Sinusoidal lining cell damage: the critical injury in cold preservation of liver allografts in the rat

We have previously defined viability limits in a rat transplantation model. All liver allografts stored in a simple preservation solution (NaCl 0.9%, CaCl2 2 mM) at 4 degrees C for 4 hr or at 37 degrees C for 1 hr were viable upon transplantation, but all those stored at 4 degrees C for 8 hr or at 37 degrees C for 2 hr were nonviable. Only cold-preserved, nonviable livers showed increased vascular resistance, platelet trapping and an initially low, but then high, rise in aspartate transaminase (AST) upon reperfusion, all suggesting injury to the microcirculation, with secondary injury to the hepatocyte. In the present study, we investigated the morphological changes that occur in livers stored for the defined critical times, using light and electron microscopy after perfusion-fixation. Accurate and reproducible identification of specimens as belonging to viable or nonviable and warm- or cold-preserved could be made in this way. Preservation in the cold first resulted in reversible changes consisting of cellular swelling, alterations of intracellular organelles, and partial denudation of the sinusoidal lining (cold-preserved viable group). Later, under conditions of nonviable cold preservation, detachment of cell bodies of sinusoidal lining cells with nuclear changes and almost complete denudation of the sinusoidal lining was observed. Endothelial cells of larger vessels were only injured mildly. In contrast, under conditions of warm preservation, changes involving mitochondria and later nuclei were found in hepatocytes, and blebbing was more extensive. Endothelial cells were spared relatively. We also examined livers stored in isotonic citrate solution at 4 degrees C for 8 hr and 16 hr, the critical times determined for this solution in another model of rat liver transplantation. The findings were very similar to storage in saline with respect to the changes in the sinusoidal lining cells after cold preservation for the two critical times. The results provide convincing evidence of a qualitative difference between warm and cold preservation injury, with relatively selective damage to hepatocytes or sinusoidal lining cells, respectively. Endothelial damage represents the primary event, resulting in the loss of organ viability following hypothermic storage. Thus morphology may serve as a useful viability marker after preservation.     

Assessment of different methods to detect increased autochthonous production of immunoglobulin G and oligoclonal immunoglobulins in multiple sclerosis.

The formulae for immunoglobulin G (IgG) synthesis rate, IgG(loc), IgG index, and IgG extended index in determining increased autochthonous production (intra-blood-brain barrier synthesis) of IgG was assessed in 50 chronic progressive multiple sclerosis patients. The results of all four formulae clearly show elevated intra-blood-brain barrier IgG synthesis in 35 patients, 94% of whom had oligoclonal immunoglobulins detected by the method of isoelectric focusing with immunofixation and silver staining (IEF-IS). The results from the four formulae are all normal in seven patients (none have oligoclonal immunoglobulins by IEF-IS) and are discordant in eight patients (five have oligoclonal immunoglobulins by IEF-IS). Whenever intra-blood-brain barrier synthesis of IgG is suspected, IEF-IS should be used to assay for oligoclonal immunoglobulins because this method is more sensitive than agarose electrophoresis with either Coomassie blue dye or silver stain (94% vs. 74% vs. 54%).     

Anthracycline cardiotoxicity.

Anthracycline drugs have been widely used as chemotherapeuticagents against a range of cancers, including sarcomas, carcinomas,leukaemias, and lymphomas. However, cardiotoxic effects, inparticular the development of cardiomyopathy, have limited theirclinical use. The observation of dose-dependent cardiotoxicityhas resulted in a recommended empirical dose limit of 450 mg/m²of body surface area. Age, gender, pre-existing heart disease,hypertension, and mediastinal irradiation have also been implicatedas factors contributing to the development of doxorubicin-associatedcardiomyopathy. However, cardiotoxicity may still occur at relativelylow levels of drug administration, even in individuals withno additional risk factors, and the onset may be delayed bymany years.¹ More recently, the use of trastuzumab, a monoclonalantibody directed against the HER2 receptor, has been     

Continuous Preperitoneal Infusion of Ropivacaine Provides Effective Analgesia and Accelerates Recovery after Colorectal Surgery: A Randomized, Double-blind, Placebo-controlled Study

Background: Blockade of parietal nociceptive afferents by the use of continuous wound infiltration with local anesthetics may be beneficial in a multimodal approach to postoperative pain management after major surgery. The role of continuous preperitoneal infusion of ropivacaine for pain relief and postoperative recovery after open colorectal resections was evaluated in a randomized, double-blinded, placebo-controlled trial.

Methods: After obtaining written informed consents, a multiholed wound catheter was placed by the surgeon in the preperitoneal space at the end of surgery in patients scheduled to undergo elective open colorectal resection by midline incision. They were thereafter randomly assigned to receive through the catheter either 0.2% ropivacaine (10-ml bolus followed by an infusion of 10 ml/h during 48 h) or the same protocol with 0.9% NaCl. In addition, all patients received patient-controlled intravenous morphine analgesia.

Results: Twenty-one patients were evaluated in each group. Compared with preperitoneal saline, ropivacaine infusion reduced morphine consumption during the first 72 h and improved pain relief at rest during 12 h and while coughing during 48 h. Sleep quality was also better during the first two postoperative nights. Time to recovery of bowel function (74 +/- 19 vs. 105 +/- 54 h; P = 0.02) and duration of hospital stay (115 +/- 25 vs. 147 +/- 53 h; P = 0.02) were significantly reduced in the ropivacaine group. Ropivacaine plasma concentrations remained below the level of toxicity. No side effects were observed.     

Characteristics of apathy in Parkinson's disease.

The objective of this study was to use the Lille Apathy Rating Scale to assess apathy in a large population of Parkinson's disease (PD) patients and identify several different apathy profiles. One hundred fifty-nine patients with probable PD and 58 healthy controls participated in the study. Apathy was assessed using the Lille Apathy Rating Scale. Motor, cognitive, and depressive symptoms were rated on standardized scales. Data were analyzed using linear regression and multivariate analyses of variance. Thirty-two percent of the PD patients were classified as apathetic. Apathy was more frequent in patients with dementia. The four apathy dimensions contributed differently to the overall severity of the apathetic condition. Action initiation and intellectual curiosity had a marked influence. Linear regression analysis revealed that the apathy level was mainly determined by cognitive impairment, not associated with the severity of motor symptoms, and only associated with the apathy subcomponent of the Montgomery and Asberg Depression Rating Scale. Apathy is highly prevalent in PD patients. Apathy profiles vary according to the clinical presentation of PD. The high prevalence of apathy in PD suggests the involvement of frontal-subcortical circuits. Although the neurochemical substrate of apathy remains poorly characterized, the strong link between apathy and cognitive impairment observed in several studies suggests the participation of nondopaminergic circuits.