Naphthalimido derivatives as antifolate thymidylate synthase inhibitors

A new series of N-(substituted)benzyl-1,8-naphthalimides 4, structurally related to the previously reported thymidylate synthase (TS) inhibitor naphthaleins 3, were synthesized and compounds tested for their inhibition of several species of TS. Moreover, their in vitro cytotoxicity together with antimycotic and antibacterial properties were assayed. While no activity was detected in the antibacterial tests, the m-nitro (4ae) and the p-nitro (4af) derivatives were found able to partially inhibit TS at low micromolar concentrations. Introduction of nitro or (substituted)-amino groups in position 4 of the naphthalic ring always led to less active compounds.     

Is it possible to prevent bacterial adhesion onto ureteric stents?

The aim of this study was to determine whether the use of bactericidal coatings or immersion in antibiotic solution reduces or prevents bacterial adhesion onto ureteric stents. Precut segments of full silicone, silver-coated and hydrogel-coated ureteric stents were incubated with two uropathogenic bacterial strains with and without previous immersion in antibiotic solution. Tobramycin, ceftriaxone and ciprofloxacin solutions were used, as these antibiotics are commonly administered for the prophylaxis and treatment of urinary tract infection (UTI). Microbiological analysis showed that immersion of ureteric stents in ceftriaxone and ciprofloxacin yielded a significant reduction of bacterial adhesion, whereas immersion in tobramycin did not. The surface material of the stents had no direct influence on bacterial adhesion. In this experimental study, neither the silver nor the hydrogel coat reduced bacterial adhesion onto ureteric stents whereas immersion in a suitable antibiotic solution significantly reduced and even prevented this phenomenon, probably due to the adhesion of the antibiotic onto the stent surface. Prevention of bacterial adhesion onto ureteric stents is essential to reduce the risk of UTI in connection with these devices.     

Treatment of a Giant Haemangioma of the Liver With Kasabach-Merritt Syndrome by Orthotopic Liver Transplant

We describe a case of giant cavernous haemangioma of the liver with disseminated intravascular coagulopathy (Kasabach-Merritt syndrome) which was cured by orthotopic liver transplant.A 47 year old man presented with bleeding and tender massive hepatomegaly after tooth extraction. Investigations showed disseminated intravascular coagulopathy and a giant hepatic haemangioma involving both lobes of the liver. Initial treatment failed to resolve the coagulopathy and liver resection was attempted. At laparotomy the turnout was unresectable and the only option for cure was to offer a liver transplantation. The orthotopic liver transplant was performed 20 days after initial laparotomy. Subsequently, all coagulation parameters returned to normal and the patient remains well after 12 months. Orthotopic liver transplant can be considered for giant hepatic haemangioma with Kasabach-Merritt syndrome when resection is necessary and a partial hepatectomy is not technically feasible.     

Effects of low-dose propofol administration on central respiratory drive, gas exchanges and respiratory pattern

The effects of sedative-hypnotic doses of propofol on respiratory drive and pattern have not yet been extensively described. Repeated small boluses of propofol (0.6-0.3 mg.kg-1) were administered to ten ASA I patients undergoing carpal tunnel release using regional anaesthesia. Airway pressure, capnography and pneumotachography were continuously recorded. With respect to basal values, no significant variations of respiratory rate, minute volume, tidal volume, inspiratory and expiratory time, total expiratory cycle, Ti/Ttot, TV/Ti, P0.1, EtCO2 and blood gas analysis were observed. Low doses of propofol, to maintain conscious sedation of light sleep, have not been shown to cause respiratory depression.     

Body mass and acute myocardial infarction. GISSI-EFRIM Investigators.

BACKGROUND. The relation between body mass index and acute myocardial infarction was analyzed using data from a multicentric case-control study conducted in Italy between September 1988 and June 1989 within the framework of the GISSI-2 trial. METHODS. Subjects were 916 patients with acute myocardial infarction and no history of cardiovascular disease and 1,106 controls hospitalized for acute conditions not related to known or suspected risk factors for ischaemic heart disease. RESULTS. Relative to the lowest quintile of the Quetelet Index (weight/height2) the estimated risks for subsequent quintiles were 1.2 (95% confidence intervals, (CI): 0.9 to 1.6), 1.7 (95% CI: 1.2 to 2.2), 1.8 (95% CI: 1.4 to 2.4), and 2.2 (95% CI: 1.7 to 3.0) when adjustment was made for age, sex, education, and smoking habits by means of logistic regression. The association was consistent across strata of sex, education, and smoking status, but not age. The estimated risk for subjects in the fifth quintile of the Quetelet Index relative to those in the first was 4.1 under 55 years of age, but only 1.7 between 55 and 64 years and 1.5 above age 65. CONCLUSION. The relation between body mass and myocardial infarction was explained, at least in part, by higher serum cholesterol levels and the prevalence of diabetes and hypertension among fatter subjects. This does not, however, totally eclipse a possible causal relation between body mass and risk of myocardial infarction, since these conditions are a consequence, rather than a confounder, of overweight.     

Varicocele and its surgical management

A discussion of the present role of varicocele in the management of the subfertile couple is presented, with emphasis on detection techniques and the increasing awareness of the presence of bilateral varicocele. The indications and techniques of surgical management are discussed, with particular emphasis on the use of the operating microscope to dissect the spermatic cord at the level of the external inguinal ring under local anesthesia on an outpatient basis with significant cost savings to the patient.