Application of stress-only myocardial perfusion imaging.

BACKGROUND: Single-photon emission computed tomography myocardial perfusion study is usually a sequence of stress and rest part. In case of a normal stress study rest part can be given up. The objective of this study was to examine factors affecting concordance of results of stress-only (SO) and stress-rest (SR) studies. MATERIAL AND METHODS: SO and SR studies without and with attenuation correction (AC) of 212 selected patients (without cardiomyopathy, history of myocardial infarction or coronary artery bypass grafting) were analyzed visually. Influence of percutaneous coronary intervention (PCI) in the past, type of stress (physical/pharmacological) and application of AC (in form of combined method of non-corrected and corrected images - CM), patient body mass index (BMI) and gender on concordance rates of SO and SR studies were examined. RESULTS: Neither a history of PCI, nor a type of stress affected concordance rate. AC (in form of CM) improved concordance rate significantly, from 60% to 68% (p = 0.018). Patient BMI affected concordance rates - 72% in non-obese and 59% in obese patients (p = 0.05). In the whole group, risk of overlooking patients with abnormal perfusion in SO study was small (< 2%), but it grew significantly with patient BMI. Rest study was necessary in about 20% of non-obese and in about 50% of obese patients. CONCLUSION: MPS can be limited to stress part in appropriately selected, especially non-obese, patients provided that AC is applied, due to a low risk of overlooking patients with abnormal perfusion. In case of obese patients, careful analysis of exercise images for their normality is particularly important.

The symptoms asymmetry of drug-induced parkinsonism is not related to nigrostriatal cell degeneration: a SPECT-DaTSCAN study.

AIM: Drug-induced parkinsonism (DIP) is the most common form of parkinsonism after Parkinson's disease (PD) itself. It has been widely believed that DIP is characterised by symmetry of symptoms. Studies of patients with DIP in whom PD had been ruled out by SPECT-DaTSCAN have shown that symptom asymmetry is a common element of DIP clinical presentation. The aim of our study was to determine whether the asymmetry of symptoms in DIP is related to any abnormality within the presynaptic part of the nigrostriatal dopaminergic system. MATERIALS AND METHODS: Eleven patients with the diagnosis of DIP and asymmetric symptoms were studied. Their individual SPECT-DaTSCANs were normal. Indices calculated for the whole group of radiotracer uptake in the whole striatum, putamen and caudate contralateral to more severe DIP symptoms were compared to values obtained in the opposite hemisphere. RESULTS: We did not find significant differences in radiotracer uptake in structures contralateral to more severe clinical symptoms when compared to the homolateral hemisphere. CONCLUSIONS: Our results have not confirmed the presence of a presynaptic nigrostriatal deficit which could be related to asymmetry of DIP. The factors responsible for the asymmetry of DIP symptoms should be sought in the postsynaptic part of the nigrostriatal dopaminergic system.

Should non-movement specialists refer patients for SPECT-DaTSCAN?

BACKGROUND: SPECT with radioligand DaTSCAN (SPECT-DaTSCAN) is a sensitive tool used for assessing the functional integrity of the presynaptic part of the nigrostriatal dopaminergic system. The procedure is useful whenever there is a need to distinguish between neurodegenerative parkinsonism and other parkinsonian syndromes in subjects with equivocal signs and symptoms. It can be assumed that the neurologist's decision to perform SPECT-DaTSCAN depends on his or her experience and skill in the diagnosis of parkinsonian and tremor syndromes. AIMS: To assess the accuracy of referrals to SPECT-DATSCAN made by non-movement disorders specialists. MATERIAL AND METHODS: Sixty seven patients referred for SPECT-DaTSCAN by a general neurologist were studied. In all subjects, a movement disorder specialist performed the neurological examination, collected medical history, and analysed previous treatments and the results of diagnostic tests. RESULTS: Evaluation carried out by a movement disorder specialist did not confirm an indication for SPECT-DaTSCAN in 31 patients (46.3%). General neurologists needed support for clinical diagnosis with SPECT-DaTSCAN most frequently in subjects with parkinsonism even though they were presenting a full-blown disease manifestation and even though the patients met the diagnostic criteria for Parkinson's disease or one of the atypical parkinsonian syndromes. CONCLUSIONS: Our presented results probably reflect the limited experience of general neurologists in the evaluation of parkinsonian syndromes and tremor. The use of SPECT-DaTSCAN by non-movement disorders specialists is associated with a significant risk of overuse of this tool. To minimise this risk, the skills of general neurologists in diagnosing parkinsonian and tremor syndromes should be improved. Moreover, patients should be provided with access to movement disorders specialists.

