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The results of recently published articles on the etiology and pathogenesis of "Adherent Perinephric Fat" (APF) are presented in the review. The current possibilities for predicting the presence of APF based on clinical data and imaging methods are highlighted, as well as the to an influence of ARF on perioperative results of organ-sparing procedures using various surgical approaches in patients with localized kidney parenchyma tumors.

Aim. To summarize the list of medicines that can be used at various stages of the treatment of burn disease and wound healing at the hospital stage in the military personnel; conduct the marketing analysis of the Ukrainian market of these medicines in order to determine the feasibility of creating an ointment for the treatment of inflammatory skin diseases and burns. Materials and methods. The study objects were the “State Register of Medicinal Products of Ukraine” information and search system and the Compendium. When conducting our studies the following scientific and system-review methods of the information search were used: bibliographic, documentary, content analysis, comparison method, system analysis, marketing research. Results. As a result of the study of the range of drugs for wound healing presented at the pharmaceutical market of Ukraine, it has been found that 64 % are drugs of the Ukrainian production, foreign drugs are 36 %. The distribution of soft drug forms registered in Ukraine has been carried out by pharmacological groups; it has been found that the percentage of antimicrobial and antifungal drugs is almost the same (15.8 % and 15.2 %, respectively). Steroidal anti-inflammatory drugs predominate over nonsteroidal ones (14.9 % and 11.4 %, respectively). The studies conducted have shown that at the domestic market there are many drugs of foreign production, which have no Ukrainian analogs. The marketing research has shown that combined drugs are more effective for the treatment of burns. They act simultaneously in several directions and facilitate the healing process. Among the drugs considered combined medicines occupy 42 %, while the share of monocomponent drugs is 58 %. The amount of synthetic drugs is 88 % and significantly exceeds the number of herbal medicines (12 %). Conclusions. The concept and methodology for the treatment of burns are summarized. It has been determined that the drugs of choice are complex soft drug forms. As a result of the marketing research on the structure and nomenclature of soft drug forms it has been found that at the domestic pharmaceutical market soft drug forms of foreign production is 36 %, and domestic ones – 64 %. It has been determined that the number of drugs for local wound healing is about 6 % of the total range of soft drug forms and presented mainly by monocomponent drugs (58 %). The analysis of the range of drugs with the anti-burn and antiseptic action by dosage forms has shown that ointments are the largest share – 67%, drugs in the form of creams – 18%. Key words: marketing analysis; servicemen; burn disease; wound process; hospital stage of treatment.

Aim to evaluate the features pathologic results of organ-sparing interventions in patients aged up to 40 years and older and assess an influence of patient age on the recurrence-free survival in case of pathologically proven renal cell cancer. Materials and methods A retrospective analysis of laparoscopic organ-sparing removal of kidney tumors in 314 patients performed from January 2012 to May 2017 was conducted. The mean patient age was 54.4+/-10.9 (25-78) years. There were 178 males (56.7%) and 136 females (43.3%). All patients were divided into two groups. In Group 1 a total of 37 patients aged less or equal 40 years (11.8%) were included and Group 2 consisted of 277 patients (88.2%) over 40 years. In Group 1 there was no family cases of renal cell cancer. Results In Group 1 malignant tumors were more common (n=33 cases (89.2%)), and benign tumors were diagnosed in 4 (9.8%) cases. Among patients older than 40 years the malignant and benign tumors were determined in 242 cases (87.4%) and 35 cases (12.6%), respectively. It was estimated that there were no differences in neither malignant tumors rate (p=0.75), nor in proportion of different pathologic forms of benign (p=0.68) and malignant neoplasms (p=0.25), nor in proportion of various degrees of anaplasia (=0.33). A mortality rate was 0.6% (2 patients in Group 2), and there was 3 relapse (1.1%). A proportion of censored cases was 99.4% for overall survival and 98.9% for recurrence-free survival. A point estimate of overall survival after 36-months follow-up was 35.77+/-0.16 months. The mean disease-free survival was 35.47+/-0.24 months. The survival differences between two groups were not significant due to absence of relapse and mortality in patients aged less or equal 40 years. Conclusion During the planning of surgical treatment of patients with kidney tumors aged less or equal 40 years a preference to organ-sparing interventions should be given. The postoperative genetic counselling is recommended to exclude hereditary renal cell cancer. Considering a high risk of local recurrence in all patients aged less or equal 40 years meticulous and regular follow-up is needed.

Aim. To assess results of Meshalkin National Research Medical Center and Tomsk National Research Medical Center in surgical treatment of DeBakey type I aortic dissection using hybrid technologies (“frozen elephant trunk”) compared with classical standard interventions.Material and methods. The study included patients operated on successively in the 2002­2010 timeframe with a diagnosis of acute and subacute DeBakey type I aortic dissection. A retrospective observational comparison of the surgical treatment results of patients (two groups) was performed: using standard surgical approaches (beveled anastomosis or aortic arch replacement using multi­branched prosthesis) and frozen elephant trunk (FET) intervention. The groups included 70 and 31 patients, respectively. Mortality and morbidity were evaluated in the postoperative period, the frequency of aorto­related events — during the observation period.Results. Mortality and the frequency of complications between the groups in the early and late postoperative periods did not differ. Aorto­related events of the groups in the long­term period differed statistically significantly in favor of hybrid interventions (p=0,005).Conclusion. The hybrid technology of thoracic aorta reconstruction using “frozen elephant trunk” type allows to make one­step reconstruction of the aorta during its multilevel lesion. Observation of patients in the long­term period allows us to announce of a longtime, stable result of surgical treatment in the absence of additional perioperative risks.

