Univariate and multivariate conditional entropy measures for the characterization of short-term cardiovascular complexity under physiological stress.

OBJECTIVE: A defining feature of physiological systems under the neuroautonomic regulation is their dynamical complexity. The most common approach to assess physiological complexity from short-term recordings, i.e. to compute the rate of entropy generation of an individual system by means of measures of conditional entropy (CE), does not consider that complexity may change when the investigated system is part of a network of physiological interactions. This study aims at extending the concept of short-term complexity towards the perspective of network physiology, defining multivariate CE measures whereby multiple physiological processes are accounted for in the computation of entropy rates. APPROACH: Univariate and multivariate CE measures are computed using state-of-the-art methods for entropy estimation and applied to time series of heart period (H), systolic (S) and diastolic (D) arterial pressure, and respiration (R) variability measured in healthy subjects monitored in a resting state and during conditions of postural and mental stress. MAIN RESULTS: Compared with the traditional univariate metric of short-term complexity, multivariate measures provide additional information with plausible physiological interpretation, such as (i) the dampening of respiratory sinus arrhythmia and activation of the baroreflex control during postural stress; (ii) the increased complexity of heart period and blood pressure variability during mental stress, reflecting the effect of respiratory influences and upper cortical centers; (iii) the strong influence of D on S, mediated by left ventricular ejection fraction and vascular properties; (iv) the role of H in reducing the complexity of D, related to cardiac run-off effects; and (v) the unidirectional role of R in influencing cardiovascular variability. SIGNIFICANCE: Our results document the importance of employing a network perspective in the evaluation of the short-term complexity of cardiovascular and respiratory dynamics across different physiological states.

Fat crystallisation at oil-water interfaces.

This review focuses on recent advances in the understanding of lipid crystallisation at or in the vicinity of an interface in emulsified systems and the consequences regarding stability, structure and thermal behaviour. Amphiphilic molecules such as emulsifiers are preferably adsorbed at the interface. Such molecules are known for their ability to interact with triglycerides under certain conditions. In the same manner that inorganic crystals grown on an organic matrix see their nucleation, morphology and structure controlled by the underlying matrix, recent studies report a templating effect linked to the presence of emulsifiers at the oil/water interface. Emulsifiers affect fat crystallisation and fat crystal behaviour in numerous ways, acting as impurities seeding nucleation and, in some cases, retarding or enhancing polymorphic transitions towards more stable forms. This understanding is of crucial importance for the design of stable structures within emulsions, regardless of whether the system is oil or water continuous. In this paper, crystallisation mechanisms are briefly described, as well as recent technical advances that allow the study of crystallisation and crystal forms. Indeed, the study of the interface and of its effect on lipid crystallisation in emulsions has been limited for a long time by the lack of in-situ investigative techniques. This review also highlights reported interfacial effects in food and pharmaceutical emulsion systems. These effects are strongly linked to the presence of emulsifiers at the interface and their effects on crystallisation kinetics, and crystal morphology and stability.

K-nearest-neighbor conditional entropy approach for the assessment of the short-term complexity of cardiovascular control.

Complexity analysis of short-term cardiovascular control is traditionally performed using entropy-based approaches including corrective terms or strategies to cope with the loss of reliability of conditional distributions with pattern length. This study proposes a new approach aiming at the estimation of conditional entropy (CE) from short data segments (about 250 samples) based on the k-nearest-neighbor technique. The main advantages are: (i) the control of the loss of reliability of the conditional distributions with the pattern length without introducing a priori information; (ii) the assessment of complexity indexes without fixing the pattern length to an arbitrary low value. The approach, referred to as k-nearest-neighbor conditional entropy (KNNCE), was contrasted with corrected approximate entropy (CApEn), sample entropy (SampEn) and corrected CE (CCE), being the most frequently exploited approaches for entropy-based complexity analysis of short cardiovascular series. Complexity indexes were evaluated during the selective pharmacological blockade of the vagal and/or sympathetic branches of the autonomic nervous system. We found that KNNCE was more powerful than CCE in detecting the decrease of complexity of heart period variability imposed by double autonomic blockade. In addition, KNNCE provides indexes indistinguishable from those derived from CApEn and SampEn. Since this result was obtained without using strategies to correct the CE estimate and without fixing the embedding dimension to an arbitrary low value, KNNCE is potentially more valuable than CCE, CApEn and SampEn when the number of past samples most useful to reduce the uncertainty of future behaviors is high and/or variable among conditions and/or groups.

Short-term complexity indexes of heart period and systolic arterial pressure variabilities provide complementary information.

