Characterization of an asymmetric add-on collimator used with a hand-held gamma probe for radioguided surgery and sentinel node detection: a demonstration of an alternative collimation method.

OBJECTIVE: The aim of the study was to investigate a new principle for collimation of gamma probes for radioguided surgery and sentinel node detection: the use of asymmetric lateral shielding. The intension was to maintain the sensitivity in the lateral and forward directions on the unshielded side while at the same time to shield the probe against high activity sources that could mask the signal from the object to be detected. METHODS: The device was constructed to shield only against photons that come from a region in space that spans approximately 180° sideways and forwards relative to the detector. The intension of the study was to demonstrate the principle rather than to document its use in the clinic. Sensitivity profiles were derived from measurements obtained while stepwise moving the probe relatively to a point source of known activity surrounded by water. The measurements were taken in the symmetry plane of the collimator where the shielding effects were expected to be most pronounced. RESULTS: The asymmetric collimator led to nearly unchanged sensitivity in the lateral and forward directions. At the same time, the field of view was effectively shrunk on the shielded side. Contributions from sources lateral and close to the shield were reduced by factors up to 45. CONCLUSION: By rotating the probe around its longitudinal axis, an asymmetric add-on shield collimator could potentially make it easier to detect a sentinel node when this is located close to a neighbouring high activity region like the urinary bladder or the injection site.

4-D blood flow in the human right ventricle.

Right ventricular (RV) function is a powerful prognostic indicator in many forms of heart disease, but its assessment remains challenging and inexact. RV dysfunction may alter the normal patterns of RV blood flow, but those patterns have been incompletely characterized. We hypothesized that, based on anatomic differences, the proportions and energetics of RV flow components would differ from those identified in the left ventricle (LV) and that the portion of the RV inflow passing directly to outflow (Direct Flow) would be prepared for effective systolic ejection as a result of preserved kinetic energy (KE) compared with other RV flow components. Three-dimensional, time-resolved phase-contrast velocity, and balanced steady-state free-precession morphological data were acquired in 10 healthy subjects using MRI. A previously validated method was used to separate the RV and LV end-diastolic volumes into four flow components and measure their volume and KE over the cardiac cycle. The RV Direct Flow: 1) followed a smoothly curving route that did not extend into the apical region of the ventricle; 2) had a larger volume and possessed a larger presystolic KE (0.4 ± 0.3 mJ) than the other flow components (P < 0.001 and P < 0.01, respectively); and 3) represented a larger part of the end-diastolic blood volume compared with the LV Direct Flow (P < 0.01). These findings suggest that diastolic flow patterns distinct to the normal RV create favorable conditions for ensuing systolic ejection of the Direct Flow component. These flow-specific aspects of RV diastolic-systolic coupling provide novel perspectives on RV physiology and may add to the understanding of RV pathophysiology.

Fatty acid metabolism in the liver, measured by positron emission tomography, is increased in obese individuals.

BACKGROUND & AIMS: Hepatic lipotoxicity results from and contributes to obesity-related disorders. It is a challenge to study human metabolism of fatty acids (FAs) in the liver. We combined (11)C-palmitate imaging by positron emission tomography (PET) with compartmental modeling to determine rates of hepatic FA uptake, oxidation, and storage, as well as triglyceride release in pigs and human beings. METHODS: Anesthetized pigs underwent (11)C-palmitate PET imaging during fasting (n = 3) or euglycemic hyperinsulinemia (n = 3). Metabolic products of FAs were measured in arterial, portal, and hepatic venous blood. The imaging methodology then was tested in 15 human subjects (8 obese subjects); plasma (11)C-palmitate kinetic analyses were used to quantify systemic and visceral lipolysis. RESULTS: In pigs, PET-derived and corresponding measured FA fluxes (FA uptake, esterification, and triglyceride FA release) did not differ and were correlated with each other. In human beings, obese subjects had increased hepatic FA oxidation compared with controls (mean +/- standard error of the mean, 0.16 +/- 0.01 vs 0.08 +/- 0.01 micromol/min/mL; P = .0007); FA uptake and esterification rates did not differ between obese subjects and controls. Liver FA oxidation correlated with plasma insulin levels (r = 0.61, P = .016), adipose tissue (r = 0.58, P = .024), and systemic insulin resistance (r = 0.62, P = .015). Hepatic FA esterification correlated with the systemic release of FA into plasma (r = 0.71, P = .003). CONCLUSIONS: PET imaging can be used to measure FA metabolism in the liver. By using this technology, we found that obese individuals have increased hepatic oxidation of FA, in the context of adipose tissue insulin resistance, and increased FA flux from visceral fat. FA flux from visceral fat is proportional with the mass of the corresponding depot.