Some studies have proven possible potentiating toxic effect of combined pesticides. The potentiating effect may be related to the impact of a certain substance on enzymatic activity of another one. Due to combined preparations popularity, the importance of evaluating probability of summation and synergetic or antagonizing action of the one-purpose substances becomes particularly important. Aim of the researchisto studypeculiarities of histomorphological liver changes associated with combined effect of active substances with one-purpose action. Methods.The authors have used toxicological, histochemical and statistical study methods. 45 rats have been used for the study. The liver specimens for histochemical analysis were selected immediately after dissection of the rats, from which the 5 micrometer sections were prepared, using freezing microtome. After leaving the sections in cold acetone, the histochemical reaction on determining the γ-glutamyl transpeptidase, a transformed hepatocyte marker, which forms nodules while proliferates, was conducted. Results.The authors have established thatthe above-mentioned characteristics inanimals which were administered the drug (benthiavalicarb-isopropyl+folpet) do not differ from negative control group. General specific area of nodules per сm2and specific quantity of nodules per сm2haven’t reliably changed, the control group exceeding these data by 18 % and 12 %, respectively. Discussion.The study of the benthiavalicarb-isopropyl and folpet mixture effect on animals has not revealed liver tissue proliferation of the carcinogen-transformed cells and appearance of hyperplastic nodes, which express the γ-glutamyl transpeptidase, a histochemical marker of pre-tumor changes. So, the fungicide (benthiavalicarb-isopropyl+folpet) has not induced multiplication or size increase of glutamyl transpeptidase nodules, which evidences about loss of the modifying effect of folpet on the benthiavalicarb-isopropyl carcinogenicity in this preparation formula. The obtained results may be used when deciding on administration of combined fungicides with active substances of one-purpose action.

Досліджено таксономічний склад і популяційний рівень мікробіоти вмісту порожнини товстої кишки 95 хворих на діарейний ешерихіоз та 87 практично здорових осіб. Встановили, що гострий діарейний ешерихіоз розвивається на фоні порушень таксономічного складу і популяційного рівня автохтонної облігатної анаеробної грампозитивної мікробіоти (Bifidobacterium та Lactobacіllus), зі зростанням кількості бактерій родів Bacterоides, Peptostreptococсus, Clostridium та факультативних анаеробних і аеробних бактерій роду Escherichia, Proteus, Staphylococcus і дріжджоподібних грибів роду Candida, контамінацією і колонізацією порожнини товстої кишки умовно-патогенними ентеробактеріями (Citrobacter, Enterobacter, Proteus та ін.), пептококами, дріжджоподібними грибами роду Candida, а також ростом та проліферацією ентеропатогенних, ентероінвазивних, ентерегеморагічних ешерихій і гемолітичних (E. сoli Hlу+) та лактозонегативних кишкових паличок. У 57,89 % хворих на гострий ентероколіт наявний дисбактеріоз, у 42,11 % – дисбіоз. Серед них у 63,16 % осіб діагностували дисбактеріоз 3-го і 4-го ступеня, у 36,84 % – дисбактеріоз 1-го і 2-го ступеня (c2=13,16; р

Thirty-eight Mallards were collected on the territory of Ukrainian Polissia to study the fauna of their gastro-intestinal helminths. Materials were collected in 1998-2000, 2014 and 2016 on the territory of Volyn and Chernihiv Regions. In total, 33 species of helminths were found. Th e prevalence of cestode infection was 78.9 %. We found 18 cestode species: Aploparaksis furcigera, Cloacotaenia megalops, Dicranotaenia coronula, Diorchis acuminatus, D. stefanskii, Fimbriaria fasciolaris, F. teresae, Microsomacanthus compressa, M. spiralibursata, M. paracompressa, M. paramicrosoma, M. parvula, M. hopkinsi, Platyscolex ciliata, Retinometra venusta, Sobolevicanthus aculeostyleticus, S. gracilis, S. stolli. Th e prevalence of trematode infection was 73.7 %. Th ere were 10 trematode species: Bilharziella polonica, Apatemon gracilis, Echinoparyphium aconitum, E. cinctum, Echinostoma revolutum group, Hypoderaeum conoideum, Notocotylus attenuatus, Parastrigea robusta, Prosthogonimus ovatus, P. cuneatus.Th e prevalence of nematode infection was 7.9 %. Th ere were four nematode species: Capillaria anatis, Capillariidae gen. sp., Eucoleus contorta, Tetrameres fi ssispina. Th e prevalence of an acanthocephalan Filicollis anatis was 18.4 %. Th e most common species of helminths were A. furcigera, B. polonica, A. gracilis, Echinostoma revolutum group, F. fasciolaris, H. conoideum. Th e helminth faunas of Mallards from the territory of Ukrainian Polissia and from the Black Sea Region of Ukraine were compared. Th e results of comparison demonstrated a high level of their qualitative similarity.

The radioligand 2-[(18)F]fluoro-A-85380 has been developed for imaging alpha(4)beta(2) nAChRs with PET. However, it has slow kinetics and a large fraction of bound activity is nondisplaceable. In an attempt to address these problems, two epibatidine-based alpha(4)beta(2) nicotinic antagonists, coded FPhEP and F(2)PhEP, were evaluated in vivo in baboons. They were radiolabeled with fluorine-18 from the corresponding N-Boc-protected bromo-derivatives and the no-carrier-added K[(18)F]F-Kryptofix(222) complex. Radiochemically pure [(18)F]FPhEP or [(18)F]F(2)PhEP was obtained in 80 min in amounts of 1.11-2.22 GBq (111-185 GBq/micromol). After injection of 215 MBq of [(18)F]FPhEP or [(18)F]F(2)PhEP, dynamic PET data were acquired. Thalamic radioactivity peaked at 20 min (4.9% +/- 0.2% ID/100 mL tissue) for [(18)F]FPhEP. For [(18)F]F(2)PhEP, the peak was at 45 min (3.3% +/- 0.1% ID/100 mL tissue). Regional distribution of both radiotracers was in accordance with the known distribution of nAChRs. In presaturation experiments, nicotine, cytosine, or FPhEP reduced brain radioactivity of [(18)F]FPhEP. In a displacement experiment with nicotine only a small amount of [(18)F]F(2)PhEP was dislodged. In spite of a moderate to high in vitro affinity, both ligands do not fulfill the widely adopted criteria for a PET radioligand.

