Exudative ascites complicating infectious mononucleosis.

A case of Epstein-Barr virus mononucleosis with the unusual complication of exudative ascites is presented. The patient was a 22-yr-old man with the typical symptoms and physical findings of hepatitis secondary to infectious mononucleosis. Extensive evaluation including liver biopsy, failed to show another cause for the patient's ascites. The ascites and hepatitis disappeared with resolution of the acute mononucleosis infection. He is well 12 months after this illness with no evidence for chronic liver disease. This case adds to the list of causes for exudative ascites associated with acute hepatitis.

Low incidence of hepatotoxicity associated with long-term, low-dose oral methotrexate in treatment of refractory psoriasis, psoriatic arthritis, and rheumatoid arthritis. An acceptable risk/benefit ratio.

Thirty patients with psoriasis or other nonmalignant diseases had liver biopsies done before treatment with low-dose methotrexate, 15 mg/week, and then at one- to two-year intervals as long as they continued the methotrexate. All patients were symptomatically improved on this regimen. The 15 patients who had normal liver biopsies at the start of the study had normal biopsies after methotrexate. Fifteen others had minor hepatic histologic abnormalities before treatment. Eleven patients had fatty infiltration. Ten showed no significant change after treatment while one had increased fat and portal fibrosis on a fourth liver biopsy done seven years after MTX was begun. This last patient, a former alcohol abuser, continued methotrexate and showed no further worsening at 8 years. The remaining four had portal fibrosis before treatment. One patient had less fibrosis after methotrexate, two patients slightly more fibrosis, and one a marked increase in portal fibrosis. No patient developed cirrhosis or clinical liver disease. Our results suggest that in the absence of alcohol consumption, low-dose weekly methotrexate treatment rarely causes clinically significant liver damage.

Towards enzyme replacement in GM2 gangliosidosis: organ disposition and induced central nervous system uptake of human beta-hexosaminidase in the cat.

The rapid plasma clearance of human placental beta-hexosaminidase in the cat is due mainly to a receptor-mediated mechanism recognizing terminal N-acetyl glucosaminyl and mannosyl residues on glycoproteins. Using a sensitive single radial immunodiffusion assay, specific for human beta-hexosaminidase, we have shown that, in normal cats, the liver is responsible for most of the clearance of human beta-hexosaminidase. Two hours after injection of approximately 6 X 10(6) U beta-hexosaminidase/kg bw, 70-90% of the enzyme was recovered in the liver. Spleen, kidney, lung, bone, bone, pancreas, adrenals, testes and ovaries, cardiac and skeletal muscle, lymph nodes, and placenta, however, also participated in the clearance, although specific uptake in most organs was < 5% of that of liver. Exogenous beta-hexosaminidase was also present in bile, indicating that the hepatocytes are involved in clearance. Injection of terminal mannose-rich S. cerevisiae mannans (50-150 mg/kg bw), prolonged the plasma half-life of the enzyme (t 1/2 up to 290 min). In these animals, beta-hexosaminidase uptake by liver was reduced to < 10% of controls but uptake by other organs was not proportionally or uniformly reduced, suggesting the existence of different uptake mechanisms in different tissues. Permeability of the blood-brain barrier was induced by exposing cats to 100% O2 at 2.5 ATA for 90 min. Injection of 6 X 10(6) U beta-hexosaminidase/kg bw during or immediately after exposure resulted in apparent uptake of enzyme by nervous tissue, qualitatively detectable by immunologic methods, but below the limits of sensitivity of the radial immunoassay(ie < 150 U/gr). When enzyme uptake by liver was inhibited by injection of ovomucoid or mannans, however, the hyperbaric oxygen-induced apparent uptake of beta-hexosaminidase by brain, cerebellum, and spinal cord was 200-500 U/gr of blood-free tissue, suggesting that the transport mechanism involved (presumably at the level of the nervous system vascular endothelium) is different from the carbohydrate-dependent hepatic uptake. The mechanism by which hyperbaric oxygenation induces permeability of the blood-brain barrier is not clear. The combination of this procedure (routinely used in human therapy) with specific inhibition of hepatic uptake, however, appears to be a promising approach for lysosomal enzyme targeting to the central nervous system.

Changes in the permeability of the blood-brain barrier under hyperbaric conditions.

Hyperbaric oxygen therapy (HBO) has been used in the treatment of cerebral edema with variable results. Two different actions of HBO, one decreasing and the other increasing cerebral edema, have been postulated. We examined the permeability of the blood-brain barrier (BBB) in rats and cats. Animals of each species were treated for 90 min/d with 100% oxygen at a pressure of 2.5 atm for 5 consecutive days. Following treatment, cadmium-free ferritin was injected intravenously. Sections of the brain were prepared for electron microscopic evaluation of the capillaries and their neighboring structures. Perivascular edematous zones were observed. Ferritin particles penetrated through the capillary endothelium and into the pericapillary structures. Hyperbaric oxygenation appears to increase the permeability of cerebral vessel walls in normal animals. Further work on this phenomenon may provide a more rational basis for the treatment of cerebral edema with HBO.