De novo sensitization during subcutaneous allergen specific immunotherapy - an analysis of 51 cases of SCIT and 33 symptomatically treated controls

Since the beneficial implementation of allergen specific subcutaneous immunotherapy (SCIT), there are only a few studies on the risk of SCIT-induced neosensitizations. In 51 patients, we retrospectively analyzed sIgE and sIgG patterns by a multiplex ELISA as well as demographic and clinical features before and after SCIT. 33 allergic patients, who only received symptomatic treatment, served as controls. In 12 of 51 SCIT-treated patients (24%), we found new sIgE against allergen components of the allergen source treated by SCIT;eight of them were adults. Among controls, no adult patient showed neosensitization to components of the primarily affected allergen source. Only two children of the control group were affected by neosensitization, which was limited to major allergen components and rarely accompanied by sIgG. In the SCIT-treated group, neosensitization affected major and minor allergen components, and was accompanied by a strong induction of sIgG against major components. A clear clinical predictor of neosensitization during SCIT was not found. Comparing symptom scores, patients seem to profit more from SCIT, if neosensitization remained absent. Patients undergoing SCIT might carry an enhanced risk of neosensitization towards formerly unrecognized allergen components. According to anamnestic data, these neosensitizations might be of clinical relevance - supporting attempts towards personalized recombinant vaccines

A holistic resilience framework development for rural power systems in emerging economies

Infrastructure and services within urban areas of developed countries have established reliable definitions of resilience and its dependence on various factors as an important pathway for achieving sustainability in these energy systems. However, the assessment, design, building and maintenance of power systems situated in rural areas in emerging economies present further difficulties because there is no a clear framework for such circumstances. Aiming to address this issue, this paper combines different visions of energy-related resilience both in general and under rural conditions in order to provide a robust practical framework for local and international stakeholders to derive the right actions in the rural context of emerging economies. An in-depth review is implemented to recompile information of resilience in general, in energy systems and in rural areas in particular, and a number of existing frameworks is also consulted. In order to acknowledge the particular circumstances and identify the important factors influencing the resilience of rural electrification in emerging economies, a holistic rural power system resilience framework is developed and presented. This consists of twenty-one indicators for technical resilience, eight indicators for social resilience, and thirteen indicators for economic resilience. This framework can be used by system owners and operators, policy makers, NGOs and communities to ensure the longevity of power systems. This work also paves the way for the creation of appropriate and effective resilience standards specifically targeted for application in these regions - aiming to achieve the delivery of global and local sustainability goals

Brain glucose utilization in systemic lupus erythematosus with neuropsychiatric symptoms: A controlled positron emission tomography study

In contrast to morphological imaging [such as magnetic resonance imaging (MRI) or computed tomography], functional imaging may be of advantage in the detection of brain abnormalities in cases of neuropsychiatric systemic lupus erythematosus (SLE). Therefore, we studied 13 patients (aged 40±14 years, 11 female, 2 male) with neuropsychiatric SLE who met four of the American Rheumatism Association criteria for the classification of SLE. Ten clinically and neurologically healthy volunteers served as controls (aged 40±12 years, 5 female, 5 male). Both groups were investigated using fluorine-18-labelled fluorodeoxyglucose brain positron emission tomography (PET) and cranial MRI. The normal controls and 11 of the 13 patients showed normal MRI scans. However, PET scan was abnormal in all 13 SLE patients. Significant group-to-group differences in the glucose metabolic index (GMI=region of interest uptake/global uptake at the level of the basal ganglia and thalamus) were found in the parieto-occipital region on both sides: the GMI of the parieto-occipital region on the right side was 0.922±0.045 in patients and 1.066±0.081 in controls (P<0.0001, Mann WhitneyU test), while on the left side it was 0.892±0.060 in patients and 1.034±0.051 in controls (P=0.0002). Parietooccipital hypometabolism is a conspicuous finding in mainly MRI-negative neuropsychiatric SLE. As the parieto-occipital region is located at the boundary of blood supply of all three major arteries, it could be the most vulnerable zone of the cerebrum and may be affected at an early stage of the cerebrovascular diseas

