Pharmacokinetics, hepatic biotransformation and biliary and urinary excretion of bromosulfophthalein (BSP) in an experimental liver disease mimicking biliary cirrhosis

We studied the hepatic handling of bromosulfophthalein in healthy rabbits with hepatic coccidiosis 28 days after an experimental infection with sporulated oocysts of Eimeria stiedai, an experimental model of liver disease histopathologically resembling primary biliary cirrhosis in man. A pharmacokinetic study of the results was performed following a multicompartmental model with 7 transfer constants to describe the physiological disposition of the dye. The study showed that the plasma disappearance, distribution volume (Vi), hepatic biotransformation and the biliary and urinary elimination of conjugated (BSPc) and unconjugated (BSPu) bromosulfophthalein were markedly altered. Whereas Vi and urinary excretion of the dye were significantly increased, the hepatic clearance, biotransformation and biliary excretion of BSPc and BSPu were drastically reduced in infected rabbits. Satisfactory agreement was obtained between the experimental and estimated data, particularly those relating to biotransformation clearance and biliary and urinary excretion of the dye. These results demonstrate that severe liver disease in rabbits with histopathological liver alterations resembling several hepatic dysfunctions in man markedly reduce hepatic uptake, metabolism and biliary excretion of a xenobiotic such as BSP.     

Data compression: effect on diagnostic accuracy in digital chest radiography

High-resolution digital images make up very large data sets that are relatively slow to transmit and expensive to store. Data compression techniques are being developed to address this problem, but significant image deterioration can occur at high compression ratios. In this study, the authors evaluated a form of adaptive block cosine transform coding, a new compression technique that allows considerable compression of digital radiographs with minimal degradation of image quality. To determine the effect of data compression on diagnostic accuracy, observer tests were performed with 60 digitized chest radiographs (2,048 x 2,048 matrix, 1,024 shades of gray) containing subtle examples of pneumothorax, interstitial infiltrate, nodules, and bone lesions. Radiographs with no compression, with 25:1 compression, and with 50:1 compression ratios were presented in randomized order to 12 radiologists. The results suggest that, with this compression scheme, compression ratios as high as 25:1 may be acceptable for primary diagnosis in chest radiology.     

Video-EEG Study of Psychogenic Nonepileptic Seizures: Differential Characteristics in Patients with and without Epilepsy

Summary:  Purpose: Psychogenic nonepileptic seizures (PNES) are episodes that may resemble epileptic seizures (ES) but are not associated with abnormal electrical discharges in the brain. Video-EEG recording of a typical episode is considered the best diagnostic tool available. PNES are, however, also documented in patients with epilepsy (PNES/ES). The purpose of this study was to assess this comorbid population, focusing on the differences between patients with PNES/ES and patients with PNES alone.
Methods: We reviewed 110 PNES episodes, occurring spontaneously or induced by means of suggestion techniques, recorded in our video-EEG laboratory over a period of eight years. We identified two subgroups of patients, consisting of 85 PNES cases and 25 PNES/ES cases, and assessed any differences in their characteristics by reviewing a number of variables (age, sex, clinical features, antiepileptic therapy, age of onset, time to diagnosis, pathological history, and length of follow-up).
Results: The comparison between the two subgroups revealed that PNES/ES patients displayed some statistically significant differences when compared with PNES alone patients, i.e., younger age, a higher percentage of spontaneously activated events, a shorter disease duration, a longer time to PNES diagnosis, and a lower percentage lost at follow-up.
Conclusions: This study confirms that PNES is a common, though probably underestimated, occurrence in epilepsy services. Our results shed light on some different characteristics between PNES and PNES/ES patients.     

High levels of functional endopeptidase 24.11 (CD10) activity on human thymocytes: preferential expression on immature subsets.

Although it is now well established that cells of the immune system express most of the exopeptidases described so far, little information is available concerning the identification and the characterization of the peptidases associated with the surface of human thymocytes. In the present study we have focused on CD10 expression on thymocytes using both FACS and enzymatic analysis. Unfractionated intact human thymocytes were shown to express significant levels of CD10-specific enzymatic activity, as assessed by the hydrolysis of the neutral endopeptidase (NEP) substrate Suc-Ala-Ala-Phe-pNA and of D-Ala2-Leu-enkephalin, a typical NEP substrate. CD10 activity was abolished by specific NEP inhibitors, including thiorphan, retrothiorphan and phosphoramidon. Moreover, high performance liquid chromatography (HPLC) analysis showed that intact thymocytes and purified NEP hydrolysed thymopentin, a thymic factor known to induce the maturation of prothymocytes into thymocytes. Finally, CD 10/NEP was preferentially associated with CD3- CD3low and immature CD4- CD8- thymocytes. The data demonstrate for the first time that human thymocytes express functional NEP and suggest a role for this enzyme in the maturation of human thymocytes.     

