Assessment of global and regional left ventricular function and volumes with 64-slice MSCT: a comparison with 2D echocardiography.

BACKGROUND: In patients with coronary artery disease (CAD), LV function and volumes are important parameters for long-term prognosis. Multislice computed tomography (MSCT) allows noninvasive assessment of the coronary arteries, but the accuracy of 64-slice MSCT for the assessment of left ventricular (LV) volumes and function is unknown. METHODS AND RESULTS: A head-to-head comparison between 64-slice MSCT and 2-dimensional (2D) echocardiography was performed in 40 patients with known or suspected CAD. The LV end-diastolic volume (LVEDV) and LV end-systolic volume (LVESV) were determined and the LV ejection fraction (LVEF) was derived. Regional wall motion was assessed visually using a 17-segment model. A 3-point scoring system was used to assign to each segment a wall motion score: 1 = normokinesia, 2 = hypokinesia, 3 = akinesia or dyskinesia. Two-dimensional echocardiography served as the gold standard. MSCT agreed well with 2D echocardiography for assessment of LVEDV (r = 0.97; p < .0001) and LVESV (r = 0.98; p < .0001). An excellent correlation between MSCT and 2D echocardiography was shown for the evaluation of LVEF (r = 0.91; p < .0001). Agreement for the assessment of regional wall motion was excellent (96%, kappa = 0.82). CONCLUSIONS: An accurate assessment of global and regional LV function and volumes is feasible with 64-slice MSCT.     

Brain cyclosporin A levels are determined by ontogenic regulation of mdr1a expression.

Cyclosporin A (CyA) toxicity is a common occurrence in pediatric organ transplant patients. We hypothesized that reduced mdr1a expression in newborn and developing mice would affect CyA accumulation within organs and/or toxicity. For functional studies, CyA was administered (5 mg kg(-1) i.p.) to 1-, 12-, and 19-day, and adult male and female mdr1a+/+ and mdr1a-/- mice. Peak blood CyA was lower in 1-, 12-, and 19-day-old (1000 ng ml(-1)) versus adult (1500 ng ml(-1)) mice but was similar in mdr1a+/+ and mdr1a-/- mice. Kidney mdr1a expression (measured by quantitative polymerase chain reaction) increased 2.5-fold in 19-day-old male and female mice and increased another 4-fold in adult females compared with adult males. Liver mdr1a expression increased 6-fold by day 12 compared with neonatal mice. Thereafter, maintenance of hepatic mdr1a expression in females and a reduction to neonatal levels in males was observed. Kidney/blood (8- to 9-fold) and liver/blood (12- to 15-fold) CyA levels were highest on days 12 and 19 and were not dependent on maturational changes in mdr1a mRNA levels. Adults had higher brain expression of mdr1a mRNA (3-fold), a corresponding 5-fold increase in immunodetectable P-glycoprotein, and 80% lower brain accumulation of CyA compared with 1-day-old mice. Conversely, in mdr1a-null mice, brain/blood CyA was similar in newborn and adult mice. A similar pattern was observed for the brain accumulation of the mdr1a substrate 3H-digoxin. We conclude that the risk for central nervous system drug toxicity could be higher in neonates or young children as a consequence of underdeveloped P-glycoprotein.     

Use of computerized CT analysis to discriminate between Alzheimer patients and normal control subjects

A newly developed computerized technique was used to analyze the CT scans of 49 patients with dementia of the Alzheimer type and 31 normal control subjects. Nine brain regions distributed across five CT slices were evaluated for each individual. For the purpose of analysis, the patients and controls were divided into an exploratory set and a test set. Several discriminant functions were conducted on the exploratory set and applied to the test set. The combination of variables that focused on regions in the temporal lobe was most accurate in differentiating Alzheimer patients from controls (94%). This degree of accuracy was achieved only when subjects younger than 65 years old were analyzed separately from those 65 years old and older. The newly developed computer software program was able to discriminate between independently selected groups of Alzheimer patients and control subjects. The program was most effective when the analysis emphasized regions in the temporal lobe and when subjects younger than 65 years old were analyzed separately from those 65 years old and older.     

Ugandan HIV-1 V3 loop sequences closely related to the U.S./European consensus.

