Quantification of perfusion fMRI using a numerical model of arterial spin labeling that accounts for dynamic transit time effects.

A new approach to modeling the signal observed in arterial spin labeling (ASL) experiments during changing perfusion conditions is presented in this article. The new model uses numerical methods to extend first-order kinetic principles to include the changes in arrival time of the arterial tag that occur during neuronal activation. Estimation of the perfusion function from the ASL signal using this model is also demonstrated. The estimation algorithm uses a roughness penalty as well as prior information. The approach is demonstrated in numerical simulations and human experiments. The approach presented here is particularly suitable for fast ASL acquisition schemes, such as turbo continuous ASL (Turbo-CASL), which allows subtraction pairs to be acquired in less than 3 s but is sensitive to arrival time changes. This modeling approach can also be extended to other acquisition schemes.     

Molecular biology in prostate cancer

Summary Genes involved in cancer generation are usually tumor suppressors and oncogenes. Progressive genetic alterations in these genes are involved in the mechanisms of tumorigenesis. In prostate cancer, additionally several chromosomal loci that should harbor mutated genes have been proposed. Some genes have been found altered in prostate cancer, such as PTEN, TP53, AR, RNASEL (HPC1), ELAC2 (HPC2), CDKN2A and MSR1 and those can be natural targets for new strategies of treatment. Besides, gene therapy has been suggested to be suitable for prostate cancer treatment. This approach includesex vivo corrective therapy, suicide, and antisense therapy.     

Inter-observer agreement in interpreting chest X-rays on children with acute lower respiratory tract infections and concurrent wheezing.

CONTEXT AND OBJECTIVE: Many children with acute lower respiratory tract infections (ALRI) present to the emergency ward with concurrent wheezing. A chest x-ray is often requested to rule out pneumonia. We assessed inter-observer agreement in interpreting x-rays on such children. DESIGNS AND SETTING: Prospective consecutive case study at Instituto de Salud del Ni?o, Lima, Peru. METHODS: Chest x-rays were obtained from eligible children younger than two years old with ALRI and concurrent wheezing who were seen in the emergency ward of a nationwide pediatric referral hospital. The x-rays were read independently by three different pediatric residents who were aware only that the children had a respiratory infection. All the children had received inhaled beta-adrenergic agonists before undergoing chest x-rays. Lobar and complicated pneumonia cases were excluded from the study. RESULTS: Two hundred x-rays were read. The overall kappa index was 0.2. The highest individual kappa values for specific x-ray findings ranged from 0.26 to 0.34 for rib horizontalization and from 0.14 to 0.31 for alveolar infiltrate. Inter-observer variation was intermediate for alveolar infiltrate (kappa 0.14 to 0.21) and for air bronchogram (kappa 0.13 to 0.23). Reinforcement of the bronchovascular network (kappa 0.10 to 0.16) and air trapping (kappa 0.05 to 0.20) had the lowest agreement. CONCLUSIONS: There was poor inter-observer agreement for chest x-ray interpretation on children with ALRI and concurrent wheezing seen at the emergency ward. This may preclude reliable diagnosing of pneumonia in settings where residents make management decisions regarding sick children. The effects of training on inter-observer variation need further studies.     

Neonatal splenic necrosis not related to wandering spleen.

Splenic necrosis is extremely rare in neonates, the cases recorded so far being secondary to torsion of wandering organs. A newborn with an abdominal mass who underwent exchange transfusions through an umbilical catheter is presented here. Comprehensive investigation led to the suspicion of enteric duplication, but a splenic necrosis with no features of wandering spleen was found at laparotomy. The pathogenesis and preoperative diagnostic work-up of splenic necrosis are emphasised.     

Antibody Responses to Asian and American Genotypes of Dengue 2 Virus in Immunized Mice

The possibility of a correlation between dengue virus genotype groups and disease severity is currently under discussion. The objective of this investigation was to identify any immunogenic difference between the American and Asian dengue 2 virus genotypes through the study of antibody development (virus-binding immunoglobulin G and neutralizing antibodies) in mice. Differences in the neutralization pattern between the strains studied were observed, suggesting the presence of slight antigenic variations among them. The lack of recognition of one of the Asian genotype strains was remarkable.     

