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Objectives: The purpose of our study was to determine the probability of developing Parkinson’s disease in various syndromes of isolated tremor. Material and methods: We performed a retrospective analysis of the diagnostic process in patients with isolated upper limb tremor where single-photon emission computed tomography (SPECT)-DaTSCAN was performed. Twenty-four consecutive subjects (9 males, 15 females) with isolated tremor of one or both upper limbs were studied. The patients were referred for SPECT by neurologists from various centres. Cases of diagnosed structural, metabolic or druginduced tremor were not included in the study. All patients were examined by a movement disorder specialist before and 1–3 years after SPECT-DaTSCAN. All subjects were classified according to the Consensus Statement on the Classification of Tremors (2018). Results: The lowest probability of developing Parkinson’s disease was found in patients with rest and action (postural and kinetic) tremor, both unilateral and bilateral. The risk was also low in subjects with postural and kinetic tremor. In cases of a combination of rest and postural tremor (both unilateral and bilateral), the likelihood of neurodegenerative parkinsonism was high. Conclusion: Performing SPECT-DaTSCAN in selected cases of isolated of tremor with a high probability of Parkinson’s disease avoids the unnecessary use of drugs recommended in the therapeutic algorithms applicable in essential tremor.

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.

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.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.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.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.

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.

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.

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.

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.59 patients (38 women, 21 men, between 18 and 82 years old, average age 50) with the pelvis dilatation10 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.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).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).

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.

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).

Background: Protection of nuclear medicine unit employees from hazards of the ionizing radiation is a crucial issue of radiation protection services. We aimed to assess the severity of the occupational radiation exposure of technicians performing scintigraphic examinations at the Nuclear Medicine Department, Central Teaching Hospital of Medical University in Łódź, where thousands of different diagnostic procedures are performed yearly. Materials and Methods: In 2013 the studied diagnostic unit has employed 10 technicians, whose exposure is permanently monitored by individual dosimetry. We analyzed retrospective data of quarterly doses in terms of Hp(10) dose equivalents over the years 2001-2010. Also annual and five-year doses were determined to relate the results to current regulations. Moreover, for a selected period of one year, we collected data on the total activity of radiopharmaceuticals used for diagnostics, to analyze potential relationship with doses recorded in technicians performing the examinations. Results: In a 10-year period under study, the highest annual dose recorded in a technician was 2 mSv, which represented 10% of the annual dose limit of 20 mSv. The highest total dose for a 5-year period was 7.1 mSv, less than 10% of a 5-year dose limit for occupational exposure. Positive linear correlation was observed between total activity of radiopharmaceuticals used for diagnostics in the period of three months and respective quarterly doses received by technicians performing examinations. Conclusions: Doses received by nuclear medicine technicians performing diagnostic procedures in compliance with principles of radiation protection are low, which is confirmed by recognizing the technicians of this unit as B category employees. Med Pr 2013;64(4):503–506

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.

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.

Gałecki P, Florkowski A, Bobińska K, Śmigielski J, Bieńkiewicz M, Szemraj J. Functional polymorphism of the myeloperoxidase gene (G-463A) in depressive patients.Objective:Myeloperoxidase (MPO) is an enzyme involved in the production of hypochloric acid as well as other reactive oxygen species. This enzyme plays a significant role in inflammatory processes. In view of the observed associations between depression and such inflammatory processes, as well as of the reports that confirm the presence of oxidative stress in depression, this study was designed to assess the correlation, if any, between the single nucleotide polymorphism G-463A of the MPO gene and the risk of recurrent depressive disorders (DD).Methods:The study was carried out in a group of 149 patients with recurrent DD and 149 healthy control subjects. Genotyping was performed by PCR/restriction fragment length polymorphism.Results:A comparison between healthy controls and depressive patients showed a statistically significant difference in genotype distribution and allele frequency in the studied groups. Genotype distribution and allele frequency did not correlate with clinical variables of the patients.Conclusion:The obtained results of the study allow us to draw a cautious conclusion about the role of the analysed G-463A MPO polymorphism in recurrent DD development, which, however, requires eventual confirmation in further studies.

INTRODUCTION: The role of matrix metalloproteinases (MMPs) in type 2 diabetes mellitus (DM) is not clear as increased activation of MMPs in the vasculature contrasts with decreased activity of MMPs in the kidneys, contributing to development of nephropathy. MATERIAL AND METHODS: We measured serum MMP-2 and MMP-9 in 22 subjects with type 2 DM age (mean ± SD) 56.7 ±16.8 years, BMI 31.8 ±4.6 kg/m(2), HbA(1c) 8.45 ±1.78% and in 32 controls, age 39.2 ±16.0 years, BMI 35.2 ±8.5 kg/m(2). In 15 subjects with 2 DM we also measured MMP-2 and MMP-9 at discharge from hospital and after 3 months (n = 8). In controls, MMP-2 and -9 were also measured during 75 g oral glucose tolerance test (OGTT). RESULTS: Concentrations of MMP-2 and MMP-9 were lower in subjects with type 2 DM (219 ±62 ng/ml vs. 305 ±63 ng/ml and 716 ±469 ng/ml vs. 1285 ±470 ng/ml, for MMP-2 and MMP-9, respectively, p < 0.05). MMP-9 concentrations fell at 120 min of OGTT from 1675 ±372 ng/ml to 1276 ±422 ng/ml (p < 0.05). In diabetic subjects there was a correlation between MMP-9 and HbA(1c) (r = 0.51, p< 0.05). In subjects with diabetes there was a fall of HbA(1c) from 9.77 ±1.76% to 8.36 ±1.54% (p < 0.01), at three months post-discharge. There was no difference in MMP-2, but there was a fall in MMP-9 at three months post-discharge in comparison to concentrations observed at admission (854 ±560 ng/ml vs. 500 ±235 ng/ml, p= 0.02). CONCLUSIONS: Matrix metalloproteinases in type 2 and MMP-9 concentrations were lower in subjects with 2 DM than in non-diabetic controls. Regulation of MMPs appears to be complex as hyperglycaemia during OGTT results in a decrease in MMP-9, while chronic hyperglycaemia, reflected by HbA(1c), correlates with MMP-9 concentrations in subjects with 2 DM.