Assessment of the relation between pelvicalyceal dilatation in ultrasound and features of obstructive uropathy in dynamic renal scintigraphy.

BACKGROUND: Ultrasound is the first-line imaging in the diagnostics of the urinary system. It provides valuable morphological information, but its usefulness in assessment of the function of renal parenchyma is limited. Dynamic renal scintigraphy provides much more accurate information about parenchymal function of kidneys and urinary outflow. The aim of the study was to establish morphological ultrasound criteria for high likelihood of obstructive uropathy. MATERIAL AND METHODS: 59 patients (38 women, 21 men, between 18 and 82 years old, average age 50) with the pelvis dilatation > 10 mm in one or both kidneys newly diagnosed in ultrasound, without earlier history of kidney and urinary tract diseases or renal surgery. A total of 79 kidneys were included in the study. Ultrasound and dynamic renal scintigraphy were performed on the same day. In ultrasound, maximum anteroposterior diameter of the renal pelvis (mAPD) and anteroposterior pelvic diameter at hilum (hAPD) were obtained. The ratio of total pelvicalyceal area to the whole kidney area (%PCS) was also calculated. Uropathy was determined by the positive diuretic test in renal scintigraphy performed using 111 MBq of 99mTc-EC. RESULTS: In dynamic renal scintigraphy, features of uropathy were found in 18 out of 79 kidneys (23%). Optimal thresholds for detection of obstructive uropathy for measured ultrasound parameters were determined based on the ROC curves: mAPD ≥ 23 mm (sensitivity 94%, specificity 76%, accuracy 80%, AUROC 0.91) hAPD ≥ 20 mm (sensitivity 78%, specificity 87%, accuracy 85%, AUROC 0.82) PCA/WKA ≥ 22% (sensitivity 83%, specificity 74%, accuracy 76%, AUROC 0.85). CONCLUSIONS: Determined thresholds of parameters measuring pelvicalyceal dilatation in ultrasound, including the easiest one to obtain in routine diagnostics - mADP, provide satisfactory effectiveness in isolating kidneys with high likelihood of obstructive uropathy. Their application can optimize the selection of patients for further kidney diagnostic imaging (dynamic renal scintigrapy or urography).

Is nigrostriatal dopaminergic deficit necessary for Holmes tremor to develop? The DaTSCAN and IBZM SPECT study.

Holmes's tremor (HT) is assumed to be the result of coexistence of nigrostriatal dopaminergic system impairment and the lesion of cerebello-thalamic pathways. It was suggested that dopaminergic deficiency is responsible for rest tremor, and lack of compensatory cerebellar function leads to spill of tremor into voluntary movements. Cases of HT with and without abnormalities of the presynaptic part of dopaminergic nigrostriatal were published and these findings raised the question of possibility of the postsynaptic lesion. Three patients with HT diagnosed according to criteria of Consensus Statement on Tremor were studied. In all of them SPECT imaging with ligands of presynaptic (I 123-FP CIT-DaTSCAN) and postsynaptic (I 123-iodobenzamide-IBZM) nigrostriatal dopaminergic neurons was performed. Indices of uptake in caudate and putamen normalized to nonspecific uptake in occipital cortex and indices of asymmetry for each whole striatum as well as for putamen and caudate separately were calculated. SPECT studies did not reveal asymmetry of DaTSCAN and IBZM binding in striatum in all studied subjects. The current clinical diagnostic criteria of HT are presumably insufficiently specific and when using them we identify patients both with and without the involvement of dopaminergic system. These two groups may represent tremor disorders of similar phenomenology but of different pathomechanism.

Usefulness of parametric renal clearance images in the assessment of basic risk factors for renalnal clearance images in the assessment of basic risk factors for renal scarring in children with recurrent urinary tract infections.