The third variable (V3) loop of the human immunodeficiency virus type 1 (HIV-1) envelope protein is an important determinant for virus neutralization and cell tropism. V3 loop sequences from uncultured lymphocytes obtained in 1990 from 22 Ugandan HIV-1-infected patients could, with the exception of two patients' sequences, be divided into two groups (A and B) on the basis the V3 loop size and sequence. The V3 loop consensus sequences from both groups showed a high degree of homology to a U.S./European consensus, a characteristic also reflected by the results of peptide serology. In the case of group B the difference in sequence was only five amino acids. In contrast, the V3-flanking regions for both groups showed greater homology to an earlier (1986/1987) Ugandan consensus. The discovery of these two new Ugandan V3 loop genotypes, which are closely related to the U.S./European consensus, has implications for the understanding of the evolution of HIV-1 and for the future design of a vaccine for use in Africa.     

Capillary-oxygenation-level-dependent near-infrared spectrometry in frontal lobe of humans.

Brain function requires oxygen and maintenance of brain capillary oxygenation is important. We evaluated how faithfully frontal lobe near-infrared spectroscopy (NIRS) follows haemoglobin saturation (SCap) and how calculated mitochondrial oxygen tension (PMitoO2) influences motor performance. Twelve healthy subjects (20 to 29 years), supine and seated, inhaled O2 air-mixtures (10% to 100%) with and without added 5% carbon dioxide and during hyperventilation. Two measures of frontal lobe oxygenation by NIRS (NIRO-200 and INVOS) were compared with capillary oxygen saturation (SCap) as calculated from the O2 content of brachial arterial and right internal jugular venous blood. At control SCap (78%+/-4%; mean+/-s.d.) was halfway between the arterial (98%+/-1%) and jugular venous oxygenation (SvO2; 61%+/-6%). Both NIRS devices monitored SCap (P<0.001) within approximately 5% as SvO2 increased from 39%+/-5% to 79%+/-7% with an increase in the transcranial ultrasound Doppler determined middle cerebral artery flow velocity from 29+/-8 to 65+/-15 cm/sec. When SCap fell below approximately 70% with reduced flow and inspired oxygen tension, PMitoO2 decreased (P<0.001) and brain lactate release increased concomitantly (P<0.001). Handgrip strength correlated with the measured (NIRS) and calculated capillary oxygenation values as well as with PMitoO2 (r>0.74; P<0.05). These results show that NIRS is an adequate cerebral capillary-oxygenation-level-dependent (COLD) measure during manipulation of cerebral blood flow or inspired oxygen tension, or both, and suggest that motor performance correlates with the frontal lobe COLD signal.     

Comparison of airway diameter measurements from an anthropomorphic airway tree phantom using hyperpolarized 3He MRI and high-resolution computed tomography.

An anthropomorphic airway tree phantom was imaged with both hyperpolarized (HP) 3He MRI using a dynamic projection scan and computed tomography (CT). Airway diameter measurements from the HP 3He MR images obtained using a newly developed model-based algorithm were compared against their corresponding CT values quantified with a well-established method. Of the 45 airway segments that could be evaluated with CT, only 14 airway segments (31%) could be evaluated using HP 3He MRI. No airway segments smaller than approximately 4 mm in diameter and distal to the fourth generation were adequate for analysis in MRI. For the 14 airway segments measured, only two airway segments yielded a non-equivalent comparison between the two imaging modalities, while eight more had inconclusive comparison results, leaving only four airway segments (29%) that satisfied the designed equivalence criteria. Some of the potential problems in airway diameter quantification described in the formulation of the model-based algorithm were observed in this study. These results suggest that dynamic projection HP 3He MRI may have limited utility for measuring airway segment diameters, particularly those of the central airways.     

Genetic diversity of the Leptospiral immunoglobulin-like (Lig) genes in pathogenic Leptospira spp.

