Haemodynamic and pharmacokinetic study of intravenous fenoldopam in patients with hepatic cirrhosis

1. The effect of intravenous fenoldopam-an arterial vasodilator-was assessed in twelve patients with cirrhosis and portal hypertension. Six patients had compensated (Grade A or B Child-Pugh classification) and six decompensated (Grade C) liver disease. 2. A significant dose dependent reduction in systemic blood pressure with a concomitant fall in systemic vascular resistance and increase in cardiac index was observed. Estimated portal pressure (WHVP-FHVP) increased (15.4 +/- 3.2 to 19.3 +/- 3.7 mm Hg, P less than 0.05) due to a rise in wedged hepatic venous pressure (24.6 +/- 4.3 to 29.0 +/- 5.8 mm Hg, P less than 0.05). Hepatic blood flow did not change significantly. Similar haemodynamic effects were observed in both compensated and decompensated patients. 3. Fenoldopam plasma clearance and ICG clearance were found to decrease with increasing infusion concentration, indicating possible increase of the intrahepatic shunting. 4. With the observed rise in portal pressure there must be some concern with respect to the long-term use of this drug in patients with previous variceal bleeding.     

Avian retrovirus S13: properties of the genome and of the transformation-specific protein

The avian retrovirus S13 codes for an env-linked transformation-specific glycoprotein with a molecular weight of 155,000 (gp155). Treatment of gp155 with endoglycosidase H or growth of S13-infected cells in the presence of tunicamycin reduces the molecular weight of gp155 to about 140K, but these gp155-related molecules may still contain sugar residues. The gp155 protein is not incorporated into virions; it is phosphorylated, but in immunoprecipitates does not show protein kinase activity. The genome of S13 is an 8.5-kilobase (kb) RNA; the helper virus genome is 7.5 kb in size. The putative onc sequences of S13 do not hybridize to DNA probes representing src, erb A, erb B, myc, myb, fps, fms, H-ras, B-lym, abl, rel, and ets.     

High incidence of endogenous depression in migraine: confirmation by tyramine test.

Forty patients with migraine who were attending a specialist clinic were interviewed with the Schedule for Affective Disorders and Schizophrenia--Lifetime version. Sixteen (40%) had a history of major depression which was of endogenous type in 15, according to Research Diagnostic Criteria. The tyramine test, a previously established trait marker for endogenous depression, showed that the migraine group as a whole had significantly low values compared with 14 normal controls, due almost entirely to low values in the endogenous depressive subgroup; there were no differences between diet-sensitive and non-diet-sensitive migraine patients. Thus depression in patients with migraine seems unlikely to be secondary to migraine per se. A substantial subgroup of patients with migraine may possess an inherent predisposition to endogenous depression.     

Enhanced strength of endothelial attachment on polyester elastomer and polytetrafluoroethylene graft surfaces with fibronectin substrate

Successful development of a vascular prosthesis lined with endothelium may depend on the ability of the attached cells to resist shear forces after implantation. The purpose of this article is to describe a model for measurement of endothelial detachment caused by shear stress and to identify biomaterials that resist loss of attached cells as a result of shear stress. With human umbilical venous endothelium labeled with indium 111-oxine, cellular attachment to uncoated and fibronectin-coated polyester elastomer and expanded polytetrafluoroethylene (e-PTFE) graft surfaces was quantified after an 18-hour incubation. PTFE grafts prepared by immediate seeding were also studied. The relative strength of endothelial attachment was determined by the percentage of the original inoculum remaining after the seeded graft surfaces were subjected to a physiologic shear stress of 15 dynes/cm2 during in vitro perfusion. In polyester elastomer grafts, fibronectin did not significantly increase initial attachment but did increase the percentage of inoculum remaining after perfusion (92.1% vs. 39.74%, p = 0.001). A similar relationship existed between fibronectin-coated e-PTFE and immediately seeded e-PTFE preparations with 61.6% and 25.8%, respectively, of the inoculum remaining after perfusion (p = 0.001). Furthermore, the percentage of inoculum retained on fibronectin-coated polyester elastomer was significantly greater than on fibronectin-coated e-PTFE (p = 0.001). In comparing uncoated grafts, polyester elastomer had 39.7% of the inoculum retained after perfusion whereas only 1.8% was remaining on the e-PTFE grafts (p = 0.0001). We conclude that polyester elastomer permits better endothelial cell attachment than e-PTFE and that fibronectin coating enhances the strength of attachment to both graft materials.     

