Hereditary protein C deficiency and portal-vein thrombosis

Inherited defects of the natural coagulation inhibitors predispose patients to thrombosis. These disorders have similar clinical presentations with a strong family history of thrombosis, episodes of recurrent venous thromboembolism, beginning in early adulthood. We report a case of upper gastrointestinal bleeding in a patient with portal hypertension due to portal-vein thrombosis secondary to hereditary protein C deficiency, an association that has seldom been reported.     

Familias Unidas: The Efficacy of an Intervention to Promote Parental Investment in Hispanic Immigrant Families

This paper reports a test of the efficacy of Familias Unidas, a Hispanic-specific, ecologically focused, parent-centered preventive intervention, in promoting protection against and reducing risk for adolescent behavior problems. Specifically, the intervention was designed to foster parental investment, reduce adolescent behavior problems, and promote adolescent school bonding/academic achievement, all protective factors against drug abuse and delinquency. One-hundred sixty seven Hispanic families of 6th and 7th grade students from three South Florida public schools were stratified by grade within school and randomly assigned to intervention and no-intervention control conditions. Results indicated that Familias Unidas was efficacious in increasing parental investment and decreasing adolescent behavior problems, but that it did not significantly impact adolescent school bonding/academic achievement. Summer-vacation rates of adolescent behavior problems were six times higher in the control condition than in the intervention condition. Furthermore, change in parental investment during the intervention was predictive of subsequent levels of adolescent behavior problems. The findings suggest that Familias Unidas is efficacious in promoting protection and reducing risk for adolescent problem behaviors in poor immigrant Hispanic families.     

Choledochoenterostomy with an anti-reflux mechanism

A new technique of choledochoenterostomy was devised to solve some of the problems of enterobiliary anastomosis with a normal calibre. The distal extremity of the common bile duct is completely surrounded by the bowel mucosa to a length of 3 cm after seromyectomy of a bowel wall rectangle of 4 × 1 cm. Experimental studies in rats and dogs demonstrated that this procedure prevents the risks of anastomotic disruption and functions like a mechanical unidirectional valve, which has great efficacy in stopping enterobiliary reflux. Studies in ten patients with obstructive jaundice with an extrahepatic biliary dilation less than 1.2 cm diameter submitted to this procedure Confirmed the experimental results. All patients were asymptomatic, without jaundice and with normalization of the liver enzymes after 2 months. The permeability of the valvular anastomosis studied by cholangiography, the HIDA ^99mTc test and manometry was quite similar to other classical biliary-enteric anastomosis. In contrast, anti-reflux efficacy was only demonstrated in patients with a valvular anastomosis.     

Serotonin 5- HT (2C) receptor knockout mice: autoradiographic analysis of multiple serotonin receptors.

Quantitative receptor autoradiography was used to study possible alterations of the densities of multiple serotonin (5-HT) receptor subtypes and of serotonin transporter in the brain of 5-HT(2C) receptor knockout mice. The radioligands employed were [(3)H]citalopram, [(3)H]WAY100,635, [(3)H]8-OH-DPAT, [(3)H]GR125743, [(3)H]sumatriptan, [(3)H]MDL100,907, [(125)I](+/-)DOI, [(3)H]mesulergine, [(3)H]5-HT, [(3)H]GR113808, and [(3)H]5-CT. As expected, radioligands that label 5-HT(2C) receptors showed a complete absence of labeling in mutant mice choroid plexus and significantly reduced densities in other brain regions expressing 5-HT(2C) receptors. With the rest of the radioligands, no significant alterations in the densities of labeled sites were found in any brain region. In situ hybridization showed no changes in 5-HT(2A) receptor and serotonin transporter mRNA levels, whereas 5-HT(2C) receptor mRNA levels were reduced in certain brain regions. The present results indicate that the mouse serotonergic system does not exhibit compensatory up- or down-regulation of the majority of its components (serotonin transporter and most 5-HT receptor subtypes) in response to the absence of 5-HT(2C) receptors.     

Differential effects of monoclonal antibodies to tumor necrosis factor alpha and gamma interferon on induction of hepatic nitric oxide synthase in experimental gram-negative sepsis.

To investigate the stimuli required for the induction of nitric oxide synthase (NOS) in sepsis, we have analyzed the levels of this enzyme in the livers of mice infected with a 90% lethal dose of Escherichia coli in a model of gram-negative sepsis. Hepatic NOS levels are markedly induced in this model, with peak values occurring 12 to 22 h following infection. Treatment with TN3-19.12, a neutralizing monoclonal antibody to tumor necrosis factor alpha (TNF-alpha), resulted in complete protection from death in this model of sepsis but had no significant effect on the level of induction of hepatic NOS. Treatment with H22, a monoclonal antibody to gamma interferon (IFN-gamma), also gave significant protection against death and, in addition, did lead to a decrease in the level of induction of the hepatic NOS. Treatment of mice with pure TNF-alpha (0.2 microgram), IFN-gamma (2,000 U), or a combination of the two did not induce the hepatic NOS, but treatment with the combination led to significant mortality (probability of survival at 22 h, 0.32). Thus, the level of induction of NOS within the liver either in sepsis or by the coadministration of TNF-alpha and IFN-gamma does not correlate with death.     