BACKGROUND: Clinically confirmed incidents of acute pyelonephritis (APN) following recurrent infections of urinary tract (UTI) form basic risk factors for renal scarring in children. Vesico-uretheral reflux (VUR) of higher grade is additional risk factor for this scarring. Opinions on diagnostic value of summed sequential images of renal uptake phase (SUM) of dynamic renal scintigraphy in detection of renal scars are diverse. However, several publications point to higher diagnostic efficacy of clearance parametric images (PAR) generated from this study. THE AIM OF THE STUDY: To establish a clinical value of parametric renal clearance images in detection of renal scarring. MATERIAL AND METHODS: A prospective study was performed in a group of 91 children at the age of 4 to 18 years with recurrent UTI. Clinically documented incidents of APN were noted in 32 children: in 8 cases - one and in the remaining 24 - 2 to 5 (mean 3) incidents. In the remaining 59 patients only infections of the lower part of urinary tract were diagnosed. Static renal 99mTc-DMSA SPECT study and after 2-4 days dynamic renal studies (99mTc-EC) were performed in every patient not earlier than 6 months after the last documented incident of UTI. PAR images generated from a dynamic study by in-house developed software and SUM images were compared with a gold standard SPECT study. RESULTS: Percentages of children with detected renal scar(s) with SPECT and PAR methods amounted to 55% and 54%, respectively and were statistically significantly higher (p < 0.0001) than with SUM method - 31%. Scars in children with history of APN detected with SPECT and PAR methods were significantly more frequent than with infections of only lower part of urinary tract (72% vs. 46%; p = 0.017 and 69% vs. 46%; p = 0.036, respectively). A SUM method did not reveal statistically significant differences between frequencies of detection of scars in groups specified above - 38% vs. 27% (p = 0.31). Both SPECT and PAR methods showed also that frequencies of occurrence of renal scars in children with higher grades of VUR were higher than without or with lower grades of VUR: 79% vs. 50% (p = 0.048) and 79% vs. 49% (p = 0.04). A SUM method did not reveal higher frequency of renal scars in children with high VUR grades: 36% vs. 30% (p = 0.44). CONCLUSION: Results obtained with PAR and SPECT methods were similar. An advantage of PAR over SUM images obtained from a dynamic renal scintigraphy in detection of renal scars in children with UTI was confirmed.

Diagnostic value of optimised real-time sonoelastography in the assessment of liver fibrosis in chronic hepatitis B and C.

AIM: To optimise the method of real-time elastography (RTE) in the assessment of liver fibrosis using an in-house prepared method for elastogram analysis, as well as a semiquantitative analysis based on newly introduced parameters. MATERIAL AND METHODS: Sonoelastography was performed in 94 patients with various degrees of liver fibrosis and also in 25 healthy volunteers. As a reference method for diagnostic efficacy of sonoelastography-based parameters used for the assessment of fibrosis degree in patients with chronic B and C hepatitis, a liver biopsy was used. Patient's elastograms were analysed using in-house prepared software, Pixel Count, calculating two semiquantitative parameters: mean stiffness fraction (MSF%) and intrinsic stiffness ratio (ISR). RESULTS: Statistically significant differences between distributions of the above presented parameters for different degrees of liver fibrosis were revealed. Indices of diagnostic efficacy for detection of significant liver fibrosis (F ≥ 2) using MSF% amounted to: sensitivity - 76%, specificity - 87% and ISR: 81% and 87%, respectively. Sensitivity of both parameters in detection of cirrhosis (F = 4) was equal to 88% and specificity amounted to: for MSF% - 84% and ISR - 86%. Interobserver reproducibility determined for both of the above parameters was high, intraclass correlation coefficients (ICC) were 0.91 for MSF% and 0.93 for ISR. CONCLUSIONS: Real-time elastography applied in this study, using in-house prepared Pixel Count software, provided good reproducibility and diagnostic efficacy, especially specificity, in the assessment of liver fibrosis degree.

Usefulness of clearance parametric images in detection of regional renal parenchyma dysfunction.

BACKGROUND: The aim of the study was to examine whether parametric clearance images (PAR) enhance diagnostic potential of a dynamic renal scintigraphy with detection of local dysfunction of kidneys, on a model of kidneys after treatment with extracorporeal shock wave lithotripsy (ESWL), MATERIAL AND METHODS: Kidneys after ESWL were accepted as a proper model for the implementation of this objective because of the previously proven damaging effect of a shock wave on renal parenchyma and known region of ESWL application. Forty patients (23 males and 17 females) at the age of 37 to 70 years (mean value 54) with untreated earlier single, one-sided nephrolithiasis, currently treated with ESWL, underwent a study. A dynamic renal 99mTc-EC scintigraphy was performed three times: before ESWL, a week and a month after this therapeutic intervention. PAR images generated with use of an in-house developed software were compared with summation (SUM) of images obtained from radiopharmaceutical uptake phase and quantitative global function parameters (GFP) of each kidney, like split function, MTT - mean transit time and PTT - parenchymal transit time. RESULTS: PAR and SUM images of all 40 kidneys before ESWL were normal. PAR images revealed local or diffused defects a week and a month after therapeutic intervention in statistically significantly larger numbers of kidneys than SUM images (19 vs. 6, p = 0.002 and 16 vs. 5, p = 0.003, respectively). A week after ESWL, when defects in PAR images were observed in about a half of all renal segments (29/57 - 51%) all GFP values were significantly worse than in kidneys without defects. A month after ESWL defects in PAR images could be observed in ab. 1/3 (17/48 - 35%) of segments and were less extensive, whereas GFP values did not differ significantly from values in kidneys without clearance function impairment in the PAR images. CONCLUSIONS: PAR images enhance diagnostic potential of a dynamic renal scintigraphy with detection of local function defects. These images allow to detect more local renal function defects than SUM images.

