Khazal Paradis

Pig organs may offer a solution to the shortage of human donor organs for transplantation, but concerns remain about possible cross-species transmission of porcine endogenous retrovirus (PERV). Samples were collected from 160 patients who had been treated with various living pig tissues up to 12 years earlier. Reverse transcription-polymerase chain reaction (RT-PCR) and protein immunoblot analyses were performed on serum from all 160 patients. No viremia was detected in any patient. Peripheral blood mononuclear cells from 159 of the patients were analyzed by PCR using PERV-specific primers. No PERV infection was detected in any of the patients from whom sufficient DNA was extracted to allow complete PCR analysis (97 percent of the patients). Persistent microchimerism (presence of donor cells in the recipient) was observed in 23 patients for up to 8.5 years.

Hereditary tyrosinemia results from an inborn error in the final step of tyrosine metabolism. The disease is known to cause acute and chronic liver failure, renal Fanconi's syndrome, and hepatocellular carcinoma. Neurologic manifestations have been reported but not emphasized as a common problem. In this paper, we describe neurologic crises that occurred among children identified as having tyrosinemia on neonatal screening since 1970. Of the 48 children with tyrosinemia, 20 (42 percent) had neurologic crises that began at a mean age of one year and led to 104 hospital admissions. These abrupt episodes of peripheral neuropathy were characterized by severe pain with extensor hypertonia (in 75 percent), vomiting or paralytic ileus (69 percent), muscle weakness (29 percent), and self-mutilation (8 percent). Eight children required mechanical ventilation because of paralysis, and 14 of the 20 children have died. Between crises, most survivors regained normal function. We found no reliable biochemical marker for the crises (those we evaluated included blood levels of tyrosine, succinylacetone, and hepatic aminotransferases). Urinary excretion of delta-aminolevulinic acid, a neurotoxic intermediate of porphyrin biosynthesis, was elevated during crises but also during the asymptomatic periods. Electrophysiologic studies in seven patients and neuromuscular biopsies in three patients showed axonal degeneration and secondary demyelination. We conclude that episodes of acute, severe peripheral neuropathy are common in hereditary tyrosinemia and resemble the crises of the neuropathic porphyrias.

OBJECTIVE: Cavernous transformation of the portal vein is defined as the formation of venous channels within or around a previously thrombosed portal vein. The purpose of this work was to study the hemodynamic consequences of cavernous transformation of the portal vein in a group of afflicted patients by use of Doppler sonography. We wished to study the evolution from portal vein thrombosis to the formation of cavernous transformation, the extent of resulting extrahepatic collateral channels, and the patterns of splanchnic collateral circulation. MATERIALS AND METHODS: Seventy-five patients (48 adults and 27 children) with cavernous transformation of the portal vein were studied with color and/or pulsed Doppler sonography. Blood flow in the extrahepatic portal vein, in its segmental branches, in the hepatic veins and artery, and in the splanchnic veins was examined. Collateral pathways were sought. For nine patients with acute thrombosis of the portal vein, serial examinations were performed during the formation of cavernous transformation. RESULTS: In nine patients, a fresh thrombus filled and distended the portal vein and became recanalized within a few days. Tortuous vessels appeared at the porta hepatis. These were characterized as veins or arteries with Doppler sonography. Soon the portal vein could no longer be identified within the mass of tortuous vessels. The cavernous transformation developed within 6-20 days of the acute thrombosis. A spongelike mass of collateral vessels around the main portal vein was seen in all but two patients. Intrahepatic extension of the cavernous transformation was seen in 57 patients (76%) and involved one or more intrahepatic portal veins. Two types of collateral circulation were observed: portosystemic, mainly through the left gastric and the perisplenic veins (the caput medusae, i.e., the paraumbilical-to-abdominal venous route, was never seen); and portoportal, from the periportal or pericholecystic venous channels to the intrahepatic portal veins. In nine patients, flow within unaffected intrahepatic branches of the portal vein was reversed as directed toward the cavernous transformation surrounding other, thrombosed intrahepatic segments of the portal vein. CONCLUSION: After thrombosis of the portal vein, portoportal venous channels may form not only at the porta hepatis but also within the liver. Intrahepatic blood may be shunted from one segmental portal vein to another. In addition, portosystemic collateral channels are formed, suggesting that, despite extensive hemodynamic adaptations, portal hypertension ensues.

A previous study (Savoie et al, Blood 83:2715, 1994) identified eight transplant patients who acquired Epstein-Barr virus (EBV) infection during the peritransplant period. Three of these patients subsequently developed B-cell lymphoproliferative disease within 4 months of transplantation. Among these, there was a 16-year-old liver transplant patient who was negative for EBV at the time of transplant and who received an EBV-negative organ. After transplant, this patient was transfused with 9 U of packed red blood cells. Eight of the donors were EBV-positive and one was EBV-negative. We succeeded in obtaining spontaneous lymphoblastoid cell lines (LCLs) from the blood of three of these donors, one of whom also yielded a cord-blood line established with his throat-wash EBV. Blood from a fourth donor did not yield an LCL, but his throat washing did have transforming activity when inoculated onto cord-blood leukocytes. We initially could establish spontaneous LCLs only from the recipient's blood. However, a throat-wash sample taken 11 weeks later did show transforming activity. The recipient was shown to have acquired the EBV infection from one of eight EBV-seropositive blood donors. Analysis of fragment length polymorphisms after polymerase chain reaction amplification of the EBV BamHI-K fragment was used to establish strain identity. Western blot analysis for existence of size polymorphisms in three classes of Epstein-Barr nuclear antigens (EBNA-1, EBNA-2, and EBNA-3) confirmed the DNA results. It is noteworthy that the blood donor responsible for transmitting his EBV strain to the recipient had experienced clinical infectious mononucleosis 15 months before donating blood. Our results may, thus, indicate a requirement for leukodepletion of blood destined for immunosuppressed EBV-negative patients. Finally, blood donors with a recent history of infectious mononucleosis should probably be identified so that their blood is not given to EBV-negative transplant patients.