LIVER BIOPSY VERSUS ULTRASOUND IN METHOTREXATE-TREATED PSORIASIS: A DECISION ANALYSIS

Before starting methotrexate therapy for cases of recalcitrant psoriasis, a liver biopsy has been usual in order to exclude cirrhosis and moderate or severe fibrosis, which are contraindications for methotrexate treatment. As mortality and morbidity of liver biopsy are not negligible, and as this invasive procedure is unpleasant for the patient and urges clinical admission, we evaluated the possibility of ruling out severe liver pathology by means of ultrasonography, which we compared to liver biopsy. We made this comparison by means of a decision tree. The advantages of this analysis are the clear definition of the decision problem and its alternatives, and the possibility of calculating the risk of each alternative, thus being able to choose the best diagnostic method. In this study, the results of various research groups are discussed, in which liver biopsy and liver ultrasound were compared. In our decision tree we used some of these results and other assumptions, based on comparable studies. We varied the biopsy mortality and the sensitivity of ultrasound to show the change in the risk of each alternative. Our analysis shows that the differences of expected values between the liver biopsy branch and the ultrasonography branch are relatively small. Therefore, we advise each center, which has at its disposal a specialist in liver ultrasonography, to re-evaluate its guidelines with regard to the detection of severe liver pathology before starting methotrexate for the treatment of psoriasis.     

Studies on the In-vitro Percutaneous Penetration of Indomethacin from Gel Systems in Hairless Mice

The influence of co-solvents on the in-vitro percutaneous penetration of indomethacin from gel systems was studied using a simplex lattice experimental design. Gel formulations were prepared by gelling the vehicle mixture of water, either alcohol or isopropanol and either propylene glycol or PEG 400 with 1% w/w Carbomer 940. Hairless mouse skin was employed as the barrier in a Franz-type diffusion cell. The penetration rates at steady state for seven formulations were fitted to a polynomial equation based on this simple lattice method and a three-dimensional plot was constructed. The formulation having the maximal penetration rate was determined to be the vehicle with a solvent ratio of water: alcohol: propylene glycol equal to 15:33:52, and which possessed a solubility parameter of 15 and a drug solubility of around 10 mg mL^?1. When the solubility parameter of the vehicle was > 15, the drug solubility increased. However, the penetration rate decreased with an increasing solubility parameter. For those vehicles with a solubility parameter < 15, both the drug solubility and the penetration rate decreased with a decrease in the solubility parameter. There was shown to be an approximately 20-fold increase in the relative enhancement factor when using both alcohol and isopropanol, but only a threefold increase for both propylene glycol and PEG 400, when compared with water.     

Decreased incidence of headache after accidental dural puncture in caesarean delivery patients receiving continuous postoperative intrathecal analgesia

To examine the effects of prolonged (> 24 h) intrathecal catheterization with the use of postoperative analgesia on the incidence of post–dural puncture headache (PDPH), charts of 45 obstetric patients who had accidental dural puncture following attempts at epidural block were reviewed retrospectively. Three groups were identified: Group I (n = 15) patients had a dural puncture on the first attempt at epidural block, but successful epidural block on a repeated attempt; Group II (n=17) patients had a dural puncture with immediate conversion to continuous spinal anaesthesia with catheterization lasting only for the duration of caesarean delivery; Group III (n= 13) patients had an immediate conversion to spinal anaesthesia and received post–caesarean section continuous intrathecal patient–controlled analgesia consisting of fentanyl 5 (ig'ml^-1 with bupivacaine 0.25 mg·ml^-1 and epinephrine 2 μg·ml^-1 with catheterization lasting >24 h. No parturient in group III developed a PDPH. This was substantially lower ( P < 0.009) than the 33% incidence for group I and the 47% incidence for group II. The incidence of a PDPH did not differ between group I and II. Similarly, there was no difference between group I and II with regard to requests for a blood patch. Patients receiving continuous intrathecal analgesia had excellent pain relief, could easily ambulate and none complained of pruritus, nausea, vomiting, sensory loss or weakness. In conclusion, indwelling spinal catheterization > 24 h with continuous intrathecal analgesia following accidental dural puncture in parturients may for some patients be a suitable method for providing PDPH prophylaxis and postoperative analgesia.     

