SPARC, an extracellular matrix glycoprotein containing the follistatin module, is expressed by astrocytes in synaptic enriched regions of the adult brain

Although extracellular matrix (ECM) glycoproteins play important roles in neural development, their levels are generally believed to decrease in the adult brain. Immunohistochemical analysis indicates that the anti-adhesive ECM glycoprotein SPARC/osteonectin, which contains a follistatin ‘module’, is expressed in the adult rabbit nervous system. In the cerebellum, SPARC is present in Bergmann glia, with a strong signal along their radial fibres. SPARC, while enriched in membrane fractions, is not a transmembrane protein. In the hippocampus, colocalization of SPARC is observed in cells which express the astrocytic marker GFAP. The expression of SPARC by a subset of astrocytes, particularly in synaptic enriched areas, suggests a continuing role for the ECM in the adult brain.     

Diagnosis of ligament rupture of the ankle joint: Physical examination, arthrography, stress radiography and sonography compared in 160 patients after inversion trauma

We prospectively enrolled 160 consecutive patients with inversion trauma of the ankle in a diagnostic protocol that included physical examination within 2 days and at 5 days after trauma, arthrography, stress radiography, and ultrasonography. 135 patients had pathological lateral ligament laxity on the later physical examination or lateral ligament rupture diagnosed on arthrography and they were operated on. 122 of these patients had ligament ruptures.

At clinical follow-up after a minimum of half a year, all of the patients who were not operated on had stable joints without signs of previous ligament ruptures.

Delayed physical examination at 5 days after the injury led to the highest overall sensitivity (96%) and specificity (84%) for the detection of a ligament rupture. Additional diagnostic procedures, at a considerable cost, yielded little additional information.     

Behavioral treatment of bisexual aggression of an adult with developmental disabilities

This case study describes the use of a behavioral intervention to treat bisexual aggression of an adult with developmental disabilities. Treatment involved the suppression of deviant sexual behavior and enhancement of appropriate social interactions. Implementation of the intervention resulted in an immediate reduction in sexual aggression. Long-term follow-up indicated no further occurrences of the behavior.Discussion focuses on the limited data regarding the assessment and treatment of persons who are developmentally disabled and engage in deviant sexual behavior, determination of consenting sexual relations, and development of behavioral interventions.The comments of Lew Lewin are appreciated. Reprints can be obtained by contacting Duane Lundervold at LINC Behavioral Services, 1430 Willamette, Suite 363, Eugene, Oregon 97401.     

Brain Death Further Promotes Ischemic Reperfusion Injury of the Rabbit Myocardium

Background. Little is known about preload-dependent cardiac function after brain death (BD) and subsequent graft preservation.

Methods. A validated model of BD in rabbits was developed and myocardial performance was studied after BD induction and 1 hour of subsequent global hypothermic ischemia using a validated rabbit model and an isolated work-performing heart preparation.

Results. Significant decreases in stroke work, left ventricular contractility, and left ventricular relaxation were observed 2 hours after BD. After global hypothermic ischemia, significant decreases in stroke work, left ventricular contractility, and left ventricular relaxation were observed in the BD group compared with controls. Cardiac output and coronary flow were also significantly decreased in BD hearts compared with controls. Creatine kinase release was increased by 32.5% in BD hearts compared with controls.

Conclusions. In a rabbit model, BD combined with global hypothermic ischemia causes a significant decrease in left ventricular function compared with global hypothermic ischemia. This dysfunction may be attributed to a significant decrease in coronary flows in BD hearts.     

Carrier-mediated transport in the hepatic distribution and elimination of drugs, with special reference to the category of organic cations

Carrier-mediated transport of drugs occurs in various tissues in the body and may largely affect the rate of distribution and elimination. Saturable translocation mechanisms allowing competitive interactions have been identified in the kidneys (tubular secretion), mucosal cells in the gut (intestinal absorption and secretion), choroid plexus (removal of drug from the cerebrospinal fluid), and liver (hepatobiliary excretion). Drugs with quaternary and tertiary amine groups represent the large category of organic cations that can be transported via such mechanisms. The hepatic and to a lesser extent the intestinal cation carrier systems preferentially recognize relatively large molecular weight amphipathic compounds. In the case of multivalent cationic drugs, efficient transport only occurs if large hydrophobic ring structures provide a sufficient lipophilicity-hydrophilicity balance within the drug molecule. At least two separate carrier systems for hepatic uptake of organic cations have been identified through kinetic and photoaffinity labeling studies. In addition absorptive endocytosis may play a role that along with proton-antiport systems and membrane potential driven transport may lead to intracellular sequestration in lysosomes and mitochondria. Concentration gradients of inorganic ions may represent the driving forces for hepatic uptake and biliary excretion of drugs. Recent studies that aim to the identification of potential membrane carrier proteins indicate multiple carriers for organic anions, cations, and uncharged compounds with molecular weights around 50,000 Da. They may represent a family of closely related proteins exhibiting overlapping substrate specificity or, alternatively, an aspecific transport system that mediates translocation of various forms of drugs coupled with inorganic ions. Consequently, extensive pharmacokinetic interactions can be anticipated at the level of uptake and secretion of drugs regardless of their charge.     