Myocardial perfusion quantitation with 15O-labelled water PET: high reproducibility of the new cardiac analysis software (Carimas).

PURPOSE: Carimas (Cardiac Image Analysis System) is a new software package developed at the Turku PET Centre for the quantitation of PET studies of the heart with a broad range of tracers. The goal of this study was to assess the reproducibility of results the package provides for myocardial perfusion (MP) quantitation using (15)O-labelled water. METHODS: Four observers with various levels of experience in nuclear medicine independently analysed 20 MP studies (10 rest flow: "rest", 10 adenosine-induced hyperaemia: "stress"). Each study was analysed twice. The linear mixed model for repeated measures was fitted to the data to calculate intraclass correlation coefficients (ICC), differences between the repeats (the intraobserver differences) and differences between the observers (the interobserver differences). Also, Pearson correlation coefficients (r) were calculated and Bland-Altman plots were drawn. The reproducibility of MP was assessed on global, regional and segmental levels. Thereafter, this analysis was applied in 48 consecutive clinical patients with suspected coronary heart disease (CHD). RESULTS: For the experienced observer the Pearson r for all segments was 0.974 at rest and 0.978 at stress (p < 0.0001), and the repeatability coefficients were 0.145 ml/g per min (15.5% of the average) and 0.389 ml/g per min (14.9%), correspondingly. The ICC reflected very good overall reproducibility. The intraobserver and interobserver differences were small, and the difference between the most and the least experienced observers at stress was 8.5% for the global MP. The clinical accuracy of the perfusion in the detection of CHD was excellent (positive predictive value 91% and negative predictive value 88%) against invasive angiography. CONCLUSION: The results demonstrate high reproducibility of myocardial perfusion quantitation with (15)O-labelled water PET using Carimas. The results support the feasibility of robust analysis and good clinical accuracy.

The lowering of hepatic fatty acid uptake improves liver function and insulin sensitivity without affecting hepatic fat content in humans.

Lipolysis may regulate liver free fatty acid (FFA) uptake and triglyceride accumulation; both are potential causes of insulin resistance and liver damage. We evaluated whether 1) systemic FFA release is the major determinant of liver FFA uptake in fasting humans in vivo and 2) the beneficial metabolic effects of FFA lowering can be explained by a reduction in liver triglyceride content. Sixteen healthy subjects were subdivided in two groups of similar characteristics to undergo positron emission tomography with [(11)C]acetate and [(11)C]palmitate to quantify liver FFA metabolism (n = 8), or magnetic resonance spectroscopy (MRS) to measure hepatic fat content (n = 8), before and after the acute lowering of circulating FFAs by using the antilipolytic agent acipimox. MRS was again repeated after a 1-wk treatment period. Acipimox suppressed FFA levels while stimulating hepatic fractional extraction of FFAs (P < 0.05). As a result, fasting liver FFA uptake was decreased by 79% (P = 0.0002) in tight association with lipolysis (r = 0.996, P < 0.0001). The 1-wk treatment induced a significant improvement in systemic (+30%) and liver (+70%) insulin sensitivity (P < 0.05) and decreased circulating triglycerides (-20%, P = 0.06) and liver enzymes (ALT -20%, P = 0.03). No change in liver fat content was observed after either acute or sustained FFA suppression. We conclude that acute and sustained inhibitions of lipolysis and liver FFA uptake fail to deplete liver fat in healthy human subjects. Liver FFA uptake was decreased in proportion to FFA delivery. As a consequence, liver and systemic insulin sensitivity were improved, together with liver function, independently of changes in hepatic triglyceride accumulation.

Biodistribution of the fatty acid analogue 18F-FTHA: plasma and tissue partitioning between lipid pools during fasting and hyperinsulinemia.