Background Major depression is characterised by increased nitric oxide (NO) levels. Inhibition of the NO synthesizing enzymes, neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase (iNOS), results in antidepressant-like effects, whereas the expression of iNOS and nNOS is increased in depression. Recent studies have indicated that NOS participates in the mechanisms of antidepressants. The aim of this study was to examine whether a single nucleotide polymorphism (SNP) present in the genes encoding iNOS and nNOS can contribute to the risk of developing recurrent depressive disorder (rDD). Methods The study was carried out in a group of 181 depressive patients and 149 control subjects of Polish origin. SNPs were assessed using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analyses. Results The genotype distributions of the polymorphisms in exon 22 of the NOS2A gene and in exon 29 of the nNOS gene were significantly different between rDD patients and controls. The results showed that the G/A SNP of the gene encoding iNOS was associated with an increased susceptibility to rDD, whereas A/A homozygous carriers had a decreased risk of developing rDD. There was also a significant association between the C/T SNP of the gene encoding nNOS; the presence of the CC homozygous genotype decreased the risk of rDD, whereas the T allele and T/T homozygous genotype increased the vulnerability to rDD. Conclusions Our results suggest that polymorphisms in the iNOS and nNOS genes confer an increased susceptibility or resistance to rDD. Future research should examine genetic variants and their associations to the expression of NOSs and NO level in depressive patients.

Evidence indicates that depressive disorder is a heterogenic disease, and oxidative stress, inflammation and impairment of neurogenesis play a role in its aetiology. Moreover, there are data suggesting that genetic factors affect the development of depression. Nitric oxide (NO) is a biological molecule with both a beneficial and a detrimental role in brain. One of the three enzymes generating NO is inducible nitric oxide synthase (iNOS). Recent studies have shown that depressed patients are characterised by excessive NO production. In addition, iNOS inhibitors are effective in depression treatment. This study investigated the importance of a functional single nucleotide polymorphism (SNP), -1026C/A, located in the promoter region of the human NOS2A gene, for the risk of recurrent depressive disorder (RDD) vulnerability. The study was carried out in a group of 181 patients with RDD and 149 ethnically matched controls. Genotyping was performed by direct sequencing of the polymerase chain reaction (PCR) products. The genotype distribution of the -1026C/A polymorphism between depressed patients and healthy controls was significantly different. Individuals who were homozygous for the CC genotype exhibited an increased risk of developing RDD. In conclusion we cautiously conclude that polymorphism in the NOS2A gene promoter may play a role in the background of RDD.

Depressive disorder (DD) is characterised by disturbances in blood melatonin concentration. It is well known that melatonin is involved in the control of circadian rhythms, sleep included. The use of melatonin and its analogues has been found to be effective in depression therapy. Melatonin synthesis is a multistage process, where the last stage is catalysed by acetylserotonin methyltransferase (ASMT), the reported rate-limiting melatonin synthesis enzyme. Taking into account the significance of genetic factors in depression development, the gene for ASMT may become an interesting focus for studies in patients with recurrent DD. The goal of the study was to evaluate two single-nucleotide polymorphisms (SNPs) (rs4446909; rs5989681) of the ASMT gene, as well as mRNA expression for ASMT in recurrent DD-affected patients. We genotyped two polymorphisms in a group of 181 recurrent DD patients and in 149 control subjects. The study was performed using the polymerase chain reaction/restriction fragment length polymorphism method. The distribution of genotypes in both studied SNPs in the ASMT gene differed significantly between DD and healthy subjects. The presence of AA genotype of rs4446909 polymorphism and of GG genotype of rs5989681 polymorphism was associated with lower risk for having recurrent DD. In turn, patients with depression were characterised by reduced mRNA expression for ASMT. In addition, ASMT transcript level in both recurrent DD patients and in healthy subjects depended significantly on genotype distributions in both polymorphisms. In conclusion, our results suggest the ASMT gene as a susceptibility gene for recurrent DD.

Background: Depressive disorder (DD) is characterized by an inflammatory process and oxidative stress. Cyclooxygenase-2 (COX-2), the expression of which increases in depression, is an enzyme involved in inflammation and free radical processes. The aim of our study was to assess the correlation between single nucleotide polymorphism G–765C of the COX-2 gene and recurrent DD. Methods: The study was carried out in a group of 181 patients treated for recurrent DD, and in 149 healthy subjects of the control group (CG). Polymerase chain reaction/restriction fragment length polymorphism was used for genotyping. Results: A statistically significant difference in genotype distribution was observed as a result of the comparison between the CG and the patients with DD. We demonstrated that the presence of the –765G allele in the COX-2 gene increased 2.1-fold the risk of DD development, whereas the presence of a homozygote (G–765G) in the analyzed gene increased the risk of DD development 2.5-fold. Conclusion: According to the obtained results, it may be proposed with some caution that the presence of both the –765G allele and the G–765G genotype in the COX-2 gene may confer a susceptibility to an increased risk of recurrent DD in the Polish population.