The in vivo characteristics of [ 11 C]befloxatone were assessed in myocardium of rats and monkeys. A complete multicompartmental model was developed to quantify monkey cardiac monoamine oxidase A (MAO-A) binding sites using positron emission tomography (PET) and was applied to assess the acute effects of inhalation of tobacco smoke. Unknown compounds contained in tobacco smoke inhibit brain MAO. In vitro, befloxatone inhibits selectively, competitively, and reversibly MAO-A in human tissues. [ 11 C]Befloxatone (1.85 MBq) was i.v. injected into rats. Animals were sacrificed, dissected, and samples were assessed for radioactivity. Another group of rats was pretreated with clorgyline (10 mg/kg i.v.). Monkeys were injected with [ 11 C]befloxatone (222–370 MBq), and the chest was imaged with PET for 2 h. Presaturation and displacement experiments were performed using unlabeled befloxatone. For quantification of myocardial binding sites ( B max ), [ 11 C]befloxatone was first injected as a tracer dose (2.7–9.3 nmol) and 20 min later injected as a mixture of labeled and unlabeled befloxatone (labeled, 10.3–41.9 nmol; unlabeled, 407–765 nmol). In rodents, cardiac uptake was high (3.39 ± 0.5% injected dose/g tissue) and strongly inhibited (80%) by clorgyline. In monkeys, administration of unlabeled befloxatone displaced 85% of cardiac radioactivity. B max was found to be 208 ± 13 pmol ml -1 tissue. Inhalation of tobacco smoke decreased B max : 150 ± 6.2 pmol ml -1 , whereas nicotine did not. [ 11 C]Befloxatone allows a good visualization of the heart. Cardiac MAO-A B max was quantified and a clear effect of acute inhalation of tobacco smoke was evidenced. Therefore, a single cigarette can interfere with the cardiac turnover of catecholamines.

2-[18F]fluoro-3-[2(S)-2-azetidinylmethoxy]pyridine ([18F]fluoro-A-85380) is an α4β2 subtype selective nicotinic cholinergic agonist with potential suitability for studying changes in endogenous acetylcholine synaptic concentration. Physostigmine, a potent AChE inhibitor, and galantamine, an allosteric modulator of nAChRs, are widely used for the treatment of Alzheimer's disease. Before studying patients with this neurodegenerative disease, positron emission tomography (PET) studies in monkeys were performed to assess the impact of these two compounds on the radiotracer distribution volumes. Physostigmine was administered i.v. at two dosages: 150 μg/kg/h and 37.5 μg/kg/h for 160 min. Galantamine was administered i.v. at two dosages: 2 or 4 mg over 20 min. For PET data analysis, a model with one tissue (radioactivity of the parent compound in plasma and radioactivity in brain tissue) compartment was chosen because reliable parameter estimates could not be obtained with a more complex model. The higher dose of physostigmine produced a 40%, 23%, and 30% reduction of distribution volumes in the putamen, the temporal, and frontal cortices, respectively. The lower dose of physostigmine produced a reduction of 33%, 31%, and 24% in the same structures, respectively. Galantamine (4 mg or 2 mg) produced no significant change of distribution volumes in the basal ganglia, the temporal and frontal cortex. The effects of physostigmine, a more potent AChE inhibitor than galantamine, could be interpreted as a desensitization of nAChRs, due to a prolonged exposure to high synaptic concentration of acetylcholine or as a competition with acetylcholine. Synapse 56:217–221, 2005. © 2005 Wiley-Liss, Inc.

We prospectively compared the impact of the standard approach, of fluorodeoxyglucose positron emission tomography (FDG PET) and of FDG dual-head coincidence gamma camera imaging (DHC) in preoperative staging of patients with non-small-cell lung cancer (NSCLC). In addition to traditional staging, 42 patients were studied with a PET system and a DHC system. The number of lesions detected on DHC and on PET were compared independently of the proof of a tumoural invasion. Then, for the sub-group of lesions with the proof of a tumoural invasion, the sensitivity of the different imaging modalities was compared. Finally, stagings were compared with final staging established by histopathological findings (n=28), additional imaging modalities (n = 4), clinical and traditional imaging follow-up over at least 4 months. DHC detected 105 of the 145 lesions considered as pathological on PET (73%, P = 0.01), with a concurrence of 89% (NS) in lesions larger than 1.5 cm, and only 17% (P=0.03) in those smaller or equal to 1 cm. Traditional staging detected 87 of the 114 verified tumoural lesions (76%), PET 110/114 (96%, P = 0.01 vs traditional staging), DHC 88/114 (77%, NS vs traditional staging, P = 0.01 vs PET). PET correctly predicted the N stage in 39/42 (93%) patients, DHC in 38/42 (90%), and computed tomography in 32/42 (76%). PET correctly predicted the M stage in 42/42 (100%) patients, DHC in 41/42 (98%), and traditional staging in 38/42 (90%). Identical NM staging was obtained with DHC and PET in 38/42 (90%) patients. Compared to traditional NM staging, PET correctly up-staged 9/42 (21%) patients and down-staged 3/42 (7%), with one additional false N up-staging. DHC correctly up-staged 7/42 (17%) patients and down-staged 3/42 (7%), with one additional false N down-staging. PET correctly reclassified 4/42 (9.5%) patients from resectable to unresectable and incorrectly reclassified one. DHC correctly reclassified 3/42 (7%) patients without false therapeutic reclassification. Although DHC detected fewer lesions than PET, DHC is a possible alternative to PET since the impact on staging was high as compared with traditional staging and was very similar to that of PET.

