[Hypercalcemia, symptoms, differential diagnostics and treatment, or importance of calcium investigation]. / Hyperkalcemie, príznaky, diferenciální diagnostika a lécba aneb dulezitost vysetrování kalcia.

UNLABELLED: The concentration of calcium is carefully maintained under physiological conditions with parathormone, calcitonin and 1,25-dihydroxyvitamin D at appropriate levels. There are multiple causes that may bring about increased concentrations of calcium which exceed physiological values. Increased production of parathormone in parathyroid glands is only one of the possible causes. Malignant diseases are a very frequent cause of hypercalcemia, due to their creating mediators which stimulate osteoclasts and thereby osteolysis. A less frequent cause is represented by granulomatous processes, a typical example of which is sarcoidosis, whose cells increasingly (independently of parathormone) hydroxylate 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D. However there are also hereditary forms of hypercalcemia. One of the causes of the hereditary form of hypercalcemia is mutations of the calcium sensing receptor. In order to locate the adenoma of parathyroid glands, essential apart from sonographic imaging is scintigraphy 99mTc-methoxyisobutylisonitrile (MIBI) and even more exact is PET-CT examination with a radio-pharmaceutical 18F-fluorocholine. PET-CT examinations are beneficial with regard to detecting a malignant cause of hypercalcemia in until then undetected malignancy or an undetected granulomatous process. The essential treatment procedures for malignant hypercalcemia include appropriate hydratation of ionic solutions without calcium, administering of bisphosphonates or denosumab. The text describes in detail the symptoms of hypercalcemia and diagnostics of causes of hypercalcemia. KEY WORDS: bisphosphonates - cinacalcet - denosumab - granulomatous diseases - hereditary hypercalcemia - hypercalcemia - hypercalciuria - hyperparathyreosis - calcimimetics - calcitonin - multiple myeloma - malignant hypercalcemia - parathormone - sarcoidosis - 1,25-dihydroxyvitamin D.

[A rare case of multiple myeloma: multiple solitary plasmacytomas of distal extremities]. / Raritní prípad mnohocetného myelomu: vícecetný solitární plazmocytom kostí bércu a predloktí.

This article describes a case of 68-years-old male with very atypic variation of multiple myeloma occuring as multifocal osteolysis limited to tibiae, cuboid bone, radius and ulna, in the absence of diffuse bone marrow infiltration. The main goal of this article is to point out the importance of permanent awareness during diagnostics and treatment of this insidious disease.

[PET-CT documented complete remission of Erdheim-Chester disease, lasting more than 4 years from treatment initiation with cladribine]. / PET-CT dokumentovaná kompletní 4letá remise Erdheimovy-Chesterovy nemoci po lécbe kladribinem.

Erdheim-Chester disease is a very rare histiocytic disease. It represents one form of juvenile xanthogranuloma in WHO classification of blood diseases. The disease often causes B symptoms, skeletal pain and also may cause diabetes insipidus and retroperitoneal fibrosis. Selection of therapy depends on published case reports and small clinical trials. There are no recommendations for treatment based on randomized studies. Interferon α is probably the most commonly used drug for this disease. Some remissions have been described after treatment. However, long-term interferon α application is needed which is associated with numerous side effects. There are limited experiences with clabridine in this indication. In Pubmed Medline database, we have found 3 publications dedicated to description of treatment response after cladribine in Erdheim-Chester disease and other 7 papers evaluating effect of cladribine on juvenile xanthogranuloma forms, mostly with positive outcome. Based on these 10 publications we choose cladribine as first-line treatment in our patient. The treatment started in October 2009 with combination of 2-chlorodeoxyadenosine (Litak) 5 mg/m2 sc. + cyclophosphamide 150 mg/m2 iv. + dexamethasone 24 mg iv., five days consecutively. These cycles were repeated monthly. Mentioned formula was submitted 4 times and 3 times in limited application on day 1 - 3. The reason of that was neutropenia grade 3. All symptoms disappeared after treatment. Only diabetes insipidus persisted because damage of pituitary stalk is irreversible. Therapeutic effect was monitored by PET-CT imaging, initially every 6 months, later in 12-month intervals. PET-CT imaging showed complete remission of disease and 4.5 years duration of remission after treatment. The treatment was well tolerated with no complications implying hospitalization. Only mild thrombocytopenia and neutropenia remains after 4.5 years. Based on case report and publications we consider cladribine as appropriate firs-line drug for Erdheim-Chester disease. Therapeutic failure after 3-4 cycles may suggest other options (interferon α, anakinra, vemurafenib), but only in the case if healthcare provider is willing to cover this new and more expansive treatment than therapy with cladribine.