Objective There are numerous reports indicating disturbed equilibrium between oxidative processes and antioxidative defense in patients with depression. Moreover, depressive patients are characterized by the presence of elements of an inflammatory process, which is one of the sources of reactive oxygen species (ROS). In view of the above, it was decided to study both the effect of fluoxetine monotherapy and that of fluoxetine co-administered with acetylsalicylic acid on lipid peroxidation and antioxidative defense in patients with the first depressive episode in their life. Method Seventy seven patients with major depressive disorder (MDD), divided into two groups were included in the study. The first group, consisting of 52 patients, received fluoxetine 20 mg, and the second one, in addition to fluoxetine 20 mg, received 150 mg of acetylsalicylic acid. The activity of antioxidative enzymes, copper-zinc superoxide dismutase (CuZnSOD, SOD1), catalase (CAT), glutathione peroxidase (GPSH-x) and the concentration of malonyldialdehyde (MDA) was determined in erythrocytes, whereas the total antioxidant status (TAS) was determined in the plasma. All parameters were measured before and after three month therapy. Results The obtained results indicate a significant decrease in the activity of SOD1, CAT and GSHP-x, as well as in MDA concentration after the combined therapy. Also a significant TAS increase was observed after the combined therapy. The study demonstrated that combined therapy with fluoxetine and ASA is characterized by the same efficacy and clinical safety as fluoxetine monotherapy, resulting additionally in improvement of oxidative stress parameters in the patients treated for depression. Copyright © 2009 John Wiley & Sons, Ltd.

Retinol-binding protein-4 (RBP-4) may increase insulin resistance (IR) in animals, with elevated levels reported in humans with obesity and type 2 diabetes. There are, however, few data on concentrations of RBP-4 in gestational diabetes mellitus (GDM).We measured fasting serum levels of RBP-4, soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) in 50 women at 28 weeks of gestation, divided according to the results of a 50 g glucose challenge test (GCT) and a 75 g oral glucose tolerance test (OGTT): (1) controls (n = 20), normal responses to both GCT and OGTT; (2) intermediate group (IG) (n = 15): false positive GCT, but normal OGTT; and (3) GDM group (n = 15), both GCT and OGTT abnormal. IR was assessed by homeostasis model assessment (HOMA-IR) and by insulin resistance index (IRI) based on glycemia and insulinemia during OGTT.All groups were matched for age and body mass index (BMI). RBP-4 levels (microg/ml, mean+/-standard deviation) were higher in women with GDM vs. controls (53.9 +/- 17.9 vs. 29.7 +/- 13.9, por = 0.001), with a trend towards higher RBP-4 in GDM compared with IG (38.0 +/- 19.3, p = 0.07). There was no significant correlation between RBP-4 and age, BMI, insulin, IRI or HOMA-IR, but there was a moderate, significant negative correlation between RBP-4 and sVCAM-1 (r(2) = 0.20, p = 0.001).RBP-4 levels are elevated in women with GDM, but do not correlate with IR indices and correlate negatively with sVCAM-1. The physiological significance of RBP-4 rise in women with GDM remains to be elucidated.

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.

Background: Matrix metalloproteinases (MMPs) are implicated in numerous disease states including cardiovascular disease and cancer. Because recent studies have shown a detrimental effect of hormone replacement therapy on cardiovascular disease and breast cancer, we investigated whether there are any differences in the concentrations of MMPs and their tissue inhibitors (TIMPs) in women receiving various forms of postmenopausal therapy.Material and Methods: A total of 195 healthy postmenopausal women were assessed: 46 were taking tibolone, 47 were taking transdermal estradiol, 46 were taking conjugated equine estrogens (CEE), and 56 were not taking any menopausal therapy (CTR). Plasma levels of MMP-2 and -9 and TIMP-1 and TIMP-2 were measured by ELISA methods.Results: MMP-9 levels were significantly higher in the CEE group in comparison with healthy women not receiving menopausal therapy (P < 0.05). In contrast, MMP-9 levels in the tibolone group were significantly lower than in any other group (P < 0.01, compared with transdermal estradiol and CTR, and P < 0.001, compared with CEE). MMP-9 to TIMP-1 ratio was also significantly higher in the CEE, compared with CTR (P < 0.05), and lower in the tibolone group (P < 0.01, compared with all groups). MMP-2 levels were higher in the CEE group, compared with healthy women not receiving any menopausal therapy, and women taking tibolone (P < 0.05).Conclusions: Our study demonstrates differential effects of various forms of postmenopausal therapy on serum levels of MMP-9 and MMP-2. It remains to be established whether these differences might be associated with differences in risks of cardiovascular disease and cancer in these women.

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.

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 99m Tc-EC, although such values were already determined for 131 I-OIH, 99m Tc-DTPA and 99m Tc-MAG3. The aim of this study is an assessment of inter- and intraobserver reproducibility of MTT and PTT for 99m Tc-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 99m Tc-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.

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 ethanolicO. paradoxaextract polyphenols on monocyte and neutrophil oxidative burstin vitroactivated by different stimuli, including opsonized bacteriaE. 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 withE. coliand 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-β-(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 ethanolicO. paradoxaextract, 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 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.

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.

A quantified evaluation of planar cardiac perfusion scintigrams (the objective of the study), obtained using technetium-99m methoxyisobutylisonitrile (MIBI) was performed on the basis of an analysis of circumferential profile curves, representing the perfusion as seen in three typical projections. The analysis involved the curves obtained both at rest and after stress, and was based on a comparison of their shape (trend) with the normal trend (normative evaluation). The latter was obtained by means of an original method of iterative fitting of individual curves into the database. The base consisted of curves recorded in 53 patients (separately in males and females) with normal perfusion of the left ventricle (group I, the reference group). A group of 90 patients suspected of having coronary artery disease (group II) was subdivided into two subgroups on the basis of coronary arteriography: (a) those with and (b) those without critical stenosis of at least one artery. Profile curves characterising the LV perfusion were obtained at rest and after stress. Defects of perfusion were quantified by comparison of individual curves with the normal trends. By means of multivariate analysis it was demonstrated that vectors of mean values characterising the scintigraphically assessed defects of LV perfusion in the two subgroups of group II differed very significantly (P10(-5)). Applying methods of discriminant analysis, a classification of patients from group II was performed into those with probable defects of perfusion and those free of such defects. The sensitivity, specificity and accuracy of diagnosis of coronary ischaemia, based on quantified planar 99mTc-MIBI scintigraphy, reached 86%, 87% and 87%, respectively.