Reactivated recombinant plasminogen activator inhibitor-1 (rPAI-1) effectively prevents thrombolysis in vivo.

The effects of human recombinant plasminogen activator inhibitor (rPAI-1) on thrombolysis with recombinant tissue-type plasminogen activator (rt-PA) were studied in a rabbit model of jugular vein thrombosis. Two functionally distinct rPAI-1 preparations were used in these experiments, including latent rPAI-1 (approximately 2 units of t-PA neutralizing activity per micrograms protein) and reactivated rPAI-1 (approximately 150 units/micrograms). Simultaneous intravenous infusion over 4 h of 1.7 mg/kg of reactivated rPAI-1 (inhibitory capacity approximately 0.5 mg/kg rt-PA) with 0.5 mg/kg of rt-PA completely prevented lysis of a jugular venous thrombus, whereas an equivalent amount of latent PAI-1 did not significantly influence clot lysis. These findings demonstrate that reactivated human rPAI-1 efficiently neutralizes thrombolysis with rt-PA in vivo. Since previous studies have suggested that elevated endogenous levels of PAI-1 do not attenuate the thrombolytic potency of rt-PA in the endotoxin-treated model, we compared the stability of complexes formed by 125I-rt-PA with reactivated human rPAI-1 and with rabbit PAI-1 in vitro. Our findings indicate that both forms of PAI-1 form SDS-stable complexes following incubation with 125I-rt-PA. Thus, it seems likely that elevated levels of active PAI-1 can negate the thrombolytic effects of rt-PA in vivo and argues against the possibility that t-PA can dissociate from PAI-1 and have its activity restored in the presence of a thrombus.(ABSTRACT TRUNCATED AT 250 WORDS)     

Failure of gas bladder inflation in striped bass: Effect on selenium toxicity

Young striped bass (Morone saxatilis) with uninflated gas bladders were less sensitive to selenate and more sensitive to selenite exposure than normally developing striped bass in 96-hour acute toxicity tests. Gas bladder inflation failure is a common problem in the culture of striped bass and some other species, and care should be taken to avoid the use of fish with uninflated gas bladders in research.     

Acute Renal Failure after Lung Transplantation: Incidence, Predictors and Impact on Perioperative Morbidity and Mortality

The incidence, predictors and clinical significance of acute renal failure (ARF) after lung transplantation are not well described. We retrospectively collected data on 296 patients transplanted at our center between April 1992 and December 2000; follow-up was extended until December 2002. Patients were initially divided into two groups: ARF (doubling of baseline creatinine within 2 weeks after surgery) and NoARF. The ARF group was subdivided into ARFD (dialyzed) and ARFnD (not dialyzed). The incidence of ARF was 56% (166/296), but most cases were ARFnD (n = 143). Independent predictors of ARFD (n = 23) were: baseline GFR (OR 0.98, CI 0.96-0.99, p = 0.012), pulmonary diagnosis other than COPD (OR 6.80, CI 1.5-30.89, p = 0.013), mechanical ventilation > 1 d (OR 6.16, CI 1.70-22.24, p = 0.006) and parenteral amphotericin B use (OR 3.04, CI 1.03-8.98, p = 0.045). Both ARFnD and ARFD were associated with longer duration of mechanical ventilation, increased hospital stay and increased early mortality. One-year patient survival was 92.3%, 81.8% and 21.7% in the NoARF, ARFnD and ARFD groups, respectively (p < 0.0001). After controlling for important covariates, ARFD remained associated with an increased hazard of dying (HR 6.77, CI 4.00-11.44, p < 0.0001). In conclusion, ARF occurs commonly after lung transplantation and affects important clinical outcomes, especially when dialysis is required.     

The imaging quality of angiodynography in the ilio-femoral tract

The imaging quality of angiodynography (Quantum; Philips) in the ilio-femoral tract was compared with uniplanar angiography. One hundred ilio-femoral tracts were investigated with both translumbar conventional angiography and angiodynography. The ilio-femoral tract was divided into five parts; proximal and distal common iliac, proximal and distal external iliac and common femoral. Stenosis was scored from 0-24, 25-49, 50-74, 75-99 and 100% and the lengths of those of 25% or more were measured in centimeters. Because the thickness of the subcutaneous fat layer decreases the depth range (normally 11.5 cm) of the 5.0 MHz transducer it was also measured in centimetres. The results showed that a significantly larger number of vessels were not seen (especially the common iliac) with an increasing thickness of the subcutaneous fat. The results based on the real-time imaging quality alone of angiodynography showed a reasonable accuracy of 83.9% when detecting stenoses graded from 0-24, 25-49, 50-74, 75-99 up to 100%. The clinically more important discrimination between a haemodynamically important stenosis of more than 50% showed a sensitivity of 88% and specificity of 98% on visual information alone. By integrating the peak velocity measurements to the results, this sensitivity rose to 95% and the specificity became 99%. The correlation in length was within a range of 1 cm in 94% and within 1-2 cm in 6% of the stenoses. In conclusion, angiodynography is a reliable technique for investigating the ilio-femoral tract.