Diagnostic performance of myocardial perfusion single-photon emission computed tomography with attenuation correction.

BACKGROUND: Myocardial perfusion single-photon emission computed tomography (SPECT) is one of the basic tools used for the purpose of diagnosis of coronary artery disease (CAD), prognosis of its unfavourable consequences, and evaluation of therapy effectiveness. However, its efficacy is compromised by a relatively low specificity of detection of perfusion defects, which is attributed to attenuation of gamma rays inside the patient's body, causing artefacts erroneously taken for perfusion defects. It is expected that attenuation correction (AC) could eliminate such artefacts. AIM: To evaluate whether visual, semi-quantitative analysis of attenuation-corrected myocardial perfusion imaging provides an advantage over a non-corrected study. METHODS: A retrospective study applying AC was performed in 107 patients who had coronary angiography within three months. Patients underwent a stress/rest Tc-99m methoxyisobutylisonitrile (MIBI, POLATOM) double day SPECT/CT myocardial perfusion imaging. Images were analysed by two experienced nuclear medicine specialists (a consensus) applying a visual semiquantitative method. Coronary angiography findings were used as a reference for the analysis of diagnostic performance of myocardial perfusion study protocols. RESULTS: AC increased the specificity of detection of CAD in the whole group of patients from 63% to 86% (p = 0.0005), with a slight reduction in sensitivity (from 83% to 79%). The improved specificity was also noted in subgroups of male and female patients. Accuracy in the whole group of patients increased from 71% to 83% (p = 0.01). AC improved the specificity and accuracy of the method in the detection of perfusion defects in the right coronary artery (RCA) area from 73% to 88% (p = 0.005) and from 74% to 83% (p = 0.04), respectively, and the accuracy of the method in the left anterior descending (LAD) artery area from 79% to 87% (p = 0.043). It also reduced the number of ambiguous results of the study. CONCLUSIONS: AC improved the diagnostic performance of myocardial perfusion study in the detection of CAD and identification of critically stenosed LAD and RCA vessels, with enhanced comfort of study interpretation.

Perfusion lung scintigraphy for the prediction of postoperative residual pulmonary function in patients with lung cancer.

BACKGROUND: Accurate prediction of postoperative pulmonary function in patients with non-small cell lung cancer is crucial for proper qualification for surgery, the only effective therapeutic method. The aim of the study was to select the most accurate method for acquisition and processing of lung perfusion scintigraphy (LPS) combined with spirometry for prediction of postoperative pulmonary function in patients qualified for surgery. MATERIAL AND METHODS: LPS was performed in 70 patients (40 males, 30 females), with preoperative spirometry (mean FEV1preop = 2.26 ± 0.72 L), after administration of 185 MBq of 99mTc-microalbumin/macroaggregate, using planar (appa) and SPECT/CT methods. Predicted postoperative lung function (FEV1pred) was calculated as a part of active lung parenchyma to remain after surgery. A non-imaging segment counting method was also applied. FEV1pred(appa, SPECT, SPECT/CT, segm.) were further compared with actual FEV1postop values obtained from postoperative spirometry. RESULTS: In the whole studied group (47 lobectomies, 23 pneumonectomies) mean value of FEV1postop was equal to 1.76 (± 0.56) L. FEV1pred(appa, SPECT, SPECT/CT, segm.) were equal to 1.75 (± 0.58) L, 1.71 (± 0.57) L, 1.72 (± 0.57) L and 1.57 (± 0.58) L, respectively. A segment counting method systematically lowered predicted FEV1 values (p < 10-5). Moreover, in 31 patients with FEV1preop < 2 L error of predicted values was assessed with Bland-Altman method. Mean absolute differences FEV1postop - FEV1pred amounted to: appa - (0.04 ± 0.13) L, SPECT - (0.07 ± 0.14) L, SPECT/CT - (0.06 ± 0.14) L and segm. - (0.21 ± 0.19) L, respectively. Lower limit of 95% confidence interval calculated for planar - optimal method, was equal to -220 mL (also determined separately in subgroups after lobectomy and pneumonectomy). CONCLUSIONS: This study shows that planar LPS may be applied for prediction of postoperative pulmonary function in patients qualified for pneumonectomy and lobectomy. If actual FEV1postop value is to be ≥ 800 mL, predicted value should exceed 1000 mL.