Adenosine receptors (ARs), belonging to the G-protein-coupled receptors (GPCRs), are present in the majority of human cells and tissues. Depending on their biochemical and pharmacologic properties, four subtypes of ARs (i.e. A₁, A(2A), A(2B), and A₃) have been distinguished. Currently, these receptors are attractive molecular targets for pharmacological interventions in various diseases, including diabetes. The literature published to date has shown an altered expression of ARs in several types of cells under diabetic conditions. However, there has been no publication devoted to the investigation of ARs expression in leukocytes of subjects with gestational diabetes mellitus (GDM). Therefore, this study was aimed to determine the expression level of AR subtypes in leukocytes of GDM patients and its relationship to anthropometric and biochemical parameters.Gene expression of four AR subtypes in leukocytes of both healthy (n = 34) and GDM (n = 67) subjects in the third trimester of pregnancy (from 24 to 33 weeks) was investigated. Multiple regression analyses were used to assess the association between the expression level of ARs and both anthropometric and biochemical parameters.Statistically significant (p0.05) higher levels of A(2A) and A(2B) mRNAs were observed in leukocytes of the GDM subjects compared to the control group. There was a positive correlation of A(2B) mRNA level with glucose concentration at 120 min of oral glucose tolerance test (OGTT) (r = 0.24, p = 0.041).Overexpression of A2BAR in leukocytes of the GDM subjects and, additionally, the existence of a relationship between its elevated expression level in these cells and abnormal values of glucose concentration at 120 min of OGTT for GDM, suggest that this subtype might be involved in the pathogenesis of GDM.

As increased frequency of gonadotrophin-releasing hormone (GnRH) pulses is characteristic for polycystic ovary syndrome (PCOS), we assessed gonadotrophin response to GnRH in women with PCOS with normal and raised androgens and in regularly menstruating controls.The study involved 155 subjects: PCOS, n=121, age (mean±SD) 24.8±5.4 yrs, BMI 24.5±6.0 kg/m2, all with oligo-/amenorrhoea and PCO morphology, and 34 controls. Gonadotrophins were measured in early follicular phase after GnRH stimulation (0, 30 and 60 minutes).Fifty four (41.9%) women with PCOS had androgens (testosterone, androstendione, dihydroepiandrosterone sulphate) within the reference range, and would fulfil the "Rotterdam", but not the Androgen Excess Society PCOS criteria. Baseline and stimulated LH concentrations were higher in PCOS (9.09±5.56 vs 4.83±1.71 IU/l, 35.48±31.4 vs 16.30±6.68 IU/l, 33.86±31.8 vs 13.45±5.2 IU/l, at 0, 30 and 60 min post GnRH, respectively, p0.0001). An LH/FSH ratio in PCOS increased further after GnRH stimulation. ROC analysis revealed that LH30min/FSH30min2.11 or LH60min/FSH60min1.72 had 78.3% and 87.5% sensitivity and 81.7% and 81.3% specificity for diagnosis of PCOS. Both baseline and GnRH-stimulated LH and FSH concentrations were similar in women with PCOS and raised androgens and with androgens within the reference range (p=0.71 and p=0.20 for LH and FSH, respectively).Regardless of their androgen status, women with PCO morphology and oligo-/amenorrhoea have higher baseline and GnRH-stimulated LH concentrations and higher GnRH-stimulated LH/FSH ratio than controls, suggestive of similar underlying mechanism accounting for menstrual irregularities. These observations support validity of PCOS diagnostic criteria based on the Rotterdam consensus.

Increased activity of the coagulation system is associated with the increased risk of many arterial thrombotic diseases and atherosclerosis. The purpose of this study was to evaluate the influence of selected polymorphisms in genes coding for coagulation factor V (1691 G/A, the so-called Leiden mutation), factor VII (−323 0/10 bp insertion/deletion) and fibrinogen β chain (−455 G/A) on the risk of abdominal aortic aneurysm, a particular form of atherothrombosis. We conducted a case-control study of 153 Polish patients hospitalized due to abdominal aortic aneurysm (AAA) and compared the results to those obtained from matched healthy control subjects. The polymorphisms were ascertained through genotyping by polymerase chain reaction and restriction digestion of amplified fragments. The study revealed that individuals carrying heterozygous genotype GA for the fibrinogen β chain −455 G/A mutation had at least a 2-fold greater likelihood of AAA development compared to control subjects (OR=3.01; 95% CI 1.83–4.96). The cases possessing homozygous mutant genotype (AA) had no significant risk of developing AAA compared to the control subjects (OR=1.12; 95% CI 0.33–2.44; p=0.83). Concerning factor V 1691 G/A and factor VII −323 0/10 bp mutations, we did not find any statistically significant correlation between them and AAA occurrence. In conclusion, we suggest that the −455G/A polymorphism of the fibrinogen β chain gene is a potential genetic marker to identify the risk of AAA.