The aim of this study was to compare the degree of occupancy of central nicotinic acetylcholine receptors (nAChR) in isoflurane anaesthetized baboon brain following inhalation of tobacco smoke (one cigarette containing 0.9 mg nicotine) or i.v. nicotine (0.6 mg i.v.). [18F]Fluoro-A-85380 and positron emission tomography (PET) were used to assess the distribution volumes (DV) of the radiotracer in selected brain areas using a one-compartment model. Eighty minutes after nicotine i.v., DV was reduced by 50 and 66% in the thalamus and putamen, respectively. Six hours after nicotine, a reduction in DV (27% in the thalamus) was still observed. Eighty minutes after inhalation of tobacco smoke, DV was decreased by 52 and 65% in the thalamus and putamen, respectively. Previous PET experiments have demonstrated a short-lasting interaction of [11C]nicotine with nAChRs. Thus, we hypothesized that a metabolite of nicotine with high affinity and long half-live (several hours) could bind at nAChRs. Eighty minutes after a high dose of nornicotine (0.5 mg i.v.), DV was reduced by 53 and 31% in thalamus and putamen, respectively. No significant effect was observed following 0.15 mg nornicotine. Therefore, nornicotine could contribute to the long-lasting occupancy of central nAChRs after smoking.

Anew simple method is proposed to detect, using PET and [11C]raclopride, changes in striatal extracellular dopamine concentration during a rewarded effortful task. This approach aimed to increase the sensitivity in detection of these effects. It requires a single-dynamic PET study and combines the classic kinetic compartmental model with the general linear model of SPM to provide statistical inference on changes in [11C]raclopride time–activity curve due to endogenous dopamine release during two short periods of activation. Kinetic simulations predicted that 100% dopamine increase during two 5-min periods starting at 30 and 60 min after the injection can be detected. Moreover the effects of dopamine release on the [11C]raclopride time-activity-curve are different from those induced by CBF increase. These simulated curves were used to construct the statistical linear model and to test voxel-by-voxel in healthy subjects the hypothesis that dopamine is released in the ventral striatum during periods of unexpected monetary gains, but not during periods of unexpected monetary loss. The experimental results are in line with the expected results although the amplitude of the effects due to dopamine release is moderate. The advantages and the limits of this method as well as the relevance of the results for dopamine involvement in reward processing are discussed.

The results of several recent papers have shown a significant influence of the endogenous neurotransmitters on the exogenous ligand kinetics measured by positron emission tomography. For example, several groups found that the percentage of D2 receptor sites occupied by the endogenous dopamine ranged from 25% to 40% at basal level. An obvious consequence of this significant occupancy is that the ligand-receptor model parameters, usually estimated by a model that does not take into account the endogenous ligand (EL) kinetics, can be significantly biased. In the current work, the authors studied the biases obtained by using the multiinjection approach. The results showed that in the classical ligand-receptor model, the receptor concentration is correctly estimated and that only the apparent affinity is biased by not taking the EL into account. At present, all absolute quantifications of the EL have been obtained through pharmacologic manipulation of the endogenous transmitter concentration, which is often too invasive a method to be used in patients. A theoretical reasoning showed that a noninvasive approach is necessarily based on both the apparent affinity measurement and on a multiregion approach. The correlation between the receptor concentration and the apparent affinity, previously observed with some ligands, verifies these two conditions; thus, the authors suggest that this correlation could be the result of the EL effect. To test this assumption experimentally, the effect of reserpine-induced dopamine depletion on the interactions between the D2 receptor sites and the FLB 457 is studied. With untreated baboons, the apparent FLB 457 affinity was smaller in the receptor-rich regions (striatum) than in the receptor-poor regions. This discrepancy disappeared after dopamine depletion, strongly suggesting that this affinity difference was related to the EL effect. Therefore, the purpose of the current study was to test the ability to quantify the EL based on the observed correlation between the receptor concentration and the apparent affinity. This approach offers a method for estimating the percentage of receptor sites occupied by the EL and, if its affinity is known, the free EL concentration. From the data obtained using FLB 457 with baboons, the authors found that approximately 53% of the D2 receptor sites are occupied by dopamine in the striatum and that the free dopamine concentration is approximately 120 nmol/L at basal level. This approach is transferable to patients, because the experimental data are obtained without pharmacologically induced modification of the EL.

Background. Neuropsychological and imaging studies suggest that frontal dysfunction may occur in apparently normal chronic alcoholic subjects.Methods. To investigate this issue further, we performed neuropsychological and fluorodeoxy-glucose-PET studies in 17 chronic alcoholics without patent neurological and psychiatric complications.Results. Metabolic abnormalities were found in the mediofrontal and in the left dorsolateral prefrontal cortex, but not in the orbitofrontal cortex. Neuropsychological testing revealed significantly reduced verbal fluency and impaired performance on the Stroop test. The mediofrontal hypometabolism correlated with the reduction in verbal fluency and the time necessary to perform the interference condition of the Stroop test. The left dorsolateral prefrontal hypometabolism correlated with the number of errors on the Stroop test.Conclusion. These data indicate that circumscribed frontal dysfunctions may occur in chronic alcoholic subjects before clinically obvious neurological complications, and may account for some of the alcohol-related neuropsychological and behavioural impairments.