Regional cerebral flow velocity waveforms in the human fetus.

The purpose of this study was to determine regional cerebral flow velocity waveforms in the human fetus. Flow velocity waveforms were determined at the level of the middle cerebral artery, vertebral artery, and intracerebellar arteries in 25 fetuses between 23 and 39 weeks' gestation. The pulsatility index was used to quantify the waveforms. Technically acceptable waveforms were obtained at all three vessels in 20 fetuses. The pulsatility index was lowest for the intracerebellar artery in all the fetuses studied. The pulsatility indices of the vertebral artery and middle cerebral artery were not significantly different. These data suggest that significant fetal regional cerebral blood flow differences occur in utero, with intracerebellar arterial resistance being lower than resistance in other regions of the brain.     

Imaging of acute mesenteric ischemia using multidetector CT and CT angiography in a porcine model

Acute mesenteric ischemia, a frequently lethal disease, requires prompt diagnosis and intervention for favorable clinical outcomes. This goal remains elusive due, in part, to lack of a noninvasive and accurate imaging study. Traditional angiography is the diagnostic gold standard but is invasive and costly. Computed tomography (CT) is readily available and noninvasive but has shown variable success in diagnosing this disease. The faster scanning time of multidetector row CT (M.D.CT) greatly facilitates the use of CT angiography (CTA) in the clinical setting. We sought to determine whether M.D.CT-CTA could accurately demonstrate vascular anatomy and capture the earliest stages of mesenteric ischemia in a porcine model. Pigs underwent embolization of branches of the superior mesenteric artery, then imaging by M.D.CT-CTA with three-dimensional reconstruction protocols. After scanning, diseased bowel segments were surgically resected and pathologically examined. Multidetector row CT and CT angiography reliably defined normal and occluded mesenteric vessels in the pig. It detected early changes of ischemia including poor arterial enhancement and venous dilatation, which were seen in all ischemic animals. The radiographic findingsd—compared with pathologic diagnosesd—predicted ischemia, with a positive predictive value of 92%. These results indicate that M.D.CT-CTA holds great promise for the early detection necessary for successful treatment of acute mesenteric ischemia. Presented at the Forty-Sixth Annual Meeting of The Society for Surgery of the Alimentary Tract, Chicago, Illinois, May 14–18, 2005 (oral presentation). Supported by the Karin Grunebaum Research Fellowship, Harvard Medical School (D.E.R.), the German Research Fellowship, German Research Foundation STR 690/1-1 (O.S.), and the Phillip H. Meyers Grant from the Society of Gastrointestinal Radiologists (S.P.T.).     

Reduction in the middle cerebral artery pulsatility index after decompression of polyhydramnios in twin gestation.

Amniotic fluid decompression was performed for symptomatic polyhydramnios complicating four sets of discordant twin gestations. Doppler ultrasound waveforms of the middle cerebral artery were determined before and after the procedure in seven of the eight fetuses. After amniocentesis, the pulsatility index of the middle cerebral artery (PIMCA) was reduced in all fetuses (p < 0.01). When one considers only the larger twin in each set, the magnitude of the change in PIMCA was relatively consistent among the different sets (-0.60 +/- 0.14; p < 0.01; range, -0.45 to -0.79). The smaller twins showed a much more variable response (-0.82 +/- 0.70; range, -0.05 to -1.75). The pulsatility index of the umbilical artery (PIUA) showed no consistent trend in the five subjects in which it was determined. In principle, the cerebrovascular dilation indicated by the PIMCA measurements may in part be due to acute increases in maternal and fetal carbon dioxide tensions following relief of maternal restrictive lung dysfunction. More importantly, the acute fall in amniotic fluid pressure--the external pressure to which the fetoplacental unit is exposed--leads to pooling of blood in fetal and placental veins, and thereby reduces the effective blood volume of the fetoplacental unit. This effective hypovolemia, functionally analogous to that produced by fetal hemorrhage, elicits changes in regional vascular resistances that favor cerebrovascular perfusion. The impact of acute amniotic fluid decompression on the fetal circulation reflected in the marked changes in PIMCA suggests a role for monitoring to avoid large acute changes in pressure during therapeutic amniocentesis.