RET Proto-Oncogene Germline Mutation in Pheochromocytoma Patients - Incidence and Clinical Consequences

Wstęp Dotychczasowe badania wskazują, że częstość zespołu mnogiej gruczolakowatości (MEN 2), w skład którego wchodzi guz chromochłonny, jest większa niż dotychczas sądzono. Zespół ten dziedziczony jest w sposób autosomalny dominujący i wywołuje go mutacja protoonkogenu RET. Celem pracy jest ocena częstości występowania oraz kliniczne znaczenie mutacji protoonkogenu RET u chorych z guzem chromochłonnym. Materiał i metody Badania genetyczne w kierunku mutacji protoonkogenu RET przeprowadzono u 106 chorych (średni wiek: 49 &plusmn; 14,1 roku, 26M, 80K) z rozpoznanym i potwierdzonym histopatologicznie guzem chromochłonnym. Pacjenci ci byli uprzednio hospitalizowani i leczeni w Klinice Chorób Wewnętrznych i Nadciśnienia Tętniczego Akademii Medycznej w Warszawie w latach 1957&#8211;1998 oraz w Klinice Nadciśnienia Tętniczego Instytutu Kardiologii w Warszawie od roku 1980 do 2001. Oceniano również stężenie kalcytoniny (CT), zarówno w warunkach podstawowych, jak i po stymulacji pentagastryną, oraz stężenie parathormonu. Wyniki Obecność mutacji protoonkogenu RET wykazano u 8 chorych (7,4%) - w eksonie 11, w kodonie 634, TGC na CGC u 5 chorych, u pozostałych 3 odpowiednio - w eksonie 11, kodonie 634, TGC na GGC, w eksonie 11, kodonie 634, TGC na TGG oraz w eksonie 13, kodonie 791, TAT na CGC. Nadczynność komórek C potwierdzoną dodatnim testem pentagastrynowym stwierdzono u 5 nosicieli, u 2 chorych wynik testu był wątpliwy, jedynie u 1 chorego stężenie kalcytoniny było prawidłowe. Prawidłowe stężenie CT obserwowano u chorego z mutacją w eksonie 13, kodonie 791, TAT na CGC. U 4 nosicieli potwierdzono histopatologicznie obecność raka rdzeniastego tarczycy (biopsja cienkoigłowa). U 3 chorych wykonano totalną tyroidektomię, dwóch nie wyraziło zgody na dalsze leczenie (w tym jeden z pozytywnym wynikiem biopsji). Pozostali chorzy zostali poinformowani o konieczności totalnej tyroidektomii. U żadnego nosiciela nie stwierdzono nadczynności przytarczyc. Wnioski Wyniki badań autorów potwierdzają doniesienia o konieczności poddawania przesiewowym badaniom genetycznym oceniającym obecność mutacji protoonkogenu RET pacjentów z guzem chromochłonnym. Potwierdzenie nosicielstwa tej mutacji stanowi wskazanie do wykonania totalnej tyroidektomii. Genetyczne badania przesiewowe mogą mieć również znaczenie w wykrywaniu zespołu MEN 2 oraz ustaleniu dalszego postępowania u członków rodzin, u których stwierdza się mutację protoonkogenu RET.Background In patients with pheochromocytoma there may exist more often than expected the autosomal dominant cancer syndrome &#8212; multiple endocrine neoplasia type 2 (MEN 2). The susceptibility gene for MEN 2 is the RET proto-oncogene. Germline mutations can be identified by analysis of exons 10, 11, 13&#8211;16 of the RET gene. The aim of the study was to evaluate the frequency of these mutations in patients with pheochromocytoma and to report on the conclusions which patients and physicians have drawn. Material and methods We screened for germline mutations in the RET proto-oncogene and clinically evaluated 106 unselected patients with pheochromocytoma (mean age: 49 &plusmn; 14,1 years, 26 male, 80 female) histopathologically confirmed, diagnosed and treated in the years 1957&#8211;1998 in the Department of Internal Medicine and Hypertension, Warsaw School of Medicine and in the years 1980/81&#8211;2001 in the Department of Hypertension, Institute of Cardiology, Warsaw. Determination of calcitonin concentration (CT) was performed in basal conditions and after pentagastrin stimulation; parathormone level was also determined. Results Genetic testing revealed germline mutations in the RET proto-oncogene in 8 patients (7,4%). Carriers had mutation of exon 11, codon 634: TGC to CGC (5 patients), exon 11, codon 634: TGC to GGC (1 patient), exon 11, codon 634: TGC to TGG (1 patient) and in exon 13, codon 791: TAT to TTT (1 patient). Hyperactivity of thyroid C-cells was found in 5 carriers, borderline values of basal and after pentagastrin CT were found in 2 carriers and in only one patient CT concentration was normal. In four patients with RET proto-oncogene mutations, MTC was confirmed histopathologically in fine-needle biopsy. In three of them total thyroidectomy was performed. Two patients refused to be surgically treated (one with positive result of biopsy); the next three RET proto-oncogene germline mutation carriers have been informed that prophylactic total thyroidectomy should be considered. In none of the carriers hyperparathyroidism was observed. Conclusions Our study indicates that patients with pheochromocytoma should be genetically screened for mutations of the RET proto-oncogene. The carriers of these mutations should undergo thyroidectomy. In addition, genetic studies can be useful for the screening of the carriers families