Association of the DIO2 gene single nucleotide polymorphisms with recurrent depressive disorder.

Genetic factors may play a role in the etiology of depressive disorder. The type 2 iodothyronine deiodinase gene (DIO2) encoding the enzyme catalyzing the conversion of T4 to T3 is suggested to play a role in the recurrent depressive disorder (rDD). The current study investigates whether a specific single nucleotide polymorphism (SNP) of the DIO2 gene, Thr92Ala (T/C); rs 225014 or ORFa-Gly3Asp (C/T); rs 12885300, correlate with the risk for recurrent depression. Genotypes for these two single nucleotide polymorphisms (SNPs) were determined in 179 patients meeting the ICD-10 criteria for rDD group and in 152 healthy individuals (control group) using a polymerase chain reaction (PCR) based method. The specific variant of the DIO2 gene, namely the CC genotype of the Thr92Ala polymorphism, was more frequently found in healthy subjects than in patients with depression, what suggests that it could potentially serve as a marker of a lower risk for recurrent depressive disorder. The distribution of four haplotypes was also significantly different between the two study groups with the TC (Thr-Gly) haplotype more frequently detected in patients with depression. In conclusion, data generated from this study suggest for the first time that DIO2 gene may play a role in the etiology of the disease, and thus should be further investigated.

Diagnostic efficacy of parametric clearance images in detection of renal scars in children with recurrent urinary tract infections.

OBJECTIVE: Static renal scintigraphy with Tc-99m dimercaptosuccinic acid (DMSA) is considered a scintigraphic gold standard in detection of post-inflammatory renal scars. Reports on usefulness of conventional summed (SUM) Tc-99 m mercaptoacetyltriglycine (MAG3) or Tc-99m ethylene dicysteine (EC) dynamic scintigraphic images in detection of renal scarring are ambiguous and some authors emphasize low sensitivity of this method. The work aimed at assessment of a diagnostic efficacy of parametric clearance images (PAR) generated from a dynamic renal scintigraphy in detection of renal scars. METHODS: A study group consisting of 80 children (56 girls, 24 boys, age 5-18 years) with recurrent urinary tract infections (UTI) and documented one to five incidents of APN-28 children, and with recurrent UTI of the lower part of the urinary tract only-52 children. Altogether 160 kidneys were evaluated. Static renal Tc-99m DMSA SPECT scintigraphy and after 2-4 days Tc-99m EC dynamic renal scintigraphy were performed in every patient not earlier than 6 months after the last documented incident of UTI. PAR images generated from a dynamic renal scintigraphy acquired between 40 and 140 s. generated by in-house developed software and SUM images obtained in the same time period were compared with a reference Tc-99m DMSA SPECT study. RESULTS: For all kinds of images (SPECT, PAR and SUM), high indices of reproducibility were obtained-89 % (κ = 0.80), 88 % (κ = 0.78) and 89 % (κ = 0.73). Agreement in a Howard scale of a reference method (SPECT) with PAR and SUM methods amounted to 83 and 64 %, respectively (p = 0.004). Sensitivity and accuracy of PAR method as compared with SUM method were significantly higher: 89 vs. 49 % (p < 0.0001) and 88 vs. 73 % (p = 0.002), and specificity was slightly lower: 88 vs. 93 % (p = 0.043). SPECT and PAR methods revealed higher incidence of renal scars than a SUM method in patients with documented incident(s) of APN-64, 68 and 39 %, p = 0.009 and 0.008, respectively. CONCLUSION: PAR images generated from a dynamic renal scintigraphy improved sensitivity of detection of renal scars as compared with SUM images, providing a high reproducibility and diagnostic efficacy, similar to that of Tc-99m DMSA, in detection of post-inflammatory renal scarring.

Preliminary assessment of interand intraobserver reproducibility, and normative values of renal mean transit time (MTT) and parenchymal transit time (PTT) for 99mTc-etylenodicysteine.

