Inhibition of fibrinolytic system by liquoid (polyanetholesulfonate). A contributing factor in the liquoid-induced renal cortical necrosis

Liquoid induces microvascular thrombosis and renal cortical necrosis in experimental animals. We hypothesized that thrombosis and renal cortical necrosis may, at least in part, result from the inhibition of the fibrinolytic system by liquoid. Effects of liquoid on plasminogen activation by rat kidney, purified human tissue plasminogen activator (TPA), urokinase, streptokinase, and on the amidolytic activities of TPA, urokinase, and plasmin were studied using chromogenic substrates and clot lysis. Liquoid had a strong inhibitory effect on the fibrinolytic system in vivo and in vitro. The inhibition was most effective at the plasminogen activation level, with activation by streptokinase being most susceptible. The demonstrated stoichiometric binding between liquoid and plasminogen, and to a lesser degree the direct inactivation of plasminogen activators and plasmin, is probably responsible for the reduction of plasminogen activation in circulation and in the kidneys.     

Skeletonized versus pedicled internal mammary artery: impact of surgical technique on post CABG surgery pain

Objective: Recent evidence suggests that coronary artery bypass graft (CABG) surgery often results in chronic chest wall pain, termed: ‘post CABG pain syndrome’ (PCP). Direct injury to intercostal nerves during the surgical procedure was presumed to underlie this syndrome. The aim of this study was to investigate the effect of two harvesting techniques of the internal mammary artery (IMA)—skeletonization (S-LIMA) and pedicle (P-LIMA) on the occurrence and incidence of PCP. Methods: A mailed questionnaire enquiring about the presence and characteristics of PCP was sent to all 482 patients who had undergone CABG in our institution in the years 1999–2000. A randomly chosen subgroup of IMA patients reporting PCP were summoned for evaluations of pain localization and intensity, thermal and tactile sensitivity, and disability assessment using recognized tests and indices. Results: Of the 380 responders (S-LIMA: 221, P-LIMA: 125, veins only V-34) 169 (44%) reported having PCP. Its prevalence was similar between the two IMA groups (S-LIMA: 45%, P-LIMA: 50%) but significantly lower in the V group (18%, P=0.003). Physical assessment in the subgroup of 43 IMA patients (S-LIMA: 22, P-LIMA: 21) performed 40.2±8.7 months after surgery confirmed equal occurrence of mostly left and midline chest wall neuropathic pain in both IMA groups. No significant differences were found between the two groups in respect to indices of pain intensity, thermal and tactile sensitivity and disability. Conclusions: PCP is a prevalent finding in post CABG patients. The skeletonization technique of IMA harvesting although causing significantly less inner chest wall trauma does not appear to reduce the occurrence of PCP. This finding may imply that ischemic injury rather than direct mechanical injury to the intercostal nerves is the putative mechanism underlying PCP.     

Coumadin-induced Skin Necrosis

Two women developed coumadin-induced skin necrosis. A 16-year-old woman sustained necrosis on the leg after a single dose of the drug, and a 59-year-old woman developed gangrene of most of her left breast.     

Bee and wasp stings of the eye. Retained intralenticular wasp sting: A case report.

Two different stages should be considered in the management of bee and wasp stings to the eye. The first is the acute stage of activity of the specific insect venom on the structures the eye. The reaction of the eye to the particular insult is considered here in regard to the anterior and posterior segments of the eye. The second stage is that of the retained intraocular foreign body, the inert sting. Little is known about the reaction of the eye to the presence of chitinous sting and its effect on the structures of the eye. We report a follow-up study of a sting retained for 28 years, and emphasise the benign and quiescent course of the case. Guidelines for treatment and management in such cases are described.     

Transfection of RNA encoding tumor antigens following maturation of dendritic cells leads to prolonged presentation of antigen and the generation of high-affinity tumor-reactive cytotoxic T lymphocytes.

Common tumor vaccination strategies utilizing peptide-pulsed dendritic cells (DC) are limited to targeting antigens with known epitopes in patients expressing a defined restricting allele and can result in the preferential induction of low-avidity T cells that fail to recognize tumor cells. The use of dendritic cells transfected with RNA encoding tumor antigen offers the prospect of antigen-specific immunization without requiring prior knowledge of the immunogenic epitope or restricting allele, since epitopes from the translated protein are processed by the endogenous antigen-presentation machinery. However, its use in vaccine studies has been limited by low RNA transfection efficiency and the use of immature DC as recipient cells. In this study, we report an RNA transfection strategy that routinely achieves expression in 40-50% of mature DC, which are better stimulator cells. Such RNA-transfected mature DC exhibited a prolonged duration of presentation of immunogenic epitopes compared to peptide-pulsed DC, induced greater frequencies of tumor antigen-specific CTL, and generated a CTL population that exhibited higher target avidity and increased tumor lytic capacity. These studies provide compelling in vitro data supporting the evaluation of RNA-transfected mature DC in vaccination protocols as a means to overcome several obstacles to generating anti-tumor responses in vivo.     

Induction of cytotoxic T lymphocytes with dendritic cells transfected with human papillomavirus E6 and E7 RNA: implications for cervical cancer immunotherapy

Human papillomavirus (HPV) infection is associated with cervical cancer. The high-risk HPV E6 and E7 oncoproteins are constitutively expressed in most cervical carcinoma cells, and are, therefore, attractive antigens for cytotoxic T-lymphocyte (CTL)-mediated immunotherapy. The objective of this study was to evaluate the use of dendritic cells (DCs) transfected with RNA encoding the E6 and E7 protein for cervical cancer immunotherapy. The authors have shown that DCs transfected with RNA-encoding antigen stimulate potent antigen-specific CTL responses in vitro and in vivo. In this study, they tried to determine whether DCs transfected with E6 and E7 RNA stimulate primary, antigen-specific CTL responses in vitro. The results show that DCs pulsed with E6 or E7 RNA stimulate antigen-specific CTL responses that recognize and lyse DCs transfected with E6 and E7 RNA and human cervical carcinoma cells expressing the E6 and E7 products, and the lysis was comparable to that achieved with E6 and E7 peptide-pulsed DCs. Dendritic cells cotransfected with both E6 and E7 RNA stimulate CTLs that are more effective at lysing human cervical cancer cells. This study provides a rationale for the development of cervical carcinoma immunotherapy using DCs transfected with HPV E6 and E7 RNA.