The Role of Whole-Body FDG PET/CT, Tc 99m MDP Bone Scintigraphy, and Serum Alkaline Phosphatase in Detecting Bone Metastasis in Patients with Newly Diagnosed Lung Cancer

Bone scan (BS) and serum alkaline phosphatase (ALP) concentration are used to detect bone metastasis in malignancy, although whole-body fluoro-D-glucose positron emission tomography computed tomography (FDG PET/CT) is being used increasingly. But BS is still used for the detection of metastatic bone lesion. So we compared the usefulness of PET/CT, BS, and serum ALP in detecting bone metastases in patients with newly diagnosed lung cancer. The medical record database was queried to identify all patients with a new diagnosis of lung cancer between January 2004 and December 2005, who had a PET/CT, BS, and serum ALP before treatment. We retrospectively reviewed all patients' records and radiological reports. One hundred eighty-two patients met the inclusion criteria. Bone metastases were confirmed in 30 patients. The sensitivity values were 93.3% for PET/CT, 93.3% for BS, 26.7% for serum ALP concentration, and 26.7% for BS complemented with serum ALP concentration. The respective specificity values were 94.1%, 44.1%, 94.1%, and 97.3%. The kappa statistic suggested a poor agreement among the three modalities. FDG PET/CT and BS had similar sensitivity, but PET/CT had better specificity and accuracy than BS. PET/CT is more useful than BS for evaluating bone metastasis. However, in the advanced stage, because of its high specificity, BS complemented with serum ALP is a cost-effective modality to avoid having to use PET/CT

Current Trends in Functional Imaging of Pheochromocytomas and Paragangliomas

Most pheochromocytomas/paragangliomas should be evaluated with anatomical imaging (computed tomography or magnetic resonance imaging) followed by functional imaging (nuclear medicine modalities). Functional imaging assures that the tumor is indeed a pheochromocytoma/paraganglioma and enables more thorough localization, especially detecting as many lesions as possible (in particular for metastatic disease). Functional imaging for pheochromocytomas/paragangliomas, can use radiolabled ligands specific for pathways of synthesis, metabolism, and inactivation of catecholamines or nonspecific ligands. In an overview of the available nuclear medicine modalities, we summarize the accumulated experience and recommend when functional imaging should be applied to patients with pheochromocytoma/paraganglioma.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74881/1/annals.1353.041.pd

