Reproducibility and Comparability of Short- and Long-Term Heart Rate Variability Measures in Healthy Young Men

Background: In heart rate variability (HRV) studies, the duration of the electrocardiographic recordings may vary between 20 seconds and 24 hours. Little is known about the reproducibility or comparability of HRV measures calculated over observation periods of different duration. Methods: To assess the reproducibility and comparability of HRV measures computed from short recordings under standardized conditions and from ambulatory 24-hour recordings, 15 healthy young males were studied on three occasions. Results: The reliability coefficient (between subject variation divided by summed between and within subject variation) for 20-second intervals was low for all measures. For 5-minute intervals in supine position, but not standing position, the reliability coefficients of the standard deviation, root of mean squared successive differences, proportion of successive differences > 50 ms, and the proportion low frequency power were about 70%. The reliability coefficients of the 24-hour HRV measures were > 80% for all measures. Short- and long-term measures of heart rate and HRV appeared to be correlated, implying that these measures result in similar ranking of subjects. Conclusions: The results indicate that HRV measures based on 24-hour monitoring during regular activities are better reproducible than short-term measures under standardized conditions. A single 5-minute recording may suffice to characterize a group of persons in a population study, but, because of considerable day-to-day variation, it is not adequate for individual characterization.     

High- versus low-dose ACE inhibition in chronic heart failure: A double-blind, placebo-controlled study of imidapril

Objectives. To determine dose-related clinical and neurohumoral effects of angiotensin-converting enzyme (ACE) inhibitors in patients with chronic heart failure (CHF), we conducted a double-blind, placebo-controlled, randomized study of three doses (2.5 mg, 5 mg and 10 mg) of the long-acting ACE inhibitor imidapril.

Background. The ACE inhibitors have become a cornerstone in the treatment of CHF, but whether high doses are more effective than low doses has not been fully elucidated, nor have the mechanisms involved in such a dose-related effect.

Methods. In a parallel group comparison, the effects of three doses of imidapril were examined. We studied 244 patients with mild to moderate CHF (New York Heart Association class II–III: ±80%/20%), who were stable on digoxin and diuretics. Patients were treated for 12 weeks, and the main end points were exercise capacity and plasma neurohormones.

Results. At baseline, the four treatment groups were well-matched for demographic variables. Of the 244 patients, 25 dropped out: 3 patients died, and 9 developed progressive CHF (3/182 patients on imidapril vs. 6/62 patients on placebo, p < 0.05). Exercise time increased 45 s in the 10-mg group (p = 0.02 vs. placebo), but it did not significantly change in the 5-mg (+16 s), and 2.5-mg (+11 s) imidapril group, compared to placebo (+3 s). Physical working capacity also increased in a dose-related manner. Plasma brain and atrial natriuretic peptide decreased (p < 0.05 for linear trend), while (nor)epinephrine, aldosterone and endothelin were not significantly affected. Renin increased in a dose-related manner, but plasma ACE activity was suppressed similarly (±60%) on all three doses.

Conclusions. Already within 3 months after treatment initiation, high-dose ACE inhibition (with imidapril) is superior to low-dose. This is reflected by a more pronounced effect on exercise capacity and some of the neurohormones, but it does not appear to be related to the extent of suppression of plasma ACE.     

Turn-around time for chemical and endocrinology analyzers studied using simulation.

Simulation can be a means for the laboratory management to investigate the effects of proposed changes in the laboratory. Also, when specifications of analyzers are available one can investigate which analyzer should be purchased to fulfill existing needs. The potential of simulation is shown here by simulating the turn-around time of batched samples under several conditions. Three routine analyzers (DAX, AXON and Immuno-1) were modeled. The temporal pattern of the arrival of the samples at the different analyzers was determined. The impact of these patterns and the two batching methods on the turn-around time was investigated. Simulation proved to be a useful method to study the effects of batching and arrival patterns on the turn-around time.     

Alterations of protein 4.1 family members in ependymomas: a study of 84 cases.

