Family involvement with communication-impaired residents in long-term care settings.

This article describes the outcomes of a study involving family members of communication-impaired long-term care residents in a collaborative nursing/speech language pathology intervention designed to increase the residents' communication ability. Family members provided memorabilia and artifacts or produced audio or video tapes, for use in conjunction with a speech therapy enhancement program (STEP). Findings revealed that, despite a minimal improvement in speech ability, there was a dramatic increase in family members' satisfaction.     

Techniques of splenic preservation using fibrin glue

Fibrin glue (FG) was used to achieve hemostasis of 16 splenic injuries in 14 patients. The etiologies of injury included five gunshot wounds, two stab wounds, four iatrogenic injuries, and five patients with blunt splenic trauma. The intraoperative blood loss averaged 1.8 +/- 2.4 (SD) liters and patients were transfused 3 +/- 2 units of blood perioperatively. The amount of FG required to achieve splenic hemostasis averaged 11 +/- 8 ml and varied directly with the grade of injury. One patient with a splenic hilar vascular injury (Grade V) underwent splenectomy following failure to achieve complete hemostasis despite the use of 25 ml of FG. All other splenic injuries were successfully managed using less than 25 ml of FG. Postoperative computerized tomographic (CT) scanning, performed in ten patients, was negative for rebleeding or abscess formation. The overall splenic salvage rate was 86%. FG was effective in achieving hemostasis of both superficial and deep splenic injuries. Its use as an adjunct in trauma surgery should result in increased splenic salvage rates compared with that obtained using conventional surgical techniques.     

Paramyosin is the Schistosoma mansoni (Trematoda) homologue of antigen B from Taenia solium (Cestoda)

Antigen B, a major antigen of the cestode parasite Taenia solium, has been purified and a portion of amino acid sequence obtained. Paramyosin of the trematode parasite Schistosoma mansoni, an immunogenic protein that has shown promise as a vaccine candidate, has several biochemical and immunological properties in common with antigen B. A full-length cDNA clone of S. mansoni paramyosin has been obtained and the predicted translation product contains a sequence that is highly homologous to the sequence obtained for antigen B. The predicted amino acid composition and isolectric point of paramyosin are nearly identical to those established for antigen B. Recombinant S. mansoni paramyosin, expressed in Escherichia coli as a fusion protein with beta-galactosidase, was recognized by antisera against T. solium antigen B. We conclude from these results that S. mansoni paramyosin and T. solium antigen B are homologous proteins. Since S. mansoni paramyosin is thought to be a muscle protein and T. solium antigen B a secreted glycoprotein with anti-complement activity, this conclusion raises some interesting questions regarding the role of this class of proteins in the host-parasite relationship.     

Evaluation ofin vitro drug screening leads using experimental models of human ovarian cancer

Summary Five compounds which were identified as potential new anticancer drugs inin vitro screening with the human tumor colony forming assay were selected for further evaluation usingin vitro andin vivo models of human ovarian cancer. Three of five compounds were found to inhibitin vitro colony formation of ovarian cancer cell lines derived from both untreated and combination chemotherapy refractory patients. One compound was also found to prolong survival in a human ovarian carcinoma xenograft model system. This compound, chloroquinoxaline sulfonamide, was selected for development and has shown preliminary indication of activity in phase I clinical testing.     

Cationic lipids enhance cellular uptake and activity of phosphorothioate antisense oligonucleotides.

We have investigated the use of a cationic lipid preparation to enhance antisense oligonucleotide activity in human umbilical vein endothelial cells. A liposomal preparation containing the cationic lipid N-[1-(2,3-dioleyloxy)propyl]-N,N,N-trimethylammonium chloride (DOTMA) was found to increase by at least 1000-fold the potency of an antisense oligonucleotide (ISIS 1570) that hybridizes to the AUG translation initiation codon of human intercellular adhesion molecule-1. In the presence of 8 microM DOTMA, 6-15-fold more 35S-ISIS 1570 associated with cells, at oligonucleotide concentrations from 0.01 to 5 microM, than did in the absence of DOTMA. Both 35S-ISIS 1570 association with cells and antisense activity were increased as a function of DOTMA concentration and with increasing time of incubation with the cationic lipid. Fluorescein-labeled ISIS 1570 was used to assess the intracellular distribution of the oligonucleotide in the presence and absence of DOTMA. In the absence of DOTMA, the oligonucleotide localized to discrete structures in the cytoplasm of the cell, resulting in a punctate fluorescence pattern. In the presence of DOTMA, cellular fluorescence markedly increased and the oligonucleotide localized within the nucleus, as well as to discrete structures in the cytoplasm. Accumulation of the oligonucleotide in the nucleus in the presence of DOTMA was time and temperature dependent. Nuclear accumulation was inhibited by preincubation of the cells with monensin but not chloroquine, NH4Cl, nocodazole, colcemid, or brefeldin A. These data demonstrate that cationic lipids increase antisense activity by increasing the amount of oligonucleotide associated with cells and altering intracellular distribution of the oligonucleotide.     

In vitro toxicological evaluation of ISIS 1082, a phosphorothioate oligonucleotide inhibitor of herpes simplex virus.

ISIS 1082, a phosphorothioate oligonucleotide targeted to a translation initiation codon of herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) virion capsid protein UL13 inhibits in vitro viral replication. To better understand the pharmacological properties of ISIS 1082, we examined its effects in nonvirally infected HeLa cells by using a number of cytotoxicity assays. Our data indicate that ISIS 1082 had no effect on HeLa cell viability as measured by cellular proliferation and clonogenic assays at concentrations as high as 100 microM. Additionally, DNA, RNA, and protein synthesis were only inhibited by 25% in cells treated with 100 microM ISIS 1082. The effects of ISIS 1082 on DNA synthesis were compared with those of acyclovir and trifluorothymidine, two clinically used antiherpetic agents. Acyclovir displayed effects similar to that of ISIS 1082. However, trifluorothymidine, which has been reported to be a potential mutagen and teratogen, significantly altered DNA replication at concentrations from 1 to 100 microM. Isolated HeLa DNA polymerases were inhibited by the compound, with a 50% inhibitory concentration of 2 microM. The in vitro antiviral (K. Draper and V. Brown-Driver, submitted for publication; K.G. Draper and V. Brown-Driver, Antiviral Res. Suppl. 1:106, 1991) and cytotoxicity studies suggest that ISIS 1082 is a selective, nontoxic, antiherpetic therapeutic agent.     

Prospective trial of supranormal values as goals of resuscitation in severe trauma.

We prospectively tested the effect of the early postinjury attainment of supranormal values of cardiac index (> or = 4.52 L/min per square meter), oxygen delivery (> or = 670 mL/min per square meter), and oxygen consumption (> or = 166 mL/min per square meter) on outcome in traumatized patients with an estimated blood loss of 2000 mL or more. The goals in control patients were to attain normal values for all hemodynamic measurements. During the 6-month period, 33 protocol patients and 34 control patients with similar vital signs, estimated blood losses, and severity of injuries were enrolled in the study. Eight (24%) protocol patients died, while 15 (44%) control patients died. The protocol patients had fewer mean (+/- SEM) organ failures per patient (0.76 +/- 1.21 vs 1.59 +/- 1.60), shorter stays in the intensive care unit (5 +/- 3 vs 12 +/- 12), and fewer mean days requiring ventilation (4 +/- 3 vs 11 +/- 10) than did the control patients (P < .05 for each). We conclude that attaining supranormal circulatory values improves survival and decreases morbidity in the severely traumatized patient.