Poly(HEMA)--based embolic material in endovascular surgery of liver

Physico-chemical and medico-biological methods, including hematology and cytology, were used in an evaluation of properties of poly(2-hydroxyethyl methacrylate) (poly(HEMA))-based embolic material indicated in the occlusion of branches of hepatic artery of patients with focal alterations of the liver. The elastographic method helped in predicting mechanical properties of the hydrogel material. Poly(HEMA) was mechanically stable for endovascular applications, exhibited no significant loss in elasticity and possessed consistency resembling the soft tissue of the organism. Analysis of blood in contact with poly(HEMA) hydrogel provided a control of its biological inertness. Recently, 315 patients with focal alterations of the liver, including hemobilic hemorrhages and both primary and metastatic tumors, underwent endovascular occlusion with poly(HEMA) emboli as a pre-surgical step or as a simple occlusive measure. Compared with a direct operation on hemangiomatous injuries in the liver without endovascular occlusion, embolization with poly(HEMA) allowed to reduce 2.5-3 times bleeding in the operational zone. At the same time, the poly(HEMA) embolic material induced activation of general hemostatic reaction in the postembolization period.     

Test-retest reliability of the alcohol use disorder identification test in a general population sample

Background: A number of different screening tests are frequently used in alcohol research, but our knowledge about the reliability of many of them is quite limited. Recently, this problem has received more attention. This article examines the test-retest reliability of one of these instruments—the Alcohol Use Disorder Identification Test (AUDIT)—in a general population sample.
Methods: A general population sample ( n = 457) was tested and, after approximately 1 month, was retested by using the AUDIT. Correlation between the two tests has been examined with the intraclass correlation coefficient and the κ coefficient in analysis of dichotomous variables. Specificity and sensitivity at a number of different cutoff scores have also been analyzed by using the first test as a criterion.
Results: On the item level, the correlations ranged between 0.6 and 0.8. The overall reliability of total AUDIT scores was 0.84. When stratified by gender, age, and consumer status, the total score reliability approximated 0.80 for all the categories except low alcohol consumers (0.51). Agreement using the recommended cutoff score of 8+ was also examined. The reliability (κ) observed in the whole sample was 0.691, which was interpreted as a substantial agreement. By this cutoff, 91% were correctly classified at retest compared with the first test. AUDIT 8+ showed higher reliability for males, young people, and moderate consumers and low reliability among low consumers. In terms of reliability, the most optimal cutoff for women turned out to be 6 or more.
Conclusions: According to these results, the test-retest reliability of AUDIT is high. The next step might be to examine to what extent the findings apply within health-care settings, which is what the test originally was designed for.     

Oxcarbazepine treatment of bipolar disorder

OBJECTIVE: To assess the effectiveness and safety of oxcarbazepine in bipolar disorder. METHOD: A chart review of naturalistic treatment with oxcarbazepine in 42 outpatients with DSM-IV bipolar disorder (10 males, 32 females; mean +/- SD age = 33.3 +/- 12.4 years; 25 with bipolar disorder type I, 4 with bipolar disorder type II, and 13 with bipolar disorder not otherwise specified) was conducted. Patients had received oxcarbazepine monotherapy or adjunctive therapy between April 2000 and April 2002. Treatment response was defined as a Clinical Global Impressions-Improvement scale score of 1 (marked improvement) or 2 (moderate improvement). RESULTS: Oxcarbazepine was moderately to markedly effective in 24 subjects (57%). Mixed symptoms were the most common indication (52% [22/42]). The mean oxcarbazepine dose was 1056.6 mg/day, and mean treatment duration was 16.2 weeks. Sedation (17/42, 40%) was the most common side effect, but 16 patients (38%) had no side effects. Twenty-two patients (52%) stopped treatment, mostly due to side effects (12/22). Males were more likely to respond than females (10/10 vs. 14/32, p =.006). Dose, bipolar subtype, indication, past nonresponse to mood stabilizers, concurrent mood stabilizer use, and monotherapy use of oxcarbazepine did not differentially predict response. CONCLUSION: Oxcarbazepine appeared effective in about one half of patients with bipolar disorder and was well tolerated.     

Understanding the basis of CD4(+) T-cell depletion in macaques infected by a simian-human immunodeficiency virus

The efficacy of candidate AIDS vaccines to mediate protection against viral infection and pathogenesis is evaluated, at a preclinical stage, in animal models. One model that is favored because the infecting virus is closely related to HIV-1 and because of the rapidity of pathogenic outcomes is the infection of Old World monkeys by simian-human immunodeficiency virus (SHIV) chimerae. We investigated the basis for the depletion of CD4(+) T lymphocytes in a SHIV-macaque model. Molecularly cloned SHIVs, SHIV-89.6 and SHIV-KB9, differ in the ability to cause CD4(+) T-cell loss at a given level of virus replication in monkeys. The envelope glycoproteins of the pathogenic SHIV-KB9 mediate membrane-fusion in cultured T lymphocytes more efficiently than the envelope glycoproteins of the non-pathogenic SHIV-89.6. The minimal envelope glycoprotein region that specifies this increase in membrane-fusing capacity was sufficient to convert SHIV-89.6 into a virus that causes profound CD4(+) T-cell depletion in monkeys. Conversely, two single amino acid changes that decrease the membrane-fusing ability of the SHIV-KB9 envelope glycoproteins also attenuated the CD4(+) T-cell destruction that accompanied a given level of virus replication in SHIV-infected monkeys. Thus, the ability of the HIV-1 envelope glycoproteins to fuse membranes, which has been implicated in the induction of viral cytopathic effects in vitro, contributes to the capacity of the pathogenic SHIV to deplete CD4(+) T lymphocytes in vivo.     