It is unclear whether the complexity of the variability of the systolic arterial pressure (SAP) provides complementary information to that of the heart period (HP). The complexity of HP and SAP variabilities was assessed from short beat-to-beat recordings (i.e., 256 cardiac beats). The evaluation was made during a pharmacological protocol that induced vagal blockade with atropine or a sympathetic blockade (beta-adrenergic blockade with propranolol or central sympathetic blockade with clonidine) alone or in combination, during a graded head-up tilt, and in patients with Parkinson's disease (PD) without orthostatic hypotension undergoing orthostatic challenge. Complexity was quantified according to the mean square prediction error (MSPE) derived from univariate autoregressive (AR) and multivariate AR (MAR) models. We found that: 1) MSPE(MAR) did not provide additional information to that of MSPE(AR); 2) SAP variability was less complex than that of HP; 3) because HP complexity was reduced by either vagal blockade or vagal withdrawal induced by head-up tilt and was unaffected by beta-adrenergic blockade, HP was under vagal control; 4) because SAP complexity was increased by central sympathetic blockade and was unmodified by either vagal blockade or vagal withdrawal induced by head-up tilt, SAP was under sympathetic control; 5) SAP complexity was increased in patients with PD; and 6) during orthostatic challenge, the complexity of both HP and SAP variabilities in patients with PD remained high, thus indicating both vagal and sympathetic impairments. Complexity indexes derived from short HP and SAP beat-to-beat series provide complementary information and are helpful in detecting early autonomic dysfunction in patients with PD well before circulatory symptoms become noticeable.

From neurovascular coupling to neurovascular cascade: a study on neural, autonomic and vascular transients in attention.

Mental processes bring about neural, vascular and autonomic changes in the brain cortex. Due to the different nature of these modifications, their onsets show no synchrony and time dynamics is often strongly dissimilar. After acquiring data from a group of 16 subjects, we estimated temporal correlation between task and signals in order to assess possible influences induced by an attentive task on electroencephalographic (EEG), heart rate variability (HRV), oxy- and deoxy-haemoglobin concentration signals. We also investigated correlations and time delays between couples of different biological signals. This allowed for the isolation of a subgroup of subjects showing similar tracks. Cardiac frequency and deoxy-haemoglobin signals displayed a strong positive correlation with the task design, while EEG alpha rhythm and oxygenation showed a negative correlation. Neural electrical response was nearly instantaneous with respect to the task progression, and autonomic response showed a mean delay of about 15 s and a slower hemodynamic response (mean delay above 20 s) was finally induced. Globally, the task elicited a cascade of responses, in which delays can be quantified.

Study of neurovascular and autonomic response in a divided attention test by means of EEG, ECG and NIRS signals.

We evaluated neurovascular and autonomic response to a Divided Attention task within a group of 16 healthy subjects, by means of Electroencephalography, Electrocardiography, functional Near Infrared Spectroscopy techniques, acquired simultaneously. We exctracted Alpha (8-13,5 Hz) and Beta (13,5-30 Hz) power rhythms with a spectral autoregressive residual model, and inter-beat-interval (RR series) and separated superficial (extracortical) and depth NIRS contribution. Cross Correlation Function at different time lags was then calculated between each signal and the task, modeled as a square wave and among couples of signals, in order to evaluate the sequence of activation of the different physiological districts involved and the common information shared. Results showed the presence of a cascade of responses and a strong influence by the block task on each signal, representative of the neurovascular coupling elicited by the cognitive cerebral activation.

The evaluation of hepatocellular carcinoma with biphasic contrast enhanced helical CT scan.

OBJECTIVE: To evaluate the role of biphasic contrast-enhanced helical CT including Hepatic Arterial Phase (HAP) imaging with Portal Venous Phase (PVP) imaging, in the detection and characterization of hepatocellular carcinomas. METHODS: The study included 40 patients (M = 26, F = 14) with histopathologically proven HCC. Age range was between 30-85 years (mean = 55) by following consecutive patients with cirrhosis in whom Hepatocellular carcinoma was diagnosed or suspected either by raised serum a (alpha)-fetoprotein level or Ultrasound. RESULTS: Biphasic contrast-enhanced examination revealed a total of 85 lesions in these 40 patients, out of which 13 were unifocal, 12 showed a dominant mass with satellite lesions, 2 showed cluster of contiguous nodules and 13 were multifocal HCCs. Mean diameter was 3.1 cm, ranging from 0.8 to 14 cm. On HAP imaging 85% were detected. (hyperattenuating = 69, hypoattenuating = 3) while on PVP imaging detectibility was only 48% (hyperattenuating = 2, hypoattenuating = 39). Hence detectibility was significantly (p = 0.008) superior in HAP as compared to PVP imaging. In 7 patients (17%) tumor was visible only on HAP images. Venous invasion was present in 12 patients (30%) while arterio-portal shunting was seen in 5 patients (13%). CONCLUSION: Biphasic contrast enhanced helical CT is a useful method in detection and characterization of HCC.

The role of magnetic resonance cholangiopancreatography (MRCP) in obstructive jaundice.