The aim of this study was to determine which of the most popular colour scales used in the Xeleris processing system (GE) should preferably be used during a clinical interpretation of myocardial perfusion images, and to find out whether a colour scale saturation level affects the diagnostic efficacy of the study.From among 100 patients in whom a myocardial perfusion scintigraphy had been performed, a subgroup of people referred for coronary angiography, with neither prior history nor ECG signs of a myocardial infarction has been selected retrospectively. This group consisted of 41 patients (14 females) in the age group 46 to 76 years. All patients underwent two-day myocardial perfusion SPECT imaging using 99mTc-MIBI as a radiopharmaceutical. Reconstructed slices were interpreted in 3 colour scales: white-red-yellow-green-blue-black with computer-assigned thresholds (French 100%), the same French scale but without a white colour (image maximum set manually to a border value between red and white - French w.w.), and a white-yellow-violet- pink-blue-black scale (GEcolor), by consensus of two experienced nuclear medicine specialists. A semiquantitative method for evaluation of perfusion images was applied, based on myocardium segmentation. Perfusion in each segment was scored using a five-point system. Study interpretation (normal/ abnormal perfusion) was based on summed stress scores (SSS), being equal/above or below a given threshold value. The choice of optimal SSS threshold value was based on sensitivity and specificity of the study in detection of perfusion defects resulting from critical stenoses of main coronary arteriesSSS values differed among colour scales (p0.00001). The lowest values were obtained for a French 100% scale (mean value = 5.0, SD = 8.0), the highest for French w.w. (mean values = 8.1, SD = 8.7), and for GE colour scale - mean value - 5.6, SD - 7.9. A French 100% scale gave high sensitivity (88%), as well as specificity (83%), but only when a low SSS threshold value of 2, hardly acceptable for study interpreters, was used. When higher threshold values were applied, they compromised the sensitivity of the study. A French w.w. scale with SSS threshold values lower than 3 provided a slightly higher sensitivity (94%), but with a significant reduction in specificity (to values below 50%). Only a threshold value of 4 provided acceptable, but still low specificity (63%) with preserved high sensitivity (88%). At the same time, the scale GE colour provided indices of diagnostic efficacy with the SSS threshold value of 3 as high as a scale French 100% with threshold value of 2.A French scale (Xeleris, GE) is not the scale of choice for the interpretation of myocardial perfusion SPECT images. It seems that a GE colour scale is better suited for this purpose. SSS threshold values accepted as diagnostic criteria for the detection of myocardial perfusion abnormalities should be suited separately for every translation table. The choice of optimal value should be verified by results of coronary angiography.

Compounds of N-alkylated benzamide derivatives have been the subject of investigations in the last few decades from the standpoint of their possible application for scintigraphic detection of melanoma. Positive results have been observed in studies on biodistribution when using animal models and the compound IMBA (N-(2-diethylaminoethyl)-3-iodo-4-metoxybenzamide). The present study presents preliminary results of scintigraphic studies in patients with documented melanoma metastases, who were administered ¹³¹I-IMBA synthesized by modified labelling procedure (electrophilic substitution of radioactive ¹³¹I to metal organic substituent).The study was made in three patients with diagnosed melanoma metastases to tissues and organs. To each patient 111 MBq of ¹³¹I-IMBA was intravenously administered and whole body scintigraphy was performed 4 and 24 hours post injection of the radiopharmaceutical. Additionally, after 24 hours, SPECT/CT of selected regions of the body was performed.In 3 patients a total of 20 lesions of increased activity were found (15 were detected previously by other methods, 5 in the head, 4 in thorax, 2 in liver and spleen, 3 in abdomen and 6 in extremities). In the scintigrams performed 4 hours after ¹³¹I-IMBA administration, there were found 12 lesions of enhanced accumulation of the radiopharmaceutical. After 24 hours, due to reduction of background activity, there were 8 additional hot lesions detected. The mean activity tumour/background ratio for 20 lesions 4 hours post injection amounted to 1.51 ± 0.64, and the ratio increased to 2.94 ± 2.32 24 hours after administration of a radiopharmaceutical.¹³¹I-IMBA preparation, obtained by a modified labelling procedure, enabled detection of metastatic lesions in the patients. This may indicate that there is a possibility of using radioiodinated IMBA (with ¹²³I or ¹³¹I) for diagnosis of melanoma in humans. From our results it follows that scintigraphy should be performed 24 hours post injection. Further studies on diagnostic efficacy (sensitivity and specificity) of the method are necessary.

Polycystic ovary syndrome (PCOS) is characterised by increased frequency of hypothalamic GnRH pulses leading to a relative increase in LH synthesis by the pituitary. As GnRH stimulation can reveal a relative LH excess, we have endeavoured to assess whether GnRH test might be useful in the diagnosis of PCOS.The study involved 185 subjects: a PCOS group, n = 151, all with oligo- or amenorrhoea, aged (mean ± SD) 24.8 ± ± 5.4 years, BMI 24.5 ± 6.0 kg/m²; and regularly menstruating controls, n = 34, aged 26.6 ± 5.0 years, BMI 24.6 ± 5.5 kg/m². In 121 subjects with PCOS and in 32 controls, serum LH and FSH were measured before (0 minutes) and 30 and 60 minutes after GnRH stimulation (100 μg i.v.). Insulin resistance was assessed by HOMA and Insulin Resistance Index derived from glucose and insulin concentrations during 75 gram oral glucose tolerance test.Women with PCOS had higher testosterone (p = 0.0002), androstendione (p = 0.0021), 17OH-progesterone (p0.0001) and were more insulin resistant. Raised concentrations of at least one androgen were, however, found only in 58.1% of women with PCOS. Baseline and stimulated LH concentrations were higher in PCOS (9.09 ± 5.56 vs 4.83 ± 1.71 IU/L, 35.48 ± 31.4 vs 16.30 ± 6.68 IU/L, 33.86 ± 31.8 vs 13.45 ± 5.2 IU/L, at 0, 30 and 60 mins post GnRH, respectively, p0.0001). There was no difference in baseline or stimulated FSH concentrations between groups. Relative increases of LH or FSH in comparison to respective baseline values were similar in both groups. There was, however, a marked increase in LH/FSH ratio in PCOS in comparison to controls (LH0 min/FSH(₀ min) 1.59 ± 0.95 vs 0.76 ± 0.2, LH(₃₀ min) /FSH(₃₀ min) 4.07 ± 3.0 vs 1.89 ± 0.79, LH(₆₀ min)/FSH(₆₀ min) 3.56 ± 2.58 vs 1.55 ± 0.63, p0.0001 at all time points). Further analysis revealed that LH30 min/FSH(₃₀ min)2.11 or LH(₆₀ min)/FSH(₆₀ min)1.72 had 78.3% and 87.5% sensitivity and 81.7% and 81.3% specificity for the diagnosis of PCOS, respectively.Women with PCOS have higher baseline and GnRH-stimulated LH concentrations. GnRH stimulation results in an increase in LH/FSH ratio in women with PCOS. Therefore we postulate that this phenomenon might be potentially useful as an additional tool in the diagnosis of PCOS.

