Time-frequency and time-varying analysis for assessing the dynamic responses of cardiovascular control

Time-frequency or time-variant methods have been extensively applied in the study of the heart-rate variability (HRV) signal. In fact, the frequency content of HRV signal has a strong correlation with the control system assessing heart rate. In particular, the power related to the low-frequency (LF) and high-frequency (HF) components have been demonstrated to correlate to the action of sympathetic and parasympathetic branches of the autonomic nervous system. However, the analysis is restricted to stationary conditions, unless time-frequency methods are employed for detecting dynamic changes that may occur during physiological and pathological conditions.This article reviews the most diffused tools for time-frequency analysis, starting from linear decomposition of the signal (including short-time Fourier transform and wavelet and wavelet packet decomposition), to quadratic time-frequency distributions (including Wigner-Ville transform and Cohen's class of distributions), and finally to adaptive or time-variant autoregressive (AR) models, in both the mono- and bivariate forms. In the past few years, these approaches have been applied in several studies related to cardiovascular responses during nonstationary pathophysiological events. Among them, we will recall and discuss myocardial ischemia (spontaneous or induced), drug infusion, rest-tilt maneuver and syncope, neurophysiological, and sleep investigations.     

Biomedical signal processing and modeling in cardiovascular systems

This article revisits the subject of short-term heart-rate and arterial-pressure variability from the perspective of model structures that can be useful in defining signal processing algorithms. We draw a general scheme of the oscillation sources and interactions that contribute to cardiovascular control mechanisms and highlight the elements that were considered in different modeling works.The origin, superposition, and interaction of respiratory high-frequency (HF) and vasomotor low-frequency (LF) rhythms is presented as the integration of supraspinal and spinal circuits, vasomotor activity, and pressure control loops. We analyze in detail the necessity of considering all relevant interactions for the algorithms designed to estimate the baroreflex sensitivity. We also pinpoint the components of cardiorespiratory coupling in relation to the analysis of data from the acoustic quantification of the left ventricular volume. Finally, we analyze the tendency to produce complex behaviors even in extremely simplified systems involving interactions between oscillatory mechanisms.     

Identification of Echinococcus granulosus eggs

OBJECTIVE: The purpose of this QMP-LS patterns-of-practice survey was to determine quality assurance (QA) processes used in Ontario for purchased and in-house culture media, and compliance with recommended practices. METHODS: QMP-LS required laboratories to submit copies of media QC records for August to October 1998. Target media were blood agar, chocolate agar, MacConkey agar, sorbitol MacConkey agar (SMAC), Campylobacter agar, and selective media for pathogenic Neisseria spp. Procedures for acquisition and maintenance of QC stock cultures, media-type specific QC strains, time and temperature of incubation, and the test inoculum were required. Data were captured and analysed using Microsoft Excel. RESULTS: Marked variability and inadequacy of media QC records of 124 participating laboratories was noted. 12/124 prepared media in-house, most did not comply with NCCLS QA recommendations. Those purchasing prepared media frequently did not comply with NCCLS recommendations. In-house QC was not performed by 9% for chocolate agar, 87% for MacConkey agar without crystal violet, and 53% for SMAC agar. Recommended ATCC strains were used by less than half of participants. Time and temperature of incubation of the QC plates were not always appropriate. Only 65/117 laboratories used a correct inoculum to test the sensitivity and selectivity of media for pathogenic Neisseriae. Physical characteristics of prepared media were rarely recorded. Most laboratories were not aware of their supplier's QC protocols. DISCUSSION: Few Ontario laboratories comply with the NCCLS recommendations for QA of culture media. Major compliance failures were not performing QC at all, inappropriate choice of QC bacterial strains, and inoculum used. Incomplete record keeping was common and methods for maintaining stock cultures were sub-optimal. External quality assessment of this important parameter of microbiology practice needs to be undertaken on an ongoing basis.     

Efficacy of contrast chromoendoscopy of the colon after oral administration of indigo carmine dye

INTRODUCTION: Indigo carmine dye is usually spread directly over the colon in many chromoscopic techniques aiming better visualization of a lesion already detected by conventional colonoscopy. Examination of the colon already stained by oral administration of indigo carmine dye may increase detection of small lesions resulting in higher sensibility of the colonoscopy in diagnosing diminutive lesions. OBJECTIVE: Analyze the results regarding the quality of chromoscopic technique and the indigo carmine dye distribution over the colon after oral administration. PATIENTS AND METHODS: Fifty patients undergoing colonoscopy were evaluated. A capsule containing 100 mg of indigo carmine dye was offered to these patients 30 min before oral mannitol prep routinely used. The indigo carmine dye contrast effect was graded as bad, regular or good according to preestablished criteria in three segments of the colon: right and left colon and the rectum. RESULTS: In the right colon, good indigo carmine dye contrast effect was observed in only 9 (18.8%) patients, while it was considered regular and bad in 32 (66.6%) and in 7 (14.6%) patients, respectively. A good indigo carmine dye contrast effect was never observed in this series for the left colon or in the rectum. As a matter of fact, no indigo carmine dye was observed in the left colon in 80.9% and in the rectum in 92% of patients in this series. CONCLUSION: Although it may be simple and desirable, oral administration of indigo carmine dye seems ineffective for enhancing detection of diminutive lesions by chromoscopy as result of poor colonic distribution of indigo carmine dye mainly at distal colonic sites.     