Recent serologic, immunoprotection, and pathogenesis studies identified the Lig proteins as key virulence determinants in interactions of leptospiral pathogens with the mammalian host. We examined the sequence variation and recombination patterns of ligA, ligB, and ligC among 10 pathogenic strains from five Leptospira species. All strains were found to have intact ligB genes and genetic drift accounting for most of the ligB genetic diversity observed. The ligA gene was found exclusively in L. interrogans and L. kirschneri strains, and was created from ligB by a two-step partial gene duplication process. The aminoterminal domain of LigB and the LigA paralog were essentially identical (98.5 ± 0.8% mean identity) in strains with both genes. Like ligB, ligC gene variation also followed phylogenetic patterns, suggesting an early gene duplication event. However, ligC is a pseudogene in several strains, suggesting that LigC is not essential for virulence. Two ligB genes and one ligC gene had mosaic compositions and evidence for recombination events between related Leptospira species was also found for some ligA genes. In conclusion, the results presented here indicate that Lig diversity has important ramifications for the selection of Lig polypeptides for use in diagnosis and as vaccine candidates. This sequence information will aid the identification of highly conserved regions within the Lig proteins and improve upon the performance characteristics of the Lig proteins in diagnostic assays and in subunit vaccine formulations with the potential to confer heterologous protection.     

Respiratory Depression by Tramadol in the Cat: Involvement of Opioid Receptors

Background: Tramadol hydrochloride (tramadol) is a synthetic opioid analgesic with a relatively weak affinity at opioid receptors. At analgesic doses, tramadol seems to cause little or no respiratory depression in humans, although there are some conflicting data. The aim of this study was to examine whether tramadol causes dose-dependent inhibitory effects on the ventilatory carbon dioxide response curve and whether these are reversible or can be prevented by naloxone.

Methods: Experiments were performed in cats under [alpha]-chloralose-urethane anesthesia. The effects of tramadol and naloxone were studied by applying square-wave changes in end-tidal pressure of carbon dioxide (Petco2; 7.5-11 mmHg) and by analyzing the dynamic ventilatory responses using a two-compartment model with a fast peripheral and a slow central component, characterized by a time constant, carbon dioxide sensitivity, time delay, and a single offset (apneic threshold).

Results: In five animals 1, 2, and 4 mg/kg tramadol (intravenous) increased the apneic threshold (control: 28.3 +/- 4.8 mmHg [mean +/- SD]; after 4 mg/kg: 36.7 +/- 7.1 mmHg;P < 0.05) and decreased the total carbon dioxide sensitivity (control: 109.3 +/- 41.3 ml [middle dot] min-1 [middle dot] mmHg-1) by 31, 59, and 68%, respectively, caused by proportional equal reductions in sensitivities of the peripheral and central chemoreflex loops. Naloxone (0.1 mg/kg, intravenous) completely reversed these effects. In five other cats, 4 mg/kg tramadol caused an approximately 70% ventilatory depression at a fixed Pet co2 of 45 mmHg that was already achieved after 15 min. A third group of five animals received the same dose of tramadol after pretreatment with naloxone. At a fixed Petco2 of 45 mmHg, naloxone prevented more than 50% of the expected ventilatory depression in these animals.     

Differential Cellular Gene Expression in Ganglioglioma

Summary:  Purpose:  Gangliogliomas (GGs) are neuronal-glial tumors highly associated with epilepsy. We hypothesized that the expression of select gene families including neurotransmitter receptor subunits and growth factors would be distinct in neurons and astrocytes within GG compared with adjacent cortex and that these changes would yield insights into seizure onset and lesion formation.
Methods:  Candidate gene expression was defined in single immunohistochemically labeled neurons and astrocytes microdissected from GG specimens compared with neurons and astrocytes microdissected from morphologically intact cortex adjacent to the GG or normal control cortex.
Results:  Differential expression of 16 genes including glutamate transporter (EAAC1) and receptor (NMDA2C, mGluR5), growth factor (hepatocyte growth factor), and receptor (platelet derived growth factor receptor β, fibroblast growth factor receptor 3) mRNAs was detected in GG neurons compared with control neurons. In astrocytes, altered expression of p75NGF, mGluR3, TGFβ3 and Glt-1 mRNAs was detected. Nestin mRNA, a gene that exhibits enhanced expression in balloon cell cortical dysplasia, was increased in GG neurons. Because of the morphological similarities between GG and cortical dysplasia, we show that there is activation of the mTOR cascade in GG as evidenced by enhanced expression of phospho-p70S6kinase and phosphoribosomal S6 proteins.
Conclusion:  We find differential candidate gene expression in neurons and astrocytes in GG compared with adjacent cortex and show that there is activation of the mTOR pathway. These changes highlight pathways that may be pivotal for epileptogenesis and lesion growth.