Background: Differences in the pharmacokinetics of the enantiomers of ketamine have been reported. The authors sought to determine whether these differences extend to pulmonary uptake and peripheral tissue distribution and to test the hypothesis that tissue distribution of the stereoisomers differs because of carrier-mediated drug transport.
Methods: The dispositions of markers of intravascular space and blood flow (indocyanine green, ICG) and total body water and tissue perfusion (antipyrine) were determined along with S-(+)- and R-(-)-ketamine in five mongrel dogs. The dogs were studied while anesthetized with 2.0% halothane. Marker and drug dispositions were described by recirculatory pharmacokinetic models based on frequent early and less-frequent later arterial blood samples. These models characterize pulmonary uptake and the distribution of cardiac output into parallel peripheral circuits.
Results: Plasma elimination clearance of the S-(+)-ketamine enantiomer, 29.9 ml [middle dot] min-1 [middle dot] kg-1, was higher than that of the R-(-)-enantiomer, 22.2 ml [middle dot] min-1 [middle dot] kg-1. The apparent pulmonary tissue volumes of the ketamine S-(+) and R-(-)-enantiomers (0.31 l) did not differ and was approximately twice that of antipyrine (0.16 l). The peripheral tissue distribution volumes and clearances and the total volume of distribution (2.1 l/kg) were the same for both stereoisomers when elimination clearances were modeled from the rapidly equilibrating peripheral compartment. 相似文献
BACKGROUND: Premature atherosclerosis is a clinical feature in untreated acromegaly. Increased postprandial lipoprotein remnant levels are associated with premature atherosclerosis. In most studies, remnants have been measured indirectly using retinyl esters (RE) as a chylomicron core label. Remnants can also be directly quantified by immunoseparation using monoclonal antibodies to apolipoprotein (apo) AI and apo B100 to remove nonremnant lipoproteins. Cholesterol is quantified in the remaining apo E-rich remnant fraction (RLP-C). OBJECTIVE: The aim of the present study was to investigate the role of postprandial lipaemia in patients with acromegaly to further define abnormalities leading to increased susceptibility for atherosclerosis. PATIENTS: In a case-control study, the plasma postprandial lipoprotein remnant fraction (RLP-C and RE) were analysed in six patients with active acromegaly [two females, four males; aged 53 +/- 9 years; body mass index (BMI), 29 +/- 4 kg/m2] and in six normolipidaemic control subjects (matched for age, gender, BMI and apo E genotype). They underwent an oral vitamin A fat loading test. RESULTS: Baseline plasma triglycerides (TG) were not significantly different in patients (1.75 +/- 0.71 mM) and controls (1.15 +/- 0.46 mM). Lipoprotein lipase activity was significantly lower in patients than in controls (108 +/- 21 vs. 141 +/- 19 U/l, respectively; P < 0.05). Baseline plasma apo E levels were higher in patients (60.8 +/- 7.9 mg/l) than in controls (48.3 +/- 5.9 mg/l; P < 0.05). No differences were found in the area under the postprandial TG curve (AUC-TG), the incremental AUC-TG (DeltaAUC-TG) and AUC-RE in the Sf < 1000 remnant fraction. However, fasting plasma RLP-C concentrations, isolated by immunoseparation, were increased in patients with active acromegaly (0.41 +/- 0.13 mM) compared to control subjects (0.20 +/- 0.07 mM; P < 0.05). Incremental postprandial RLP-C response (corrected for fasting values) was also significantly elevated in patients (2.14 +/- 1.19 mM/h/l) compared to controls (0.86 +/- 0.34 mM/h/l; P < 0.05). In both groups, the maximal RLP-C concentration was reached between 2 and 4 h. CONCLUSIONS: In conclusion, the atherogenic postprandial remnants, represented by RLP-C, were significantly elevated at baseline and in the postprandial period, whereas the larger-sized remnants, represented by retinyl esters (Sf < 1000), were not different from controls. The disturbances in the postprandial RLP-C response increased the susceptibility for premature atherosclerosis as observed in patients with acromegaly. 相似文献
