Showing papers by "William Small published in 2003"

Cytostatic properties of some angiotensin I converting enzyme inhibitors and of angiotensin II type I receptor antagonists.

Abstract: Angiotensin converting enzyme (ACE) inhibitors and angiotensin II (AII) type 1 receptor antagonists have strong cytostatic properties on in vitro cultures of many normal and neoplastic cells. They are effective, in particular, in reducing the growth of human lung fibroblasts, renal canine epithelial cells, bovine adrenal endothelial cells, simian T lymphocytes, and of neoplastic cell lines derived from human neuroblastomas, a ductal pancreatic carcinoma of the Syrian hamsters, human salivary glands adenocarcinomas, and two lines of human breast adenocarcinomas. ACE inhibitors are also effective in protecting lungs, kidneys and bladders from the development of nephropathy, pneumopathy, cystitis, and eventually fibrosis in different models of organ-induced damage such as exposure to radiation, chronic hypoxia, administration of the alkaloid monocrotaline or bladder ligation. ACE inhibitors and AII type 1 receptor antagonists are also effective in reducing excessive vascular neoformation in a model of injury to the cornea of rats and rabbits, and in controlling the excessive angiogenesis observed in the Solt-Farber model of experimentally induced hepatoma, in methylcholantrene or radiation-induced fibrosarcomas, in radiation-induced squamous cell carcinomas and in the MA-16 viral-induced mammary carcinoma of the mouse. Captopril was, in addition, effective in controlling tumor growth in a case of Kaposi's sarcoma in humans. The inhibition of AII synthesis and/or its blockade by AII receptors is likely to be an important mechanism for this cytostatic action. The mitogenic effect of AII is well established and a reduction of AII synthesis may well explain cell and neoplasm delayed growth. Moreover, AII regulates and enhances the activity of several growth factors including transforming growth factor B (TGFB) and smooth muscle actin (SMA); and many of these factors are reduced in tissues of animals treated with ACE inhibitors and AII type 1 receptor antagonists. These processes seem to be particularly relevant in the control of fibroblast growth and in the control of the ensuing fibrosis. The ACE inhibitors containing a sulphydril (SH) or thiol radical in their moiety (Captopril and CL242817) seemed to be more effective in controlling fibrosis and the growth of some neoplastic cells than those ACE inhibitors without this thiol radical in their structure, even if the second group of these drugs show in vitro a stronger inhibitory effect on converting enzyme activity. Pharmacologically it is known that ACE inhibitors containing a thiol radical also have antioxidant properties and they are efficient in controlling metalloproteinase action. However, although these additional properties are pharmacologically relevant, the blockade of AII synthesis plays an essential role in the cytostatic activity of these two categories of drugs. These observations underline that in addition to the beneficial effect of these drugs on the cardiovascular system, new potential applications are opening for their wider deployment.

A two institution experience with 226 endoscopically placed jejunal feeding tubes in critically ill surgical patients

Abstract: Background Early jejunal feeding after surgery or trauma reduces infectious complications. Although not ideal gastric and postpyloric feedings are often used, however, because of difficulty in placing feeding tubes distal to the ligament of Treitz (LOT). Our hypothesis was that feeding tube placement distal to the LOT can be accomplished using a bedside transendoscopic technique. Methods Transendoscopic jejunal (TEJ) tube placement and TEJ tubes inserted simultaneously through percutaneous gastrostomy (PEG) tubes (PEG/TEJ) were attempted to be placed distal to the LOT. Results In all, 226 feeding tubes (185 TEJ, 41 PEG/TEJ) were placed in 179 trauma and 47 nontrauma patients over 3 years (August 20, 1998 to July 15, 2001). Tube location was jejunal in 93.8% of trauma patients, 76.6% of nontrauma patients, and 90.3% of all patients. (Confidence intervals were 89.3% to 96.5%, 62.8% to 86.4%, and 85.7% to 93.5%). Days of total parenteral nutrition were reduced 71.3% in trauma patients, 22.8% in nontrauma patients, and 45% overall at one institution. Conclusions Bedside TEJ and PEG/TEJ placement is safe and successful in placing feeding tubes distal to the LOT in more than 90% of critically ill surgical patients.