The aim of this study was to investigate the incidence, reversibility, and severity of LV perfusion abnormalities in patients with isolated myocardial bridges using a gated myocardial perfusion SPECT study (GSPECT).A retrospective study involved 42 patients without history of myocardial infarction, with isolated myocardial bridges detected in coronary angiography and no substantial evidence of atherosclerotic changes in coronary arteries. In all patients a gated SPECT study was performed at both rest and stress, after intravenous administration of (99m)Tc MIBI. Reconstructed slices were analyzed using a 20-segment model of the left ventricle.Incidence and severity of stress-induced ischemia were related to degree of artery constriction (P = .002 and .00014, respectively). Perfusion abnormalities were detected only in patients with critical narrowing (≥ 50%) of artery (in 12 out of 28, i.e., 43% of patients). Summed stress scores (SSS) ranged from 4 to 11 (mean 7), indicating slight or moderate defect intensity. Only 1 patient presented with a SSS value of 31 (severe defect). Perfusion defects were stress induced in 70 out of 72 (97%) segments with abnormal perfusion.Perfusion abnormalities were observed in ab. 40% of patients with critical (≥ 50%) narrowing of artery affected by bridging and were mild, stress induced.

Cicatrisation of the renal cortex is closely related to chronic infections of the urinary system. Static renal scintigraphy is used as the method enabling detection of local defects of radiopharmaceutical uptake, and is treated as the "gold standard" in the diagnosis of renal scars. The aim of the reported investigation was a comparison of the diagnostic efficacy of parametric clearance images and the conventional summation images - obtained from dynamic scintigraphy - in the detection of local defects of renal function. As the "gold standard" for the above comparison, the static scintigraphy of kidneys was accepted.Forty-one patients (age 4-19 years), 28 girls and 13 boys, participated in the study. Altogether, 73 kidneys were analyzed (in 9 patients, only one kidney). In each patient dynamic renal scintigraphy was performed after IV administration of 99mTc EC (ethylenedicysteine) and static planar renal scintigraphy using 99mTc-DMSA (dimercaptosuccinic acid) as a reference method. From the dynamic study, summation and parametric clearance images were generated. Each kidney was divided into 3 segments (upper, middle, lower); altogether 219 segments were evaluated by modified Howard's scale. Planar and oblique projection images were compared with corresponding summation and parametric clearance images.Parametric clearance imaging has a higher sensitivity and accuracy for detection of regional post-inflammatory changes in the kidneys than conventional summation images (p0.05) and shows parenchymal changes similarly to static scintigraphy (high Cohen's kappa index).

Polymorphisms (rs 4753426 and rs 794837) and expression of the melatonin MT(2) receptor gene were evaluated in 181 patients with recurrent depressive disorder (rDD) and 149 healthy subjects of Polish origin. We found an increased risk for rDD in patients with the C allele and a decreased risk in patients with the T allele (rs4753426). Patients with the AT heterozygote (rs794837) had an increased mRNA level. The significance of the MT(2) receptor gene and the risk of rDD are suggested.

Gajos A, Bogucki A, Schinwelski M, Soltan W, Rudzinska M, Budrewicz S, Koszewicz M, Majos A, Gorska-Chrząstek M, Bienkiewicz M, Kuśmierek J, Slawek J. The clinical and neuroimaging studies in Holmes tremor. Acta Neurol Scand: 2010: 122: 360–366. © 2010 The Authors Journal compilation © 2010 Blackwell Munksgaard. Aim – Holmes tremor (HT) is a combination of rest, postural and action tremor. A parallel dysfunction of cerebello-thalamic and nigrostriatal pathways seems necessary to produce this kind of tremor. We present the clinical and neuroimaging study verifying that hypothesis. Material and methods – A total of 10 patients: five male, five female, fulfilling consensus criteria were included. Demographic, clinical and neuroimaging data (MRI = 9; CT = 1, SPECT with the use of 123-I-FP CIT: DaTSCAN in six patients to assess the presynaptic dopaminergic nigrostriatal system involvement, indices of asymmetry for ligand uptake for each striatum were calculated) were analyzed. Results – Hemorrhage was the most frequent etiology and thalamus – the most commonly involved structure. Contrary to the previous reports, the visual assessment did not reveal remarkable interhemispheric differences of DaTSCAN uptake. Quantitative measurements showed only minimal differences. Conclusions – It is open to debate whether nigrostriatal pathway damage is crucial for the phenomenology of HT. Alternative hypothesis is presented that HT represents the heterogeneous spectrum of tremors with similar phenomenology, but different pathophysiology.

