Effects of diffuse fatty infiltration of the liver on portal vein flow hemodynamics

PURPOSE: To investigate the effects of various degrees of diffuse fatty infiltration of the liver on portal vein blood flow with Doppler sonography. METHODS: One hundred forty subjects were examined with color and spectral Doppler sonography. The subjects were divided into 4 groups of 35 subjects each according to the degree (normal, grade 1, grade 2 and grade 3) of hepatic fatty infiltration assessed on gray-scale images. The portal vein pulsatility index (VPI) and time-averaged mean flow velocity (MFV) were calculated for each subject. VPI was calculated as (peak maximum velocity - peak minimum velocity) / peak maximum velocity. RESULTS: VPI and MFV values were, respectively, 0.32 +/- 0.06 and 16.8 +/- 2.6 cm/second in the normal group, 0.27 +/- 0.07 and 14.2 +/- 2.2 cm/second in the group with grade 1 fatty infiltration, 0.22 +/- 0.06 and 12.2 +/- 1.8 cm/second in the group with grade 2 fatty infiltration, and 0.18 +/- 0.04 and 10.8 +/- 1.5 cm/second in the group with grade 3 fatty infiltration. There was a negative inverse correlation between the grade of fatty infiltration and both VPI (f = 55.3, p < 0.001) and MFV (f = 43.9, p < 0.001). CONCLUSION: The pulsatility index and mean velocity of the portal vein blood flow decrease as the severity of fatty infiltration increases.     

Dexmedetomidine attenuates the hemodynamic and neuroendocrinal responses to skull-pin head-holder application during craniotomy

We tested dexmedetomidine, an alpha2 agonist, for its ability to decrease heart rate, arterial blood pressure, and neuroendocrinal responses to skull-pin head-holder application during craniotomy. In a randomized, double-blinded, placebo-controlled study, 40 patients undergoing craniotomy with attachment of a pin head-holder were randomly assigned to one of 2 equal groups. The placebo group received saline, whereas the treatment group (DEX group) received a single bolus dose of dexmedetomidine (1 microg/kg) intravenously over 10 minutes before induction of anesthesia. Arterial blood pressure, heart rate, and sequential concentrations of circulating cortisol, prolactin, insulin, and blood glucose were measured. Relative to baseline and the other group, arterial blood pressure and heart rate decreased significantly after the administration of dexmedetomidine through skull pinning (P<0.05). In the placebo group, patients' heart rate and arterial blood pressure measures increased at 1 and 5 minutes after skull-pin insertion, compared with baseline and the DEX group (P<0.05). In both groups, plasma cortisol, prolactin, and blood glucose increased significantly relative to baseline after skull-pin insertion. However, the values were significantly higher in the placebo group compared with the DEX group (P<0.05). Although insulin levels were not significantly altered in the DEX group, the plasma concentrations of insulin decreased significantly after pin insertion in the placebo group. Our results suggested that, a single bolus dose of dexmedetomidine before induction of anesthesia attenuated the hemodynamic and neuroendocrinal responses to skull-pin insertion in patients undergoing craniotomy.     

Mismatch negativity at acute and post-acute phases of first-episode schizophrenia

The objective of this study was to evaluate the mismatch negativity (MMN) in patients with first-episode schizophrenia at acute and post-acute phases in order to determine the contribution of trait and/or state features to MMN disturbances in schizophrenia. Subject groups comprised 30 patients with first-episode schizophrenia at the acute phase and 34 healthy controls. Ten patients were neuroleptic-naive during testing at the acute phase. Twenty-one patients were retested at the post-acute phase when their symptoms improved. All patients were taking antipsychotic medication at the post-acute retest session. MMN amplitude of the patients at acute phase did not differ from controls. However, MMN amplitude at post-acute phase was reduced compared to both controls and acute phase. Similar results were obtained when the analyses were confined to neuroleptic-naive patients. The sensory memory functions indexed by MMN seem to be unaffected at the onset of schizophrenia but deteriorated during the post-acute illness phase. MMN reduction at the post-acute phase might be emerged from antipsychotic medication.     