Myotonic dystrophy (DM) is caused by an expansion of a CTG triplet repeat sequence in the 3′-noncoding region of a protein kinase gene, yet the mechanism by which the triplet repeat expansion causes disease remains unknown. Impaired glucose penetration into brain tissues has been described in DM patients and is a phenomenon that remains unexplained. The present study shows that altered brain glucose metabolism is triplet repeat dependent. We studied brain glucose metabolism (CMRGlu, μ mol/100 g/min) by the use of positron emission tomography and 18 F-fluoro-2-deoxy-d-glucose in 11 ambulatory non-obese DM patients and in 11 age and sex matched healthy subjects. All subjects underwent a glucose tolerance test with plasma insulin determinations. The expansion of CTG triplet repeats was analyzed in patients with the probe cDNA25 after Eco RI digestion. As compared to controls, in DM patients, the CMRGlu was significantly decreased (26.26±5.05 vs. 33.43±2.18, μ mol/100 g/min, P =0.004), and after oral glucose loading, plasma insulin levels were significantly higher and plasma glucose levels remained unchanged (respectively, F =11.21, P =0.004 and F =0.20, P =0.66). Subsequently, the glucose/insulin ratio was significantly lower in DM patients ( F =6.25, P =0.02). The length of the expansion of the CTG repeats correlated negatively with the CMRGlu ( r 2 =0.63, P =0.003) and positively with the area under the curve for insulin changes over time after oral glucose ( r 2 =0.49, P =0.016). We conclude that, in DM patients, the brain metabolism of glucose is impaired in a repeat dependent manner.

A related set of kinetic studies of the norepinephrine analog [76Br]-meta-bromobenzylguanidine (MBBG) were performed with an isolated working rat heart preparation. A series of constant infusion studies over a wide range of MBBG concentrations allowed estimation of the Michaelis-Menten constants for transport by the neuronal norepinephrine transporter (uptake1) and the extraneuronal uptake system (uptake2). Pharmacological blocking studies with inhibitors of uptake1, uptake2 and vesicular uptake were performed to delineate the relative importance of these norepinephrine handling mechanisms on the kinetics of MBBG in the rat heart. Bolus injection studies were done to assess the ability of compartmental modeling techniques to characterize the kinetics of MBBG. These studies demonstrate that MBBG shares many of the same uptake mechanisms as norepinephrine in the rat heart. PET imaging studies with MBBG would be useful for assessing sympathetic nerve status in the living human heart.

Background Congestive heart failure is associated with decreased stimulated myocardial adenylate cyclase activity, increased G i -binding protein, attenuated parasympathetic tone, and increased modulation of β-adrenergic inotropic left ventricular stimulation by parasympathetic agonists. Despite these abnormalities, changes in the density or affinity of ventricular muscarinic receptors have not been demonstrated in patients. Methods and Results The density and affinity constants of myocardial muscarinic receptors were evaluated noninvasively by means of positron emission tomography with 11 C-MQNB (methylquinuclidinyl benzilate), a specific hydrophilic antagonist, in 20 patients with congestive heart failure due to idiopathic dilated cardiomyopathy (mean left ventricular ejection fraction, 22±9%) and compared with values in 12 normal subjects. The mean receptor concentration was significantly higher in patients than in control subjects ( B′ max , 34.5±8.9 versus 25±7.7 pmol/mL, P P r =.45, P Conclusions Congestive heart failure is associated with an upregulation of myocardial muscarinic receptors. This may be an adaptive mechanism to β-agonist stimulation and should increase the number of potential targets for pharmacological intervention.

The development of functional brain asymmetry during childhood is confirmed by changes in cerebral blood flow measured at rest using dynamic single photon emission computed tomography. Between 1 and 3 years of age, the blood flow shows a right hemispheric predominance, mainly due to the activity in the posterior associative area. Asymmetry shifts to the left after 3 years. The subsequent time course of changes appear to follow the emergence of functions localized initially on the right, but later on the left hemisphere (i.e. visuospatial and later language abilities). These findings support the hypothesis that, in man, the right hemisphere develops its functions earlier than the left.

The influence of the collimator on the contrast recovery of hyperfixation was studied using a dual-headed single photon emission computed tomography (SPECT) system with standard clinical acquisition parameters. Three parallel collimator sets and two fan beam collimator sets were tested with a Jaszczak phantom. The six spheres of the phantom were filled with /sup 99m/Tc, and four background levels were progressively obtained by adding radioactivity to the cylinder of the phantom, providing four hyperfixation levels. The effects of angular sampling and reconstruction filters have been tested. The statistical analysis was performed with analysis of variance (ANOVA). This study demonstrates the advantage of ultra-high resolution fan beam collimators for contrast recovery of hyperfixation with SPECT when using 64 projections over 360/spl deg/, in particular when the contrast is low. The authors also demonstrate that fan beam collimators permit smaller size hyperfixation detection.

Magnetic resonance imaging was used to determine total fat mass of patients with neuromuscular disorders, accounting for intramuscular fat. Nineteen boys aged 9 to 12 (eight with Duchenne muscular dystrophy, three with type II spinal muscular atrophy and eight control subjects) underwent whole-body magnetic resonance imaging examination and anthropometric measurements. Whole-body fat mass was deduced from automated analysis of images normalized by a reference signal. Intramuscular and subcutaneous fat masses were deduced from manual analysis of twelve reference slices. Affected children significantly differed from control subjects for higher total fat mass, mostly related to intramuscular fat mass. Shorter protocols validated from whole-body data were shown to be more accurate than fat mass estimation derived from anthropometric measurements.

Background In myotonic dystrophy (DM), striated muscle is involved in relation to the size of the DNA mutation. Smooth muscle may be similarly impaired at the level of the urinary and digestive apparatus and possibly at the level of small vessels, since microangiopathy has been described in the iris and digital capillaries. Our purpose was to study the function of the myocardial microvasculature in relation to the size of the mutation in DM patients without clinical cardiac involvement and with normal left ventricular dimensions and function and normal large coronary arteries. Methods and Results In 6 control subjects and 10 DM patients, we investigated the coronary blood flow reserve using positron emission tomography with 15 O-labeled water. Global and regional flow reserves were obtained from myocardial regions of interest manually drawn on a static FDG image encompassing, respectively, the whole left ventricle and the anterior, septal, and lateral walls. The DNA mutation size was determined on circulating lymphocytes in each DM patient. Compared with control subjects, DM patients had decreased global (2.39±0.39 versus 4.00±0.67, P =.00003) and regional (anterior, 2.39±0.64 versus 3.87±0.92, P =.002; septal, 2.60±0.48 versus 4.00±0.70, P =.0003; lateral, 2.26±0.58 versus 4.16±1.11, P =.0005) coronary reserves. In DM patients, the coronary reserve correlated strongly and inversely with the DNA mutation size ( r =−.77, P =.009). Conclusions The study demonstrated that global and regional coronary reserves are impaired, in relation to the DNA mutation size, in symptom-free DM patients with normal ventricular dimensions and function and normal large coronary vessels. We suggest that a gene-related blunted coronary reserve resulting from an impairment of vascular smooth muscle is an early component of DM cardiomyopathy.