Total 18F-dopa PET tumour uptake reflects metabolic endocrine tumour activity in patients with a carcinoid tumour

Positron emission tomography (PET) using 6-[(18)F]fluoro-L-dihydroxyphenylalanine ((18)F-dopa) has an excellent sensitivity to detect carcinoid tumour lesions. (18)F-dopa tumour uptake and the levels of biochemical tumour markers are mediated by tumour endocrine metabolic activity. We evaluated whether total (18)F-dopa tumour uptake on PET, defined as whole-body metabolic tumour burden (WBMTB), reflects tumour load per patient, as measured with tumour markers. Seventy-seven consecutive carcinoid patients who underwent an (18)F-dopa PET scan in two previously published studies were analysed. For all tumour lesions mean standardised uptake values (SUVs) at 40% of the maximal SUV and tumour volume on (18)F-dopa PET were determined and multiplied to calculate a metabolic burden per lesion. WBMTB was the sum of the metabolic burden of all individual lesions per patient. The 24-h urinary serotonin, urine and plasma 5-hydroxindoleacetic acid (5-HIAA), catecholamines (nor)epinephrine, dopamine and their metabolites, measured in urine and plasma, and serum chromogranin A served as tumour markers. All but 1 were evaluable for WBMTB; 74 patients had metastatic disease. (18)F-dopa PET detected 979 lesions. SUV(max) on (18)F-dopa PET varied up to 29-fold between individual lesions within the same patients. WBMTB correlated with urinary serotonin (r = 0.51) and urinary and plasma 5-HIAA (r = 0.78 and 0.66). WBMTB also correlated with urinary norepinephrine, epinephrine, dopamine and plasma dopamine, but not with serum chromogranin A. Tumour load per patient measured with (18)F-dopa PET correlates with tumour markers of the serotonin and catecholamine pathway in urine and plasma in carcinoid patients, reflecting metabolic tumour activity

Imaging with non-FDG PET tracers: outlook for current clinical applications

Apart from the historical and clinical relevance of positron emission tomography (PET) with 18F-fluorodeoxyglucose (18F-FDG), various other new tracers are gaining a remarkable place in functional imaging. Their contribution to clinical decision-making is irreplaceable in several disciplines. In this brief review we aimed to describe the main non-FDG PET tracers based on their clinical relevance and application for patient care

Murine Models and Cell Lines for the Investigation of Pheochromocytoma: Applications for Future Therapies?

Pheochromocytomas (PCCs) are slow-growing neuroendocrine tumors arising from adrenal chromaffin cells. Tumors arising from extra-adrenal chromaffin cells are called paragangliomas. Metastases can occur up to approximately 60% or even more in specific subgroups of patients. There are still no well-established and clinically accepted “metastatic” markers available to determine whether a primary tumor is or will become malignant. Surgical resection is the most common treatment for non-metastatic PCCs, but no standard treatment/regimen is available for metastatic PCC. To investigate what kind of therapies are suitable for the treatment of metastatic PCC, animal models or cell lines are very useful. Over the last two decades, various mouse and rat models have been created presenting with PCC, which include models presenting tumors that are to a certain degree biochemically and/or molecularly similar to human PCC, and develop metastases. To be able to investigate which chemotherapeutic options could be useful for the treatment of metastatic PCC, cell lines such as mouse pheochromocytoma (MPC) and mouse tumor tissue (MTT) cells have been recently introduced and they both showed metastatic behavior. It appears these MPC and MTT cells are biochemically and molecularly similar to some human PCCs, are easily visualized by different imaging techniques, and respond to different therapies. These studies also indicate that some mouse models and both mouse PCC cell lines are suitable for testing new therapies for metastatic PCC