A comparison of thrombolytic therapy with primary coronary angioplasty for acute myocardial infarction. Myocardial Infarction Triage and Intervention Investigators

BACKGROUND: Several relatively small randomized trials have shown that primary angioplasty results in a better short-term outcome than thrombolytic therapy in patients with acute myocardial infarction. These results, however, have not been duplicated other than in investigational trials. METHODS: We compared mortality during hospitalization and long-term mortality, as well as the use of resources, among 1050 patients in a primary-angioplasty group and 2095 patients in a thrombolytic-therapy group. Patients were selected from the Myocardial Infarction Triage and Intervention Project Registry cohort of 12,331 consecutive patients admitted with acute myocardial infarction to 19 Seattle hospitals between 1988 and 1994. Because of the potential for selection bias, several subgroup analyses were performed that included patients eligible for thrombolysis, high-risk patients, and patients in the primary-angioplasty group who were treated at hospitals with high volumes of angioplasty. RESULTS: There was no significant difference in mortality during hospitalization or long-term follow-up between patients in the thrombolytic-therapy group and those in the primary-angioplasty group (mortality during hospitalization, 5.6 percent and 5.5 percent, respectively; P=0.93; adjusted hazard ratio for the risk of death within three years after primary angioplasty, 0.95; 95 percent confidence interval, 0.8 to 1.2). There was also no significant difference in mortality between high-risk subgroups of patients in the two treatment groups. The rates of procedures and costs were lower among patients in the thrombolytic-therapy group both at the time of hospital discharge and after three years of follow-up (30 percent fewer coronary angiograms, 15 percent fewer coronary angioplasties, and 13 percent lower costs after three years of follow-up). CONCLUSIONS: In a community setting, we observed no benefit in terms of either mortality or the use of resources with a strategy of primary angioplasty rather than thrombolytic therapy in a large cohort of patients with acute myocardial infarction.     

Efficacy and acceptability of two monophasic oral contraceptives containing ethinylestradiol and either desogestrel or gestodene

In this study, we have examined the effects of authentic nitric oxide (NO), NO+ (NOBF4), glutathione (GSH), glutathione disulphide (GSSG), and S-nitrosoglutathione (GSNO) in the presence and absence of Cu2+, which thermally releases NO from S-nitrosothiols on the transport of L-arginine into the human platelet. The K(M,apparent) was unaffected by NO, NO+, GSH, and GSNO. However, Cu2+ lowered K(M,apparent) by approximately 2.85-fold. Cu2+-dependent lowering of K(M,apparent) was also observed, albeit to a smaller extent when this ion was mixed with GSH (approximately 1.9-fold lower) and GSNO (approximately 2.0-fold). GSSG also lowered K(M,apparent) by approximately 1.5-fold. The Vmax,apparent of L-arginine uptake was unaffected by NO, NO+, GSH, and Cu2+. Vmax,apparent was stimulated by to the largest extent by GSNO (approximately 2.28-fold) and GSNO plus Cu2+ (approximately 2.7-fold). GSSG and GSH plus Cu2+ also increased Vmax,apparent by approximately 1.9-fold. When these parameters are expressed in terms of transport efficiency (Vmax/K(M)) the largest effect of nearly 4.7-fold (over controls) was obtained by a combination of GSNO plus Cu2+. These results suggest that platelet L-Arg transport is not affected either by NO or NO+ but by a thiol-disulphide exchange reactions on the platelet L-Arg transporter, brought about by GSNO and GSSG. Based on these results, a GSNO/GSSG/Cu2+ dependent regulatory mechanism for the uptake of L-arginine in human platelets has been proposed.     

Rational design of novel antimicrobials: blocking purine salvage in a parasitic protozoan

All parasitic protozoa obtain purine nucleotides solely by salvaging purine bases and/or nucleosides from their host. This observation suggests that inhibiting purine salvage may be a good way of killing these organisms. To explore this idea, we attempted to block the purine salvage pathway of the parasitic protozoan Tritrichomonas foetus. T. foetus is a good organism to study because its purine salvage depends primarily on a single enzyme, hypoxanthine-guanine-xanthine phosphoribosyltransferase (HGXPRTase), and could provide a good model for rational drug design through specific enzyme inhibition. Guided by the crystal structure of T. foetus HGXPRTase, we used structure-based drug design to identify several non-purine compounds that inhibited this enzyme without any detectable effect on human HGPRTase. One of these compounds, 4-[N-(3, 4-dichlorophenyl)carbamoyl]phthalic anhydride (referred to as TF1), was selected for further characterization. TF1 was shown to be a competitive inhibitor of T. foetus HGXPRTase with respect to both guanine (in the forward reaction; Ki = 13 microM) and GMP (in the reverse reaction; Ki = 10 microM), but showed no effect on the homologous human enzyme at concentrations of up to 1 mM. TF1 inhibited the in vitro growth of T. foetus with an EC50 of approximately 40 microM. This inhibitory effect was associated with a decrease in the incorporation of exogenous guanine into nucleic acids, and could be reversed by supplementing the growth medium with excess exogenous hypoxanthine or guanine. Thus, rationally targeting an essential enzyme in a parasitic organism has yielded specific enzyme inhibitors capable of suppressing that parasite's growth.     