Agyria-pachygyria or lissencephaly type I, a diffuse cortical malformation, provides infantile spasms (IS) which are refractory and persisting after the first decade, an age at which IS have disappeared in the other causes. In order to study the functional postnatal development of the lissencephalic cortex, we measured regional cerebral blood flow (rCBF) using SPECT (Single photon emission computed tomography) and 133Xe in 14 children with lissencephaly, aged from 4 months to 12 years (mean = 40 months) compared to normal children of the same age range and to children with cryptogenic IS aged from 3 months to 3 years (mean = 13 months). rCBF was calculated in frontal (FR) and parieto-temporo-occipital (PTO) cortex as well as the ratio FR/PTO. FR/PTO was higher in lissencephalic patients than in controls (P < 0.001) due to higher FR rCBF (P < 0.001), particularly in patients aged less than 3 years. FR/PTO was also higher in lissencephalic patients than in patients with cryptogenic IS (P < 0.001) also due to higher FR rCBF (P < 0.001). The values of FR/PTO and FR rCBF remained stable during the first years of life and did not exhibit any age- or topography-related changes as they do in controls or in patients with cryptogenic IS. These results suggest that the normal process of postnatal development in the brain is lacking in agyria-pachygyria. That could play a role in determining the persistance of epileptic spasms, the specific seizure type of this malformation.

Objective The authors investigated the metabolic maturation of the frontal cortex in pre-school autistic children. Method Regional cerebral blood flow (CBF) in five children with primary autism diagnosed according to the DSM-III-R criteria was studied longitudinally. Regional CBF in each of the autistic children was measured with single photon emission computed tomography twice during their development: at the age of 3-4 years and 3 years later. At each stage, the autistic children were compared to an age-matched comparison group of five nonautistic children with normal development. Results A transient frontal hypoperfusion was found in the autistic children at ages 3-4 years; this corresponded to the pattern of perfusion observed in much younger normal children. By the ages of 6-7, the autistic children's frontal perfusion had attained normal values. Conclusions Since CBF patterns in children are related to maturational changes in brain function, these results indicate a delayed frontal maturation in childhood autism. Such a delayed brain maturational process is consistent with the clinical data and cognitive performance of autistic children.

Using repeated measurements of regional cerebral blood flow with positron emission tomography, we investigated the regional cortical activations induced in 10 normal subjects, by two different finger motor tasks, i.e., a repeated flexion-extension of all fingers and a repeated flexion-extension of the middle finger. The all-finger movement only activated the primary sensorimotor cortex (SM) and the supplementary motor area (SMA) contralateral to the movement. However, the activation of the SMA was clearly task related during this motor task, because it was only observed when the movement was triggered by an auditory cue but not when it was self-paced. The middle finger movement was performed during self-paced conditions. It induced a much more complex pattern of activation than the all-finger movement, characterized by a high degree of SM and SMA activation contralateral to the side of the movement, as well as a slight ipsilateral activation of these areas. We suggest that this pattern of cortical activation may reflect the process of individuating finger movement or the early stages of motor learning of this unusual and technically difficult movement. Our data also confirm that the SM activation is closely linked to the intrinsic parameters of the movement; while the SMA may be activated by different aspects of the movement realization and preparation.

Scintigraphic images of myocardial iodine 123-labeled metaiodobenzylguanidine (MIBG) reflect the relative distribution of adrenergic neurodensity and function in the myocardium. In patients with hypertrophic cardiomyopathy or after infarction, MIBG uptake in hypertrophied myocardium and the infarct-related myocardium was found to be decreased in comparison to blood flow distribution, delineated with thallium 201. Most intriguingly, semiquantitative measurements in patients with congestive heart failure demonstrated reduced myocardial MIBG uptake. This reduction correlated directly with indexes of left ventricular function. Decreases in neuronal density, dysfunction of adrenergic neurons, or chronically elevated circulating norepinephrine levels may account for this diminished myocardial uptake, which, as demonstrated in a pilot study of 90 patients with congestive heart failure, was found to be of predictive value for survival.

Mostin vivostudies of striatal D2receptor (SD2R) density with positron emission tomography in schizophrenia have attempted to relate this variable to the diagnosis of the illness. In the present study, a relationship between SD2R and clinical dimensions of this psychosis was searched for in a highly selected group of young negative schizophrenics (8 drug-naïve and 2 drug-free). The SD2R density index measuredin vivousing76Br-bromolisuride and PET correlated negatively (r= 0.80,P< 0.01) with a psychomotor dimension of schizophrenia involving blunted affect and alogia. The mean SD2R index of the patients did not differ from that of age-matched control subjects. Therefore, this behavioural dimension accounts for the variance of the SD2R, suggesting that the striatal dopamine system modulates symptoms such as flattened affect and alogia.

