Warfarin or Low-Molecular-Weight Heparin Therapy does not Prolong Pig-To-Primate Cardiac Xenograft Function

Microvascular thrombosis is a prominent feature in cardiac delayed xenograft rejection (DXR). We investigated the impact of warfarin or low-molecular-weight heparin (LMWH) anti-coagulation on xenograft function using a heterotopic pig-to-primate model. Donor hearts were from CD46 transgenic pigs and baboon immunosuppression included tacrolimus, sirolimus, anti-CD20 and TPC, an alpha-galactosyl-polyethylene glycol conjugate. Three groups of animals were studied. Group 1 (n = 9) was treated with warfarin, Group 2 (n = 13) with LMWH and Group 3, received no anti-coagulant drugs. The median duration of xenograft function was 20 days (range 3-62 days), 18 days (range 5-109 days) and 15 days (range 4-53 days) in Groups 1 to 3 respectively. Anti-coagulation achieved the targeted international normalized prothrombin ratio (INR) and anti-factor Xa levels consistent with effective in vivo therapy yet, no significant impact on median xenograft function was observed. At rejection, a similar histology of thrombosis and ischemia was apparent in each group and the levels of fibrin deposition and platelet thrombi in rejected tissue was the same. Anti-coagulation with warfarin or LMWH did not have a significant impact on the onset of DXR and microvascular thrombosis. However, a role for specific anti-coagulant strategies to achieve long-term xenograft function cannot be excluded.     

Aplanatic gonioscopic contact lens of one piece for glaucoma laser surgery

A heterocentric aplanatic contact of one piece has been designed for optimal efficiency of laser surgery for ALT and YLT in the angle of the anterior chamber.     

Flavin analogs with antimalarial activity as glutathione reductase inhibitors

10-(4'-Chlorophenyl)-3-methylflavin has antimalarial activity in vitro and in vivo (Cowden et al., J Med Chem 31: 799, 1988). This flavin analog and two of its derivatives were found to inhibit the antioxidant flavoenzyme glutathione reductase from human erythrocytes in its isolated form as well as in hemolysates. The mixed-type inhibition was completely reversible, the Ki-values being of the order of 1 microM. Surprisingly, the drugs were not competitive with FAD, but with GSSG, one of the enzyme's substrates. Malaria parasite glutathione reductase, extracted from Plasmodium falciparum, could also be inhibited by the compounds. Studies on the effects of the substances on P. falciparum in vitro, which were demonstrated morphologically and by growth inhibition, confirmed previous observations with 10-(4'-chlorophenyl)-3-methylflavin and showed similar parasiticidal characteristics for the two new derivatives. The activities of five other erythrocytic enzymes tested were not impaired by the drugs, nor was the nucleotide metabolism of erythrocytes and/or parasites significantly changed. Permeation into red blood cells was demonstrated for one compound by 19F-NMR-spectroscopy. Inhibition of glutathione reductase might contribute to, or account for, the antimalarial activity of this group of flavin analogs.     

Simultaneous thermal and optical breakdown mode dual laser action.

Tests on blood agar and human tissue prove that the combined simultaneous dual laser action of a thermal and an optical breakdown mode laser ablates tissue by a mechanism of mutual enhancement of each laser's effect. The force of pressure and the energy of heat combine to ablate tissue in sclerostomy and iridotomy procedures without inducing bleeding.     

Effect of 7.2% Hypertonic Saline/6% Hetastarch on Left Ventricular Contractility in Anesthetized Humans

Background: Although a positive inotropic effect of hypertonic saline has been demonstrated in isolated cardiac tissue as well as in animal preparations, no information exists about a possible positive inotropic action of hypertonic saline in humans. The aim of this investigation was to determine whether a clinically relevant positive inotropic effect can be demonstrated in humans.

Methods: Twenty-six patients without cardiovascular disease were randomized to receive 4 ml/kg of either 7.2% hypertonic saline/6% hetastarch or 6% hetastarch (control) at a rate of 1 ml *symbol* kg sup -1 *symbol* min sup -1 while under general endotracheal anesthesia. Transesophageal echocardiography was used to evaluate left ventricular function. Arterial pressure, heart rate, and left ventricular end-systolic and end-diastolic diameter, area, and wall thickness were measured immediately before and after administration of either solution. Fractional area change, end-systolic wall stress, and the area under the end-systolic pressure-length relationship curve (ESPLRarea) were calculated. ESPLRarea was used to assess left ventricular contractility.

Results: Administration of hypertonic saline/hetastarch resulted in a significant decrease of mean arterial pressure and end-systolic wall stress from 77 plus/minus 14 (mean plus/minus SD) to 64 plus/minus 17 mmHg (P < 0.01) and from 52 plus/minus 14 to 32 plus/minus 11 103 dyne/cm2 (P > 0.01), respectively. End-diastolic area and fractional area change increased from 16.5 plus/minus 2.9 to 21.7 plus/minus 3.3 cm2 (P < 0.01) and from 0.53 plus/minus 0.07 to 0.70 plus/minus 0.06 (P < 0.01), respectively, whereas there was only a minor change of ESPLRarea from 38 plus/minus 13 to 44 plus/minus 13 mmHg.cm (P < 0.05).     

Laparoscopic bile duct injuries. Risk factors, recognition, and repair.

Records of 11 patients undergoing biliary reconstruction after laparoscopic cholecystectomy are reviewed. Ductal injuries resulted from failure to define the anatomy of Calot's triangle. Risk factors include scarring, acute cholecystitis, and obesity. Presenting findings included anorexia, ileus, failure to thrive, pain, ascites, and jaundice. All patients required hepaticojejunostomies, which were multiple and above the hepatic bifurcation in four patients. Given the extensive nature of these injuries and the frequent need for intrahepatic anastomosis and early stenosis of repairs by referring physicians, we recommend reconstruction be undertaken by an experienced hepatobiliary surgeon. To avoid injuries, a greater appreciation of risk factors and anatomic distortion and variance and strict adherence to principles of dissection and identification of anatomic structures are suggested. The use of cholangiography and a low threshold for conversion to the open procedure are advised.