UNLABELLED: Alterations of free fatty acid (FA) metabolism in several organs are implicated in the pathogenesis of chronic disorders. The aim of this study was to investigate the biodistribution and partitioning of the FA analog, 14(R,S)-(18)F-fluoro-6-thia-heptadecanoic acid ((18)F-FTHA), across different lipid pools in plasma and in metabolically important organs and its response to insulin. METHODS: Eight anesthetized pigs were studied during fasting or euglycemic insulin stimulation. Plasma samples from the carotid artery, hepatic vein, and portal vein were collected at 10 and 40 min after (18)F-FTHA injection via indwelling catheters. The animals were then sacrificed and tissue biopsies rapidly obtained from the heart, brain, liver, subcutaneous and visceral fat, pancreas, intestine, and skeletal muscle. Radioactivity was assessed in the FA, phospholipid, and triglyceride or glycerol ester pools. RESULTS: The tissue-to-plasma intact (18)F-FTHA ratio was high in all tissues, with the highest values being in the heart and liver; (18)F-FTHA accumulated in the brain to a significant extent. Hyperinsulinemia was associated with higher plasma (18)F-FTHA clearance (P < 0.05) and lower labeled triglyceride appearance (P

[11C]palmitate kinetics across the splanchnic bed in arterial, portal and hepatic venous plasma during fasting and euglycemic hyperinsulinemia.

PURPOSE: The liver is fundamental in regulating lipid metabolism, and it supplies fatty acids (FA) to the rest of the body in the form of triglycerides (TG); the time-related relevance of this process is incompletely defined. The aim of the study was to investigate the appearance of labeled TG in the hepatic vascular bed after [11C]palmitate injection during fasting and insulin stimulation. METHODS: Plasma [11C]palmitate kinetics in arterial, portal and hepatic venous lipid fractions was studied in eight anesthetized pigs during fasting or euglycemic hyperinsulinemia. Plasma analyses were conducted at 10 and 40 min after tracer injection. Corresponding liver positron emission tomography (PET) images were acquired for the semiquantitative determination of hepatic FA uptake. RESULTS: At 10 min, plasma levels of unchanged [11C]palmitate were lower in hyperinsulinemic than in fasting experiments in the artery and in the portal vein (P< or=.03), suggesting faster clearance. Levels of unmetabolized [11C]palmitate did not differ between portal and arterial plasma. In the fasting state, a tendency to a positive arterial and portal vs. hepatic venous gradient was observed, indicative of net hepatic [11C]palmitate extraction. Labeled TG were already detectable at 10 min (fasting vs. hyperinsulinemia, ns) and were higher in fasting than in hyperinsulinemic animals at 40 min (92+/-1% and 82+/-6% of arterial plasma radioactivity). Higher proportions of labeled TG were recovered in portal vein plasma, suggesting release by the gut. The portal and the arterial-portal vs. hepatic venous TG gradient tended to be positive. Accordingly, hepatic FA uptake was higher, but declined more rapidly during fasting than during hyperinsulinemia. CONCLUSION: The study indicates that the redistribution of [11C]palmitate between different lipid pools occurs within the short time interval of most PET experiments and is strongly influenced by insulin. Labeled TG constitute an additional [11C]palmitate source in the modeling of PET data.

Successful use of Molecular Absorbent Regenerating System (MARS) dialysis for the treatment of fulminant hepatic failure in children accidentally poisoned by toxic mushroom ingestion.

BACKGROUND: Acute liver failure (ALF) as a result of mushroom poisoning is associated with a high mortality (particularly in children), despite optimal medical therapy (OMT), including charcoal haemoperfusion and haemodiafiltration. MARS is a new, cell-free, extracorporeal liver assistance method utilizing an albumin dialysate for the removal of albumin-bound toxins. METHODS: We describe the first series in the literature (also first MARS treatments in Romania) with ALF because of mushroom poisoning in children (M/F=2/4, age=7-16 years). Liver function was evaluated pre-MARS and 15-min post-MARS, 24 h following each treatment and 30 days post-MARS. FINDINGS: All patients had severe hepatic dysfunction: hepatic encephalopathy (HE; four grade II, one grade III, one grade IV), ALT=4082 (3400-5600) IU/L, bilirubin=6.3 (2-10) mg/dL, prothrombin time (PT)=52.5 (23-141) s. MARS was uneventful and well-tolerated. Two 6-h sessions per patient were performed with a similar immediate impact on liver tests: mean drop in ALT of -33 and -35%, respectively, and in bilirubin of -39 and -36%, respectively. ALT levels 24 h following MARS-1, remained unchanged but continued to drop by a further -28% following MARS-2. By contrast, all patients had a significant rebound in bilirubin (+39%) 24 h following MARS-1; however, following MARS-2 a rebound was seen only in two cases (+220%). PT improved by 37% after MARS-1 and normalized in four patients after MARS-2. OUTCOME: Four patients survived and completely recovered the hepatic function. Negative prognostic markers: lack of complete correction of PT, continuous rebound and increase in bilirubin, and lack of improvement in HE post-MARS-1. Survival in six well-matched cases, treated by OMT=0/6 (P<0.05). CONCLUSIONS: MARS is a safe and highly effective depurative therapy in children with ALF. Survival is predicted only by the impact/results of the initial MARS sessions and not by any of the baseline parameters.

