to the most recent developments in the field. The software package is a step forward towards harmonization and standardization. Embedded functionalities render it a suitable tool for education, research, and for receiving distant expert's opinions. Another objective of this effort is to allow introducing clinically useful parameters of drainage, including normalized residual activity and outflow efficiency. Furthermore, it provides an effective teaching tool for young professionals who are being introduced to dynamic kidney studies by selected teaching case studies. The software facilitates a better understanding through practically approaching different variables and settings and their effect on the numerical results. An effort was made to introduce instruments of quality assurance at the various levels of the program's execution, including visual inspection and automatic detection and correction of patient's motion, automatic placement of regions of interest around the kidneys, cortical regions, and placement of reproducible background region on both primary dynamic and on postmicturition studies. The user can calculate the differential renal function through 2 independent methods, the integral or the Rutland-Patlak approaches. Standardized digital reports, storage and retrieval of regions of interest, and built-in database operations allow the generation and tracing of full image reports and of numerical outputs. The software package is undergoing quality assurance procedures to verify the accuracy and the interuser reproducibility with the final aim of launching the program for use by professionals and teaching institutions worldwide.
Purpose
To investigate dynamic ictal perfusion changes during temporal lobe epilepsy (TLE).
Methods
We investigated 37 patients with TLE by ictal and interictal SPECT. All ictal injections were ...performed within 60 s of seizure onset. Statistical parametric mapping was used to analyse brain perfusion changes and temporal relationships with injection time and seizure duration as covariates.
Results
The analysis revealed significant ictal hyperperfusion in the ipsilateral temporal lobe extending to subcortical regions. Hypoperfusion was observed in large extratemporal areas. There were also significant dynamic changes in several extratemporal regions: ipsilateral orbitofrontal and bilateral superior frontal gyri and the contralateral cerebellum and ipsilateral striatum.
Conclusion
The study demonstrated early dynamic perfusion changes in extratemporal regions probably involved in both propagation of epileptic activity and initiation of inhibitory mechanisms.
Background
Sentinel lymph node biopsy (SLNB) is the accepted standard of care in early-stage breast cancer and cutaneous melanoma. This technology is accurate for nodal staging and determining the ...prognosis of these patients. There are several randomized controlled trials confirming the accuracy of this technique and confirming its role in reducing morbidity and improving quality of life. It is also gaining increased acceptance in the management of other solid tumors. Despite the established benefits of SLNB as a minimally invasive approach for nodal staging, the procedure is still underutilized in many developing countries.
Methods
The Human Health Division of the International Atomic Energy Agency (IAEA) convened advisory meetings with panels of multidisciplinary experts from different backgrounds with the remit to analyze the difficulties encountered by developing countries in establishing a successful SLNB program. The other remit of the panel was to recommend an effective program based on existing evidence that can be adapted and implemented in developing countries. The experience of some members of the panel in the training for this technique in Asia, Latin America, and Africa provided the insight required for the development of a comprehensive and structured program. The panel included recommendations on the technical aspects of the procedure, as well as a comprehensive training program, including theoretical teaching, practical training in surgical skills, laboratories, and hands-on proctored learning. Particular emphasis was placed on in-built quality assurance requirements to ensure that this powerful staging investigation is implemented with the highest possible standard in the management of cancer patients, with the lowest false negative rate.
Conclusions
It is hoped that this article will be a useful resource for our colleagues planning to establish a SLNB program.
Background and purpose
MR imaging, ictal single-photon emission CT (SPECT) and ictal EEG play important roles in the presurgical localization of epileptic foci. This multi-center study was ...established to investigate whether the complementary role of perfusion SPECT, MRI and EEG for presurgical localization of temporal lobe epilepsy could be confirmed in a prospective setting involving centers from India, Thailand, Italy and Argentina.
Methods
We studied 74 patients who underwent interictal and ictal EEG, interictal and ictal SPECT and MRI before surgery of the temporal lobe. In all but three patients, histology was reported. The clinical outcome was assessed using Engel’s classification. Sensitivity values of all imaging modalities were calculated, and the add-on value of SPECT was assessed.
Results
Outcome (Engel’s classification) in 74 patients was class I, 89%; class II, 7%; class III, 3%; and IV, 1%. Regarding the localization of seizure origin, sensitivity was 84% for ictal SPECT, 70% for ictal EEG, 86% for MRI, 55% for interictal SPECT and 40% for interictal EEG. Add-on value of ictal SPECT was shown by its ability to correctly localize 17/22 (77%) of the seizure foci missed by ictal EEG and 8/10 (80%) of the seizure foci not detected by MRI.
Conclusions
This prospective multi-center trial, involving centers from different parts of the world, confirms that ictal perfusion SPECT is an effective diagnostic modality for correctly identifying seizure origin in temporal lobe epilepsy, providing complementary information to ictal EEG and MRI.
Quantifying hemispheric cerebral blood flow (CBF) may improve diagnostic accuracy when combined with perfusion SPECT.
To explore the impact of measuring mean CBF on the differential diagnosis of ...dementia under clinical conditions.
CBF was calculated from anterior planar dynamic images acquired over 100 s after i.v. bolus injection of 550 MBq of (99m)Tc-HMPAO using Patlak linearization of normalized time-activity curves derived from right and left hemispheric, and aortic ROIs. Regional perfusion was evaluated from SPECT imaging carried out 20 min later. ANCOVA was applied to compare age-dependent differences of CBF; model differences at P<0.05 were considered significant. Study populations consisted of controls, 34 patients with no focal or vascular abnormality or mood disorder and with normal MR or CT brain images (F:M, 16:18; age+/-SD; 54.3+/-20.2 years); and patients with probable dementia comprised two subgroups. The first consisted of 33 patients with primary degenerative aetiology (PDD) (DAT or mixed-type microvascular and DAT, Lewy body and fronto-temporal atrophy), F/M; 17:16, age+/-SD; 68.4+/-8.8 years. The second subgroup consisted of 13 patients with dementia related to subcortical microvascular leuco-encephalopathy (vLEP), M/F 7:6, age+/-SD; 71.7+/-12.6 years. Classification was mainly based on clinical findings according to DMS-IV criteria, combined with follow-up or functional and anatomical imaging.
Computation of CBF on 100 consecutive patients showed excellent inter-user reproducibility in trained hands (variation coefficient <5%). Mean CBF in controls showed an age dependent decrease, the first order linear regression was CBF(left)=58.9-0.2 x age (r=-0.648, P<0.001) and CBF(right)=57.9-0.02 x age (r=-0.645). In comparison to controls, a slightly more pronounced but statistically insignificant age-dependent decrease in mCBF was found in the vLEP group, CBF(left)=55.5-0.21 x age (r=-0.56) and CBF(right)=64.2-0.32 x age (r=-0.645). In the PDD group CBF, after adjusting for age, was significantly lower than control values (P<0.001); CBF(left)=37-0.025 x age and CBF(right)=39-0.057 x age. More importantly, better discrimination between PDD and controls in patients of younger age (45-65 years) was found. In older patients (65-85 years) overlap slightly increased. ROC analysis of the cohort of dement patients and controls older than 46 years revealed a 93-94% sensitivity and a specificity of 73% and 77% for the left and right hemispheres, respectively, at a CBF cut-off value of 39.5 ml.min(-1).100 g(-1).
Routine quantification of mean CBF by HMPAO-RNA is a simple and reproducible method which can be easily added to the standard brain perfusion SPECT without additional cost or increasing patient's radiation burden. Combined with regional perfusion it provides an additional tool for the aetiological classification of dementia.
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