The aim of this study was to evaluate the effect of ordered‐subset expectation maximization reconstruction algorithm with scatter correction and attenuation correction based on computed tomography maps and to find out the optimum number of subsets and iterations upon image quality for 123I−DaTSCAN neuroimaging. We retrospectively studied SPECT/CT scans of 44 consecutive patients with clinical indications of Parkinson’s disease. Images were reconstructed with use of two methods: filtered back projection and OSEM. Image quality was assessed by: striatal binding indices as a measure of contrast and coefficients of variation as a measure of noise. The quality of DaTSCAN images reconstructed with the use of OSEM (4iter/10subs) with reconstruction corrections was superior to that provided by the commonly applied FBP.The aim of this study was to evaluate the effect of ordered‐subset expectation maximization reconstruction algorithm with scatter correction and attenuation correction based on computed tomography maps and to find out the optimum number of subsets and iterations upon image quality for 123I−DaTSCAN neuroimaging. We retrospectively studied SPECT/CT scans of 44 consecutive patients with clinical indications of Parkinson’s disease. Images were reconstructed with use of two methods: filtered back projection and OSEM. Image quality was assessed by: striatal binding indices as a measure of contrast and coefficients of variation as a measure of noise. The quality of DaTSCAN images reconstructed with the use of OSEM (4iter/10subs) with reconstruction corrections was superior to that provided by the commonly applied FBP.

The aim of this study was to evaluate the effect of the CT-derived attenuation correction on (99m)Tc-MIBI normal myocardial perfusion scintigrams. Rest perfusion scintigrams of patients in whom coronary artery disease was suspected, without a history or any signs in ECG of a myocardial infarction, were analysed. Patients were included in the material if their rest perfusion scintigrams were normal. This criterion was fulfilled by 61 patients (29 men and 32 women) aged between 40 and 74 (mean value 57) years, with body mass between 50 and 120 (mean value 70) kg. Tomographic reconstruction of a radionuclide study was performed with an iterative OSEM method (10 subsets, 2 iterations) sequentially without and with attenuation and scatter corrections on a dedicated Xeleris workstation, applying an ACQC tool to enable manual realignment of SPECT and CT images. SPECT studies were evaluated visually and semiquantitatively. Visual analysis of tomograms was performed with the aim of finding sites of significantly lower counts in comparison with the maximal level (in the lateral wall). Semiquantitative analysis was based on counts in 20 segments of a polar map. Attenuation correction caused a complete (in 32 of 40 - 80% of patients) or partial (in 8 of 40 - 20% of patients) filling out of all areas of lower counts in the inferior wall. However, although in the anterior wall attenuation correction caused a complete (in 11 of 35 - 31% of cases) or partial (10 of 35 - 29% of cases) filling of areas of lower counts, in 14 cases (40%) those areas remained unchanged or increased, and in 8 cases (13% of all patients) new areas of decreased counts appeared. The same was true for the apical region, in which areas of decreased counts were detected in 14 of 61 (23%) cases without attenuation correction, but after application of the correction number of apical defects, this figure grew to 22 (36%) patients. Altogether, attenuation correction reduced the total number of lower count areas from 104 to 66. Semi-quantitative analysis revealed that attenuation correction reduced nonuniformity in counts in the whole myocardium - the mean difference between segment with maximum counts and values in all segments was reduced from 17.5 +/- +/- 12% to 11.0 +/- 10.3% (p0.0001) in male patients, and in female patients, from 11.5 +/- 9% to 10.5 +/- 8.6%, thus equalling non-uniformities in myocardial scintigrams of both sexes. Misalignment of CT and SPECT studies was observed in 17 (28%) patients but only in 2 (3% of all patients) patients did CT realignment evidently change the attenuation corrected scintigrams. Although attenuation correction can cause artefacts, its use is justified by the reduction of the total number of areas of lower counts and the improvement of uniformity of images of normally perfused myocardium.

The quality of visually and semi-quantitatively assessed DaTSCAN images is crucial for differential diagnostics of extrapyramidal diseases. Neuroimaging with the use of presynaptic tracers of the dopaminergic system provides evidence of nigrostriatal degeneration and may support the clinical diagnosis of Parkinsonism. During the last two years (2007-2008) we tried to elaborate the optimal methodology of SPECT/CT examination with the use of DaTSCAN ((123)I-Ioflupane), and we sought to evaluate the effect of the reconstruction and attenuation correction method on semi-quantitative measures of relative uptake in the striatum. In a present study, we retrospectively studied DaTSCAN scans of 44 consecutive patients with clinical indications of Parkinson's disease or uncertain Parkinsonian syndromes. The quality of DaTSCAN images reconstructed with the use of ordered-subset expectation maximization reconstruction technique (OSEM) with attenuation correction based on CT maps was found to be superior to that provided by the commonly applied filtered backprojection method (FBP) with Chang attenuation correction. OSEM reconstructed transverse slices were more legible for clinical interpretation because of increased contrast and improved delineation between striatum structures. Semi-quantitative assessments of relative striatum uptake for OSEM reconstructed slices secured better intra-operator reproducibility than that obtained by FBP method.

Matrix metalloprotenases (MMPs) are proteolytic enzymes active in inflammatory states. We have examined MMP-9, MMP-2, and their respective tissue inhibitors: TIMP-1 and TIMP-2 in sera of women with gestational diabetes mellitus (GDM) and various degrees of insulin resistance (IR) in the third trimester of pregnancy.Fasting serum levels of MMP-9, MMP-2, TIMP-1 and TIMP-2 were measured in 26th-28th week of gestation in 51 women divided according to their response to a 50-g glucose challenge test (GCT) and a 75-g OGTT: controls (n = 20): both tests normal; the GDM group (n = 16) both tests abnormal; the intermediate group (IG; n = 15) abnormal GCT and normal OGTT. MMPs and TIMPs were correlated with the parameters of IR: homeostasis model assessment (HOMA) and insulin resistance index (IRI).MMP-9, MMP-2, TIMP-1 and MMP-9/TIMP-1 ratio were not different among the groups. TIMP-2 levels were significantly higher in the GDM and IG groups than in controls (p0.01). MMP-2/TIMP-2 ratio was lower in the GDM group than in the other groups (p0.01) and was correlated to HOMA and IRI (r = -0.465 and r = -0.43 respectively, p0.01).Serum MMP levels do not reflect inflammation in GDM. Elevated TIMP-2 and consequently lower MMP-2/TIMP-2 levels in GDM need to be clarified, but are unlikely to be a consequence of inflammation.

