Intracellular phosphorylation of broad-spectrum anti-DNA virus agent (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine and inhibition of viral DNA synthesis

The acyclic nucleotide analogue (S)-9-(3-hydroxy-2-phosphonyl-methoxypropyl)-adenine [(S)-HPMPA], which contains a phosphonate-substituted aliphatic chain, is a potent and selective inhibitor of the replication of various DNA viruses, including herpes simplex virus type 1 (HSV-1). We have synthesized radiolabeled (S)-[U-14C-adenine]HPMPA and investigated its metabolism by HSV-1-infected and mock-infected cells. The drug is as such taken up by the cells and subsequently converted to its monophosphoryl [(S)-HPMPAp] and diphosphoryl [(S)-HPMPApp] derivatives by cellular enzymes. It is incorporated to a very low extent into DNA of both mock-infected and HSV-1-infected Vero cells. (S)-HPMPA inhibits HSV-1 DNA synthesis at a concentration that is several orders of magnitude lower than the concentration required for inhibition of cellular DNA synthesis. Thus the selectivity of (S)-HPMPA as an antiviral agent cannot be attributed to a differential phosphorylation by virus-infected or uninfected cells but resides in a specific inhibitory effect on viral DNA synthesis. The exact basis for the latter effect is under investigation.     

Total abdominal hysterectomy and bilateral salpingo-oophorectomy. A sufficienttreatment for patients with low risk endometrial carcinoma

Leijon T; Rosenberg P; Boeryd B. Total abdominal hysterectomy and bilateralsalpingo-oophorectomy. A sufficient treatment for patients with low riskendometrial carcinoma. Int. J. Gynecol Cancer 1997; 7:376–380.
In this prospective study, 248 surgical state I endometrial carcinomapatients with favorable prognostic factors were included. All patients weretreated only with total abdominalhysterectomy and bilateral salpingo-oophorectomy. The clinical outcome andrelapse rate were the endpoints. Only 3% of the patients recurred andthe total survival rate was96% during a median observation time of 42 months. We conclude that atotal abdominal hysterectomy and bilateral salpingo-oophorectomy is adequatetreatment for this groupof patients. In this material seven out of nine recurrences were detected byscheduled controls. Among the five patients with local recurrences, four wereasymptomatic and diagnosed during scheduled follow-up examination.     

Interaction of complement and clusterin in renal injury.

Clusterin is a heterodimeric glycoprotein that has been associated with such diverse biologic functions as reproduction, cell regression, cell aggregation, and regulation of the cytolytic activity of the membrane attack complex of complement. Clusterin is a component of glomerular immune deposits in the kidney, and increased clusterin expression occurs in a number of renal injury states. To further explore the interaction between clusterin and complement, the requirement for an intact complement system for renal clusterin induction in an acute (folic acid nephropathy) and a chronic (subtotal renal ablation) model of renal injury was examined. After it was first demonstrated that folic acid increased renal clusterin mRNA in the rat, a species in which renal clusterin was highly inducible by other stimuli, the effects of folic acid (250 mg/kg ip) on clusterin mRNA and immunoreactivity were examined in mice sufficient and deficient for the fifth component of complement. Similar increases in clusterin mRNA and immunoreactivity were seen in both the C5-sufficient and C5-deficient mice compared with their respective vehicle-injected control groups. Renal clusterin mRNA was also increased to a similar extent in the remaining kidney of both C5-sufficient and C5-deficient mice 10 days after subtotal nephrectomy. In conclusion, the induction of clusterin after folic acid administration or subtotal nephrectomy was independent of the presence of an intact complement system, because similar increases in clusterin expression were observed in C5-sufficient and C5-deficient mice.     

Assessment of technical surgical skills.

OBJECTIVE: To review methods of assessment of technical surgical competence, and to point out the potential benefit of such assessment to training and safe practice. DESIGN: Review of publications about methods of evaluation of technical surgical competence. Studies were identified through MEDLINE using the keywords surgery, assessment, operative skills, training, and competence. The references cited in these studies were reviewed to find out whether any other trials fitted the selection criteria. SETTING: Teaching hospital, Denmark. RESULTS: There are several validated methods that allow objective assessment of operative skills for both open and laparoscopic surgery. CONCLUSIONS: Objective assessment of technical surgical skills is possible and reliable and valid methods are available. There are good reasons to implement evaluation programmes as a part of surgical education.     

An electric artificial heart for clinical use.

Advances in microelectronics, high-strength magnets, and control system design now make replacement of the heart using an implantable, electrically powered pump feasible. The device described herein is a compact, dual pusher plate unit with valved polyurethane sac-type ventricles positioned at either end. The power unit consists of a small, brushless direct current motor and a motion translator. A microprocessor control system is used to regulate heart beat rate and provide left-right output balance. Bench studies lasting for as long as 1 year have been performed. Heart replacement with the electric heart has been performed in 18 calves since 1984. The longest survivor lived for more than 7 months. Among the causes of termination were component failure, thromboembolic complications, and bleeding. No major problem has been identified that precludes prolonged use of the electric heart. In the future the patient with end-stage heart disease will have an electric artificial heart as one therapeutic option.