The in vivo determination of the density of dihydropyridine (DHP) binding sites will allow the assessment of pathophysiological changes associated with heart disease. The calcium channel antogonist S 11568: ( + )(amino-7 dioxa-2,5 heptyl)-2(dichloro -2,3 phenyl) -4 methyl-6dihydro -1,4 pyridine has an in vitro profile of high potency and of high selectivity for the L-type Ca2+ channel. S 11568 was labelled by a reaction between 11C-diazomethane and the precursor 6-(7-amino-2,5-dioxa heptyl)-4-(2,3-dichloro phenyl)-5-(ethoxycarbonyl)-2 methyl-1,4 dihydro nicotinic acid. (+)-PN 200 110, a DHP with in vitro high affinity for the L-type Ca2+channel, was also radiolabeled. Positron emission tomographic (PET) studies of both 11C-DHP myocardial uptake were performed in Beagle dogs. 11C-(+)-PN 200 110 had a rapid wash-out from myocardium. In contrary, after a bolus injection, 11C-S 11568 myocardial concentration increased to reach a maximum in 1–2 minutes and then remained in a plateau with a slight downslope while the blood concentration fell rapidly. Myocardial uptake was 2 to 4 fold higher than lung uptake, leading to a good contrast on PET images. Pre-treatment with unlabeled S 11568 (2 μmol/kg or 6 μmol/kg over 15 minutes) reduced myocardial uptake by 60% and 80%, respectively. Specific binding was estimated during a displacement experiment: bolus of unlabeled S 11568 : 1 μmol/kg followed by a continuous infusion of 3 μmol/kg over 2 hours. It was found to represent 80% of the total binding. To assess influence of S11568 on coronary blood flow and therefore on the myocardial tracer delivery, coronary blood flow was measured using 15O-H2O and PET at baseline and following bolus injections of 0.4, 0.8, 2 μmol/kg of S 11568. Only the higher dose increased coronary blood flow. This is the in vivo demonstration of the binding characteristics to myocardial tissue of a DHP ligand. Such properties make S 11568 suitable for PET experiments. The studies of DHP binding sites will provided new insights concerning physiological situations as well as heart disease.

Most metabolic myopathies (like glycogenoses and mitochondrial myopathies) are related to inborn errors of muscle energy metabolism and often present clinically as exercise intolerance (inability to sustain normal exercise). We investigated whether the previously observed absence of normal exercise-induced variation in the T2 of muscle in McArdle's disease (a metabolic myopathy caused by muscle phosphorylase deficiency) was specific for this disease and whether the variations in T2 could be used for screening patients suspected of having metabolic myopathy.Exercise-induced variations in proton MR signal and in intracellular pH were studied in the forearm flexor muscles of nine healthy subjects and 49 patients with exercise intolerance due to muscle pain, suggesting a metabolic myopathy. The relative increase in T2, delta T2/T2, was measured from MR spin-echo images before and after exercise. Phosphocreatine (used as a control of the degree of exercise) and intracellular pH were measured from phosphorus-31 spectra before and during exercise. The progressive 4.5-min handgrip exercise reached maximal exertion capability at the end of exercise and decreased phosphocreatine to less than 50% of its rest value.Variations in T2 and end-exercise pH were correlated. The nine healthy subjects showed a delta T2/T2 ranging from +19% to +44% (but little T1 variation). Ten patients with McArdle's disease showed only slight delta T2/T2 (0-10%). There was no overlap with values for healthy subjects, but there was some with values for other patients. Of the 21 subjects with a delta T2/T2 less than 19%, 19 had a metabolic myopathy. The other two had a congenital neuromuscular disorder (one central core disease, one nemaline myopathy) with type I fiber predominance (type I muscle fibers are characterized by a high oxidative metabolism and a low lactic acid production).The altered increase in T2 was sensitive but not specific for McArdle's disease. However, as variations in T2 reflect variations in pH, they seem to be specific for myopathies in which there is little exercise-induced decrease in pH (some metabolic myopathies and congenital neuromuscular disorders with type I fiber predominance) among patients in whom exercise intolerance is the main symptom. Our results suggest that MR imaging might be useful as a screening test for these diseases.

Summary: Focal cortical disturbances are frequent sequelae in West syndrome (WS) even though it is a generalized epileptic syndrome. Functional neuroimaging was used to determine whether focal perfusion abnormalities exist at WS onset and change during evolution. We studied regional cerebral blood flow (rCBF) at different stages of WS. Mean CBF (mCBF) and rCBF were measured using SPECT (single photon emission computed tomography) and 133Xe in 13 WS patients: at onset (20 cases), just after steroids (17 cases), and after a mean follow-up of 2 years (26 cases). At WS onset, interictal mCBF was increased as the result of foci of hyper- and hypoperfusion, which were, respectively, mainly located in the frontal and posterior cortex. Just after steroid therapy, mCBF decreased without any focal predominance. During follow-up, hypoperfused foci remained unchanged whereas the frontal hyperperfused foci decreased after spasm control. Our results show that focal abnormalities are present at WS onset. Focal hypoactivity could reflect a cortical lesion responsible for WS and focal hyperactivity could play a role in the persistence of generalized epilepsy.

BACKGROUND Positron emission tomography (PET) with 11C-labeled CGP-12177 (CGP) has been shown to have the potential to noninvasively measure beta-adrenergic receptor concentration in dog heart. The present study was undertaken to evaluate the clinical value of this technique. METHODS AND RESULTS Eight normal subjects and 10 patients with heart failure related to an idiopathic cardiomyopathy were studied. Estimation of beta-receptor concentration was based on a graphic method applied on myocardial PET time-concentration curves obtained after an intravenous injection of 11C-CGP followed 30 minutes later by a coinjection of labeled and unlabeled CGP. The clinical tolerance of these injections was good. Left ventricular concentration of beta-receptors was decreased in patients compared with controls (3.12 +/- 0.51 versus 6.60 +/- 1.18 pmol/mL, respectively; p < 0.001). This 53% decrease agrees with previous in vitro data. In eight of the 10 patients, the beta-receptor concentration obtained from PET was compared with the beta-receptor density determined on left ventricular endomyocardial biopsy samples by in vitro binding technique using 3H-CGP-12177. Results obtained with both techniques were correlated (r = 0.79, p = 0.019). Moreover, decreased beta-receptor concentration correlated with the beta-contractile responsiveness to intracoronary dobutamine infusion (r = 0.83, p = 0.003), indicating a direct link between changes in the receptor number and its biological function. CONCLUSIONS PET appears to be a safe and reliable method of assessing in vivo changes in the number of left ventricular beta-adrenergic receptor sites of patients with idiopathic cardiomyopathy.