Parametric kidney scintigraphy gives the possibility of regional function distribution assessment of these organs; the clinical application of the method has thus far been limited. The usefulness of the method for the assessment of postinflammatory scars and diabetic nephropathy has been demonstrated. Preliminary data also indicate that this type of imaging allows the assessment of kidney function after extracorporeal shock wave lithotripsy. The aim of this study was the evaluation of the reproducibility of semiquantitative parametric kidney image evaluation.The results of 98 dynamic kidney scintigraphic series were evaluated, obtained from examination of 44 patients (20 males, 24 females) with nephrolithiasis, who had been treated by means of lithotripsy. The semiquantitative assessment involved conventional renoscintigraphic images obtained from summation of scintigraphic serial records in the secretory phase, and parametric clearance images. A 5-level score was applied for assessment of both types of images, based upon numbers of detected defects of the regional function (0 - no defects; 1, 2, 3 - for 1, 2 or 3 defects, and 4 for higher numbers). Altogether, 196 kidney images were evaluated. The assessment was performed independently by 2 observers: A - an experienced specialist in nuclear medicine, who evaluated the images twice, and B - a resident physician with limited experience in the field.The agreement between the two evaluations by the specialist (intra-observer test) reached a level of 96% for conventional images and 90% for the parametric ones. In the inter-observer test, full agreement reached the levels of 84% and 71% for conventional and parametric images, respectively. If +/- 1 degree of the image score was taken as factual agreement, the intra-observer concordance reached 100%, and for inter-observer comparison, the agreement reached 99% and 97% for conventional and parametric images, respectively.The concordance of image assessment for conventional and parametric images is very good. In observations by two physicians, a somewhat closer agreement was reached for conventional than for parametric images; the difference between the two series of image assessments was small.

Secretory products from adipocytes may contribute to deterioration in glycaemic control and increased insulin resistance (IR). Retinol-binding protein 4 (RBP-4) may increase IR in mice, with elevated levels in insulin-resistant mice and humans with obesity and type 2 diabetes. However, the mechanisms regulating RBP-4 synthesis remain not fully understood. It is not clear whether short-term glucose-induced hyperglycaemia and hyperinsulinaemia as well as glucocorticosteroid-induced increase in IR might be reflected in alterations in serum RBP-4 levels in humans. In order to investigate this, we measured serum RBP-4, glucose and insulin concentrations during 75.0 gram oral glucose tolerance test (OGTT) - Study 1, as well as before and after oral administration of dexamethasone - Study 2.Both studies included 35 subjects (8 males), age (mean +/- SD) 39.1 +/- 15.6 years, BMI 35.8 +/- 8.7 kg/m(2). Twenty-four of those subjects (5 males), age 38.7 +/- 15.1 years, BMI 34.4 +/- 8.3 kg/m(2), had 75 gram oral glucose tolerance test (OGTT) - Study 1. Blood samples were taken before (0 minutes), and at 60 and 120 minutes of OGTT. 17 subjects (3 males, 4 subjects with type 2 diabetes), age 43.1 +/- 18.1 years, BMI 36.7 +/- 9.0 kg/m(2) underwent screening for Cushing's disease/syndrome (Study 2). Dexamethasone was administered in a dose of 0.5 mg every 6 hours for 48 hours. Fasting serum concentrations of RBP-4, glucose and insulin were assessed before (D0) and after 48 hours of dexamethasone administration (D2). IR was assessed by HOMA in all non-diabetic subjects and in subjects participating in study 1 also by Insulin Resistance Index (IRI), which takes into account glucose and insulin levels during OGTT.Glucose administration resulted in significant increases in insulin and glucose (p0.0001). There was, however, no change in RBP-4 concentrations (124.1 +/- 32 mg/ml at 0 minutes, 123 +/- 35 mg/ml at 60 minutes and 126.5 +/- 37.5 mg/ml at 120 minutes of OGTT, p = ns). All subjects in Study 2 achieved suppression of cortisol below 50 nmo/l. Dexamethasone administration resulted in an increase in fasting insulin (from 11.6 +/- 6.8 to 17.1 +/- 7.2 muU/ml; p = 0.003), and an increase in HOMA (from 2.73 +/- 1.74 to 4.02 +/- 2.27; p = 0.015), although without a significant change in RBP-4 levels (119 +/- 26.8 vs. 117.5 +/- 24.8 mg/ml, p = ns). RBP-4 correlated with fasting insulin (r = 0.40, p = 0.025), fasting glucose (r = 0.41, p = 0.02) and HOMA (r = 0.43, p = 0.015), but not with IRI (r = 0.19, p = 0.31). There was, however, only a moderate correlation between HOMA and IRI (r = 0.49 [r(2) = 0.24]; p = 0.006, Spearman rank correlation), while the best correlation was obtained between the product of glucose and insulin levels at 60 min of OGTT and IRI in a non-linear model (r = 0.94 [r(2) = 0.88]; p0.00001). In subjects who received dexamethasone, a positive correlation between RBP-4 and HOMA (p = 0.01) was lost after two days of dexamethasone administration (p = 0.61).RBP-4 levels do not change during oral glucose tolerance test or after a dexamethasone-induced increase in insulin resistance. This implies that it is highly unlikely that RBP-4 is involved in short-term regulation of glucose homeostasis in humans and that it responds to short-term changes in insulin resistance. A moderate correlation between RBP-4 and some insulin resistance indices (HOMA) does not exclude the fact that RBP-4 might be one of many factors that can influence insulin sensitivity in humans.