Thrombolytic Therapy Within One Hour of the Onset of Acute Myocardial Infarction

Between 1986 and 1988, 239 consecutive patients with acute myocardialinfarction received thrombolytic therapy up to 285 minutes afteronset of symptoms; in 39 (17 with anterior infarction, 21 inferior,one lateral infarction) recombinant tissue plasminogen activatoror anistreplase was administered a mean of 51 minutes (range20–60 minutes) after the onset of symptoms. The patencyrates (26 of 30; 87 per cent), rapid ST segment resolution (36of 38; 95 per cent) and QRS score of 3 (28 of 38; 74 per cent)were statistically significantly higher for those seen and treatedin the first hour in comparison with those seen and treatedlater. For those treated within the first hour mean peak creatine kinasewas 1264 U/I for those with TIMI grade 2 or 3 (partial or completeperfusion) compared with 3005 U/I for those with TIMI grade0 or 1 (no perfusion or penetration without perfusion) (p=0.02):mean peak creatine kinase-MB for those with TIMI grade 2 or3 perfusion was 115 U/I compared with 312 U/I for those withTIMI grade 0 or 1 (p=0.01). Four of the 39 patients developedventricular fibrillation following thrombolytic therapy, threewithin 24 hours of infarction and one following reinfarctionon day 15. There were no significant bleeding complications.One patient died. Thrombolytic therapy within 1 hour of the onset of symptomsled to a very high angiographic patency rate, rapid ST segmentresolution with preservation of left ventricular function. Thistherapy is without significant complications.     

Topical clindamycin versus systemic tetracycline in the treatment of acne: Results of a multiclinic trial

In a multiclinic double-blind trial, 305 patients with moderate to severe acne vulgaris were treated with oral tetracycline hydrochloride, 250 mg (N: 103), a 1% solution of clindamycin phosphate (N: 105), or placebo (N: 97) twice daily for 8 weeks. The response to treatment was evaluated by lesion counts and overall clinical improvement at 2, 4, 6, and 8 weeks. Both topical clindamycin and oral tetracycline significantly reduced papule and pustule counts compared to placebo; they were rated significantly higher than placebo on the physician's and the patient's overall evaluation at the end of the treatment period. No serious side effects were reported with any of the study medications.     

The growth of brain tumors can be suppressed by multiple transplantation of mesenchymal stem cells expressing cytosine deaminase

Suicide genes have recently emerged as an attractive alternative therapy for the treatment of various types of intractable cancers.The efficacy of suicide gene therapy relies on efficient gene delivery to target tissues and the localized concentration of final geneproducts.     

Screening for breast cancer with MRI: recent experience from the Australian Capital Territory

The American Cancer Society now recommends annual MRI screening for women at 20–25% or greater lifetime risk of breast cancer. The role of MRI screening in other risk subgroups is unproved because of insufficient data. Our study comprised 209 breast MRI scans carried out in 171 asymptomatic patients (age range 22–67 years, mean 46 years), referred between January 2005 and June 2008. Targeted ultrasound was carried out in 32 episodes (15%) and biopsies were taken in 23 patients (13%). In four patients, MR‐guided procedures were required to establish a diagnosis, two using hook‐wire localization and two by means of vacuum‐assisted biopsy. Seven cancers were detected by MRI in the 171 patients, with a yield of 4.1%. Only one of the seven cancers was also shown by x‐ray mammography. Four patients had invasive ductal cancer (all axillary node negative) and three had high‐grade ductal carcinoma in situ or pleomorphic lobular carcinoma in situ. The three women with in situ disease were all potentially high risk, based on the National Breast and Ovarian Cancer Centre (NBOCC) criteria. Three women with invasive breast cancer were at only average risk based on NBOCC criteria, but two of these had extremely dense breasts. A fourth patient, found to have multifocal invasive cancer, had a personal history of contralateral breast cancer, but no relevant family history. Our findings suggest that breast MRI could be used to screen a larger Australian population at increased risk of developing breast cancer.     

Characterization of recombinant plasminogen activator production by primate endothelial cells transduced with retroviral vectors

Retroviral vector-mediated expression of plasminogen activators (PAs) from endothelial cells (ECs) has been proposed as a potential therapeutic approach for intravascular thrombosis. To define the potential for gene transfer to increase fibrinolytic activity in a primate system, baboon ECs were transduced with retroviral vectors expressing wild-type and glycosylphosphatidylinositol-anchored urokinase, as well as wild-type and serpin-resistant tissue PA (t-PA). Expression of either t-PA or urokinase was increased by one log over baseline levels. There was no specific effect of either t-PA or urokinase overexpression on endogenous t-PA, urokinase, or PA inhibitor 1 (PAI-1) expression. Recombinant urokinase could be anchored to the cell surface at a level eight-fold above that of receptor-bound urokinase. The majority of secreted urokinase accumulated in conditioned medium as a free proenzyme, whereas both wild-type and serpin-resistant t-PA accumulated almost exclusively in complexes with PAI-1. In most but not all of the assays, the urokinase vectors conferred PA activity above that of the t-PA vectors. These data show that PA synthesis and activity are specifically increased subsequent to retroviral vector-mediated gene transfer in primate ECs. However, definition of an optimal PA vector will require in vivo experimentation.