CpG oligonucleotides induce strong humoral but only weak CD4+ T cell responses to protein antigens in rhesus macaques in vivo

Oligonucleotides containing CpG motifs (CpG ODN) are strong adjuvants for humoral immune responses but data on cellular immune responses in primates are scarce. Rhesus macaque blood contained similar numbers of plasmacytoid dendritic cells and B cells, the key sensors of CpG ODN, as human blood, and these cells were activated by CpG-A and CpG-B in vitro. In vivo, both ODNs induced equal plasma levels of interferon-inducible protein 10 and similarly enhanced antibody responses following i.m. injections of the ODNs, protein antigen, and aluminium hydroxide into rhesus macaques, whereas antigen-specific CD4(+) T cell responses were only slightly increased by CpG ODN.     

On-line hemodiafiltration does not induce inflammatory response in end-stage renal disease patients: results from a multicenter cross-over study

BACKGROUND: On-line hemodiafiltration (HDF) represents the supreme blood purification modality for end-stage renal disease (ESRD) patients. Large-volume infusion of on-line prepared substitution fluid may, however, expose patients to inflammatory contaminants. As a result, on-line HDF might aggravate chronic inflammation, which correlates with malnutrition, cardiovascular disease, and mortality among ESRD patients. METHODS: In a multicenter cross-over study, 27 ESRD patients were randomly assigned to treatment with on-line HDF and low-flux hemodialysis (HD). After 6 months, patients were crossed to the other treatment modality, and treatment continued for another 6 months. Both on-line HDF and low-flux HD were conducted with polysulfone membranes and ultrapure dialysis fluid. Samples were drawn at the end of each treatment period. RESULTS: Inflammatory parameters were elevated in the study population when compared to healthy controls. Induction of interleukin-1 receptor antagonist (IL-1Ra) and tumor necrosis factor alpha (TNF-alpha) was comparable for on-line HDF and low-flux HD, and there was no intradialytic increase in cytokine production. As a result, interleukin-6 (IL-6) plasma levels did not differ significantly between the two treatment modalities. Similarly, no difference between on-line HDF and low-flux HD was observed for C-reactive protein (CRP) and albumin. Markers of endothelial cell activation (soluble intercellular and vascular cell adhesion molecules sICAM-1 and sVCAM-1) as well as the cardiovascular risk marker cardiac troponin T (cTnT) remained elevated compared to healthy subjects, but showed no difference between the two treatment modalities. CONCLUSIONS: On-line HDF, as the most effective renal replacement therapy, does not provoke inflammatory response and is both safe and highly biocompatible.     

Evoked electromyographic technique for quantitative assessment of the innervation status of laryngeal muscles

OBJECTIVES: The purpose of this study was to develop a minimally invasive, noninjurious evoked electromyographic technique that could accurately quantitate the level of innervation of laryngeal muscles with recurrent laryngeal nerve stimulation. METHODS: A four-phase study was conducted in 24 canines, including 1) identification of the best stimulation-recording configuration, 2) statistical analysis of sensitivity and accuracy, 3) evaluation of safety, and 4) identification of the laryngeal muscle(s) that contribute to the evoked response. RESULTS: The results demonstrated that an entirely noninvasive technique is not feasible. The stimulating cathode must be invasive to ensure discrete activation of the recurrent laryngeal nerve, whereas both recording electrodes should remain on the surface with one overlying the thyroid ala. This configuration proved to be highly accurate, with an error rate of only 6% to 7%, and with sensitivity sufficient to detect a signal in a nerve with fewer than 1% of the axons intact. There was no evidence of nerve injury in any animal over the course of 350 stimulus needle penetrations. By use of neuromuscular blockade to identify those muscles generating the surface response, the thyroarytenoid muscle was found to be the primary contributor, whereas the posterior cricoarytenoid muscle was uninvolved. CONCLUSIONS: This evoked electromyographic technique could provide quantitative information regarding the extent of muscle innervation during denervation and regeneration in case of laryngeal paralysis.     

Altered hetero- and homeometric autoregulation in the terminally failing human heart

OBJECTIVE AND METHODS: To further investigate length-dependent force generation in human heart, nonfailing (donor hearts, NF) and terminally failing (heart transplants, dilated cardiomyopathy, DCM) left ventricular myocardium was studied under various preload (4-40 mN/mm2) or length conditions. In addition, morphological studies (van Giesson Trichrome staining, electron microscopy) were performed. RESULTS: In NF, a biphasic increase in force of contraction (FOC) was observed after elevating the preload (4-40 mN/mm2): there was an immediate fast increase (FOCf,), followed by a slow increase over several minutes (FOCs), which was paralleled by an increase in the systolic fura-2 transient. In DCM, FOCf, FOCs and the systolic fura-2 transient were blunted and diastolic tension was increased at increasing muscle length. Only in NF, a stretched induced increase in diastolic fura-2 ratio was observed. In DCM, no obvious interstitial fibrosis and no difference in basement membrane structure and attachment were observed. CONCLUSIONS: Since FOCf has been attributed to the Frank-Starling mechanism, whereas FOCs represents a length-dependent increase in the intracellular Ca2+-transient, the impaired length-dependent force generation in failing myocardium results from a dysregulation of both myofibrillar Ca2+-sensitivity as well as the intracellular Ca2+-homeostasis. Interstitial fibrosis may have only minor impact on force generation in human end-stage heart failure.