Interference of factor V Leiden on protein S activity: evaluation of a new prothrombin time-based assay.

Protein S activity in plasma from factor V Leiden (FVL)-positive patients may be lower than expected. We investigated a new commercially available method for protein S for such interference. Protein S activity was measured for plasmas from 50 individuals with FVL and their results were compared with those obtained for plasmas from 47 sex-matched and age-matched individuals without FVL. We assumed that the median protein S activity value from a relatively large number of individuals with or without FVL would not be significantly different if there is no influence from FVL. The FVL-positive plasmas gave relatively (albeit not significantly) lower protein S levels than FVL-negative plasmas when both were tested undiluted (86 versus 93 IU/dl, P = 0.06). Those differences were reduced (98 versus 102 IU/dl, P = 0.58) when testing was performed on diluted plasmas. Furthermore, the proportion of patients with FVL identified as low-abnormal on the basis of the specific cut-off values (undiluted = 64 U/dl; diluted = 71 IU/dl), which was 8% when testing was performed on undiluted plasmas, was reduced to 4% when testing was performed on diluted plasmas. Conversely, the corresponding proportions of patients without FVL remained unaltered (4.3 versus 4%). In conclusion, these results indicate that the evaluated method is somewhat affected by FVL and that dilution of plasma prior to testing improves specificity. Protein S activity measurement for FVL-positive patients should be performed on diluted plasma and the results interpreted on the basis of the cut-off value specifically determined for diluted plasmas.     

Intestinal cystic pneumatosis and gastric banding. Etiopathogenic considerations on a clinical case

The authors describe a case of intestinal cystic pneumatosis in a patient submitted to gastric banding and then proceed with a critical review of the literature on the subject, examining the state of the art with regard to the pathogenetic hypotheses and the clinical manifestations of the disease and outlining the advantages of the instrumental investigations employed. On the basis of clinical considerations, an integrated pathogenetic hypothesis is advanced which takes account of the various indications expressed in the literature. In particular, recurrent vomiting is believed to bring about epithelial microlesions which, in the presence of severe respiratory impairment, the execution of endoscopic examinations and a mainly carbohydrate-based diet, are thought to cause onset of cystic pneumatosis.     

The Role of Health Literacy in Predicting Multiple Healthcare Outcomes Among Hispanics in a Nationally Representative Sample: A Comparative Analysis by English Proficiency Levels

Health literacy (HL) research among Hispanics currently focuses on individuals with limited English proficiency but impacts of HL on healthcare outcomes among other English language proficiency groups is relatively unknown. Regression models assessed associations between HL and healthcare outcomes for Hispanics overall (n = 4013) and for proficiency level sub-populations using the 2007 Pew Hispanic Health Survey. Overall, Hispanics with adequate HL percieved US medical care as “excellent,” were more satisfied with their doctor’s help, and reported “excellent” overall health. In the sub-population analysis, “excellent” perception of US healthcare was associated with HL among the Spanish and English dominant groups. Among bilinguals, adequate HL was associated with decreased use of traditional medicine. The effect of adequate HL varied within English proficiency groups. HL research that focuses only on Spanish dominant speakers can exclude a substantial percentage of English proficient or bilingual populations who have low HL.     

Effects of a novel Nodal-targeting monoclonal antibody in melanoma

Nodal is highly expressed in various human malignancies, thus supporting the rationale for exploring Nodal as a therapeutic target. Here, we describe the effects of a novel monoclonal antibody (mAb), 3D1, raised against human Nodal. In vitro treatment of C8161 human melanoma cells with 3D1 mAb shows reductions in anchorage-independent growth and vasculogenic network formation. 3D1 treated cells also show decreases of Nodal and downstream signaling molecules, P-Smad2 and P-ERK and of P-H3 and CyclinB1, with an increase in p27. Similar effects were previously reported in human breast cancer cells where Nodal expression was generally down-regulated; following 3D1 mAb treatment, both Nodal and P-H3 levels are reduced. Noteworthy is the reduced growth of human melanoma xenografts in Nude mice treated with 3D1 mAb, where immunostaining of representative tumor sections show diminished P-Smad2 expression. Similar effects both in vitro and in vivo were observed in 3D1 treated A375SM melanoma cells harboring the active BRAF(V600E) mutation compared to treatments with IgG control or a BRAF inhibitor, dabrafenib. Finally, we describe a 3D1-based ELISA for the detection of Nodal in serum samples from cancer patients. These data suggest the potential of 3D1 mAb for selecting and targeting Nodal expressing cancers.     

