Treatment of cardiogenic shock in myocardial infarction by intraaortic balloon counterpulsation surgery.

Thirty-seven patients in cardiogenic shock due to acute myocardial infarction were treated with intraaortic balloon counterpulsation and/or surgery. Eighteen of these patients were treated with counterpulsation alone; eight survived and five were in functional class I or II at the time of follow-up; two were in functional class III, and one was in functional class IV. Nineteen patients were treated surgically, eight survived and seven were in functional class I or II at the time of follow-up; one was in functional class III. Good functional recovery with counterpulsation alone is most common with inferior infarction. With surgery, functional recovery depends not only on the extent of the infarction and the coronary anatomy, but also on the ability to perform surgery within 12 hours of infarction or to support the patient with mechanical means for 10 to 14 days after the infarction and then perform surgery.     

Ventricular fibrillation during coronary angiography in dogs: the role of calcium-binding additives

Coronary angiography with Renografin 76 (RG76) occasionally results in ventricular fibrillation (VF). Angiovist 370 (AV370) is a contrast medium similar to RG76 except the calcium-sequestering agents, sodium citrate and EDTA in RG76 have been replaced by calcium EDTA. To determine whether these sequestering agents contribute to contrast medium-induced VF, a comparison was made of the effects of intracoronary injections of RG76, AV370, and saline solutions containing sodium citrate and EDTA (CIT/EDTA) and calcium EDTA (CA EDTA) on myocardial conduction, local QT intervals, and incidence of spontaneous and induced VF in 32 dogs. Four milliliters of RG76 produced a 111 +/- 12-ms increase in local QT intervals, compared with a 73 +/- 8-ms increase with AV370 (p less than 0.001). Spontaneous VF occurred in 12 of 16 six-milliliter injections of RG76, compared with 4 of 16 injections of AV370 (p less than 0.02) An early-cycle premature impulse applied after every fourth beat induced VF in 15 of 16 four-milliliter injections of RG76 compared with 5 of 16 injections of AV370 (p less than 0.01). As the premature beat conducted through the left anterior descending region, conduction slowing and fractionation occurred, which was less with AV370 than with RG76. The CIT/EDTA solution produced a greater increase in QT intervals (77 +/- 5 ms) than the CA EDTA solution (29 +/- 3 ms) or 0.9% saline solution alone (28 +/- 2 ms) (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Cleavage of HIV-1 gag polyprotein synthesized in vitro: sequential cleavage by the viral protease

The virally encoded protease of human immunodeficiency virus is responsible for the processing of the gag and gag-pol polyprotein precursors to their mature polypeptides. Since correct processing of the viral polypeptides is essential for the production of infectious virus, HIV protease represents a potential target for therapeutic agents that may prove beneficial in the treatment of AIDS. In this study, full-length gag polyprotein has been synthesized in vitro to serve as a substrate for bacterially expressed HIV-1 protease. Expression of the protease in E. coli from the lac promoter was enhanced approximately five-fold by deletion of a potential hairpin loop upstream from the codon determining the amino terminus of mature protease. Extracts of induced cultures of E. coli harboring a protease-containing plasmid served as the source of protease activity. The gag polyprotein synthesized in vitro was cleaved by such lysates, producing fragments corresponding in size to p17 plus p24 and mature p24. Immunoprecipitations with monoclonal antibodies to p17 and p24 polypeptides suggest that initial cleavage of gag polyprotein occurs near the p24-p15 junction. The proteolysis was inhibited by pepstatin with an IC50 of 0.15 mM for cleavage at the p24-p15 junction and 0.02 mM for cleavage at the p17-p24 junction.     

Chemoprevention of colorectal cancer with nonsteroidal anti‐inflammatory drugs

Colorectal carcinoma is one of the commonest solid organ tumors in the world and its prevalence appears to be increasing in Asia. Recently, there has been much interest in various chemotherapeutic agents for the management of this condition, in particular nonsteroidal anti‐inflammatory drugs (NSAIDs). There is a large amount of data that suggest traditional NSAIDs, as well as the new cyclooxygenase (COX)‐2 selective inhibitors such as rofecoxib and celecoxib, have a role in the setting of primary and secondary prevention, and adjuvant therapy of both sporadic colorectal carcinoma and familial adenomatous polyposis. This review examines some of this data, as well as the potential problems and limitations of using these agents, particularly in light of the recent withdrawal of rofecoxib.     

Suppression of DNA synthesis in hepatoma cells exposed to glucocorticoid hormone in vitro

Glucocorticoid hormone is shown to markedly suppress DNA synthesis in a line of rat hepatoma cells in vitro. In the presence of 300 nM hydrocortisone or 30 nM dexamethasone the incorporation of radioactive thymidine falls to 50% of control levels by 36 hr, and at higher concentrations of hormone inhibition can be noted as early as 12 hr and is nearly complete by 24 hr. This inhibition of radioactive thymidine incorporation reflects a true suppression of DNA synthesis, is accompanied by a corresponding inhibition of cell proliferation, and is readily reversible upon subsequent removal of hormone. In contrast to previously described effects of the glucocorticoid hormones on various cells of lymphoid origin, the inhibition of DNA synthesis in these hepatoma cells is not accompanied by appreciable cell lysis or by degradation of preformed DNA, and even when [(3)H]thymidine incorporation into DNA is inhibited by 90% or more, incorporation of [(14)C]uridine into RNA proceeds with little change. These findings all parallel previous observations on the effects of glucocorticoid hormone on the livers of intact animals and suggest that studies on the mechanism of the inhibition of DNA synthesis in the present more isolated system may lead to a better understanding of the means by which these compounds inhibit liver growth in vivo.Despite the ready suppressibility of DNA synthesis in these hepatoma cells and in two other cell lines of liver origin, none of these cell lines was found to be inducible for tyrosine aminotransferase. The apparent dissociation between two "steroid-sensitive" phenomena is of interest and warrants further investigation.     

Infidelity of DNA synthesis associated with bypass of apurinic sites.

The mutagenic potential of apurinic sites in vivo has been studied by transfection of depurinated phi X174 DNA containing amber mutations into SOS-induced Escherichia coli spheroplasts. Mutagenicity is abolished by treatment of the depurinated DNA with an apurinic endonuclease from Hela cells, establishing the apurinic site as the mutagenic lesion. The frequency of copying apurinic sites in vitro was analyzed by measuring the extent of DNA synthesis using E. coli DNA polymerase I and avian myeloblastosis DNA polymerase. The inhibition of DNA synthesis by apurinic sites was less with avian myeloblastosis DNA polymerase, suggesting that this error-prone enzyme copies apurinic sites with greater frequency. Consistent with this conclusion is the observation that, upon transfection into (normal) spheroplasts, the reversion frequency of depurinated phi X174 am3 DNA copied with avian myeloblastosis virus DNA polymerase is much greater than that of the same DNA copied with E. coli DNA polymerase I. Sequence analysis of the DNA of 33 revertant phage produced by depurination indicates a preference for incorporation of deoxyadenosine opposite putative apurinic sites. The combined results indicate that mutagenesis resulting from apurinic sites is associated with bypass of these noncoding lesions during DNA synthesis.