BACKGROUND: The clinical significance of MTT and PTT, determined by deconvolution of renographic curves, is arguable. Their usefulness in diagnosis of obstructive uro- and nephropathy, renovascular hypertension and monitoring of transplanted kidneys is pointed out, but susceptibility of deconvolution methods to errors resulting from "statistical noise" is also stressed. So far there are no reports on normative MTT values for 99mTc-EC, although such values were already determined for ¹³¹I-OIH, 99mTc-DTPA and 99mTc-MAG3. The aim of this study is an assessment of inter- and intraobserver reproducibility of MTT and PTT for 99mTc-EC, and determination of normative values for these parameters. MATERIALS AND METHODS: 31 patients (17 women and 14 men aged 19-75, average 44 years) referred for dynamic renal scintigraphy with: unilateral flow impairment (11), unilateral nephrolithiasis (2), control after unilateral lithotripsy (4), moderate hypertension (demographically with > 99% probability of primary hypertension) (4), suspected cirrhosis of one kidney (3), future kidney donors (3), control after abdominal injuries (3), incontinence (1). 42 functionally efficient kidneys were included in the study. Criteria for recognition of a kidney as functionally efficient were: - no earlier history of renal disease, signs of renal damage in basic blood and urine tests, or abnormalities in ultrasonography; - normal result of dynamic renal scintigraphy (in terms of sequential images and renographic curve). MTT and PTT values were determined independently by two operators, using a matrix method for deconvolution of renographic curves. RESULTS: Differences between mean MTT and PTT from two studies by one operator were insignificant and those values were closely correlated (r = 0.99 and r = 0.97, respectively). Differences of values obtained by both operators were practically insignificant for MTT (r = 0.93), and significant for PTT (r = 0.81 and p < 0.001). These differences do not disqualify that processing method. The upper limits of normative values of MTT and PTT were based on the results from first study performed by more experienced operator - 200 s and 170 s, respectively. CONCLUSIONS: The procedure of processing dynamic renal scintigraphy used in this study is reproducible. Normative values of MTT and PTT for 99mTc-EC were established as 200 s and 170 s, respectively. An attempt to optimize and standardize the technique of determining parenchymal ROI in a matrix deconvolution method, followed by an evaluation of clinical usefulness of these parameters in the diagnosis of chosen renal function impairments would be a logical continuation of this initial research.

Dual stimulus-dependent effect of Oenothera paradoxa extract on the respiratory burst in human leukocytes: suppressing for Escherichia coli and phorbol myristate acetate and stimulating for formyl-methionyl-leucyl-phenylalanine.

Although a growing body of evidence suggests that plant polyphenols can modulate human immune responses, their simultaneous action on monocyte and neutrophil oxidative burst is currently poorly understood. Based on the hypothesis that various polyphenols contained in plant extracts might affect the oxidative burst of phagocytes, we evaluated the effects of ethanolic O. paradoxa extract polyphenols on monocyte and neutrophil oxidative burst in vitro activated by different stimuli, including opsonized bacteria E. coli, phorbol 12-myristate 13-acetate (PMA), and formyl-methionyl-leucyl-phenylalanine (fMLP). Samples were analyzed by the dihydrorhodamine flow cytometry assay. Our results showed that the extract repressed significantly and dose-dependently reactive oxygen species production in both cell types stimulated with E. coli and PMA (P < 0.05) and its inhibitory efficiency was stimulus- and cell-type-dependent. Interestingly, there was significant stimulatory effect of the extract on bursting phagocytes induced by fMLP (P < 0.05). Additionally, several flavonoids and phenolic compounds as well as penta-galloyl-ß-(D)-glucose (PGG), the representative of hydrolyzable tannins, were identified in the 60% extract by high-performance liquid chromatography (HPLC) coupled to electrospray ionization in negative ion mode. In summary, the ethanolic O. paradoxa extract, rich in flavonoids and phenolic compounds, exhibits dual stimulus-dependent effect on the respiratory burst in human leukocytes; hence, it might affect immune responses in humans.

The study of t-PA, u-PA and PAI-1 genes polymorphisms in patients with abdominal aortic aneurysm.

The most important feature of abdominal aortic aneurysm (AAA) pathogenesis is an enzymatic degradation of elastic lamellae and extracellular matrix proteins particularly with participation of matrix metalloproteinases. Plasmin, which is responsible for the dissolution of fibrin in blood vessels, plays also a key role in the cascade for activation of the metalloproteinases. The purpose of this study was to evaluate the influence of selected polymorphisms in genes coding for tissue plasminogen activator (-7351 C/T polymorphism), urokinase-type plasminogen activator (1788 C/T polymorphism) and plasminogen activator inhibitor 1 (-675 4G/5G and -844 G/A polymorphism) on the susceptibility to AAA. We performed a case-control study of 153 polish patients hospitalized due to AAA and compared them with matched healthy control subjects. The polymorphisms were ascertained through genotyping by polymerase chain reaction and restriction digestion of amplified fragments or through high-resolution melting analysis. In this study we have found lower frequency of wild-type GG genotype of the -844G/A PAI-1 polymorphism in cases than in controls, what may suggest the protective effect of this genotype for the risk of AAA development. None of the remaining polymorphisms tested were associated with AAA occurrence.