Mitochondrial DNA variability detected in a single wheat regenerant involves a rare recombination event across a short repeat

The mitochondrial genome of the selfed progeny of a plant regenerated from long-term somatic tissue culture displays specific structural rearrangements characterized by the appearance of novel restriction fragments. A mitochondrial DNA library was constructed from this selfed progeny in the SalI site of cosmid pHC79 and the novel fragments were subsequently studied. They were shown to arise from reciprocal recombination events involving DNA sequences present in the parental plant. The regions of recombination were sequenced and the nucleotide sequences were aligned with those of the presumptive parental fragments. We characterized an imperfect short repeated DNA sequence, 242 bp long, within which a 7-bb DNA repeat could act as a region of recombination. The use of PCR technology allowed us to show that these fragments were present in both parental plants and tissue cultures as low-abundance sequence arrangements.     

Modulation of trenimon-induced cytotoxicity by DT-diaphorase in isolated rat hepatocytes under aerobic versus hypoxic conditions.

Trenimon belongs to a class of aziridinylbenzoquinone anticancer drugs that cross the blood-brain barrier. In this study we have investigated the molecular mechanisms for trenimon-induced toxicity in aerobic versus hypoxic conditions with the use of freshly isolated rat hepatocytes. The following evidence suggests the mechanisms for trenimon detoxification involves reduction by DT-diaphorase, while the cytotoxic mechanism involves macromolecular alkylation under hypoxic conditions as well as oxidative stress under aerobic conditions. (a) Hepatocyte cytotoxicity induced by trenimon (250 microM) under aerobic conditions ensued following an initial induction of cyanide-resistant respiration and partial oxidation of glutathione to oxidized glutathione. Trenimon reduction to the hydroquinone by the hepatocytes was rapid. Inhibition of hepatocyte DT-diaphorase by dicumarol increased trenimon-induced cytotoxicity by approximately 10-fold, and markedly inhibited hydroquinone formation. Furthermore, both cyanide-resistant respiration and oxidized glutathione formation were markedly increased, resulting in depletion of oxygen in the media. Trenimon reduction to the hydroquinone then occurred. This suggests that DT-diaphorase in normal hepatocytes prevents the formation of the semiquinone that causes cytotoxic protein alkylation and oxidative stress. (b) Hepatocyte cytotoxicity induced by trenimon (350 microM) under hypoxic conditions ensued following glutathione depletion without oxidized glutathione formation. Inactivation of hepatocyte DT-diaphorase by dicumarol under hypoxic conditions increased trenimon-induced cytotoxicity by approximately 3.5-fold and increased semiquinone radical levels 2-fold without affecting its reduction rate. This suggests that the cytotoxic mechanism involves protein alkylation by semiquinone radicals formed by reductases catalyzing a one-electron reduction of trenimon.     

Transesophageal echocardiography-guided cardioversion of atrial fibrillation. Selection of a low-risk group for immediate cardioversion.

INTRODUCTION: In patients (pts) with atrial fibrillation (AF) of more than 48 hours' duration, electrical cardioversion (ECV) should only be performed after 3 weeks of effective anticoagulation. Transesophageal echocardiography (TEE) allows earlier ECV; however, despite exclusion of thrombi in the atrium and left atrial appendage (LAA), cases of thromboembolism related to ECV have been documented in AF. To define a low-risk group for cardioversion without previous anticoagulation, pts were selected for immediate ECV if no thrombi or dynamic spontaneous echo contrast (auto-contrast) were found after TEE and if LAA velocity was more than 0.25 m/sec. METHODS AND RESULTS: We performed TEE in 31 consecutive pts referred for ECV for AF of more than 48 hours' duration and without previous anticoagulation. After TEE the pts eligible for immediate ECV began anticoagulation with low molecular weight heparin (enoxaparin), subcutaneously in therapeutic doses, together with warfarin immediately before cardioversion. Enoxaparin was continued until an INR of over 2 was reached. Based on the TEE findings, the pts were divided in 2 groups: immediate ECV, group A, 20 pts with a mean age of 62 +/- 13 years, 6 female; and conventional therapy with warfarin before ECV, group B, 11 pts, mean age of 67 +/- 10 years (p < 0.05), 2 female. None of the pts in either group had mitral stenosis or previous episodes of thromboembolism. The mean transverse diameter of the left atrium in the 31 pts was 47 +/- 4.5 mm, without statistically significant differences between the 2 groups. Of the 11 pts in group B, 3 had a thrombus in the LAA, 6 dynamic spontaneous echo contrast and the remainder LAA velocities of less than 0.25 m/sec. ECV was achieved in all the pts, with no complications. Oral anticoagulation was maintained for at least a month. At one month, sinus rhythm was maintained in 75% of group A and 45% of group B (p < 0.01). CONCLUSION: In pts with AF of more than 48 hours' duration and no previous history of thromboembolism, the use of our exclusion criteria during TEE enabled stratification of a low-risk population for immediate ECV, which was accomplished effectively and safely in 2/3 of the pts. This strategy is associated with early symptomatic improvement, and may contribute to maintenance of sinus rhythm after one month, which was significantly better than in the pts who had prolonged therapy with warfarin before ECV, despite the differences found in age and left ventricular function.