Striatal dopamine transporter imaging correlates with depressive symptoms and tower of London task performance in Parkinson's disease.

We studied whether the (123)I-FP-CIT uptake in the striatum correlates with depressive symptoms and cognitive performance in patients with Parkinson's disease (PD). Twenty patients with PD without major depression and/or dementia (mean age 61.7 +/- 12.7 years) underwent the (123)I-FP-CIT SPECT. Depressive symptoms and cognitive performance were assessed in the ON state. The ratios of striatal to occipital binding for the entire striatum, putamina, and putamen to the caudate (put/caud) index were calculated in the basal ganglia. The association between neuropsychiatric measures and dopamine transporter (DAT) availability was calculated; multiple regression analysis was used to assess association with age and disease duration. We found significant correlations between Montgomery and Asberg Depression Rating Scale (MARDS) and Tower of London (TOL) task scores and (123)I-FP-CIT uptake in various striatal ROIs. Multiple regression analysis confirmed the significant relationship between TOL performance and put/caud ratio (P = 0.001) and to age (P = 0.001), and between MADRS and left striatal (P = 0.005) and putaminal DAT availability (P = 0.003). Our pilot study results demonstrate that imaging with (123)I-FP-CIT SPECT appears to be sensitive for detecting dopaminergic deficit associated with mild depressive symptoms and specific cognitive dysfunction in patients with PD, yet without a current depressive episode and/or dementia.

Individual differences in the effectiveness of intracoronary bone marrow cell transplantation assessed by gated sestamibi SPECT/FDG PET imaging.

BACKGROUND: The impact of different levels of tracer uptake on improvements of left-ventricular (LV) function was analyzed in patients treated by intracoronary bone marrow cell (BMC) transplantation. METHODS AND RESULTS: Thirty-one patients with irreversible damage after their first acute myocardial infarction (MI), as confirmed by sestamibi single-photon emission computed tomography (MIBI SPECT)/fluorodeoxyglucose positron emission tomography (FDG PET), underwent high-dose (1 x 10(8) cells) BMC transplantation, whereas 31 similar patients were randomly integrated into a control group. In 11 BMC-treated patients with very low sestamibi uptake at less than 30% of maximum in the infarcted area, the mean left-ventricular ejection fraction (LVEF) improved after 3 months of follow-up by 3% only, and mean end-diastolic/end-systolic volumes (EDV/ESV) enlarged by 10/1 mL (P = NS vs controls). In 20 BMC-treated patients with higher sestamibi uptake in the range of 31% to 50% of maximum, LVEF improved by 7%, and EDV/ESV decreased by 5/12 mL (P < .05 vs BMC-treated subgroup with low MIBI uptake and controls). No similar categorization was seen in the control group: in patients with higher sestamibi uptake or very low uptake, the LVEF increased by 2% and 3% only, and the EDV/ESV enlarged in both subgroups by 12/4 mL and 12/2 mL, respectively (P = NS). CONCLUSIONS: Our results suggest the capability of SPECT/PET imaging to select patients who will receive the maximum benefit from BMC therapy.

Cell therapy in patients with left ventricular dysfunction due to myocardial infarction.

OBJECTIVES: The purpose of this study was to determine the impact of autologous transplantation of mononuclear bone marrow cells on myocardial function in patients with left ventricular (LV) dysfunction due to an acute myocardial infarction. METHODS: The randomized study included 82 patients with a first acute myocardial infarction treated with a stent implantation. This presentation is a subanalysis of 47 patients with left ventricular dysfunction-EF (ejection fraction)

Autologous transplantation of mononuclear bone marrow cells in patients with acute myocardial infarction: the effect of the dose of transplanted cells on myocardial function.