The genotoxic effects in lymphocyte cultures of children treated with radiosynovectomy by using yttrium-90 citrate colloid

The aim of this study was to investigate the genotoxic effect on the peripheral blood lymphocytes potentially induced by yttrium-90 citrate colloid (Y-90) in children who were undergoing radiosynovectomy for hemophilic synovitis, using chromosomal aberration analysis (CA) and the micronuclei (MN) assay for detecting chromosomal aberrations, as well as the sister chromatid exchanges (SCE) technique for assessed DNA damage. MATERIALS AND METHODS: Cytogenetic analyses were undertaken in 18 boys (mean age, 14.5 +/- 2.1 years) with hemophilic synovitis who underwent radiosynovectomy with Y-90. CA, MN, and SCE were evaluated just prior to, then at 2 and 90 days following radiosynovectomy from the peripheral lymphocytes of the children. An activity of 185 MBq of Y-90 was injected into the 18 knee joints under aseptic conditions. To check the possibility of leakage from the joint and its migration within the body, the patients underwent scanning under a dual-headed gamma camera at the hours 2 and 48 following the procedure. RESULTS: The procedure was well tolerated in all the children, and there was no extra-articular activity owing to extra-articular leakage of radioactive material in whole-body imaging. The mean frequency of CA in lymphocytes determined prior to the onset of therapy (0.31 +/- 0.48/900 cells) was not significantly increased, in comparison to the control values obtained 2 (0.30 +/- 0.48/900 cells) and 90 days (0.15 +/- 0.37/900 cells) after radiosynovectomy (p = 1.0 and 0.625, respectively). We observed that MN frequency was mildly increased in lymphocytes 2 days after therapy (8.30 +/- 1.89 MN/1000 binucleated cells vs. 9.23 +/- 1.79 MN/1000 binucleated cells; p = 0.013). But there was no significant difference between the baseline and the day 90 control levels of MN (p = 0.196). In the analysis of SCE frequency, there were no significant differences between the baseline (8.11 +/- 0.77) and the control analysis performed 2 and 90 days following radiosynovectomy (8.18 +/- 0.77 and 8.07 +/- 0.74; p = 0.710 and 0.662, respectively). CONCLUSIONS: The results of this study indicated that high radiation doses are not obtained by peripheral lymphocytes of children who undergo Y-90 radiosynovectomy and, therefore, they contradict a high cancer risk.     

Hush sign: a new clinical sign in temporal lobe epilepsy

Neurologists have been analyzing the clinical behaviors that occur during seizures for many years. Several ictal behaviors have been defined in temporal lobe epilepsy (TLE). Ictal behaviors are especially important in the evaluation of epilepsy surgery candidates. We propose a new lateralizing sign in TLE originating from the nondominant hemisphere-the "hush" sign. Our patients were 30- and 21-year old women (Cases 1 and 2, respectively). Their epileptogenic foci were localized to the right mesial temporal region after noninvasive presurgical investigations. Case 1 had no cranial MRI abnormality, whereas cranial MRI revealed right hippocampal atrophy in Case 2. These women repeatedly moved their right index fingers to their mouth while puckering their lips during complex partial seizures. We have named this ictal behavior the "hush" sign. Anterior temporal lobectomy with amygdalohippocampectomy was performed in both patients, and pathological examinations revealed hippocampal sclerosis. The "hush" sign no longer occurred after seizures were controlled. They were seizure free as of 30 and 31 months of follow-up, respectively. We believe that the "hush" sign may be supportive of a diagnosis of TLE originating from the nondominant hemisphere. This sign may occur as a result of ictal activation of a specific brain region in this hemisphere.     

