Post-transplant acute limbic encephalitis: clinical features and relationship to HHV6.

BACKGROUND: Acute limbic encephalitis has been reported in the setting of treatment-related immunosuppression and attributed to human herpesvirus-6 (HHV6) infection. Clinical and laboratory features of the syndrome, however, have not been well characterized. METHODS: We describe the clinical, EEG, MRI, and laboratory features of nine patients with acute limbic encephalitis after allogeneic hematopoietic stem cell transplantation (HSCT). To explore the relationship between HHV6 and this syndrome, we reviewed available CSF HHV6 PCR results from all HSCT patients seen at our center from March 17, 2003, through March 31, 2005. RESULTS: Patients displayed a consistent and distinctive clinical syndrome featuring anterograde amnesia, the syndrome of inappropriate antidiuretic hormone secretion, mild CSF pleocytosis, and temporal EEG abnormalities, often reflecting clinical or subclinical seizures. MRI showed hyperintensities within the uncus, amygdala, entorhinal area, and hippocampus on T2, fluid-attenuated inversion recovery (FLAIR), and diffusion-weighted imaging (DWI) sequences. CSF PCR assays for HHV6 were positive in six of nine patients on initial lumbar puncture. All patients were treated with foscarnet or ganciclovir. Cognitive recovery varied among long-term survivors. The one brain autopsy showed limbic gliosis and profound neuronal loss in amygdala and hippocampus. Among 27 HSCT patients with CSF tested for HHV6 over a 2-year period, positive results occurred only in patients with clinical limbic encephalitis. CONCLUSIONS: Patients undergoing allogeneic hematopoietic stem cell transplantation are at risk for post-transplant acute limbic encephalitis (PALE), a distinct neurologic syndrome. Treatment considerations should include aggressive seizure control and, possibly, antiviral therapy. PALE can be associated with the CSF presence of human herpesvirus-6, but the pathogenic role of the virus requires further exploration.

Low-dose methotrexate therapy for cutaneous vasculitis of rheumatoid arthritis.

A patient with classic rheumatoid arthritis who developed leukocytoclastic vasculitis is described. Low-dose methotrexate produced prompt healing of the skin lesions. After discontinuation of methotrexate, the lesions recurred, with resolution after a second course of the drug. Methotrexate may be useful in the treatment of cutaneous vasculitis associated with rheumatoid arthritis.

Effects of dietary fish oil supplementation on polymorphonuclear leukocyte inflammatory potential.

Polymorphonuclear leukocytes (PMNLs) are an important contributor to inflammation and are thus a part of the pathophysiology of many human diseases. We assessed the effect of fish oil on PMNL inflammatory potential by measuring chemiluminescence and superoxide production before and after six weeks of daily cod liver oil ingestion by healthy volunteers. Phagocytosing PMNLs demonstrated a 27% decrease in chemiluminescence (P less than 0.05) and a 64% decrease in superoxide production (P less than 0.01), following the cod liver oil supplementation. Analysis of PMNL and platelet fatty acids revealed the appearance of eicosapentaenoic acid and a significant decrease in arachidonic acid in both types of cells.

Differential cyclic AMP responses to calcitonin among human ovarian carcinoma cell lines: a calcitonin-responsive line derived from a rare tumor type.

Several human tumor cell lines have been reported to have specific receptors for calcitonin (CT) and CT-responsive adenylate cyclase. In order to correlate patterns of responsiveness to CT, parathyroid hormone (PTH) and prostaglandin E2 (PGE2) with tumor morphology and intermediate filament protein expression, we examined four human ovarian tumor cell lines (BIN-16, BIN-22, BIN-53, BIN-67) which had been cultured from cells of metastatic foci. In two cell lines (BIN-53 and -16) there were small increases in cAMP content after exposure to CT and in three cell lines (BIN-53, -16, and -22) larger increases with PGE2. There was no cAMP response in any of the cells to PTH. In BIN-67 cells, however, CT induced a striking (greater than 20-fold) increase in cAMP content. Histologically, the CT-nonresponsive tumor lines were derived from serous adenocarcinomas while the CT-responsive tumor line was from a rare small cell carcinoma. Gel electrophoretic and immunofluorescence microscopic analyses had previously disclosed that the CT-nonresponsive cell lines contained high levels of simple epithelial keratins and no or very low levels of vimentin (characteristic of ovarian surface epithelial cells), while the CT-responsive cell line contained almost exclusively vimentin. Thus, cells cultured from a rare type of ovarian tumor were CT-responsive and were distinguishable from CT-nonresponsive ovarian tumor cells by initial tumor histology and intermediate filament protein expression.