A Critical Period of Ventricular Fibrillation More Susceptible to Defibrillation: Real-Time Waveform Analysis Using a Single ECG Lead

Previous studies have suggested that variations in the underlying ventricular fibrillation (VF) waveform may be one of the factors responsible for the probabilistic nature of defibrillation. The heart appeared to be more susceptible to defibrillation at higher absolute VF voltages (AVFV). This study investigated in an open-chest canine model (n = 8), a newly developed system that analyzed the VF waveform in real-time, instantaneously determined the time to shock, and immediately delivered a fixed low energy DC shock. A two parameter tracking technique using a running long-term and short-term AVFV average was devised to automatically identify a high voltage peak area of the VF waveform, which has been hypothesized to represent a critical period susceptible to defibrillation. Using a DC shock estimated at the 50% success level, the performance using this technique in 58 defibrillation trials was compared to the performance of the conventional method of shocking at a fixed time (random shock method) in 62 trials. Patch size, electrode location, and discharge voltage were kept constant while VF duration, transmyocardial resistance (TMR), energy delivered, and AVFV at the point of shock were measured. Shock energy and current, TMR, and VF duration were similar with both shock methods. A significantly higher AVFV was observed for trials performed with the peak shock method (0.66 ± 0.02 mV) as compared to trials performed with the random shock method (0.25 ± 0.09 mV) (P < 0.003). Using lead II as the only sensing lead, the success rate was increased in 6 of 8 dogs (75%) with the new method. One animal showed identical performance, and one animal a worse performance. The overall increase in success rate was 24% using a single ECG lead (range 0%-100%; P < 0.04). Our data document that using this algorithm a period of high VF voltage can be detected in realtime. The improved success in the majority of animals supports the hypothesis that a critical period susceptible to defibrillation exists during VF. However, the high AVFV detected using a single ECG lead did not translate to an improved success rate in all animals. This suggests that other factors in addition to the VF voltage measured on a single lead of the ECG are important in characterizing this critical period.     

Rate-Related and Autonomic Effects on Atrioventricular Conduction Assessed Through Beat-to-Beat PR Interval and Cycle Length Variability

Atrioventricular Conduction Variability. Introduction: Atrioventricular AV) conduction time varies on a beat-by-beat basis in response to the influences of cardiac efferent autonomic activity and rate-dependent electrical recovery processes. The goals of this study were to distinguish these effects on AV conduction time and to compare the variability in sinoatrial and AV nodal function. Methods and Results: The PR interval on the surface ECG served as an index of AV conduction time in this study of 14 adult human subjects undergoing a random interval breathing protocol. P and R waves were located by a template-matching algorithm. Spectral analysis allowed frequency-domain comparisons between PR and RR interval variability. Spectra of PR and RR intervals had similar power distributions, although the power of the RR interval spectra was much greater. Autonomic blockade with atropine plus propranolol reduced the power of both spectra. Standing significantly decreased the spectral power from 0.15 to 0.5 Hz for PR and RR spectra, and introduced a peak near 0.1 Hz in the mean PR and RR spectra, although the latter finding was significant only for the RR interval spectra. Propranolol had no significant effects on the PR and RR interval spectra. Linear regression analysis allowed quantification of the autonomic and recovery effects on AV conduction and showed which effect predominated. Simple linear regression confirmed in adults a previous finding in children that conduction time may be either positively or negatively correlated with cycle length. By multiple regression and transfer function analysis, the inverse relation seen in some subjects was attributed to the effect of recovery from the preceding cycle. With the preceding recovery period accounted for, the conduction time and cycle length of the current beat were positively correlated, presumably due to the parallel autonomic effects on the sinoatrial and AV nodes. The magnitude of the recovery effect predicted by the regression analysis was similar to published values. Conclusion: A noninvasive evaluation of the surface ECG can be used to compare variability in AV conduction time and cycle length and characterize the effects of autonomic efferent activity and rate-related recovery on AV nodal function.