Arterial intimal damage in avulsion and crush injuries in rat limbs

A stereotypical pattern of arterial intimal damage has been demonstrated in rat avulsed and crushed injuries. These intimal tears can be found up to 6 cm proximal to the site of injury in avulsion injuries and are found at a delayed time with crush injuries. In both types of injury, circumferential intimal and subintimal tears spaced approximately 1 mm apart were demonstrated. These findings suggest a structural arrangement of the muscular artery wall that predisposes it to a reproducible pattern of damage. Veins undergoing the same avulsion and crushing procedure did not manifest any change. The presence of musculature rings or a weakened medial layer in artery walls after avulsion and crush injuries may influence short term patency and also long-term clinical replantation results.     

An extended two-point dixon algorithm for calculating separate water,fat, and B0 images

A new algorithm is presented that provides separate water, fat, and B₀ images utilizing the in-phase and opposed-phase acquisitions of the two-point Dixon (2PD) method. The accuracy of the extended method (E2PD) compares favorably with the three-point Dixon (3PD) method, and the acquisition requires 2/3 the 3PD scan time. Slightly increased mismapping may occur in pixels containing an admixture of water and fat due to reduced SNR in the B₀ field map compared with the 3PD method.     

Effect of papaverine on endothelial cell harvest from canine external jugular veins.

Endothelial cell seeding procedures have been developed to line prosthetic bypass grafts used in peripheral vascular disease; however, because of current inefficient cell harvest techniques a high ratio of vein-to-graft area is necessary. This study was done to determine if the use of papaverine, a smooth muscle cell relaxant, would affect the number or viability of endothelial cells harvested from canine external jugular veins. Using a 0.12 mg/ml solution of papaverine in tissue culture medium to bathe the veins during dissection and excision, the viable cell yield was 2.20 +/- 1.16 (cells x 10(4)/cm2). A control group of veins using standard dissection technique gave a yield of 0.97 +/- 0.40 (p = 0.025). A second group of veins dissected while bathed in tissue culture medium alone gave a yield of 1.82 +/- 0.75, compared to a yield of 2.73 +/- 0.45 for papaverine harvested veins (p = 0.009). Percent cell viability was not significantly different for any of the groups: 73, 70, and 76% for papaverine, control and media only veins, respectively. The papaverine-harvested cells and those harvested with medium alone grew to 95% confluence in tissue culture in 9.8 +/- 1.1 and 9.9 +/- 0.9 days, respectively. Compared to conventional surgical techniques, use of papaverine more than doubled the endothelial cell yield from excised vein segments without adversely affecting viability or rate of growth in cell culture.     

Unusual presentation of cis-platinum neuropathy

Symptoms and signs of cis-diamminedichloroplatinum II (DDP) neuropathy usually develop during treatment and stabilize or improve when DDP is stopped. We report three patients whose symptoms began 3 to 8 weeks after the last dose of DDP and progressed over 1 or 2 months to moderate-marked disability. The clinical picture in each was consistent with DDP neuropathy, and no other cause could be identified. Two of the patients improved over 8 and 27 months to become asymptomatic; the other died 2 months after presentation. It is important to recognize that DDP neuropathy can present after treatment has been discontinued since the clinical picture mimics the paraneoplastic dorsal root ganglionitis, which has a different prognosis.