Ependymomas are common pediatric and adult CNS malignancies with a wide biologic spectrum that is often hard to predict using classic prognostic variables. The molecular pathogenesis is also poorly understood and few reproducible genetic alterations have been identified. The most common genetic alteration has been the loss of the Protein 4.1 family member, NF2, predominantly in spinal ependymomas. In contrast, a pilot study suggested that 4.1B deletions might be more common in intracranial ependymomas. These findings prompted us to study Protein 4.1 family members (NF2, 4.1B, 4.1R, 4.1G) in a larger cohort of 84 ependymomas (51 intracranial and 33 spinal; 11 WHO grade I, 43 grade II, 30 grade III). Fluorescence in situ hybridization was performed using NF2, 4.1B, 4.1R and 4.1G probes and immunohistochemical staining was performed in a subset using merlin, Protein 4.1B and Protein 4.1R antibodies. Additionally, frozen tissue from nine ependymomas (four intracranial and five spinal) was obtained for Western blot analysis for merlin, 4.1B and 4.1R expression. The majority of cases harbored one or more detectable genetic alterations, but we found that 4.1B gene deletions and 4.1R loss of expression were statistically more common in the pediatric vs adult, intracranial vs spinal, and grade III vs grade I/II subsets (P-values of 0.038 to <0.001). Also, 4.1G deletions were seen in 11/27 (41%) patients who either died of disease or had residual/recurrent tumor vs 5/41 patients with no evidence of disease at last follow-up (P=0.009). We conclude that alterations of Protein 4.1 family members are common in ependymal tumors and that specific alterations are associated with distinct clinicopathologic subsets.     

Generation of kidney cancer-specific antitumor immune responses using peripheral blood monocytes transduced with a recombinant adenovirus encoding carbonic anhydrase 9.

PURPOSE: Carbonic anhydrase 9 (CA9) is the most promising molecular marker described for renal cell carcinoma (RCC) to date. We investigated whether transduction of monocytes from peripheral blood with adenovirus encoding the CA9 gene (AdV-CA9) could stimulate a T-cell mediated immune response against cancer cells expressing CA9. The ability to consistently generate a T-cell response is an important step toward the development of a CA9-specific RCC vaccine. EXPERIMENTAL DESIGN: AdV-CA9 was generated using the AdEasy system. AdV-CA9-transduced peripheral blood mononuclear cell (PBMC)-derived monocytes were used to raise CTLs from autologous peripheral blood lymphocytes (PBLs). The ability of CTLs to lyse targets expressing CA9 was assessed by (51)Cr-release. RESULTS: Monocytes were efficiently transduced with AdV-CA9. In five of six experiments, AdV-CA9-transduced monocytes were able to induce a population of CTLs from bulk PBLs. CTLs were capable of lysing autologous, but not allogeneic monocytes expressing CA9. Furthermore, CTLs were able to lyse autologous RCC tumor cells expressing CA9. The ability of CTLs to lyse relevant targets was blocked by anti-CD3, anti-CD8, and anti-MHC class I antibodies demonstrating a MHC class I restricted response. CONCLUSIONS: These results suggest that PBMC-derived monocytes transduced with AdV-CA9 can generate RCC-specific MHC class I restricted CTLs capable of lysing CA9-expressing cancer cells. Transduction of PBMC-derived monocytes with adenovirus provides a simple and effective alternative to the use of dendritic cells for the induction of antigen-specific CTL.     

Development of a GIS-based, real-time Internet mapping tool for rabies surveillance

Background  

Oral rabies vaccination programs have been implemented to control the spread of wildlife rabies in the United States. However, current surveillance systems are inadequate for the efficient management and evaluation of these large scale vaccine baiting programs. With this in mind, a GIS-based rabies surveillance database and Internet mapping application was created. This surveillance system, RabID, provides a new resource for the rapid mapping and dissemination of data on animal rabies cases in relation to unaffected, enzootic, and baited areas where current interventions are underway.