Giant cell reparative granuloma of Paget's disease of bone: a unique clinical entity.

Giant cell tumor of bone is a rare, but well-recognized complication of Paget's disease of bone. In contrast, giant cell reparative granuloma (a benign tumor of the jaws occurring primarily in young adults) has never been described in association with Paget's disease. Five patients had giant cell lesions complicating Paget's disease. In each instance, the lesion histologically more closely resembled reparative granuloma than true giant cell tumor. The location of these lesions and their sensitivity to irradiation were consistent with reparative granuloma. Unique features included the frequency of polyostotic distribution, the occurrence only in bones affected by Paget's disease, and an apparent familial or geographic clustering of the patients. We also reviewed the histologic findings of three patients from another institution and compared the cases of all eight patients with others we believe were incorrectly diagnosed as having benign giant cell tumors in Paget's disease. We suggest that giant cell reparative granuloma of Paget's disease is a unique clinical entity with specific prognostic and therapeutic implications.

Pathogenetic role of 1 alpha,25-dihydroxyvitamin D in sarcoidosis and absorptive hypercalciuria: different response to prednisolone therapy.

Intestinal hyperabsorption of calcium (Ca) is frequently observed in sarcoidosis and is characteristic of absorptive hypercalciuria (AH). The potential pathogenetic role of 1 alpha,25-dihydroxyvitamin D [1,25(OH)2D] in these two conditions was sought by a careful assessment of the circulating concentration of this vitamin D metabolite and various measures of Ca metabolism before and after prednisolone therapy. In eight patients with sarcoidosis, prednisolone treatment (50 mg/day for 8 days) produced a significant fall in serum 1,25(OH)2D [4.8 +/) 1.9 to 3.3 +/- 1.0 (SD) ng/dl; P less than 0.025], concomitant with a significant decrease in the fracitional intestinal Ca absorption (alpha) from 0.58 +/- to 0.14 to 0.46 +/- 0.13 (+/- SD; P less than 0.005). Urinary Ca and serum parathyroid hormone did not change significantly. However, in six patients with AH, prednisolone therapy resulted in a nonsignificant rise in serum 1,25(OH)2D from 3.6 +/- 0.7 to 4.4 +/- 1.0 ng/dl and no significant fall in alpha (from 0.73 +/- 0.08 to 0.70 +/- 0.10). Urinary Ca was significantly increased in AH patients from 230 +/- 35 to 343 +/- 74 (SD) mg/day (P less than 0.005), while serum parathyroid hormone rose slightly. Serum 1,25(OH)2D and alpha were significantly correlated (r = 0.543; P less than 0.05) for patients with sarcoidosis but not in AH patients. These results suggest that the hyperabsorption of calcium in sarcoidosis is dependent on the serum concentration of 1,25(OH)2D, while in AH it may result from additional vitamin D-independent processes.

Hypoxanthine phosphoribosyltransferase deficiency: association of reduced catalytic activity with reduced levels of immunologically detectable enzyme protein.

In the present study hemolysates from fourteen patients with a genetically determined deficiency of hypoxanthine phosphoribosyltransferase (EC 2.4.2.8; IMP:pyrophosphate phosphoribosyltransferase) activity were examined immunologically for the presence of material that crossreacts with the normal enzyme. A quantitative assay for crossreacting material in enzyme-deficient hemolysates was based on the inhibition of the immunoprecipitation of the normal enzyme. As little as 3% of normal crossreacting material could be detected. One patient in this series was found to have a normal amount of crossreacting material, whereas the remainder had no detectable crossreacting protein. The lack of detectable crossreacting material in these patients raises the possibility that a defect in synthesis or degradation of enzyme protein may be present in many patients deficient in hypoxanthine phosphoribosyltransferase.