BACKGROUND: Despite the reports on successful treatment of acute myocardial infarction using autologous mononuclear bone marrow cell transplantation, many unresolved questions still remain. We studied the impact of the dose of transplanted cells on myocardial function and perfusion. METHODS: Sixty-six patients with a first acute myocardial infarction were randomized into 3 groups. Two groups were intracoronarily given mononuclear bone marrow cells in either higher (10(8) cells, higher cell dose [HD] group, n = 22) or lower (10(7) cells, lower cell dose [LD] group, n = 22) doses. Twenty-two patients without cell transplantation served as a control (C) group. RESULTS: At 3 months of follow-up, the baseline peak systolic velocities of longitudinal contraction of the infarcted wall of 5.2, 4.5, and 4.3 cm/s in C, LD, and HD groups increased by 0.0, 0.5 (P < .05 vs C group), and 0.9 cm/s (P < .05 vs LD group, P < .01 vs C group), respectively, as demonstrated by Doppler tissue imaging. Baseline left ventricular ejection fractions of 42%, 42%, and 41% in C, LD, and HD groups increased by 2%, 3%, and by 5% (P < .05 vs group C), respectively, as assessed by the gated technetium Tc 99m sestamibi single photon emission computed tomography. CONCLUSIONS: Mononuclear bone marrow cell transplantation improves regional myocardial function of the infarcted wall in a dose-dependent manner.

Combining advanced neuroimaging techniques in presurgical workup of non-lesional intractable epilepsy.

PURPOSE: The rationale for this case report is to assess the degree of congruency between the results of several advanced functional, metabolic, and structural neuroimaging techniques used in patients with MRI-negative focal epilepsy. METHODS: We investigated the presurgical evaluation and post-operative outcome of a patient with intractable, extratemporal epilepsy. Because the habitual seizures in this patient could be easily induced, six, advanced, neurodiagnostic techniques were successively applied (SISCOM, ictal FDG-PET, ictal fMRI, postictal diffusion-weighted imaging, voxel-based morphometry, and MRS imaging). RESULTS: The findings for the neuroimaging methods investigated, within the left central region, were fairly congruent. Subsequent, invasive EEG recordings revealed a seizure-onset zone at the site where most of the neuroimaging had shown abnormal findings. The surgical removal of the epileptogenic zone, as defined by concordant neuroimaging and SEEG data, resulted in seizure-free postoperative outcome. Histopathological findings revealed mild focal cortical dysplasia. CONCLUSION: Great efforts should be made to combine most of the advanced neuroimaging methods in the preoperative assessment of non-lesional epilepsy surgery candidates.

The role of quantitative Tc-99m-MIBI gated SPECT/F-18-FDG PET imaging in the monitoring of intracoronary bone marrow cell transplantation.

BACKGROUND: A lot of unresolved questions still exist concerning the exact mechanism of the beneficial effects of bone marrow cell (BMC) transplantation for myocardial regeneration. The aim of this communication is to report the cases of patients with and without post-transplantation left ventricular function improvement. MATERIAL AND METHODS: To this study we included consecutive patients with irreversible damage after a first acute ST-elevation myocardial infarction treated by coronary angioplasty with stent implantation. The irreversible damage was identified by dobutamine echocardiography and confirmed by rest gated Tc-99m-MIBI gated SPECT and in the majority of patients by F-18-FDG PET imaging as well. Using 4D-MSPECT software, we quantified MIBI/FDG uptake and gated SPECT left ventricular ejection fraction, end-diastolic/end-systolic volumes (LVEF, EDV/ESV) before BMC therapy and 3 months later. RESULTS: The results obtained in the initial group of patients in this study (27 patients in the BMC treated group, 16 patients in the control group) have been published previously [Eur J Nucl Med 2005; 32 (Suppl 1 ): S46]. Among the BMC group, we identified 13 responders to therapy with average LVEF improvement from 43.3% +/- 11% to 51.4% +/- 10.4% and EDV/ESV improvement from 145 ml/84 ml to 133 ml/67 ml. The remaining 14 patients were non-responders to therapy with no significant change in LVEF (39.1% +/- 8.1% versus 39.8% +/- 7.4%), the EDV/ESV increased from 166 ml/105 ml to 188 ml/116 ml. Responders to the cell therapy had prevailing MIBI uptake in the range of 31-50% of maximum in the infarction territory. On the other hand, non-responders to BMC therapy had prevailing MIBI uptake in the range of 0-30% of maximum. Two cases are presented in this report. CONCLUSIONS: Further studies with a larger cohort of patients would be helpful to evaluate our findings. We observed strong interindividual differences in the effectiveness of the cell therapy. Prevailing residual MIBI uptake in the range of 31-50% of maximum was in the subgroup of responders to the cell therapy.