Effects of radioiodine administration on serum concentrations of matrix metalloproteinases, adiponectin and thrombospondin-1.

BACKGROUND: In order to assess safety of radioactive iodine administration in the treatment of thyrotoxicosis, we measured concentrations of matrix metalloproteinase-2 (MMP-2), its main inhibitor - TIMP-2 (tissue inhibitor of MMP-2), matrix metalloproteinase-9 (MMP-9), its main inhibitor - TIMP-1, adiponectin, as well as pro-inflammatory and procancerogenic thrombospondin-1 (TSP-1). DESIGN AND PATIENTS: The study involved 23 patients treated with radioiodine for thyrotoxicosis. Serum concentrations of TSH, free T4, free T3, MMP-2, MMP-9, TIMP-1, TIMP-2, total adiponectin and TSP-1 were measured by immunoassays just before radioiodine administration (visit 1), and subsequently, after 7 days (visit 2), 3 months (visit 3), 6 to 8 months (visit 4) and 15-18 months after radioiodine administration (visit 5). RESULTS: There were no acute changes in serum concentrations of MMP-2, MMP-9, TIMP-1, TIMP-2, adiponectin and TSP-1 (visit 1 vs. 2). Subsequently, there was an increase in MMP-2 (from 393±106 ng/ml to 774±424 ng/ml), TIMP-1 (from 177±76 ng/ml to 296±118 ng/ml), and adiponectin (from 16442±9490 ng/ml to 23518±9840 ng/ml), visit 1 to 5, respectively (p < 0.01). Further analysis revealed no significant change in MMP-2/TIMP-2 ratio, but there was a significant decrease in MMP-9/TIMP-1 ratio (p < 0.05), suggestive of possible decrease in free MMP-9 concentrations. CONCLUSIONS: Our data reveal a significant and sustained increase in serum adiponectin, as well as possible decrease of free MMP-9 concentration after radioiodine administration. In contrast, there was no significant change of TSP-1. This might indicate overall safety of radioiodine treatment of thyrotoxicosis in terms of the risks of subsequent cardiovascular and neoplastic disease.

Reliability of different radioisotopic techniques in diagnosing solitary hot spots in the spine of patients with malignant neoplasm.

INTRODUCTION: Early diagnosis of spinal metastases is of key importance in further therapeutic management. OBJECTIVES: The aim of the study was to assess the reliability of single-photon emission computed tomography (SPECT) or SPECT and computed tomography (SPECT/CT) in the diagnosis of solitary hot nodules in the spine identified by scintigraphy. PATIENTS AND METHODS: In this retrospective study, 70 patients with neoplastic disease and a solitary nodule detected in the spine were analyzed. Using a SPECT/CT γ-camera, the type and site of the foci in the vertebra were analyzed. Bone scintigraphy, SPECT, and CT were performed. Reliability of the results was assessed depending on the applied technique. RESULTS: In malignant lesions, increased isotope uptake was observed in the vertebral body with the posterior arch (89%), the body and both arches (67%), and the body alone (14%). In benign lesions, increased uptake was observed in the body area or in the joint area. Using SPECT, 25 of 27 cases (93%) of foci were properly classified as malignant. Using SPECT/CT, malignant lesions were observed in 26 of 27 cases (96%). Using SPECT, 19 of 43 cases were identified as benign (44%), and using SPECT/CT, 31 of 43 were identified as benign (72%). The agreement between SPECT and SPECT/CT was higher for malignant lesions (89%) than for benign lesions (67%). The use of CT in SPECT/CT examinations allowed to change the SPECT diagnosis of malignant lesions to that of benign lesions in 50% of the cases. CONCLUSIONS: The criteria used in the diagnosis of solitary nodules in the spine direct the diagnosis largely towards noncancerous lesions. Reliability of positive assessment was significantly lower than that of negative one - 51% in SPECT and 68% in SPECT/CT. A hybrid SPECT/CT camera is more reliable than SPECT alone in the assessment of spinal lesions.

Vascular endothelial growth factor gene (VEGFA) polymorphisms may serve as prognostic factors for recurrent depressive disorder development.