Central venous line sepsis in the intensive care unit. A study comparing antibiotic coated catheters with plain catheters

A randomized controlled clinical trial was undertaken to evaluate the efficacy of antibiotic bonded lines in the reduction of central venous catheter infection. One hundred and seventy-six plain and bonded catheters were inserted into one hundred and ten patients in an intensive care unit, many of whom were admitted with evidence of sepsis. The catheters used in the study group, which had been pre-treated by the manufacturers with the cationic surfactant tridodecylmethylammonium chloride, were bonded with vancomycin 1 g made up in 10 ml of water immediately prior to insertion. The catheters used in the control group were neither pre-treated nor bonded with vancomycin. Eighty percent of control group catheters were infected compared with 62% of study catheters (p = 0.01). The most common organism isolated was coagulase negative staphylococcus. We conclude that antibiotic bonding can reduce central venous catheter infection even in a patient population with a high incidence of sepsis.     

Endogenous carbon monoxide in control of respiration

CASE REPORT: A patient with recurrent breast cancer was reirradiated twice on adjacent fields with a time interval of 9 months. The first time she was treated with reirradiation alone, the second time with reirradiation plus hyperthermia. The reirradiation schedule for both fields was 8 x 4 Gy in 4 weeks. Both fields overlapped partly with the field of postoperative radiotherapy, which was applied 57 and 66 months earlier to a total dose of 40.5 Gy. RESULTS: During the 52 to 61 months follow-up, a remarkable difference in telangiectasia development, between the parts of the reirradiation fields overlapping with the primary radiotherapy field, became apparent. Telangiectasia was observed 9 months after treatment with reirradiation alone and progressed to confluent in 47 months after treatment. In the reirradiation plus hyperthermia area, the maximum observed telangiectasia was slight until 52 months after treatment. DISCUSSION: The difference in the development of telangiectasia between these fields cannot be explained by differences in any of the known radiation treatment related prognostic factors. A protective effect by hyperthermia has been suggested by Haveman and coworkers, who have shown experimentally that heat treatment leads to enhanced proliferation of endothelial cells, thereby inducing a fast repopulation and replacement of X-ray damaged cells. CONCLUSION: This difference in telangiectasia formation is an interesting observation. Whether such a protective effect of hyperthermia is of general relevance has to become clear from more extensive clinical studies.     

Effects of frusemide on the urinary excretion of dopamine and 5-hydroxytryptamine in normal man

The effects of frusemide on the urinary excretion of dopamine and 5-hydroxytryptamine (5-HT) were investigated in eight healthy male subjects in a randomized, placebo-controlled, cross-over study. Frusemide produced the expected rise in urinary dopamine excretion but it did not affect 5-HT excretion when compared with placebo. The lack of an effect on 5-HT excretion in man contrasts with studies in the rat which have reported a marked increase in 5-HT excretion after administration of this loop diuretic.     

Sequential bilateral adnexal torsion after a single cycle of gonadotropin ovulation induction with intrauterine insemination

As part of a programme for the implementation of a Smoking Control Policy in our hospital, an open study, without randomization, of 65 hospital workers, who wanted to give up smoking, was carried out. The characteristics of smoking in each subject were recorded. The Fagerstrom Questionnaire was used to measure the degree of dependence on nicotine. The treatment consisted of the daily use of 16 h nicotine patches for 12 weeks. During the first 4 weeks, the patches contained 15 mg of nicotine, for the second 4 weeks, 10 mg, and for the last 4 weeks 5 mg (per patch and day). Five visits were scheduled during the 26 week study period: at the start of the study and after 4, 8, 12 and 26 weeks. The abstinence was checked by measuring carbon monoxide in end-expiratory air. The success rate was 31% after 12 weeks, and decreased to 29% after 26 weeks. In conclusion, the nicotine patches appeared safe and effective in this study.     

The effects of intravenous antioxidants in patients with septic shock

Oxidative stress is implicated in septic shock. We investigated the effect of intravenous antioxidant therapy on antioxidant status, lipid peroxidation, hemodynamics and nitrite in patients with septic shock. Thirty patients randomly received either antioxidants (n-acetylcysteine 150 mg/kg for 30 min then 20 mg/kg/h plus bolus doses of 1 g ascorbic acid and 400 mg alpha-tocopherol) or 5% dextrose. Basal vitamin C was low and redox-reactive iron was elevated in all patients. In the 16 patients receiving antioxidants, vitamin C increased (p = .0002) but total antioxidant capacity was unaffected. Lipid peroxides were elevated in all patients but did not increase further in the patients receiving antioxidants. Plasma total nitrite also increased (p = .007) in the antioxidant group. Heart rate increased in patients receiving antioxidants at 60 min (p = .018) and 120 min (p = .004). Cardiac index also increased at 60 min (p = .007) and 120 min (p = .05). Systemic vascular resistance index decreased at 120 min in the antioxidant treated patients (p = .003). The effect of antioxidants on hemodynamic variables has not previously been reported. Antioxidant administration may be a useful adjunct to conventional approaches in the management of septic shock.