Hepatic UDP-glucose 13C isotopomers from [U-13C]glucose: a simple analysis by 13C NMR of urinary menthol glucuronide.

Menthol glucuronide was isolated from the urine of a healthy 70-kg female subject following ingestion of 400 mg of peppermint oil and 6 g of 99% [U-(13)C]glucose. Glucuronide (13)C-excess enrichment levels were 4-6% and thus provided high signal-to-noise ratios (SNRs) for confident assignment of (13)C-(13)C spin-coupled multiplet components within each (13)C resonance by (13)C NMR. The [U-(13)C]glucuronide isotopomer derived via direct pathway conversion of [U-(13)C]glucose to [U-(13)C]UDP-glucose was resolved from [1,2,3-(13)C(3)]- and [1,2-(13)C(2)]glucuronide isotopomers derived via Cori cycle or indirect pathway metabolism of [U-(13)C]glucose. In a second study, a group of four overnight-fasted patients (63 +/- 10 kg) with severe heart failure were given peppermint oil and infused with [U-(13)C]glucose for 4 hr (14 mg/kg prime, 0.12 mg/kg/min constant infusion) resulting in a steady-state plasma [U-(13)C]glucose enrichment of 4.6% +/- 0.6%. Menthol glucuronide was harvested and glucuronide (13)C-isotopomers were analyzed by (13)C NMR. [U-(13)C]glucuronide enrichment was 0.6% +/- 0.1%, and the sum of [1,2,3-(13)C(3)] and [1,2-(13)C(2)]glucuronide enrichments was 0.9% +/- 0.2%. From these data, flux of plasma glucose to hepatic UDPG was estimated to be 15% +/- 4% that of endogenous glucose production (EGP), and the Cori cycle accounted for at least 32% +/- 10% of GP.     

Hyperprolactinemia inhibits natural killer (NK) cell functionin vivo and its bromocriptine treatment not only corrects it but makes it more efficient

We studied NK cell function in eight patients with pathological hyperprolactinemia by measuring⁵¹Cr release by K562 cells exposed to their mononuclear cells and found it decreased compared to normal controls (P<0.01). Bromocriptine (BrC) treatment corrected NK function but also made it more efficient at 12:1 than at 25:1 or 50:1 effector:target ratios (ANOVA;P=0.01). The study of NK cell function in agarose revealed that its decrease in hyperprolactinemia is due to their low active binding to target cells, active killing, and recycling capacity. BrC tended to correct them but also increased recycling capacity to levels higher than those of controls (P<0.05). Sequential studies in three hyperprolactinemic patients before and after BrC showed correction of NK function within 1 week but its increased efficiency at the 12:1 effector:target ratio required 8 weeks. We conclude that hyperprolactinemia decreases NK cell function. BrC corrects this by decreasing prolactin levels but also makes NK function more efficient by increasing the capacity of NK cells to recycle after killing.     

Assay of cytomegalovirus susceptibility to ganciclovir in renal and heart transplant recipients

Ganciclovir (GCV) prophylaxis or pre-emptive therapy significantly reduce the rate of cytomegalovirus (CMV) disease and viremia, but increase the potential for emergence of ganciclovir-resistant CMV strains. The inhibitor concentration at 50% (IC(50)) of GCV from 156 CMV isolates from 59 renal or heart transplant recipients was calculated by means of a rapid phenotypic susceptibility assay. Twenty-seven strains were from 14 patients undergoing GCV therapy. The IC(50) was higher in patients under the prophylaxis regimen. One CMV strain, from a heart transplant recipient, became GCV-resistant after 1 month of therapy (IC(50)=13.7 micromol/l). These data, together with clinical and virological markers, suggested that a switch to foscarnet was necessary, and good evolution was observed. Thus, assay of CMV susceptibility to GCV could be helpful in clinical management.