Recurrent depressive disorder (rDD) is a multifactorial disease. Vascular endothelial growth factor (VEGF) is one of the factors that have been suggested to play a role in the etiology and/or development of this disease. Limited information related to the role of VEGFA gene polymorphism in depressive disorder is available. The aim of the study was to analyze the association between VEGFA gene polymorphisms (+405G/C; rs2010963, +936C/T; rs 3025039), VEGFA gene expression, and its serum protein levels in rDD in the Caucasian population. In the current study, 268 patients and 200 healthy controls of the Caucasian origin were involved. Genotyping and gene expression were performed using polymerase chain reaction (PCR)-based methods. Enzyme-linked immunosorbent assay (ELISA) was used for detection of circulating serum VEGF levels. The distribution of VEGFA polymorphism +405G/C differed significantly between rDD patients and healthy subjects. The results of this study indicated that the C allele and CC genotype of VEGFA are risk factors for rDD. Haplotypes CC and TG are the important factors for depression development. Further, VEGFA mRNA expression and VEGF levels were higher in rDD patients than in controls. The VEGFA gene polymorphism may serve as a prognostic factor for rDD development. Our study showed higher levels of both VEGFA mRNA in the peripheral blood cells and serum VEGF in patients diagnosed with rDD than in healthy controls. The obtained results suggest VEGF and the gene encoding the molecule play a role in the etiology of the disease and should be further investigated.

Switching to sulphonylureas in children with iDEND syndrome caused by KCNJ11 mutations results in improved cerebellar perfusion.

OBJECTIVE: Activating mutations in the KCNJ11 gene, encoding the Kir6.2 subunit of the KATP channel, result in permanent neonatal diabetes mellitus. They also may cause neurologic symptoms such as mental retardation and motor problems (iDEND syndrome) and epilepsy (DEND syndrome). Sulphonylurea (SU) treatment is reported to alleviate both the neurologic symptoms and diabetes in such cases. The study aimed to establish the magnitude and functional basis of the effect of SUs on the neurologic phenotype in children with iDEND using neuroimaging before and after insulin replacement with glibenclamide. RESEARCH DESIGN AND METHODS: To localize and quantify the effect of glibenclamide administration, we performed single-photon emission computed tomography in seven patients with different mutations in KCNJ11. In five patients, measurements before and after initiation of SU treatment were performed. RESULTS Significant changes in single-photon emission computed tomography signal intensity after transfer to SU therapy were restricted to the cerebellum, consistent with previous data showing high Kir6.2 expression in this brain region. Cerebellar perfusion improved for both left (P = 0.006) and right (P = 0.01) hemispheres, with the mean improvement being 26.7 ± 7.1% (n = 5). No patients showed deterioration of cerebellar perfusion on SU therapy. Electrophysiological studies revealed a good correlation between the magnitude of KATP channel dysfunction and the clinical phenotype; mutant channels with the greatest reduction in adenosine 5'-triphosphate inhibition were associated with the most severe neurologic symptoms. CONCLUSIONS: We conclude it is likely that at least some of the beneficial effects of SU treatment on neurodevelopment in iDEND patients result from improved cerebellar perfusion.

Single nucleotide polymorphisms of NR3C1 gene and recurrent depressive disorder in population of Poland.

Depressive disorder is a disease characterized by disturbances in the hypothalamo-pituitary-adrenal axis. Abnormalities include the increased level of glucocorticoids (GC) and changes in sensitivity to these hormones. The changes are related to glucocorticoid receptors gene (NR3C1) variants. The NR3C1 gene is suggested to be a candidate gene affecting depressive disorder risk and management. The aim of this study was to investigate polymorphisms within the NR3C1 gene and their role in the susceptibility to recurrent depressive disorder (rDD). 181 depressive patients and 149 healthy ethnically matched controls were included in the study. Single nucleotide polymorphisms were assessed using polymerase chain reaction/restriction fragment length polymorphism method. Statistical significance between rDD patients and controls was observed for the allele and genotype frequencies at three loci: BclI, N363S, and ER22/23EK. The presence of C allele, CC, and GC genotype of BclI polymorphism, G allele and GA genotype for N363S and ER22/23EK variants respectively were associated with increased rDD risk. Two haplotypes indicated higher susceptibility for rDD, while haplotype GAG played a protective role with OR(dis) 0.29 [95 % confidence interval (CI) = 0.13-0.64]. Data generated from this study support the earlier results that genetic variants of the NR3C1 gene are associated with rDD and suggest further consideration on the possible involvement of these variants in etiology of the disease.