Superiority of SPECT/CT over planar 123I-mIBG images in neuroblastoma patients with impact on Curie and SIOPEN score values.

OBJECTIVE: The existing most common semi-quantitative systems used for neuroblastoma diagnosis include Curie and SIOPEN scores, which are based on 123I-MIBG planar scans. The purpose of our study was to find out whether a statistically significant difference exists in evaluation based on planar and SPECT/CT scans. We also compared the Curie and SIOPEN methods in terms of their use in regular practice. Patients; method: 45 patients aged 0-10 years; 213 assessments were done in total, and the Curie and SIOPEN scores were determined in each case based on planar and SPECT/CT scans. Student's T-test and the Bland-Altman plot were used for the statistical analysis. RESULTS: Both methods demonstrated a statistically significant difference (p < 0.0001) between planar and SPECT/CT evaluation. In the group of 35 patients with neuroblastoma in clinical stages 3 and 4, in 54% of the patients SPECT/CT detected a lesion that was not visible in the planar scan. In 89% of cases, the lesion was confirmed by another imaging method (CT, MRI). In the group of 10 patients in the clinical stage 1, a difference between planar and SPECT/CT scanning was found only in one patient (10%). In the whole set, 25% patients showed a pathological finding only in soft tissues. CONCLUSION: We recommend to perform semiquantitative evaluation of neuroblastoma based on SPECT/CT scans, particularly in patients in clinical stages 3 and 4. It is advisable to include soft tissues in the score assessment, as well, given that only soft tissues may be involved in up to 25.

Three-, 6-, and 12-month results of autologous transplantation of mononuclear bone marrow cells in patients with acute myocardial infarction.

BACKGROUND: There are only few data on long-term effectiveness of the stem cell therapy. AIM: We studied the time course of global and regional left ventricular function in patients with acute myocardial infarction within 1 year after the autologous mononuclear bone marrow cell transplantation. METHODS: Sixty patients with a first acute myocardial infarction, who had been randomized into 3 groups, completed a 12-month protocol. Two groups were intracoronarily given bone marrow cells in either higher (10(8) cells, HD group, n=20) or lower (10(7) cells, LD group, n=20) doses. Twenty patients without cell transplantation served as a control (C) group. Doppler tissue imaging and the gated technetium-99m sestamibi single photon emission computed tomography were performed before cell transplantation and at 3, 6, and 12 months later. RESULTS: The baseline peak systolic velocities of longitudinal contraction of the infarcted wall (S(infarct)) of 5.2 cm/s, 4.6 cm/s, and 4.4 cm/s in C, LD, and HD groups increased by 0.0 cm/s, 0.3 cm/s (p=NS vs. C group), and by 0.7 cm/s (p<0.05 vs. C group), respectively, at 3 months. At 12 months, however, the corresponding changes from baseline values of 0.1 cm/s, 0.2 cm/s, and 0.6 cm/s did not differ significantly (all p=NS). In contrast, the post-transplant improvements in the left ventricular ejection fraction by 6%, 7%, and 7% at months 3, 6, and 12, respectively, were preserved in HD group patients during the whole 12-month follow-up and remained significantly better as compared to controls. CONCLUSIONS: In our study, the autologous mononuclear bone marrow cell transplantation provided sustained improvement in global left ventricular systolic function in patients with acute myocardial infarction. However, when evaluating regional systolic function of the infarcted wall, the short-term benefit was partially lost during the 12-month follow-up.