Suppurative cervical adenopathy and pharyngeal mass due to tularemia unresponsive to medical treatment

Tularemia is a zoonotic disease caused by Francisella tularensis. Tularemia presents with various clinical forms, such as ulceroglandular, glandular, oculoglandular, oropharyngeal, pneumonic, and typhoidal tularemia forms. As an intracellular pathogen, F. tularensis causes granulomatous and suppurative lesions especially in the affected regional lymph nodes and various organs. Tularemia is seen most commonly in the Black Sea and Marmara regions of Turkey. Herein, we describe a girl with tularemia who presented with right cervical lymphadenopathy and left nasopharyngeal mass. To the best of our knowledge, this is the first reported case of tularemia with deep neck infection and also the first tularemia case from Corum, a city in the central Anatolian region of Turkey.     

TGF-beta1 gene polymorphisms and peritoneal equilibration test results in CAPD patients

Transforming growth factor-beta1 (TGF-beta1) stimulates the expression of collagen mRNA in cultured human peritoneal mesangial cells, which may predispose them to developing peritoneal fibrosis. Polymorphisms in the signal sequence genetically may be responsible for increased TGF-beta1 production (i.e., a substitution at amino acid position 10 and 25, +869 Leu(10)-Pro and +915 Arg(25)-Pro, respectively). The aim of this study was to find out whether there is any relation between peritoneal equilibration test (PET) results and TGF-beta1 gene polymorphism. Thirty-two CAPD patients and 72 healthy subjects were included into the study. Each CAPD patient had undergone two PET with a two-year interval. The patients were classified according to the results of a baseline PET as high (high-high average) and low (low-low average) transporters. In high transporters group (n = 20), the genotype frequencies were found as 45% Leu/Leu, 55% Leu/Pro for codon 10; and 85% Arg/Arg, 15% Arg/Pro for codon 25. In low transporters group (n = 12), the genotype frequencies were detected as 66.7% Leu/Leu and 33.3% Leu/Pro for codon 10; and 83.3% Arg/Arg, 16.7% Arg/Pro for codon 25. The distribution of the TGF-beta1 genotypes in our control population was compatible with a Hardy-Weinberg equilibrium. We found no relation between TGF-beta1 genotypes and peritoneal transport group (chi(2) test, p > 0.5). There was no relation between TGF-beta1 genotype and longitudinal change in peritoneal transport. This study is the first study analyzing the possible link between TGF-betal gene polymorphisms and the characteristics of peritoneal transport and longitudinal change of peritoneal transport characteristics in CAPD patients. Further work is needed to clarify the functional importance of these two polymorphisms in TGF-beta1 production and in the development of peritoneal fibrosis.     

Data mining of NCI's anticancer screening database reveals mitochondrial complex I inhibitors cytotoxic to leukemia cell lines

Mitochondria are principal mediators of apoptosis and thus can be considered molecular targets for new chemotherapeutic agents in the treatment of cancer. Inhibitors of mitochondrial complex I of the electron transport chain have been shown to induce apoptosis and exhibit antitumor activity. In an effort to find novel complex I inhibitors which exhibited anticancer activity in the NCI's tumor cell line screen, we examined organized tumor cytotoxicity screening data available as SOM (self-organized maps) (http://www.spheroid.ncifcrf.gov) at the developmental therapeutics program (DTP) of the National Cancer Institute (NCI). Our analysis focused on an SOM cluster comprised of compounds which included a number of known mitochondrial complex I (NADH:CoQ oxidoreductase) inhibitors. From these clusters 10 compounds whose mechanism of action was unknown were tested for inhibition of complex I activity in bovine heart sub-mitochondrial particles (SMP) resulting in the discovery that 5 of the 10 compounds demonstrated significant inhibition with IC50's in the nM range for three of the five. Examination of screening profiles of the five inhibitors toward the NCI's tumor cell lines revealed that they were cytotoxic to the leukemia subpanel (particularly K562 cells). Oxygen consumption experiments with permeabilized K562 cells revealed that the five most active compounds inhibited complex I activity in these cells in the same rank order and similar potency as determined with bovine heart SMP. Our findings thus fortify the appeal of mitochondrial complex I as a possible anticancer molecular target and provide a data mining strategy for selecting candidate inhibitors for further testing.