Step-down approach using either cyclosporin A or methotrexate as maintenance therapy in early rheumatoid arthritis

OBJECTIVE: To evaluate the feasibility and outcome of the step-down approach using either cyclosporin A (CSA) or methotrexate (MTX) as maintenance therapy following 6 months treatment with these 2 agents in combination in early, nonerosive rheumatoid arthritis (RA). METHODS: Fifty-seven patients younger than 65 years with early, nonerosive RA were first treated with CSA and MTX in combination for 6 months. They were then randomly stepped down to single-agent maintenance treatment for another 18 months. Safety, clinical efficacy, survival on treatment, and radiographic progression were evaluated. RESULTS: When being treated with combination therapy, 7 of the 57 patients (12.3%) withdrew because of adverse events. Of the remaining 50 patients, 42 (84.0%) were American College of Rheumatology (ACR) 20% responders, 30 (60.0%) were ACR 50% responders, and 23 (46.0%) were ACR 70% responders. At month 6, 22 patients were randomized to CSA and 27 to MTX. During this trial period, the treatment was discontinued by 16 patients taking CSA (mainly because of loss of efficacy) and by 4 taking MTX. At month 24, the probability (+/- SEM) of survival on treatment was 0.273 +/- 0.09 for CSA and 0.852 +/- 0.07 for MTX. Of the 6 CSA patients who completed the trial, 4 (66.7%) were ACR 20% responders, and 3 (50%) were both ACR 50% and ACR 70% responders. Of the 23 completers in the MTX arm, 21 (91.3%) were ACR 20% responders, 18 (78.3%) were ACR 50%, and 10 (43.5%) were ACR 70% responders. The treatment was not responsible for severe adverse events. Radiography showed a slow progression in the damage score and number of eroded joints in both treatment groups. CONCLUSION: Stepping down to single agent maintenance therapy following 6 months of combination treatment with CSA and MTX in early RA was only successful with MTX. Because this treatment did not prevent some radiographic progression, other approaches (e.g., step-up approach) may be more appropriate in early RA.     

Sustained response to recombinant human erythropoietin and intermittent all-trans retinoic acid in patients with myelodysplastic syndromes

In vitro studies suggest that all-trans retinoic acid (ATRA) synergizes with erythropoietin (EPO) for the stimulation of hematopoiesis in patients with myelodysplastic syndrome (MDS). A clinical trial was performed to evaluate whether a combination of these agents was effective in relieving the cytopenias associated with MDS. Twenty-seven patients with low- or intermediate-risk MDS were enrolled in a 12-week study. ATRA was administered orally at the dose of 80 mg/m(2) per day in 2 divided doses for 7 consecutive days every other week. Recombinant human EPO was given subcutaneously 3 times a week. The EPO dose was initiated at 150 U/kg and was increased to 300 U/kg if after 6 weeks there was no or there was suboptimal erythroid response. Patients who responded to therapy were continued on ATRA and EPO at the same doses for 6 additional months (extension phase). Further treatment was given to patients with a continued response. Clinically significant erythroid responses with increases of hemoglobin levels of at least 1 g/dL or reduction of transfusion needs were seen in 13 (48%) patients, with 4 showing improved responses after dose escalation of EPO. Ten (37%) patients displayed continued responses during 6 months of extended treatment, and 7 (26%) are still responsive after a follow-up period of 13 months. Neutrophil responses were observed in 5 of 12 patients with neutropenia, and platelet responses were observed in 6 of 9 patients with thrombocytopenia. Three patients displayed trilineage responses that were sustained during continuation therapy. Side effects were observed in all patients but were of mild entity and did not require discontinuation of therapy. It is concluded that the combination ATRA + EPO is an effective and well-tolerated treatment for patients with low- and intermediate-risk MDS. The optimal ATRA and EPO schedule and the role of maintenance treatment remain to be determined and warrant further investigation.     

Infliximab chimaeric anti-tumour necrosis factor alpha monoclonal antibody treatment for patients with myelodysplastic syndromes

Tumour necrosis factor alpha (TNF-alpha) is believed to play a major role in apoptotic death of bone marrow cells in myelodysplastic syndromes (MDS). We explored the efficacy and safety profile of infliximab chimaeric anti-TNF-alpha monoclonal antibody treatment in two MDS patients. They both had low-/intermediate-risk MDS, isolated anaemia and elevated circulating levels of TNF-alpha. Infliximab produced no adverse side-effects and resulted in sustained erythroid responses, one major and one minor. Laboratory studies indicated a remarkable decrease in the percentage of apoptotic stem cells in the bone marrow. This preliminary report indicates that infliximab may have an application as MDS therapy and warrants further investigation.