We used MR imaging to locate and monitor in vivo the pathological events taking place 2 to 4 weeks after unilateral striatal injections of ibotenic acid (IA) in the Papio papio baboon. As early as 2 weeks after IA injections, excitotoxic lesions in the caudate and the putamen were directly visualized on T1-weighted images as small areas of low signal intensity. On T2-weighted images, the lesion sites were visualized as areas of highintensity signal, spreading over larger areas than the corresponding regions in T1-weighted images. These alterations of T2-values in the lesioned striatum persisted 4 weeks after surgery. However, as the striatal degeneration progressed from 2 to 4 weeks after lesion, the size of the areas of high signal intensity on T2-weighted images decreased, whereas the same regions appeared essentially unmodified on T1-weighted images. A marked enlargement of the ipsilateral lateral ventricle (a characteristic of excitotoxic striatal lesions) could be detected 4 weeks after surgery, on both axial T1- and T2-weighted images. Comparisons of MR images with postmortem anatomical data indicated that areas of increased T1 values corresponded to regions of severe neuronal depletion (a direct result of the excitotoxic lesion), whereas areas of increased T2 values corresponded to regions of increased content in astrocytes and ferritin and probably in the early period following lesion (2 weeks) to a superimposed edema.

The mathematical models can be very useful and even essential in some areas of the medicine. We describe the example of the use of the Positron Emission Tomography in order to quantify the concentration of receptors in the human heart. This quantification is only possible by using a mathematical model including the receptor concentration as parameter. Obviously in such a case, the justification of the identified model parameters has a great importance since an error can lead to erroneous diagnosis and to a maladjusted treatment. Since some years, it has been pointed out that the complete justification of complex models imposes to take into account and to develop new technical problems such as the estimation of the parameter uncertainties, the identifiability study and the experimental design. While studying the parameter estimation of the receptor-ligand model from Positron Emission Tomography data, each of the three possible conclusions to the identifiability problem (i.e. unidentifiability, multiple solutions or unique solution) were reached depending on the experimental protocol used. However, the possible multiplicity of the solutions has been found mainly by chance and we conclude that the usual approach allowing to study the model identifiability (both theoretical global identifiability and real local identifiability using the covariance matrix), is not sufficient to prove the uniqueness and thus the validity of the parameters.

In vivo glycogen metabolism was investigated at 2 Tesla by 13C NMR in the baboon liver. Two concentric surface coils were used for 13C observation and proton decoupling, respectively. Spectra were acquired in 2 to 10 minutes with a 60 ms repetition time. After 3 hours of glucose infusion in the 48 hr fasted animal, 3 g of 99%-enriched [1-13C]glucose were injected. The distribution of the label on C-1 and also C-2, C-5 and C-6 of glycogen indicated 65% and 35% contributions of the direct and indirect pathways to glycogen synthesis from glucose, respectively. The results show that hepatic metabolic pathways and rates can be followed in vivo in large animals by 13C NMR at 2 Tesla.

Using quantitative PET, the authors studied the binding of [11C]PK11195, a marker of activated microglia, in the thalamus of patients with chronic middle cerebral artery infarcts. All patients showed increased [11C]PK11195 binding in the ipsilateral thalamus, indicating the activation of microglia in degenerating projection areas remote from the primary lesion. A persistent increase in [11C]PK11195 binding suggests active, long-term thalamic microstructural changes after corticothalamic connection damage.

International audience; The superior temporal sulcus (STS) is specifically involved in processing the human voice. Profound acquired deafness by post-meningitis ossified cochlea and by bilateral vestibular schwannoma in neurofibromatosis type 2 patients are two indications for auditory brainstem implantation (ABI). In order to objectively measure the cortical voice processing of a group of ABI patients, we studied the activation of the human temporal voice areas (TVA) by PET H(2)(15)O, performed in a group of implanted deaf adults (n=7) with more than two years of auditory brainstem implant experience, with an intelligibility score average of 17%+/-17 [mean+/-SD]. Relative cerebral blood flow (rCBF) was measured in the three following conditions: during silence, while passive listening to human voice, and to non-voice stimuli. Compared to silence, the activations induced by voice and non-voice stimuli were bilaterally located in the superior temporal regions. However, compared to non-voice stimuli, the voice stimuli did not induce specific supplementary activation of the TVA along the STS. The comparison of ABI group with a normal-hearing controls group (n=7) showed that TVA activations were significantly enhanced among controls group. ABI allowed the transmission of sound stimuli to temporal brain regions but lacked transmitting the specific cues of the human voice to the TVA. Moreover, among groups, during silent condition, brain visual regions showed higher rCBF in ABI group, although temporal brain regions had higher rCBF in the controls group. ABI patients had consequently developed enhanced visual strategies to keep interacting with their environment.

Glycogen storage disease was suspected in a 10-month-old boy. Initial technical problems did not permit the determination of the precise enzyme, deficiency, and type VI glycogen storage disease was only diagnosed at the age of 2 years. In the mean time, natural abundance 13C nuclear magnetic resonance evaluation of muscular and hepatic glycogen content indicated normal muscular glycogen and increased hepatic glycogen in our patient, a finding which strongly argued for the diagnosis of type VI glycogen storage disease. Even though the use of nuclear magnetic resonance might seem, in this situation, a somewhat circuitous means of reaching the diagnosis, it appears that nuclear magnetic resonance could provide a useful tool for a non-invasive diagnosis of glycogen storage diseases.