New HLA-DRB1* nucleotide sequence of Italian origin: HLA-DRB1*13022

High-resolution polymerase chain reaction using sequence-specific primer typing of the HLA-DRB1 gene of an Italian patient waiting for unrelated bone marrow transplantation revealed a new allelic variant of HLA-DRB1*13. Sequencing the exon 2 of DRB1* gene demonstrated a G-->C transition at the nucleotide 216 resulting in a silent mutation at codon 72: CGG-->CGC. The closest sequence was the HLA-DRB1*1302 and the new allele was named HLA-DRB1*13022. This variant was carried by the haplotype HLA-A*24; Cw*0702; B*39; DRB1*13022; DRB3*0301; DQA1*0102; DQB1*0604 as demonstrated by a family study.     

Sleep-dependent changes in the coupling between heart period and arterial pressure in newborn lambs

This study assessed whether sleep-dependent changes in the relationship between heart period (HP) and mean arterial pressure (MAP) occur in newborn life. Electrodes for electrocorticographic, electromyographic, and electrooculographic monitoring and an arterial catheter for blood pressure recordings were implanted in 11 newborn lambs. HP and MAP beat-to-beat values were computed from 120-s blood pressure recordings during quiet wakefulness, active sleep, and quiet sleep. For each recording, the time shift at which the maximum of the HP versus MAP cross-correlation function was attained was identified. For each lamb and wake-sleep state, an average correlation coefficient was then computed corresponding to the median value of such time shifts. The maximum of the cross-correlation function was attained with HP lagging behind MAP. The corresponding mean correlation coefficient was significantly higher in quiet sleep (0.51 +/- 0.05) than either in quiet wakefulness (0.31 +/- 0.05) or in active sleep (0.29 +/- 0.03). Sleep-related differences in the correlation between HP and MAP were maintained after HP and MAP data were low-pass filtered at 0.3 Hz to remove their fast ventilatory oscillations. In conclusion, data indicate that the relationship between spontaneous fluctuations in HP and those in MAP is sleep-state dependent in newborn lambs. A positive HP versus MAP correlation with HP lagging behind MAP is consistent with baroreflex control of HP. Heart rhythm thus may be more tightly controlled by the baroreceptor reflex and less dependent on central autonomic commands in quiet sleep than either in quiet wakefulness or in active sleep.     

Plasma Cholecystokinin Levels after Vertical Banded Gastroplasty: Effects of an Acidified Meal

Background: Although cholecystokinin (CCK) is involved in the short-term regulation of satiety, it has not been investigated in obese patients subjected to bariatric restrictive operations. Methods: 8 morbidly obese patients (BMI 49.1 ± 6.9), 7F and 1M, were investigated before and after vertical banded gastroplasty (VBG). 6 healthy lean volunteers served as the control group. CCK was determined (RIA) after an overnight fast and after the administration of an acidified (pH 3) liquid meal. Blood samples were taken 45 min before the meal, 5 min after it and then every 30 min for 3 hours. Results: There were no differences between groups in basal CCK levels. However, the peak of CCK after the meal was significantly higher (P <0.01) in obese patients after VBG (24.9 ± 18 pmol/l) than before VBG (9.8 ± 6.7 pmol/l) and when compared with the control group (8.0 ± 6.3 pmol/l).The time needed to reach the peak was longer in healthy volunteers (105 ± 24.9 min) than in obese patients before VBG (45 ± 40 min) and after VBG (7.5± 12 min) (P<0.01). Conclusions: VBG increases the peak of CCK secretion and shortens the time to reach it. These changes could contribute to the satiety effects of gastric restrictive operations.