OBJECTIVE: To evaluate the diagnostic value of MRCP in studying the sites and cause of obstructive jaundice in comparison with other imaging modalities at the Department of Radiology, Aga Khan University Hospital, from January 1999 to May 2001. METHODS: Forty nine consecutive patients included 19 men and 30 women, suspected of obstructive jaundice. Patients underwent ultrasound (n = 49), CT (n = 11), ERCP (n = 25) and biliary surgery (n = 17). Final diagnosis was established by surgical exploration, endoscopic sphincterectomy, cytology and clinical follow up. RESULTS: Of the 49 patients 17 had choledocholithiasis. Twenty five patients had malignant strictures, out of which 11 had non-specific malignant strictures, 7 had pancreatic carcinoma, 3 had Klatskin tumors, 3 had periampullary carcinoma and 1 had gallbladder carcinoma. Six patients had benign strictures and 1 patient had choledochal cyst. Overall, MRCP was sensitive (88%) and specific (96.8%) in detecting choledocholithiasis. MRCP sensitivity and specificity in detecting benign main bile duct stricture was equal to 83.3% and 97.6% respectively, and 92% and 100% for malignant stricture. CONCLUSION: Our prospective study confirms that MRCP, a noninvasive and well tolerated imaging technique is of value in the diagnosis of obstructive jaundice.

Unenhanced helical CT of ureterolithiasis: incidence of secondary urinary tract findings.

OBJECTIVE: To determine the incidence of secondary signs of obstruction in patients with ureteral stones on unenhanced helical CT scans. MATERIAL AND METHODS: Three hundred consecutive patients with suspected renal colic referred by the emergency department for an unenhanced helical CT scan were evaluated. One hundred and thirty two patients with ureteric calculi were viewed prospectively for the secondary signs of obstruction, which include hydronephrosis, hydroureter, perinephric stranding, nephromegaly, periureteral edema and difference in attenuation between acutely obstructed kidney and unobstructed kidney. RESULTS: In the evaluated 132 patients, calculi were present in the proximal, mid and distal ureter in 12, 18 and 112 patients respectively. Four patients had a contralateral ureteric calculus while none had more than one ureteric calculus on the same site. Concurrent renal parenchymal calculi were seen in 40 patients with ureteric stones, hydronephrosis in 69, hydroureter in 93 and perinephric strandings in 66 patients. Nephromegaly was seen in 15 and periureteral edema in 42 patients. In 87% patients with acute renal obstruction, the affected kidney was less dense than the unobstructed kidney. Only 5 of 132 patients had no associated findings. CONCLUSION: Unenhanced helical CT has rapidly become the imaging technique of choice in evaluating patients with acute ureteric colic. The secondary signs of obstruction provide supportive evidence of acute obstructive process.

Diagnosis of pulmonary embolism with helical C.T. scan.

OBJECTIVE: To determine the role of helical C.T. scan in the diagnosis of pulmonary embolism. SETTING: Radiology department, Aga Khan University Hospital. One year prospective study May 2001 to May 2002. METHODS: Sixty patients suspected of having pulmonary embolism were included in this study. Helical C.T. scan chest was performed from aortic arch to lung bases with intravenous contrast medium. Images were acquired in mediastinal and lung windows. Image interpretation was performed on the console and hard copies for main branch and segmental thrombus. RESULTS: Fifteen patients were diagnosed of having pulmonary embolism on C.T. scan. Clinical correlation and follow up with pulmonary angiography and Doppler ultrasound of leg was carried out. Pulmonary angiography was performed in one patient with embolectomy done after confirmation of diagnosis. 8 patients had associated DVT confirmed on Doppler sonography. Sensitivity of helical C.T. is 93.75%, specificity 100% and positive predictive value 95.65%. CONCLUSION: Helical CT scan is a quick, easy and accurate imaging modality for diagnosing pulmonary embolism.

A simultaneous packed column supercritical fluid chromatographic method for ibuprofen, chlorzoxazone and acetaminophen in bulk and dosage forms.

A reproducible and efficient method for the separation and estimation of ibuprofen, chlorzoxazone and acetaminophen has been developed using packed column supercritical fluid chromatography (SFC). The separations were performed on an ODS-RP JASCO column employing methanol modified supercritical fluid CO(2) as the mobile phase. The densities and polarities of the mobile phase were optimised from the effects of pressure, temperature and modifier concentration on retention times. In addition a flow programming of the mobile phase helped to obtain better resolution and a faster elution for acetaminophen. The analytes were detected using a uv detector at 254 nm. The study includes a successful attempt at quantitation of the 3 drugs. Chromatographic figures of merit, linear dynamic range, limit of quantitation (LOQ), precision and accuracy etc. were determined to assess the viability of the method. The method has been extended to commercial dosage forms containing all 3 drugs.

The adsorption of bile salts on activated carbon.

Activated carbon (AC) has been shown to be effective in reducing serum cholesterol and triglycerides. The mechanism for this action is proposed to be a result of the removal of bile salts in the gut. In this paper, the adsorption of cholate, glycocholate, taurocholate, chenodeoxycholate and deoxycholate on AC is studied in vitro. The results indicate that AC has a high capacity for bile salts, completely removing them from solutions of up to 5 mM and at a rate consistent with physiological activity. Of the 2 types of AC tested, one was shown to exhibit greater capacity and selectivity over the other. A negligible effect was seen with variation of pH through the range 7-9. Desorption occurs in the presence of bile salt-free buffer, but to a minimal extent. Based on these data, the adsorption of bile salts by AC appears to be a likely mechanism for AC-induced reduction of serum lipids.