Phosphorylation of the cohesin subunit Scc1 by Polo/Cdc5 kinase regulates sister chromatid separation in yeast.

At the onset of anaphase, a caspase-related protease (separase) destroys the link between sister chromatids by cleaving the cohesin subunit Scc1. During most of the cell cycle, separase is kept inactive by binding to an inhibitory protein called securin. Separase activation requires proteolysis of securin, which is mediated by an ubiquitin protein ligase called the anaphase-promoting complex. Cells regulate anaphase entry by delaying securin ubiquitination until all chromosomes have attached to the mitotic spindle. Though no longer regulated by this mitotic surveillance mechanism, sister separation remains tightly cell cycle regulated in yeast mutants lacking securin. We show here that the Polo/Cdc5 kinase phosphorylates serine residues adjacent to Scc1 cleavage sites and strongly enhances their cleavage. Phosphorylation of separase recognition sites may be highly conserved and regulates sister chromatid separation independently of securin.

Sister chromatid separation and chromosome re-duplication are regulated by different mechanisms in response to spindle damage.

In yeast, anaphase entry depends on Pds1 proteolysis, while chromosome re-duplication in the subsequent S-phase involves degradation of mitotic cyclins such as Clb2. Sequential proteolysis of Pds1 and mitotic cyclins is mediated by the anaphase-promoting complex (APC). Lagging chromosomes or spindle damage are detected by surveillance mechanisms (checkpoints) which block anaphase onset, cytokinesis and DNA re-replication. Until now, the MAD and BUB genes implicated in this regulation were thought to function in a single pathway that blocks APC activity. We show that spindle damage blocks sister chromatid separation solely by inhibiting APCCdc20-dependent Pds1 proteolysis and that this process requires Mad2. Blocking APCCdh1-mediated Clb2 proteolysis and chromosome re-duplication does not require Mad2 but a different protein, Bub2. Our data imply that Mad1, Mad2, Mad3 and Bub1 regulate APCCdc20, whereas Bub2 regulates APCCdh1.

Biochemical and cytogenetical study of the mycoplasmal antigen and of the cyclophosphamide action in mammalians, in vivo. The action of some immunomodulatory antioxidants.

It was proved spectrophotometrically that Mycoplasma agalactiae antigen inoculated in vivo in sheep modifies the corresponding erythrocyte lysates reactivity toward methylene blue and neutral red and induces several types of chromosomal rearrangements. The treatment in vivo of sheep with an original preparation obtained from the Phaseolus vulgaris pods restores the erythrocyte lysates reactivity toward the two redox dyes and reduces the chromosomal abnormalities frequency induced by the mycoplasmal antigen. It was also demonstrated by optical and electronical microscopy that the Smise line mouse meiocytes exhibit chromosomal abnormalities induced by the cyclophosphamide treatment in vivo. In the case of concomitant treatment with the cyclophosphamide and C vitamin the same frequency of abnormalities was recorded as in the simple treatment with the drug.

Mathematical model for energy and protein balance simulation in broilers.

The authors used the empirical equations of mathematical modelling for the energy and protein balance simulation, with the view of calculating the body weight gain in broilers fed various diets. The results found by using the model were compared with the experimental data obtained by several authors. A standard deviation of +/- 1.20% and a mean error of +/- 0.28% and a mean error of +/- 0.28% which proved that the model average was a sufficient estimate of the experimental average were found. Furthermore, using the regression method, a significant correlation of variables was evidentiated.

[Circulating Salmonella serotypes isolated in the territory served by the Sanitary-antiepidemic Center of Covasna County]. / Consideratii asupra serotipurilor circulante de Salmonella izolate în teritoriul deservit de Centrul sanitaro-antiepidemic judetean Covasna

During the 1967-1973 period, the authors followed up the circulation of various Salmonella serotypes and found new serotypes linked to the particular epidemiologic aspects recorded within a small district, without highly populated centers. The results showed a steady increase in the strains isolated during the last 3--4 years. Among the total 2103 strains isolated, S. panama, S. typhimurium and S. bredeney were predominant. The number of serotypes isolated varied between 10 (1968--1969) and 16 (1972). Salmonella strains were incriminated in the etiology of a fairly high proportion of the acute digestive disorders.