We have investigated the ability of cells obtained from both normal and immune mice by bronchoalveolar lavage (BACs) to kill Schistosoma mansoni larvae in vitro. In cultures with mechanically derived schistosomules, high levels of larvicidal activity were displayed by BACs from both normal and irradiated cercaria-immunized C57BL/6 mice. Based on effector-to-target-cell ratios, BAC-mediated killing was two- to threefold more efficient than killing mediated by macrophage-rich cell populations obtained from the peritoneal cavity. BACs from normal A/J mice were essentially as larvicidal as normal C57BL/6 cells. However, BACs from a strain of mouse (P/J) with a known macrophage defect possessed negligible larvicidal activity. Macrophages made up 85 to 95% of BACs from all three strains tested. In contrast to cells of the IC-21 macrophage cell line, B6 BACs did not show enhanced killing activity when preincubated with lymphokine-containing supernatants. Lung schistosomules harvested 10 days after cercarial penetration were refractory to BAC-mediated killing. 相似文献
Durch eine fractionierte Aufheberung des Duodenalsafts wurde folgendes festgestellt. Die PH-werte der einzelnen Proben schwanken innerhalb weiten Grenzen von PH 8.5 bis > 1.0, kleinere Schwankungen sind häufiger. Die grössten Schwankungen werden durch das Einströmen des sauren Magensafts ins Duodenum, die die neutrale oder leicht alkalische Reaktion in eine stark saure ändert, hervorgerufen. In Fällen von Achylia gastrica sind die Schwankungen der PH-Werte viel kleiner um etw. 1.5 PH. In einem Falle starker Hyperazidität wurde in allen Proben konstant sehr niedrige PH-Werte gefunden. Die Lipasemenge der einzelnen Proben ist eine sehr variierende, und schwankt im grossen und ganzen mit den PH-Werten parallel. Bei PH-Werten bis 4.5-5.0 findet man konstant eine sehr geringe Lipasewirkung, bei Werten von PH 6.5–8.5 ist die lipolytische Kraft des Duodenalsafts am stärksten, aber in den einzelnen Proben eine sehr schwankende, auch bei ungefähr derselben Reaktion. Die Diastase und das Trypsin folgen im allgemeinen die für die Lipase aufgestellten Regeln, doch findet man auch bei relativ stark saurer Reaktion eine wenn auch nicht grosse Trypsinwirkung. Es scheint als ob die Salzsäure die Lipase direkt zerstört. In einem Falle pancreatogener Fettdiarrhoe wurde in allen den aufgeheberten Proben innerhalb c. 2 1/2 Stunden konstant eine sehr geringe Lipasemenge bei einem hohen und stetig steigenden PH-Wert gefunden, was als pathologisch angesehen werden muss. 相似文献
Thirty symptomatic indirect carotid cavernous fistulas were treated between 1978 and 1986 with a variety of treatment modalities. Combined carotid artery and jugular vein compression resulted in a complete cure in seven of 23 patients (30%) and improvement in one additional patient. There were no complications from this treatment, which is performed by the patient on an outpatient basis. Patients in whom carotid jugular compression therapy failed or who demonstrated cortical venous drainage or visual decline were treated with intravascular embolization. Embolization resulted in complete cure in 17 of 22 (77%) and improvement in four of 22 (18%). One patient required surgical excision of the involved dura after embolization to achieve complete cure. There was one permanent complication (stroke), which resulted in mild weakness caused by clot formation on a catheter. 相似文献
Right-hemispheric organization of speech has been observed following early left-sided brain lesions involving the language cortex. The authors studied speech organization in hemiparetic patients with pre- and perinatally acquired lesions in the left periventricular white matter using fMRI, and found that right-hemisphere activation correlated with left facial motor tract involvement. This suggests that the impairment of speech motor output from the left hemisphere plays an important role in this alteration of language representation. 相似文献
A newborn with pulmonary atresia with intact ventricular septum (PA-IVS) was treated with radiofrequency current perforation of the atretic pulmonary valve. As the right ventricle was hypoplastic (z-value of the tricuspid valve: —4) the arterial duct was stented with a Gianturco-Roubin GR II stent. Early postinterventionally, the patient became cyunotic and compromised blood flow across the stented ductus arteriosus despite adequate stent position was detected echographically. The newborn was treated successfully with the implantation of a Palmaz stent (Johnson & Johnson Interventional Systems, Warren, NJ, USA) into the obstructed Gianturco-Roubin GR II stent. The Gianturco-Roubin GR II stents might be associated with the risk of early stent stenosis after implantation in actively contracting tissues like the ductus arteriosus. In patients with early stent stenosis after ductal stenting, bailout implantation of a subsequent stent can be performed. Transcatheter procedures can be effective means for therapy of PA-IVS . (J Interven Cardiol 2000;13:39–44) 相似文献